Short-Term Outcomes of Endoscopic Ultrasound-Guided Pancreatic Cyst Ablation: A Systematic Review and Meta-Analysis 

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Abstract Background Pancreatic cysts (PC) are increasingly detected through abdominal imaging, prompting exploration of alternatives such as endoscopic ultrasound-guided pancreatic cyst ablation (EUS-PCA) due to the risks and costs associated with surgery. This study conducts a systematic review and meta-analysis of EUS-PCA's short-term efficacy and complications for PC management. Methods A systematic review and meta-analysis were carried out on PubMed, Ovid, Cochrane, and TRIP electronic databases. The primary outcome was cyst resolution (partial and complete) and persistence on imaging 12 months after ablation. The secondary outcome was procedure-related adverse events. Results Eight studies were eligible for analysis. Complete cyst resolution on imaging 12 months after EUS ablation was 50% [95% CI 36, 63, I2 = 85.31%]. Partial cyst resolution was 27% [95% CI 15, 41, I2 = 87.07%], and cyst persistence was 17% [95% CI 11, 24, I2 = 62.11%]. The rate of complete resolution varied depending on the treatment agent (for ethanol 29% [95% CI 10, 53], lauromacrogol 51% [95% Cl 36, 67], ethanol and paclitaxel 63% [95% CI 48, 76], paclitaxel and gemcitabine 67% [95% CI 45, 83], ethanol, paclitaxel and gemcitabine 61% [95% CI 39, 80]). Post-procedure adverse events included abdominal pain in 4% [95% CI 0, 11], pancreatitis in 3% [95% CI 1, 5], and fever in 1% [95% CI 0, 3] of all patients. Conclusion The treatment of pancreatic cysts with EUS ablation results in acceptable levels of complete resolution, and low incidence of severe adverse events. The effectiveness of this treatment is further enhanced when chemoablative agents are employed.
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This study conducts a systematic review and meta-analysis of EUS-PCA's short-term efficacy and complications for PC management. Methods A systematic review and meta-analysis were carried out on PubMed, Ovid, Cochrane, and TRIP electronic databases. The primary outcome was cyst resolution (partial and complete) and persistence on imaging 12 months after ablation. The secondary outcome was procedure-related adverse events. Results Eight studies were eligible for analysis. Complete cyst resolution on imaging 12 months after EUS ablation was 50% [95% CI 36, 63, I2 = 85.31%]. Partial cyst resolution was 27% [95% CI 15, 41, I2 = 87.07%], and cyst persistence was 17% [95% CI 11, 24, I2 = 62.11%]. The rate of complete resolution varied depending on the treatment agent (for ethanol 29% [95% CI 10, 53], lauromacrogol 51% [95% Cl 36, 67], ethanol and paclitaxel 63% [95% CI 48, 76], paclitaxel and gemcitabine 67% [95% CI 45, 83], ethanol, paclitaxel and gemcitabine 61% [95% CI 39, 80]). Post-procedure adverse events included abdominal pain in 4% [95% CI 0, 11], pancreatitis in 3% [95% CI 1, 5], and fever in 1% [95% CI 0, 3] of all patients. Conclusion The treatment of pancreatic cysts with EUS ablation results in acceptable levels of complete resolution, and low incidence of severe adverse events. The effectiveness of this treatment is further enhanced when chemoablative agents are employed. Pancreatic cysts endoscopic ultrasound cyst ablation Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 What You Need to Know Background: Pancreatic cysts are a rising concern, with a prevalence of up to 10% in individuals over 70 in the US. These cysts encompass diverse pathology, notably intraductal papillary mucinous neoplasms, and their optimal management remains uncertain. Findings: EUS-PCA proves effective, achieving nearly 80% cyst resolution after 12 months, especially for larger cysts (>2 cm) and when employing chemotherapeutic agents. It also demonstrates a lower risk of complications compared to surgery, making it a valuable alternative, particularly for unsuitable surgical candidates. Implications for Patient Care: EUS-PCA is an effective and safer option for managing pancreatic cysts, with potential benefit in reducing malignancy risk. Introduction In recent years, the prevalence of pancreatic cysts (PCs) has risen significantly, primarily attributed to the widespread use of cross-sectional abdominal imaging techniques. This increase has led to a greater identification of incidental findings related to PCs. The incidence of PCs reported on computed tomography (CT) is 9% and 27% on magnetic resonance imaging (MRI) [ 1 , 2 ]. In the United States, the prevalence of PCs in the elderly is estimated at 2.5–6.6% and increases to 10% in persons over 70 years of age [ 1 , 3 , 4 ]. PCs reflect a diverse array of histopathology ranging from benign to malignant. Intraductal papillary mucinous neoplasms (IPMNs), the most common PCs, have the potential for malignant transformation. Although many guidelines have been developed, the optimal management of IPMNs remains unclear. Current management for PCs is based on the potential of malignancy and symptomology. Surgery is the primary approach for managing symptomatic and high-risk pancreatic cysts; however, it carries perioperative risks of morbidity (such as infections, pancreatic leaks, and fistulae) and rare mortality [ 5 – 7 ]. Furthermore, surgical resection may cause long-term development of diabetes and exocrine insufficiency [ 4 ]. Most patients with PCs will undergo long-term surveillance until they are unfit for surgical management or the PCs develop high risk features but this approach is very expensive with an estimated annual cost of $ 9 billion for life-long PC surveillance in patients ages 40 and 79 years [ 8 ]. Efficient and cost-effective management of pancreatic cysts is urgently needed. Endoscopic ultrasound-guided pancreatic cyst ablation (EUS-PCA) has emerged as a possible alternative for cyst management. It offers several advantages including less post-operative pain and complications compared to surgery [ 9 ]. Currently, there are diverse technical variations in reagents for EUS-PCA, including alcohol, chemotherapeutic agents, or both. However, there is a paucity of research evaluating the effectiveness and safety profile of PCA. Despite the existence of published studies, there is no consensus on the role of EUS ablation in the management of PCs, due to the lack of a comprehensive assessment of its efficacy and safety. In 2019, an international position statement was published concerning EUS-PCA, which, albeit based on weak evidence, supported the use of ethanol ablation for unilocular or oligolocular mucinous or enlarging PCLs in patients who opt to avoid surgery and in poor surgical candidates with reasonable life expectancy [ 10 ]. We conducted a systematic review and meta-analysis of PCs management with EUS-PCA to evaluate the short-term treatment efficacy and complications, and identify different techniques utilized for PCA. Methods This meta-analysis was reported following the recommendation of Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines [11, 12]. Two investigators (AS, JE) independently extracted the data, with any disagreements settled through discussion. Inclusion and exclusion criteria and analysis methods were discussed and agreed upon to ensure consistency, reduce bias, and enhance the validity and reliability of the meta-analysis findings. Inclusion and Exclusion Inclusion criteria included prospective studies that met the following criteria: 1- Participants: patients > 18 years of age with pancreatic cysts, 2- Intervention: Endoscopic ultrasound-guided cyst ablation comparing control and ablation reagents, 3- Outcome: Primary outcome was cyst resolution (partial and complete) and persistence on imaging at 12 months after ablation. It is noteworthy that outcome definitions varied among the included studies. While most defined complete cyst resolution as 25% final volume [ 13 – 17 ], three studies differed: one defined complete cyst resolution as no visible PCs, partial cyst resolution as 25% final volume [ 18 ]; another set complete cyst resolution as no visible PCs, partial cyst resolution as 30% final volume [ 19 ]. The remaining study did not specify these criteria [ 20 ]. The secondary outcome was procedure-related adverse events, including fever, infections, acute pancreatitis, abdominal pain, and injury to adjacent structures. Exclusion criteria were retrospective observational studies, those that included malignant or neuroendocrine cysts, and those that followed the patients for less than 12 months. There were no language, publication type, or comparison group restrictions. Literature search We systematically searched PubMed (3248), Ovid (2964), Cochrane (10), and Trip (52) electronic databases using the terms “Endoscopic,” “Endoscopy,” “Endoscopic Ultrasound,” “EUS,” “Ablation” and “Pancreatic cysts.” The numbers reference the quantity of articles from each initial search. A manual search of relevant article's references was also performed. The most recent search was conducted on November 11th, 2022. The detailed search process is outlined in Fig. 1. Titles and abstracts were screened by two authors independently (A.S and J.E). Any disagreement was resolved through consensus or, if required, by a discussion with a third author (A.B). Data Extraction Two authors (A.S and J.E) assessed each article independently to determine eligibility based on the inclusion criteria. Any differences were resolved by mutual agreement. The following information was extracted from each included study: The first author’s name, year of publication, sample size, gender, cyst type, location and size, type of ablation, resolution, and procedure-related adverse events. Quality Assessment Several criteria are widely used to assess quality in clinical trials with treatment and control cohorts [ 21 – 23 ]. We used the modified Downs and Black (D&B) checklist, which was designed to assess clinical trials with and without a control arm [ 24 ]. The quality assessment and risk of bias included four sections: reporting, external validity, internal validity (bias), and internal validity (confounding). We applied one modification to the D&B tool by excluding question 27 (Power calculation). Figure 2 presents how much each study scored in each category. Statistical analysis All statistical analyses were performed using Stata/SE v.17 (College Station, Texas, USA). The Metaprop command, invented by Nyaga et al. [ 25 ] was used. First, the Freeman-Tukey double arcsine transformation method was used on the proportions of outcomes before pooling to stabilize the variance. The pooled estimates were then computed using the DerSimonian-Laird random-effects method based on the transformed values. Results are presented as pooled proportions with 95% CI. A subgroup analysis was conducted using Stata/SE to explore potential differences in the effect of cyst size and ablative agent on the complete resolution among different subgroups of studies. The subgroup analysis accounted for the correlation between effect estimates within each subgroup and estimated the between-study variance using the DerSimonian-Laird random-effects method. Heterogeneity was assessed using I-squared statistics. We were unable to statistically evaluate publication bias due to the small number of studies included. [ 26 ] Results The initial search identified 6,274 reference studies, from which 182 articles were selected and reviewed. Eight studies [ 13 – 20 , 27 ] met our inclusion criteria (Fig. 1). All the included studies were published as full-text articles. The characteristics of each individual study are shown in (Table 1 ). Table 1 Study Year of publication No. of patients Sex: M/F Type of cyst Cyst location Mean diameter (mm) Technique Mucinous Serous Pseudo Indeterminate Head Body Tail Gan et al. 2005 23 5/18 17 3 1 2 8 7 8 18.33 ETOH Oh et al. 2011 47/52* 13/34 9 15 2 26 16** 17** 19** 31.8 ETOH + P DeWitt et al. 2014 22 7/15 18 4 0 0 10 8 4 25.73 ETOH + P Gómez et al. 2016 23 13/10 19 0 0 4 15 6 2 28.66 ETOH Moyer et al. 2017 39 16/23 36 0 0 3 19 19 1 25 ETOH + P + G Saline + P + G Park et al. 2016 91 24/67 0 0 0 91 35 32 24 30.7 ETOH Du et al. 2022 35 na na na na na na na na na EUS-LA (lauromacrogol) Choi et al. 2017 158 49/115 71 16 3 63 42 86 36 32 ETOH + P Total - 438 127/282 170 38 6 189 145 175 94 - - ETOH: alcohol, P: Paclitaxel, G: Gemcitabine, LA: Lauromacrogol. *5 patients lost to follow-up; 47 were the total completed follow-up for 12 months. **This categorization is from the total number of patients included in the trial, not considering the loss of follow-ups. The modified Downs and Black checklist was utilized to assess the risk of bias in the included studies. The total scores of the studies ranged from 15 to 22, with a median score of 16 out of 26. The reporting domain was adequately addressed, with a median score of 8 out of 10. However, the domains of bias and confounding displayed certain weaknesses, with median scores of 5 out of 7 and 3 out of 6, respectively. It is worth noting that the studies often lacked or insufficiently addressed external validity, with a median score of 0. (Fig. 2) The total number of patients included in this meta-analysis is 438, with a predominantly female population of 68.9% (282). The clinical diagnosis included mucinous cysts in 42.1% (n = 170), serous cystadenomas in 9.4% (n = 38), and 46.8% (n = 189) were classified as indeterminate. The mean diameter of the cysts was 27.46 ± 4.89. A total of 145 cysts were located in the head of the pancreas, 175 in the body, and 94 in the tail. Ablation was performed with ethanol alone in 31.2% (n = 137), lauromacrogol alone in 7.9% (n = 35), paclitaxel and alcohol in 51.8% (n = 227), paclitaxel and gemcitabine in 4.7% (n = 21) and paclitaxel, gemcitabine and alcohol in 4.1% (n = 18). The individual study proportions and the pooled estimate are shown in (Fig. 3). The pooled proportion for complete cyst resolution on imaging after 12 months of EUS ablation was 50% [95% CI 36, 63, I 2 = 85.31%]. Partial cyst resolution was 27% [95% CI 15, 41, I 2 = 87.07%], and cyst persistence was 17% [95% CI 11, 24, I 2 = 62.11%]. Three subgroups based on the mean cyst diameter were evaluated for resolution (Fig. 4). For cysts 3cm, the proportion of complete resolution was 35% [95% CI 19, 55], 44% [95% CI 17, 72], and 60% [95% CI 42, 77], respectively. Five subgroups based on the ablating agent were evaluated for resolution. The pooled proportion for complete resolution for ethanol alone was 29% [95% CI 10, 53], for lauromacrogol alone was 51% [95% Cl 36, 67] for ethanol and paclitaxel was 63% [95% CI 48, 76], for paclitaxel and gemcitabine was 67% [95% CI 45, 83], and for Ethanol, Paclitaxel and Gemcitabine was 61% [95% CI 39, 80] ( Fig. 5). Post-procedure adverse events included abdominal pain in about 4% [95% CI 0, 11], pancreatitis in 3% [95% CI 1, 5], and fever in 1% [95% CI 0, 3]. Additionally, two patients experienced peri-cystic spillage, leading to chemical peritonitis, and one patient developed small bowel perforation. Discussion The management of PCs has been a topic of debate for many years. The management approach depends on many factors but mainly on the type and size of the cyst, as it may reflect its malignancy potential. The use of EUS to ablate these lesions has been an ongoing area of research. Our analysis showed that EUS-PCA is an effective and safe way of managing PCs. Typical EUS-PCA includes careful assessment of the PCs, including location, size, and presence of high-risk stigmata or worrisome features, followed by cyst fluid aspiration, and injection of chemicals into the cyst. [ 13 ] The most used chemical is alcohol due to its ability to cause tissue necrosis from direct coagulation, sclerosis of the tissue in contact, denaturation of proteins, and dehydration of the epithelial cells [ 21 , 28 ]. Adding chemotherapeutic agents, such as paclitaxel and gemcitabine, to ethanol injection has improved cyst resolution [ 13 , 14 , 16 ]. Lauromacrogol, a sclerosing agent, is an emerging alternative to alcohol and chemotherapeutic agents [ 15 ]. In the present meta-analysis, we sought to determine the effectiveness of EUS-PCA in managing pancreatic cystic neoplasms. A total of 438 patients with pancreatic cysts were included in the study, with the majority classified as indeterminate (n = 189) or mucinous (n = 170). The anatomical distribution of cysts revealed a predominance in the pancreatic body, followed by the head and then the tail. The combined analysis of the studies included in our review revealed that EUS-PCA exhibits substantial effectiveness in the treatment of pancreatic cystic neoplasms, leading to cyst resolution in nearly 80% of cases (comprising 50% complete resolution and 27% partial resolution). Moreover, subgroup analysis suggests that EUS ablation permits a higher degree of complete resolution of pancreatic cysts larger than 2 cm, and when using a chemotherapeutic agent. These findings suggest that EUS-PCA represents a promising therapeutic option for patients with pancreatic cystic neoplasms, with potential benefits in reducing the risk of malignant transformation and improving patient outcomes. Our analysis also provided evidence supporting the safety of EUS-PCA, with only a few major complications observed among the included patients. Acute pancreatitis was reported in 3% of patients, while one patient experienced a small bowel perforation, and two patients exhibited peri-cystic spillage and chemical peritonitis. The occurrence of acute pancreatitis may be attributed to the activation of zymogens as a result of the cytotoxic effects of the chemicals employed during the procedure on the exposed main pancreatic duct [ 21 , 29 ]. The findings are in contrast to pancreatic surgery, which has a morbidity rate higher than 40% and a mortality rate reaching 20% [ 9 , 30 ]. EUS-PCA is a valuable alternative for patients who are deemed unsuitable for surgical intervention. Nevertheless, it is imperative to note that EUS ablation is not a suitable treatment for all types of cysts [ 10 , 31 , 32 ]. In 2019, an international position statement on EUS-guided PC ablation recommended chemoablation for surgically fit patients with an anticipated reasonable life expectancy, confirmed diagnosis of a mucinous pancreatic cyst that is 2 cm and enlarging or at least 3 centimeters in diameter [ 10 , 32 ]. Nevertheless, the group did not reach a consensus on absolute indications or contraindications for EUS-PCA. Therefore, a patient-centered approach regarding EUS ablation should consider a multidisciplinary discussion of individual circumstances and thoroughly assess the potential risks and benefits of the procedure. We utilized the modified Downs and Black checklist to assess the risk of bias in the studies included in our analysis. The results indicated variations in the overall quality of the studies, with some demonstrating a higher degree of bias risk than others. While the reporting domain was generally well-addressed, certain aspects, such as bias and confounding, displayed weaknesses. Additionally, an important finding was the frequent lack of attention or insufficient consideration of external validity in the included studies. This aspect warrants particular attention in future research, as it may significantly impact the generalizability of findings in similar studies. A primary obstacle in the implementation of EUS-PCA is the accessibility and precision in targeting pancreatic cysts. This is especially pronounced when dealing with small or hard-to-reach cysts in the tail or inferior pancreatic head. Furthermore, the use of ethanol as an ablative agent may be difficult due to trouble achieving optimal intracystic ethanol concentration [ 20 ] and potentially less efficacious in cysts with thick septations, adjacent masses, and nodules [ 18 ]. Newer agents such as lauromacrogol, which is usually used as sclerotherapy for varicose veins, are being explored as a possible ablation agent and have shown promising results with fewer side effects [ 25 ]. These limitations underscore the importance of careful patient selection, as well as skilled technical expertise, when utilizing EUS-PCA as a therapeutic option for pancreatic cystic neoplasms. All studies included in this meta-analysis were prospective where patients were followed for at least 12 months after the procedure. All studies reported positive outcomes except for Gómez et al. [ 20 ]. They explained that the results could be due to low final ethanol concentrations; however, final ethanol concentrations close to 80% were achieved in some participants, and no correlation with therapy response was found [ 20 ]. This meta-analysis has several limitations that warrant consideration. Notably, there was significant heterogeneity in the techniques employed across the included studies, potentially introducing inconsistencies in treatment outcomes. Another limitation of our study is the variation in defining primary outcomes across included studies. While most used the same volume percentages, three studies had different criteria, such as the absence of visible cysts. Additionally, not all studies reported complications in a standardized manner, raising concerns about the accuracy of reported incidence rates, particularly due to the lack of an evidence-based adverse events grading system. Moreover, the emphasis on short-term outcomes, particularly due to the limited availability of long-term data, may lead to an overestimation of the treatment's effectiveness, as negative outcomes from PCs are often seen over the long term. However, one study with a 69-month follow-up period showed positive effects [ 17 ], These promising results indicate the need for further studies assessing potential long-term benefits. Consequently, these limitations should be acknowledged when interpreting the meta-analytic findings and applying them in clinical practice. In light of the identified limitations, further research is required to fully assess the safety and efficacy of EUS-PCA and enhance its adoption for the treatment of pancreatic cysts. Specifically, prospective controlled randomized trials are needed to provide robust and conclusive evidence to support the use of this technique. Moreover, comparative studies evaluating the effectiveness of EUS-PCA against surgical excision of pancreatic cysts could offer valuable insights into the benefits and limitations of each approach. Such studies may elucidate the specific indications and optimal treatment strategies for each modality, facilitating the appropriate selection based on patient and lesion characteristics. Ultimately, these efforts may help to establish EUS-PCA as a widely accepted, safe, and effective therapeutic option for the management of pancreatic cystic lesions. Conclusion Our meta-analysis demonstrated the efficacy of EUS pancreatic cyst ablation as a viable option for managing pancreatic cysts, while highlighting the acceptable level of procedure-related complications associated with this approach. Nonetheless, a tailored approach should be adopted when determining the optimal therapeutic intervention, taking into account key variables such as cyst type, size, and location. Further, randomized controlled trials comparing EUS-PCA to conventional surgical interventions are warranted to enhance the existing body of evidence in this field. Such investigations could help provide more robust data to inform clinical decision-making regarding the use of EUS-PCA in the management of pancreatic cystic neoplasms. Abbreviations PC: pancreatic cyst, CT: computerized tomography, MRI: Magnetic Resonance Imaging, EUS: Endoscopic ultrasound, PCA: Pancreatic cyst ablation, IPMN: Intraductal papillary mucinous neoplasm. Declarations Author Contribution Ahmed Mourtada Al Qady (Conceptualization: Lead; Data curation: Lead; Formalanalysis: Lead; Investigation: Lead; Methodology: Lead; Visualization: Lead; Writing –original draft: Lead; Writing – review & editing: Lead)Kapil Dev Nayar (Writing – original draft: Equal; Writing – review & editing: Equal)joseph emran (Data curation: Equal; Investigation: Equal)Amir Beirat (Investigation: Equal; Writing – review & editing: Equal)Sasmith Menakuru (Data curation: Equal; Writing – review & editing: Equal)Dana Harris (Supervision: Equal; Writing – original draft: Equal; Writing – review &editing: Equal)Dan J. Echols (Methodology: Supporting; Writing – original draft: Supporting; Writing –review & editing: Supporting)Baoan Ji (Methodology: Supporting; Writing – original draft: Supporting)John M DeWitt (Methodology: Supporting; Supervision: Supporting; Writing – originaldraft: Supporting; Writing – review & editing: Supporting)Zhen Wang (Formal analysis: Supporting; Software: Supporting; Supervision:Supporting)Fernando F. Stancampiano (Supervision: Supporting; Writing – original draft:Supporting; Writing – review & editing: Supporting)Yan Bi (Conceptualization: Lead; Investigation: Lead; Methodology: Lead; Supervision:Lead; Writing – original draft: Lead; Writing – review & editing: Lead) Conflict of interest The authors declare no conflicts of interest. References Navarro, S.M., et al., Incidental Pancreatic Cysts on Cross-Sectional Imaging. Radiol Clin North Am, 2021. 59 (4): p. 617-629. 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Cochrane Database Syst Rev, 2016. 2 (2): p. CD006053. Moyer, M.T., J.L. Maranki, and J.M. DeWitt, EUS-Guided Pancreatic Cyst Ablation: a Clinical and Technical Review. Curr Gastroenterol Rep, 2019. 21 (5): p. 19. Ardeshna, D.R., et al., An update on EUS-guided ablative techniques for pancreatic cystic lesions. Endosc Ultrasound, 2022. 11 (6): p. 432-441. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4165948","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":285119677,"identity":"2ed3cf62-1f20-4cdf-9203-d70bc53556a6","order_by":0,"name":"Ahmed Al Qady","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAArklEQVRIiWNgGAWjYDACCSB+YHBAjg3E4SFaS4LBAWNStTAcSGwgWgv/7PaHHxIK7qT3SSQwPnjbRowld84YSyQYPMttk0hgNpxLjBaGGzkMQC2HQVrYpHmJ0SJ/I/3xD6CWdDaJBPbfRGkxuJFgBrIlAaiFjZkoLYY3cswsgFoM23geNkvOOUeEFjmgw258+HNYXr49+eCHN2VEaEECjA2kqR8Fo2AUjIJRgBsAABG0Nle9cFw2AAAAAElFTkSuQmCC","orcid":"","institution":"Indiana University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Ahmed","middleName":"Al","lastName":"Qady","suffix":""},{"id":285119680,"identity":"1ced40b6-146f-4884-b4d2-74167a1e3fe9","order_by":1,"name":"Kapil Dev Nayar","email":"","orcid":"","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Kapil","middleName":"Dev","lastName":"Nayar","suffix":""},{"id":285119683,"identity":"08ac5071-3456-4ae7-a7f5-27cc52084282","order_by":2,"name":"Joseph Emran","email":"","orcid":"","institution":"Indiana University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Joseph","middleName":"","lastName":"Emran","suffix":""},{"id":285119685,"identity":"b63edab4-c87b-4e25-9a78-e019a05c5cd7","order_by":3,"name":"Amir Beirat","email":"","orcid":"","institution":"Indiana University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Amir","middleName":"","lastName":"Beirat","suffix":""},{"id":285119686,"identity":"17cfaca0-2083-45af-8e2f-baff261f7f8d","order_by":4,"name":"Sasmith Menakuru","email":"","orcid":"","institution":"Indiana University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sasmith","middleName":"","lastName":"Menakuru","suffix":""},{"id":285119688,"identity":"47fc7da2-c0f5-484e-b587-96841b3d144e","order_by":5,"name":"Dana Harris","email":"","orcid":"","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Dana","middleName":"","lastName":"Harris","suffix":""},{"id":285119691,"identity":"a8105b89-23c5-4e38-a05e-8cdcf68bcbd6","order_by":6,"name":"Dan J. Echols","email":"","orcid":"","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Dan","middleName":"J.","lastName":"Echols","suffix":""},{"id":285119692,"identity":"89ecd477-94e7-44a7-91e4-caeef78ad0d1","order_by":7,"name":"Baoan Ji","email":"","orcid":"","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Baoan","middleName":"","lastName":"Ji","suffix":""},{"id":285119693,"identity":"d8e5b2d1-a9a8-4ede-9eab-bf20f6a15542","order_by":8,"name":"John M DeWitt","email":"","orcid":"","institution":"Indiana University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"John","middleName":"M","lastName":"DeWitt","suffix":""},{"id":285119694,"identity":"c102f889-f3ed-4c1c-a0c7-14fc508f6948","order_by":9,"name":"Zhen Wang","email":"","orcid":"","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Zhen","middleName":"","lastName":"Wang","suffix":""},{"id":285119695,"identity":"b9ce8de1-648c-4670-bc43-3482527d046c","order_by":10,"name":"Fernando F. Stancampiano","email":"","orcid":"","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Fernando","middleName":"F.","lastName":"Stancampiano","suffix":""},{"id":285119696,"identity":"93e826c8-8b55-4b80-b274-d5ea5800678c","order_by":11,"name":"Yan Bi","email":"","orcid":"","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Bi","suffix":""}],"badges":[],"createdAt":"2024-03-25 23:59:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4165948/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4165948/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53967273,"identity":"dfd64ddb-f7ab-4f80-b180-bde192281427","added_by":"auto","created_at":"2024-04-02 19:55:54","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1032106,"visible":true,"origin":"","legend":"\u003cp\u003eSearch process detailed based on PRISMA's 2020 recommendations\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4165948/v1/5386dec3bb68b7279388e00c.jpg"},{"id":53967274,"identity":"1f2aa4d4-fe06-4196-9e1b-ec6e1fc3bc2c","added_by":"auto","created_at":"2024-04-02 19:55:54","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":790921,"visible":true,"origin":"","legend":"\u003cp\u003eQuality assessment and risk of bias using the modified Downs and Black checklist\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4165948/v1/f9b528b6862a700dc44d844a.jpg"},{"id":53967275,"identity":"45fdbacc-5314-406f-a450-2e4c576568cc","added_by":"auto","created_at":"2024-04-02 19:55:54","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":964889,"visible":true,"origin":"","legend":"\u003cp\u003eForest Plot of Pooled Proportions for Complete Cyst Resolution on Imaging After 12 Months of EUS\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4165948/v1/a075ad15a74cbc8c02ced726.jpg"},{"id":53967277,"identity":"fbba00a5-60f2-41c6-90d0-afd99d006019","added_by":"auto","created_at":"2024-04-02 19:55:54","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1055564,"visible":true,"origin":"","legend":"\u003cp\u003eSubgroup analysis of the complete cyst resolution based on the mean diameter of cysts\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4165948/v1/f33b7070eabec2f60ce31f53.jpg"},{"id":53968007,"identity":"9c5bf2bd-dbe4-4109-84f3-26b989b6436f","added_by":"auto","created_at":"2024-04-02 20:03:54","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1111138,"visible":true,"origin":"","legend":"\u003cp\u003eSubgroup analysis of the complete cyst resolution based on the ablating agent. ETOH: alcohol, P: Paclitaxel, G: Gemcitabine, LA: Lauromacrogol.\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4165948/v1/de8dfa32ce5f8cdbb139a7dc.jpg"},{"id":54256050,"identity":"482eb5bc-ea82-47bf-b482-5b3309ffb12d","added_by":"auto","created_at":"2024-04-08 00:54:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":559743,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4165948/v1/e4c3e20b-42d9-4348-a4b2-177cb8cc6369.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Short-Term Outcomes of Endoscopic Ultrasound-Guided Pancreatic Cyst Ablation: A Systematic Review and Meta-Analysis ","fulltext":[{"header":"What You Need to Know","content":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePancreatic cysts are a rising concern, with a prevalence of up to 10% in individuals over 70 in the US. These cysts encompass diverse pathology, notably intraductal papillary mucinous neoplasms, and their optimal management remains uncertain.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFindings:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEUS-PCA proves effective, achieving nearly 80% cyst resolution after 12 months, especially for larger cysts (\u0026gt;2 cm) and when employing chemotherapeutic agents. It also demonstrates a lower risk of complications compared to surgery, making it a valuable alternative, particularly for unsuitable surgical candidates.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImplications for Patient Care:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEUS-PCA is an effective and safer option for managing pancreatic cysts, with potential benefit in reducing malignancy risk.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eIn recent years, the prevalence of pancreatic cysts (PCs) has risen significantly, primarily attributed to the widespread use of cross-sectional abdominal imaging techniques. This increase has led to a greater identification of incidental findings related to PCs. The incidence of PCs reported on computed tomography (CT) is 9% and 27% on magnetic resonance imaging (MRI) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In the United States, the prevalence of PCs in the elderly is estimated at 2.5\u0026ndash;6.6% and increases to 10% in persons over 70 years of age [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. PCs reflect a diverse array of histopathology ranging from benign to malignant. Intraductal papillary mucinous neoplasms (IPMNs), the most common PCs, have the potential for malignant transformation. Although many guidelines have been developed, the optimal management of IPMNs remains unclear. Current management for PCs is based on the potential of malignancy and symptomology. Surgery is the primary approach for managing symptomatic and high-risk pancreatic cysts; however, it carries perioperative risks of morbidity (such as infections, pancreatic leaks, and fistulae) and rare mortality [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Furthermore, surgical resection may cause long-term development of diabetes and exocrine insufficiency [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Most patients with PCs will undergo long-term surveillance until they are unfit for surgical management or the PCs develop high risk features but this approach is very expensive with an estimated annual cost of \u003cspan\u003e$\u003c/span\u003e9\u0026nbsp;billion for life-long PC surveillance in patients ages 40 and 79 years [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Efficient and cost-effective management of pancreatic cysts is urgently needed.\u003c/p\u003e \u003cp\u003eEndoscopic ultrasound-guided pancreatic cyst ablation (EUS-PCA) has emerged as a possible alternative for cyst management. It offers several advantages including less post-operative pain and complications compared to surgery [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Currently, there are diverse technical variations in reagents for EUS-PCA, including alcohol, chemotherapeutic agents, or both. However, there is a paucity of research evaluating the effectiveness and safety profile of PCA. Despite the existence of published studies, there is no consensus on the role of EUS ablation in the management of PCs, due to the lack of a comprehensive assessment of its efficacy and safety. In 2019, an international position statement was published concerning EUS-PCA, which, albeit based on weak evidence, supported the use of ethanol ablation for unilocular or oligolocular mucinous or enlarging PCLs in patients who opt to avoid surgery and in poor surgical candidates with reasonable life expectancy [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e We conducted a systematic review and meta-analysis of PCs management with EUS-PCA to evaluate the short-term treatment efficacy and complications, and identify different techniques utilized for PCA.\u003c/p\u003e "},{"header":"Methods ","content":"\u003cp\u003eThis meta-analysis was reported following the recommendation of Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines [11, 12]. Two investigators (AS, JE) independently extracted the data, with any disagreements settled through discussion. Inclusion and exclusion criteria and analysis methods were discussed and agreed upon to ensure consistency, reduce bias, and enhance the validity and reliability of the meta-analysis findings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion and Exclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInclusion criteria included prospective studies that met the following criteria: 1- Participants: patients\u0026thinsp;\u0026gt;\u0026thinsp;18 years of age with pancreatic cysts, 2- Intervention: Endoscopic ultrasound-guided cyst ablation comparing control and ablation reagents, 3- Outcome: Primary outcome was cyst resolution (partial and complete) and persistence on imaging at 12 months after ablation. It is noteworthy that outcome definitions varied among the included studies. While most defined complete cyst resolution as \u0026lt;\u0026thinsp;5% final volume in comparison to the original, partial cyst resolution as 5%-25% final volume, and cyst persistence as \u0026gt;\u0026thinsp;25% final volume [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e], three studies differed: one defined complete cyst resolution as no visible PCs, partial cyst resolution as \u0026lt;\u0026thinsp;=\u0026thinsp;25% final volume, and cyst persistence as \u0026gt;\u0026thinsp;25% final volume [\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e]; another set complete cyst resolution as no visible PCs, partial cyst resolution as \u0026lt;\u0026thinsp;=\u0026thinsp;30% final volume, and cyst persistence as \u0026gt;\u0026thinsp;30% final volume [\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]. The remaining study did not specify these criteria [\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]. The secondary outcome was procedure-related adverse events, including fever, infections, acute pancreatitis, abdominal pain, and injury to adjacent structures. Exclusion criteria were retrospective observational studies, those that included malignant or neuroendocrine cysts, and those that followed the patients for less than 12 months. There were no language, publication type, or comparison group restrictions.\u003c/p\u003e\n\u003ch3\u003eLiterature search\u003c/h3\u003e\n\u003cp\u003eWe systematically searched PubMed (3248), Ovid (2964), Cochrane (10), and Trip (52) electronic databases using the terms \u0026ldquo;Endoscopic,\u0026rdquo; \u0026ldquo;Endoscopy,\u0026rdquo; \u0026ldquo;Endoscopic Ultrasound,\u0026rdquo; \u0026ldquo;EUS,\u0026rdquo; \u0026ldquo;Ablation\u0026rdquo; and \u0026ldquo;Pancreatic cysts.\u0026rdquo; The numbers reference the quantity of articles from each initial search. A manual search of relevant article's references was also performed. The most recent search was conducted on November 11th, 2022. The detailed search process is outlined in Fig.\u0026nbsp;1. Titles and abstracts were screened by two authors independently (A.S and J.E). Any disagreement was resolved through consensus or, if required, by a discussion with a third author (A.B).\u003c/p\u003e\n\u003ch3\u003eData Extraction\u003c/h3\u003e\n\u003cp\u003eTwo authors (A.S and J.E) assessed each article independently to determine eligibility based on the inclusion criteria. Any differences were resolved by mutual agreement. The following information was extracted from each included study: The first author\u0026rsquo;s name, year of publication, sample size, gender, cyst type, location and size, type of ablation, resolution, and procedure-related adverse events.\u003c/p\u003e\n\u003ch3\u003eQuality Assessment\u003c/h3\u003e\n\u003cp\u003eSeveral criteria are widely used to assess quality in clinical trials with treatment and control cohorts [\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]. We used the modified Downs and Black (D\u0026amp;B) checklist, which was designed to assess clinical trials with and without a control arm [\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]. The quality assessment and risk of bias included four sections: reporting, external validity, internal validity (bias), and internal validity (confounding). We applied one modification to the D\u0026amp;B tool by excluding question 27 (Power calculation). Figure\u0026nbsp;2 presents how much each study scored in each category.\u003c/p\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n\u003ch3\u003eStatistical analysis\u003c/h3\u003e\n\u003cp\u003eAll statistical analyses were performed using Stata/SE v.17 (College Station, Texas, USA). The Metaprop command, invented by Nyaga et al. [\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e] was used. First, the Freeman-Tukey double arcsine transformation method was used on the proportions of outcomes before pooling to stabilize the variance. The pooled estimates were then computed using the DerSimonian-Laird random-effects method based on the transformed values. Results are presented as pooled proportions with 95% CI. A subgroup analysis was conducted using Stata/SE to explore potential differences in the effect of cyst size and ablative agent on the complete resolution among different subgroups of studies. The subgroup analysis accounted for the correlation between effect estimates within each subgroup and estimated the between-study variance using the DerSimonian-Laird random-effects method.\u003c/p\u003e\n\u003cp\u003eHeterogeneity was assessed using I-squared statistics. We were unable to statistically evaluate publication bias due to the small number of studies included. [\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe initial search identified 6,274 reference studies, from which 182 articles were selected and reviewed. Eight studies [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e] met our inclusion criteria (Fig.\u0026nbsp;1). All the included studies were published as full-text articles. The characteristics of each individual study are shown in (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eStudy\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eYear of publication\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNo. of patients\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSex: M/F\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eType of cyst\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eCyst location\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eMean diameter (mm)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eTechnique\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eMucinous\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSerous\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePseudo\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eIndeterminate\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eHead\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBody\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTail\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGan et al.\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e2005\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e23\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e5/18\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e17\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e18.33\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eETOH\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eOh et al.\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2011\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e47/52*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13/34\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16**\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17**\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19**\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e31.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eETOH\u0026thinsp;+\u0026thinsp;P\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDeWitt et al.\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2014\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7/15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25.73\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eETOH\u0026thinsp;+\u0026thinsp;P\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eG\u0026oacute;mez et al.\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2016\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13/10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28.66\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eETOH\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eMoyer et al.\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e39\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e16/23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eETOH\u0026thinsp;+\u0026thinsp;P\u0026thinsp;+\u0026thinsp;G\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSaline\u0026thinsp;+\u0026thinsp;P\u0026thinsp;+\u0026thinsp;G\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePark et al.\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2016\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e91\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24/67\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e91\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eETOH\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDu et al.\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2022\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ena\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ena\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ena\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ena\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ena\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ena\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ena\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ena\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ena\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEUS-LA\u003c/p\u003e\n\u003cp\u003e(lauromacrogol)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eChoi et al.\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e158\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49/115\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e71\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e63\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e86\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eETOH\u0026thinsp;+\u0026thinsp;P\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e438\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e127/282\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e170\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e38\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e189\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e145\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e175\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e94\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"13\"\u003e\u003cem\u003eETOH: alcohol, P: Paclitaxel, G: Gemcitabine, LA: Lauromacrogol. *5 patients lost to follow-up; 47 were the total completed follow-up for 12 months. **This categorization is from the total number of patients included in the trial, not considering the loss of follow-ups.\u003c/em\u003e\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe modified Downs and Black checklist was utilized to assess the risk of bias in the included studies. The total scores of the studies ranged from 15 to 22, with a median score of 16 out of 26. The reporting domain was adequately addressed, with a median score of 8 out of 10. However, the domains of bias and confounding displayed certain weaknesses, with median scores of 5 out of 7 and 3 out of 6, respectively. It is worth noting that the studies often lacked or insufficiently addressed external validity, with a median score of 0. (Fig.\u0026nbsp;2)\u003c/p\u003e\n\u003cp\u003eThe total number of patients included in this meta-analysis is 438, with a predominantly female population of 68.9% (282). The clinical diagnosis included mucinous cysts in 42.1% (n\u0026thinsp;=\u0026thinsp;170), serous cystadenomas in 9.4% (n\u0026thinsp;=\u0026thinsp;38), and 46.8% (n\u0026thinsp;=\u0026thinsp;189) were classified as indeterminate. The mean diameter of the cysts was 27.46\u0026thinsp;\u0026plusmn;\u0026thinsp;4.89. A total of 145 cysts were located in the head of the pancreas, 175 in the body, and 94 in the tail. Ablation was performed with ethanol alone in 31.2% (n\u0026thinsp;=\u0026thinsp;137), lauromacrogol alone in 7.9% (n\u0026thinsp;=\u0026thinsp;35), paclitaxel and alcohol in 51.8% (n\u0026thinsp;=\u0026thinsp;227), paclitaxel and gemcitabine in 4.7% (n\u0026thinsp;=\u0026thinsp;21) and paclitaxel, gemcitabine and alcohol in 4.1% (n\u0026thinsp;=\u0026thinsp;18).\u003c/p\u003e\n\u003cp\u003eThe individual study proportions and the pooled estimate are shown in (Fig.\u0026nbsp;3). The pooled proportion for complete cyst resolution on imaging after 12 months of EUS ablation was 50% [95% CI 36, 63, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;85.31%]. Partial cyst resolution was 27% [95% CI 15, 41, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;87.07%], and cyst persistence was 17% [95% CI 11, 24, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;62.11%].\u003c/p\u003e\n\u003cp\u003eThree subgroups based on the mean cyst diameter were evaluated for resolution (Fig.\u0026nbsp;4). For cysts\u0026thinsp;\u0026lt;\u0026thinsp;2 cm, between 2\u0026ndash;3 cm and \u0026gt;\u0026thinsp;3cm, the proportion of complete resolution was 35% [95% CI 19, 55], 44% [95% CI 17, 72], and 60% [95% CI 42, 77], respectively. Five subgroups based on the ablating agent were evaluated for resolution. The pooled proportion for complete resolution for ethanol alone was 29% [95% CI 10, 53], for lauromacrogol alone was 51% [95% Cl 36, 67] for ethanol and paclitaxel was 63% [95% CI 48, 76], for paclitaxel and gemcitabine was 67% [95% CI 45, 83], and for Ethanol, Paclitaxel and Gemcitabine was 61% [95% CI 39, 80] ( Fig.\u0026nbsp;5).\u003c/p\u003e\n\u003cp\u003ePost-procedure adverse events included abdominal pain in about 4% [95% CI 0, 11], pancreatitis in 3% [95% CI 1, 5], and fever in 1% [95% CI 0, 3]. Additionally, two patients experienced peri-cystic spillage, leading to chemical peritonitis, and one patient developed small bowel perforation.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe management of PCs has been a topic of debate for many years. The management approach depends on many factors but mainly on the type and size of the cyst, as it may reflect its malignancy potential. The use of EUS to ablate these lesions has been an ongoing area of research. Our analysis showed that EUS-PCA is an effective and safe way of managing PCs.\u003c/p\u003e \u003cp\u003eTypical EUS-PCA includes careful assessment of the PCs, including location, size, and presence of high-risk stigmata or worrisome features, followed by cyst fluid aspiration, and injection of chemicals into the cyst. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] The most used chemical is alcohol due to its ability to cause tissue necrosis from direct coagulation, sclerosis of the tissue in contact, denaturation of proteins, and dehydration of the epithelial cells [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Adding chemotherapeutic agents, such as paclitaxel and gemcitabine, to ethanol injection has improved cyst resolution [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Lauromacrogol, a sclerosing agent, is an emerging alternative to alcohol and chemotherapeutic agents [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the present meta-analysis, we sought to determine the effectiveness of EUS-PCA in managing pancreatic cystic neoplasms. A total of 438 patients with pancreatic cysts were included in the study, with the majority classified as indeterminate (n\u0026thinsp;=\u0026thinsp;189) or mucinous (n\u0026thinsp;=\u0026thinsp;170). The anatomical distribution of cysts revealed a predominance in the pancreatic body, followed by the head and then the tail. The combined analysis of the studies included in our review revealed that EUS-PCA exhibits substantial effectiveness in the treatment of pancreatic cystic neoplasms, leading to cyst resolution in nearly 80% of cases (comprising 50% complete resolution and 27% partial resolution). Moreover, subgroup analysis suggests that EUS ablation permits a higher degree of complete resolution of pancreatic cysts larger than 2 cm, and when using a chemotherapeutic agent. These findings suggest that EUS-PCA represents a promising therapeutic option for patients with pancreatic cystic neoplasms, with potential benefits in reducing the risk of malignant transformation and improving patient outcomes.\u003c/p\u003e \u003cp\u003eOur analysis also provided evidence supporting the safety of EUS-PCA, with only a few major complications observed among the included patients. Acute pancreatitis was reported in 3% of patients, while one patient experienced a small bowel perforation, and two patients exhibited peri-cystic spillage and chemical peritonitis. The occurrence of acute pancreatitis may be attributed to the activation of zymogens as a result of the cytotoxic effects of the chemicals employed during the procedure on the exposed main pancreatic duct [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The findings are in contrast to pancreatic surgery, which has a morbidity rate higher than 40% and a mortality rate reaching 20% [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEUS-PCA is a valuable alternative for patients who are deemed unsuitable for surgical intervention. Nevertheless, it is imperative to note that EUS ablation is not a suitable treatment for all types of cysts [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In 2019, an international position statement on EUS-guided PC ablation recommended chemoablation for surgically fit patients with an anticipated reasonable life expectancy, confirmed diagnosis of a mucinous pancreatic cyst that is 2 cm and enlarging or at least 3 centimeters in diameter [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Nevertheless, the group did not reach a consensus on absolute indications or contraindications for EUS-PCA. Therefore, a patient-centered approach regarding EUS ablation should consider a multidisciplinary discussion of individual circumstances and thoroughly assess the potential risks and benefits of the procedure.\u003c/p\u003e \u003cp\u003eWe utilized the modified Downs and Black checklist to assess the risk of bias in the studies included in our analysis. The results indicated variations in the overall quality of the studies, with some demonstrating a higher degree of bias risk than others. While the reporting domain was generally well-addressed, certain aspects, such as bias and confounding, displayed weaknesses. Additionally, an important finding was the frequent lack of attention or insufficient consideration of external validity in the included studies. This aspect warrants particular attention in future research, as it may significantly impact the generalizability of findings in similar studies.\u003c/p\u003e \u003cp\u003eA primary obstacle in the implementation of EUS-PCA is the accessibility and precision in targeting pancreatic cysts. This is especially pronounced when dealing with small or hard-to-reach cysts in the tail or inferior pancreatic head. Furthermore, the use of ethanol as an ablative agent may be difficult due to trouble achieving optimal intracystic ethanol concentration [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] and potentially less efficacious in cysts with thick septations, adjacent masses, and nodules [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Newer agents such as lauromacrogol, which is usually used as sclerotherapy for varicose veins, are being explored as a possible ablation agent and have shown promising results with fewer side effects [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. These limitations underscore the importance of careful patient selection, as well as skilled technical expertise, when utilizing EUS-PCA as a therapeutic option for pancreatic cystic neoplasms.\u003c/p\u003e \u003cp\u003eAll studies included in this meta-analysis were prospective where patients were followed for at least 12 months after the procedure. All studies reported positive outcomes except for G\u0026oacute;mez et al. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. They explained that the results could be due to low final ethanol concentrations; however, final ethanol concentrations close to 80% were achieved in some participants, and no correlation with therapy response was found [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis meta-analysis has several limitations that warrant consideration. Notably, there was significant heterogeneity in the techniques employed across the included studies, potentially introducing inconsistencies in treatment outcomes. Another limitation of our study is the variation in defining primary outcomes across included studies. While most used the same volume percentages, three studies had different criteria, such as the absence of visible cysts. Additionally, not all studies reported complications in a standardized manner, raising concerns about the accuracy of reported incidence rates, particularly due to the lack of an evidence-based adverse events grading system. Moreover, the emphasis on short-term outcomes, particularly due to the limited availability of long-term data, may lead to an overestimation of the treatment's effectiveness, as negative outcomes from PCs are often seen over the long term. However, one study with a 69-month follow-up period showed positive effects [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], These promising results indicate the need for further studies assessing potential long-term benefits. Consequently, these limitations should be acknowledged when interpreting the meta-analytic findings and applying them in clinical practice.\u003c/p\u003e \u003cp\u003eIn light of the identified limitations, further research is required to fully assess the safety and efficacy of EUS-PCA and enhance its adoption for the treatment of pancreatic cysts. Specifically, prospective controlled randomized trials are needed to provide robust and conclusive evidence to support the use of this technique. Moreover, comparative studies evaluating the effectiveness of EUS-PCA against surgical excision of pancreatic cysts could offer valuable insights into the benefits and limitations of each approach. Such studies may elucidate the specific indications and optimal treatment strategies for each modality, facilitating the appropriate selection based on patient and lesion characteristics. Ultimately, these efforts may help to establish EUS-PCA as a widely accepted, safe, and effective therapeutic option for the management of pancreatic cystic lesions.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur meta-analysis demonstrated the efficacy of EUS pancreatic cyst ablation as a viable option for managing pancreatic cysts, while highlighting the acceptable level of procedure-related complications associated with this approach. Nonetheless, a tailored approach should be adopted when determining the optimal therapeutic intervention, taking into account key variables such as cyst type, size, and location. Further, randomized controlled trials comparing EUS-PCA to conventional surgical interventions are warranted to enhance the existing body of evidence in this field. Such investigations could help provide more robust data to inform clinical decision-making regarding the use of EUS-PCA in the management of pancreatic cystic neoplasms.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePC: pancreatic cyst, CT: computerized tomography, MRI: Magnetic Resonance Imaging, EUS: Endoscopic ultrasound, PCA: Pancreatic cyst ablation, IPMN: Intraductal papillary mucinous neoplasm.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eAhmed Mourtada Al Qady (Conceptualization: Lead; Data curation: Lead; Formalanalysis: Lead; Investigation: Lead; Methodology: Lead; Visualization: Lead; Writing \u0026ndash;original draft: Lead; Writing \u0026ndash; review \u0026amp; editing: Lead)Kapil Dev Nayar (Writing \u0026ndash; original draft: Equal; Writing \u0026ndash; review \u0026amp; editing: Equal)joseph emran (Data curation: Equal; Investigation: Equal)Amir Beirat (Investigation: Equal; Writing \u0026ndash; review \u0026amp; editing: Equal)Sasmith Menakuru (Data curation: Equal; Writing \u0026ndash; review \u0026amp; editing: Equal)Dana Harris (Supervision: Equal; Writing \u0026ndash; original draft: Equal; Writing \u0026ndash; review \u0026amp;editing: Equal)Dan J. Echols (Methodology: Supporting; Writing \u0026ndash; original draft: Supporting; Writing \u0026ndash;review \u0026amp; editing: Supporting)Baoan Ji (Methodology: Supporting; Writing \u0026ndash; original draft: Supporting)John M DeWitt (Methodology: Supporting; Supervision: Supporting; Writing \u0026ndash; originaldraft: Supporting; Writing \u0026ndash; review \u0026amp; editing: Supporting)Zhen Wang (Formal analysis: Supporting; Software: Supporting; Supervision:Supporting)Fernando F. Stancampiano (Supervision: Supporting; Writing \u0026ndash; original draft:Supporting; Writing \u0026ndash; review \u0026amp; editing: Supporting)Yan Bi (Conceptualization: Lead; Investigation: Lead; Methodology: Lead; Supervision:Lead; Writing \u0026ndash; original draft: Lead; Writing \u0026ndash; review \u0026amp; editing: Lead)\u003c/p\u003e\n\u003ch2\u003eConflict of interest\u003c/h2\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eNavarro, S.M., et al., \u003cem\u003eIncidental Pancreatic Cysts on Cross-Sectional Imaging.\u003c/em\u003e Radiol Clin North Am, 2021. \u003cstrong\u003e59\u003c/strong\u003e(4): p. 617-629.\u003c/li\u003e\n\u003cli\u003eMella, J.M., et al., \u003cem\u003ePrevalence of incidental clinically relevant pancreatic cysts at diagnosis based on current guidelines.\u003c/em\u003e Gastroenterol Hepatol, 2018. \u003cstrong\u003e41\u003c/strong\u003e(5): p. 293-301.\u003c/li\u003e\n\u003cli\u003eGardner, T.B., et al., \u003cem\u003ePancreatic cyst prevalence and the risk of mucin-producing adenocarcinoma in US adults.\u003c/em\u003e Am J Gastroenterol, 2013. \u003cstrong\u003e108\u003c/strong\u003e(10): p. 1546-50.\u003c/li\u003e\n\u003cli\u003eFarrell, J.J., \u003cem\u003ePrevalence, Diagnosis and Management of Pancreatic Cystic Neoplasms: Current Status and Future Directions.\u003c/em\u003e Gut Liver, 2015. \u003cstrong\u003e9\u003c/strong\u003e(5): p. 571-89.\u003c/li\u003e\n\u003cli\u003ede Pretis, N., et al., \u003cem\u003ePancreatic cysts: Diagnostic accuracy and risk of inappropriate resections.\u003c/em\u003e Pancreatology, 2017. \u003cstrong\u003e17\u003c/strong\u003e(2): p. 267-272.\u003c/li\u003e\n\u003cli\u003eKneuertz, P.J., et al., \u003cem\u003eRisk of morbidity and mortality following hepato-pancreato-biliary surgery.\u003c/em\u003e J Gastrointest Surg, 2012. \u003cstrong\u003e16\u003c/strong\u003e(9): p. 1727-35.\u003c/li\u003e\n\u003cli\u003eKarim, S.A.M., et al., \u003cem\u003eThe outcomes and complications of pancreaticoduodenectomy (Whipple procedure): Cross sectional study.\u003c/em\u003e Int J Surg, 2018. \u003cstrong\u003e52\u003c/strong\u003e: p. 383-387.\u003c/li\u003e\n\u003cli\u003eMoayyedi, P., et al., \u003cem\u003eManagement of pancreatic cysts in an evidence-based world.\u003c/em\u003e Gastroenterology, 2015. \u003cstrong\u003e148\u003c/strong\u003e(4): p. 692-5.\u003c/li\u003e\n\u003cli\u003eGouma, D.J., et al., \u003cem\u003eRates of complications and death after pancreaticoduodenectomy: risk factors and the impact of hospital volume.\u003c/em\u003e Ann Surg, 2000. \u003cstrong\u003e232\u003c/strong\u003e(6): p. 786-95.\u003c/li\u003e\n\u003cli\u003eTeoh, A.Y., et al., \u003cem\u003ePosition statement on EUS-guided ablation of pancreatic cystic neoplasms from an international expert panel.\u003c/em\u003e Endosc Int Open, 2019. \u003cstrong\u003e7\u003c/strong\u003e(9): p. E1064-E1077.\u003c/li\u003e\n\u003cli\u003ePage, M.J., et al., \u003cem\u003eThe PRISMA 2020 statement: an updated guideline for reporting systematic reviews.\u003c/em\u003e Syst Rev, 2021. \u003cstrong\u003e10\u003c/strong\u003e(1): p. 89.\u003c/li\u003e\n\u003cli\u003ePage, M.J., et al., \u003cem\u003ePRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews.\u003c/em\u003e BMJ, 2021. \u003cstrong\u003e372\u003c/strong\u003e: p. n160.\u003c/li\u003e\n\u003cli\u003eOh, H.C., et al., \u003cem\u003eEndoscopic ultrasonography-guided ethanol lavage with paclitaxel injection treats patients with pancreatic cysts.\u003c/em\u003e Gastroenterology, 2011. \u003cstrong\u003e140\u003c/strong\u003e(1): p. 172-9.\u003c/li\u003e\n\u003cli\u003eMoyer, M.T., et al., \u003cem\u003eThe Safety and Efficacy of an Alcohol-Free Pancreatic Cyst Ablation Protocol.\u003c/em\u003e Gastroenterology, 2017. \u003cstrong\u003e153\u003c/strong\u003e(5): p. 1295-1303.\u003c/li\u003e\n\u003cli\u003eDu, C., et al., \u003cem\u003eLong-term outcomes of EUS-guided lauromacrogol ablation for the treatment of pancreatic cystic neoplasms: 5 years of experience.\u003c/em\u003e Endosc Ultrasound, 2022. \u003cstrong\u003e11\u003c/strong\u003e(1): p. 44-52.\u003c/li\u003e\n\u003cli\u003eDeWitt, J.M., et al., \u003cem\u003eAlterations in cyst fluid genetics following endoscopic ultrasound-guided pancreatic cyst ablation with ethanol and paclitaxel.\u003c/em\u003e Endoscopy, 2014. \u003cstrong\u003e46\u003c/strong\u003e(6): p. 457-64.\u003c/li\u003e\n\u003cli\u003eChoi, J.H., et al., \u003cem\u003eLong-term outcomes after endoscopic ultrasound-guided ablation of pancreatic cysts.\u003c/em\u003e Endoscopy, 2017. \u003cstrong\u003e49\u003c/strong\u003e(9): p. 866-873.\u003c/li\u003e\n\u003cli\u003eGan, S.I., et al., \u003cem\u003eEthanol lavage of pancreatic cystic lesions: initial pilot study.\u003c/em\u003e Gastrointest Endosc, 2005. \u003cstrong\u003e61\u003c/strong\u003e(6): p. 746-52.\u003c/li\u003e\n\u003cli\u003ePark, J.K., et al., \u003cem\u003eClinical Outcomes of Endoscopic Ultrasonography-Guided Pancreatic Cyst Ablation.\u003c/em\u003e Pancreas, 2016. \u003cstrong\u003e45\u003c/strong\u003e(6): p. 889-94.\u003c/li\u003e\n\u003cli\u003eG\u0026oacute;mez, V., et al., \u003cem\u003eEUS-guided ethanol lavage does not reliably ablate pancreatic cystic neoplasms (with video).\u003c/em\u003e Gastrointest Endosc, 2016. \u003cstrong\u003e83\u003c/strong\u003e(5): p. 914-20.\u003c/li\u003e\n\u003cli\u003eKandula, M., et al., \u003cem\u003eSuccess of endoscopic ultrasound-guided ethanol ablation of pancreatic cysts: a meta-analysis and systematic review.\u003c/em\u003e Indian J Gastroenterol, 2015. \u003cstrong\u003e34\u003c/strong\u003e(3): p. 193-9.\u003c/li\u003e\n\u003cli\u003eJadad, A.R., et al., \u003cem\u003eAssessing the quality of reports of randomized clinical trials: is blinding necessary?\u003c/em\u003e Control Clin Trials, 1996. \u003cstrong\u003e17\u003c/strong\u003e(1): p. 1-12.\u003c/li\u003e\n\u003cli\u003eStroup, D.F., et al., \u003cem\u003eMeta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.\u003c/em\u003e Jama, 2000. \u003cstrong\u003e283\u003c/strong\u003e(15): p. 2008-12.\u003c/li\u003e\n\u003cli\u003eDowns, S.H. and N. Black, \u003cem\u003eThe feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions.\u003c/em\u003e J Epidemiol Community Health, 1998. \u003cstrong\u003e52\u003c/strong\u003e(6): p. 377-84.\u003c/li\u003e\n\u003cli\u003eNyaga, V.N., M. Arbyn, and M. Aerts, \u003cem\u003eMetaprop: a Stata command to perform meta-analysis of binomial data.\u003c/em\u003e Arch Public Health, 2014. \u003cstrong\u003e72\u003c/strong\u003e(1): p. 39.\u003c/li\u003e\n\u003cli\u003eHiggins, J.P., et al., \u003cem\u003eMeasuring inconsistency in meta-analyses.\u003c/em\u003e Bmj, 2003. \u003cstrong\u003e327\u003c/strong\u003e(7414): p. 557-60.\u003c/li\u003e\n\u003cli\u003eBarthet, M., et al., \u003cem\u003eEndoscopic ultrasound-guided radiofrequency ablation for pancreatic neuroendocrine tumors and pancreatic cystic neoplasms: a prospective multicenter study.\u003c/em\u003e Endoscopy, 2019. \u003cstrong\u003e51\u003c/strong\u003e(9): p. 836-842.\u003c/li\u003e\n\u003cli\u003eBennedbaek, F.N., S. Karstrup, and L. Heged\u0026uuml;s, \u003cem\u003ePercutaneous ethanol injection therapy in the treatment of thyroid and parathyroid diseases.\u003c/em\u003e Eur J Endocrinol, 1997. \u003cstrong\u003e136\u003c/strong\u003e(3): p. 240-50.\u003c/li\u003e\n\u003cli\u003eDiMaio, C.J., J.M. DeWitt, and W.R. Brugge, \u003cem\u003eAblation of pancreatic cystic lesions: the use of multiple endoscopic ultrasound-guided ethanol lavage sessions.\u003c/em\u003e Pancreas, 2011. \u003cstrong\u003e40\u003c/strong\u003e(5): p. 664-8.\u003c/li\u003e\n\u003cli\u003eHuttner, F.J., et al., \u003cem\u003ePylorus-preserving pancreaticoduodenectomy (pp Whipple) versus pancreaticoduodenectomy (classic Whipple) for surgical treatment of periampullary and pancreatic carcinoma.\u003c/em\u003e Cochrane Database Syst Rev, 2016. \u003cstrong\u003e2\u003c/strong\u003e(2): p. CD006053.\u003c/li\u003e\n\u003cli\u003eMoyer, M.T., J.L. Maranki, and J.M. DeWitt, \u003cem\u003eEUS-Guided Pancreatic Cyst Ablation: a Clinical and Technical Review.\u003c/em\u003e Curr Gastroenterol Rep, 2019. \u003cstrong\u003e21\u003c/strong\u003e(5): p. 19.\u003c/li\u003e\n\u003cli\u003eArdeshna, D.R., et al., \u003cem\u003eAn update on EUS-guided ablative techniques for pancreatic cystic lesions.\u003c/em\u003e Endosc Ultrasound, 2022. \u003cstrong\u003e11\u003c/strong\u003e(6): p. 432-441.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Pancreatic cysts, endoscopic ultrasound, cyst ablation","lastPublishedDoi":"10.21203/rs.3.rs-4165948/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4165948/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePancreatic cysts (PC) are increasingly detected through abdominal imaging, prompting exploration of alternatives such as endoscopic ultrasound-guided pancreatic cyst ablation (EUS-PCA) due to the risks and costs associated with surgery. This study conducts a systematic review and meta-analysis of EUS-PCA's short-term efficacy and complications for PC management.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA systematic review and meta-analysis were carried out on PubMed, Ovid, Cochrane, and TRIP electronic databases. The primary outcome was cyst resolution (partial and complete) and persistence on imaging 12 months after ablation. The secondary outcome was procedure-related adverse events.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eEight studies were eligible for analysis. Complete cyst resolution on imaging 12 months after EUS ablation was 50% [95% CI 36, 63, I2\u0026thinsp;=\u0026thinsp;85.31%]. Partial cyst resolution was 27% [95% CI 15, 41, I2\u0026thinsp;=\u0026thinsp;87.07%], and cyst persistence was 17% [95% CI 11, 24, I2\u0026thinsp;=\u0026thinsp;62.11%]. The rate of complete resolution varied depending on the treatment agent (for ethanol 29% [95% CI 10, 53], lauromacrogol 51% [95% Cl 36, 67], ethanol and paclitaxel 63% [95% CI 48, 76], paclitaxel and gemcitabine 67% [95% CI 45, 83], ethanol, paclitaxel and gemcitabine 61% [95% CI 39, 80]). Post-procedure adverse events included abdominal pain in 4% [95% CI 0, 11], pancreatitis in 3% [95% CI 1, 5], and fever in 1% [95% CI 0, 3] of all patients.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe treatment of pancreatic cysts with EUS ablation results in acceptable levels of complete resolution, and low incidence of severe adverse events. 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