EUS-guided pancreatic cyst ablation: a critical review (with video) Hyoung-Chul Oh, MD, 1 William R. Brugge, MD 2

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1 TECHNICAL REVIEW EUS-guided pancreatic cyst ablation: a critical review (with video) Hyoung-Chul Oh, MD, 1 William R. Brugge, MD 2 The widespread use of cross-sectional imaging has dramatically increased the number of incidental pancreatic cystic lesions. The prevalence is age related. Based on screening CT/magnetic resonance imaging, the prevalence is 2.5% in adults and as high as 8% in the elderly. 1,2 Although most pancreatic cysts are incidentally detected, pancreatic cysts represent a wide spectrum of histopathology, and neoplastic cysts are more prevalent than previously estimated. Some histologic types including mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs) have malignant potential. 3,4 Differentiation of pancreatic cysts with malignant potential from those with benign behavior is an essential step in formulating a management strategy. High-resolution imaging technologies including CT, magnetic resonance imaging, and EUS allow a morphologic description of a pancreatic cyst in detail. However, the accuracy of cross-sectional imaging in the typing of pancreatic cysts is limited. Cyst fluid analysis for tumor markers such as carcinoembryonic antigen is useful in differentiating mucinous from nonmucinous cysts. Based on histologic controls, good diagnostic accuracy has been reported (sensitivity of 73% and specificity of 84%). 5 However, a substantial portion (as high as 50%) of pancreatic cysts remains indeterminate, even after extensive evaluation including cyst fluid aspiration. 6 On the other hand, surgical resection of a pancreatic cystic neoplasm is associated with a perioperative morbidity of 20% to 40% and a mortality rate of 2% Therefore, making a clinical decision as to whether to operate or observe an incidentally detected pancreatic cyst that is indeterminate by conventional diagnostic modality Abbreviations: IPMN, intraductal papillary mucinous neoplasm; MCN, mucinous cystic neoplasm; SCA, serous cystadenoma. DISCLOSURE: The authors disclosed no financial relationships relevant to this publication. Dr Oh was supported by the 2012 ASGE Cook Medical Don Wilson Award. This video can be viewed directly from the GIE website or by using the QR code and your mobile device. Download a free QR code scanner by searching QR Scanner in your mobile device s app store. Copyright 2013 by the American Society for Gastrointestinal Endoscopy /$ is challenging. A personalized management strategy is often deployed, applying a risk-benefit analysis to each patient. 3 This clinical dilemma has raised the need to develop a safe, effective, and minimally invasive approach for the treatment of pancreatic cysts. EUS-guided FNA of cyst fluid has been widely used for the differential diagnosis of pancreatic cysts. Based on the accumulated experience with EUSguided FNA, pancreatic tissue ablation by EUS-guided injection of ethanol or other ablative agents can be performed safely, with few procedure-related adverse events Percutaneous injection with ethanol has been widely used for the ablation of cystic lesions of the kidney, liver, 19,20 and thyroid gland without serious adverse events. EUS-guided injection of a variety of antitumor agents into pancreatic cancer has been reported to be feasible and safe By using similar principles, ablation of neoplastic cyst epithelium has been attempted with a chemotherapeutic agent. 27 EUS-guided pancreatic cyst ablation has been investigated in a variety of clinical trials. In this technical review, procedural basics and special considerations of cyst ablation and its clinical outcomes including safety and treatment response are summarized by reviewing the published literature. Briefly, the terms used for cyst ablation in this review may be defined as follows: ablation relates to the destruction of the cyst epithelium; injection refers to the act of forceful placement of an ablative agent into a cyst; and lavage is the act of repeated injections and aspiration. EUS-GUIDED CYST ABLATION TECHNIQUE An imaging evaluation of a pancreatic cystic lesion can determine the internal structure with regard to the number of septations, the wall thickness, and the presence of a mural nodule or mass. EUS imaging can be performed with a radial scanning echoendoscope or a curvilineararray echoendoscope. Both instruments provide highresolution imaging, but linear endosonography has the option of FNA. With a curvilinear-array echoendoscope, the cyst may be punctured via a transgastric or transduodenal route with the use of a 22-gauge needle. Cyst fluid aspiration is relatively simple and has a low rate of adverse events. The collection of cyst fluid provides important diagnostic material, as well as space for the ablative agent in the cyst cavity. After subtotal evacuation of the cyst, 526 GASTROINTESTINAL ENDOSCOPY Volume 77, No. 4 :

2 Oh & Brugge EUS-guided pancreatic cyst ablation Figure 1. Stepwise EUS-guided pancreatic cyst ablation therapy. Step 1: FNA (left) within a septated cyst (heavy black line). Step 2: 5-minute ethanol (middle) lavage of the cyst, followed by aspiration of the ethanol. Step 3: injection of paclitaxel (right) into the cyst, resulting in expansion of the cyst to its original diameter. injection is performed with a volume of fluid equal to that initially aspirated, and the cyst is lavaged for 3 to 5 minutes, alternately filling and emptying the cavity. Ethanol is the simplest agent for cyst ablation because it is easily obtained and injected. The injected ethanol is evacuated at the end of lavage, leaving just enough fluid to outline the cyst cavity. A second ablative agent (eg, a chemotherapeutic agent such as paclitaxel) may be injected and left in the cyst cavity; the total injection volume should not exceed the volume of aspirated fluid. During the procedure, the needle tip is carefully maintained within the cyst to avoid parenchymal injury or a leak in the cyst wall. At the completion of the injection or lavage, the needle is removed from the cyst cavity (Fig. 1) (Video 1, available online at Ablative agents Ethanol is an inexpensive, widely available, low-viscosity agent that is easy to inject through a small-gauge needle. Ethanol injected into hepatic cysts induces cell membrane lysis, protein denaturation, and vascular occlusion within 10 minutes but penetrates the fibrous capsule slowly. 28,29 The minimally effective ethanol concentration for tissue ablation in hepatic cysts is 40%. 30 The mean maximum postprocedure blood ethanol concentration is approximately 130 mg/ml at 3 to 4 hours after ethanol instillation, and clinical signs of ethanol intoxication have been noted in two thirds of cases but resolved without treatment. 21 Paclitaxel, a widely used chemotherapeutic agent, inhibits cell processes that are dependent on microtubules. It is hydrophobic and viscous in nature and hence can exert a durable effect on the epithelium within the cyst cavity with a low risk of leakage. 31 In an animal study with intravesical instillation of paclitaxel (500 g in20mlof water), the tissue concentration in the bladder wall was two- to threefold greater than the plasma concentration obtained after intravenous infusion of 250 mg/m Because of the high viscosity of its cosolvent, Cremophor (castor oil), the paclitaxel solution needs to be diluted 1:1 in 0.9% normal saline solution (a final dose concentration of 3 mg/ml paclitaxel) for injection. However, another formula of paclitaxel with a less viscous delivery vehicle (polymeric micelle) can be used without dilution (a dose concentration of 6 mg/ml). 6 Special consideration for EUS-guided cyst ablation The morphologic characteristics of a cyst will guide the approaches to cyst injection and ablation therapy. Cyst injection therapy has the greatest chance of successful ablation in unilocular or oligolocular cysts with fewer than 2 to 3 locules. In the presence of 3 or more locules, a single needle pass may not provide a sufficient drug delivery to all locules within a cyst. It is important to determine the optimal angle at which the needle can be introduced into the maximal number of targeted locules. When all punctured locules cannot be visualized on an endosonographic image, needle passage across a septation may be indicated. The simultaneous collapse of locules across the septum during cyst fluid evacuation and the spread of echogenic bubbles across the septation during injection of ablative agents are indicative of a good distribution of the ablative agent into the locules. A missed locule may result in regrowth of a cyst and treatment failure. Additional needle passes through different angles may increase not only the effectiveness of cyst ablation but also the risk of Volume 77, No. 4 : 2013 GASTROINTESTINAL ENDOSCOPY 527

3 EUS-guided pancreatic cyst ablation Oh & Brugge Table 1. Summary of previous reports of EUS-guided cyst ablations Authors No. of patients Ablative agent Follow-up period Complete resolution Gan et al %-80% ethanol 6-12 mo 35% (8/23) Oh et al %/99% ethanol with paclitaxel Median 9 mo (range 6-23 mo) 79% (11/14) Oh et al 37 * 10 99% ethanol with paclitaxel Median 8.5 mo (range 6-18 mo) 60% (6/10) DeWitt et al % ethanol 3-4 mo after second lavage 33% (12/36) Oh et al % ethanol with paclitaxel Median 20 mo (range 12-44) 62% (29/27) DiMaio et al % ethanol 13 mo after first lavage 38% (5/13) *Included only patients with a septated cyst. Included study population of 2 preliminary reports. 29,30 Included patients with multiple ablations. adverse events. A second needle puncture may be considered when it can be performed without increasing the risk of adverse events. In a case report, an 8-cm septated cyst was punctured twice at different angles, and cyst injection was performed with each needle pass. On follow-up CT, the cyst size decreased markedly, and septa observed on the initial CT scan were no longer visible. Two needle passes increased an ablation effect by improving the contact between the cyst locules and the ablative agent. 33 Nearly complete evacuation of cyst fluid before injection therapy increases the surface area directly exposed to the ablative agent and improves the efficacy of ablation. However, cyst fluid rich in mucinous content may not be effectively aspirated because of high viscosity. Even though cyst fluid may not be completely evacuated during initial aspiration, ethanol lavage may reduce the viscosity of mucin-containing fluid and lead to improved evacuation of cyst fluid as well as ablation of the epithelial lining. Therefore, ethanol lavage is usually performed before the injection of a second ablative agent. The presence of a communication between the cyst and main pancreatic duct may result in flow of the injected ablative agent through the communicating duct into the main pancreatic duct. This outflow may not only diminish the ablative effect but may also increase the risk of unexpected ductal change or pancreatitis. Although a mucous plug might obstruct the communicating duct in branchduct IPMN and lavage may not increase the frequency of pancreatitis, 34,35 repeated injection and aspiration during lavage may open an outflow tract. Dilution of the injected agent with pancreatic duct fluid will interfere with the effects of the injectant. Practically, injection and lavage rarely result in flow of the ablative agent into the main pancreatic duct. However, if a cyst is not restored to its original size during ethanol injection, vigorous lavage with repeated injection and aspiration should be avoided because of the probable communication with the main pancreatic duct. On the other hand, endoscopic retrograde pancreatography may be useful for determining the presence of communication between the main pancreatic duct and cyst, but it should be considered in select cases because of the possible risk of pancreatitis. RESULTS OF CLINICAL TRIAL To date, 3 clinical trials of cyst injection therapy, 6,34,36 3 preliminary cases series, 27,35,37 1 long-term follow-up report, 38 and 1 case report 33 have been reported. These reports were summarized in Table 1. In the initial pilot study, patients underwent ethanol lavage with a concentration escalation from 5% to 80% ethanol and were followed for 6 to 12 months. Eight of 23 patients (35%) with complete follow-up had complete resolution. All septated cysts persisted despite ethanol ablation therapy. There was no significant difference in cyst resolution according to the ethanol concentration (5%-40% vs 50%-80%). Five patients underwent surgical resection. All 5 patients had a diagnosis of MCN, and a variable degree of epithelial ablation (up to complete) was observed on surgical pathology. To increase the ablative effect, in new trials, a chemotherapeutic agent (paclitaxel) has been combined with ethanol ablation therapy. 27 It was hypothesized that the epithelial distortion by ethanol could allow the diffusion of paclitaxel in the injured epithelium. In a pilot feasibility study with ethanol and paclitaxel, 14 patients were followed for more than 6 months after injection therapy, and complete resolution was achieved in 11 patients. Paclitaxel used in the study was highly hydrophobic and viscous in nature, complicating the injection technique. Although this study was a preliminary case series, the cyst resolution rate (79%) was greater than the previously observed rate with ethanol alone (33%), suggesting a synergistic effect between ethanol and paclitaxel. One of the important factors that may influence the treatment response is the presence of septations within the cyst. In a case series of 10 patients with septated cysts, 37 complete resolution was achieved in 6 patients after eth- 528 GASTROINTESTINAL ENDOSCOPY Volume 77, No. 4 :

4 Oh & Brugge EUS-guided pancreatic cyst ablation anol lavage and paclitaxel injection. Two patients with a persistent cyst demonstrated an initial decrease in diameter at 6 months, but an increase in size at 12 months. The histopathology of the resected specimen and review of EUS images revealed that regrowth of the cyst resulted from the remnant mucinous epithelium arising from the incompletely lavaged locules. Careful patient selection and tailored intervention based on the internal structure of the cyst is required to improve ablation efficacy and minimize the missed locules, especially when a cyst is septated. Although an ablation effect was demonstrated in the resected cysts of subjects in the pilot study, further evidence of cyst ablation was demonstrated by a randomized, double-blind trial of 42 patients comparing ethanol with saline solution lavage. 36 Ethanol lavage resulted in a significant decrease in cyst size at 3 months after initial ablation compared with saline solution alone. Thirty-three of 42 patients enrolled for the initial randomization underwent a second unblinded ethanol lavage. There was no significant difference in cyst size of subjects exposed to 1 or 2 injections of ethanol. Complete resolution as shown by CT scan was achieved in 33%. Four patients underwent surgery and received a diagnosis of having an IPMN (n 3) or MCN (n 1). Epithelial ablation ranging from 0% (saline solution alone) to 50% to 100% (1 or 2 ethanol lavages) was observed in the histopathology of the resected cysts. The durability of cyst ablation is an important issue because cyst resolution achieved for a short-term period may not ensure the long-term ablative effect and ultimately the prevention of malignant transformation. In a clinical trial of 47 patients who underwent ethanol lavage and paclitaxel injection, 6 29 patients (62%) showed complete resolution of the cyst over a median follow-up of 22 months (range months) (Fig. 2). Four patients underwent surgery and had a diagnosis of MCN (n 2), serous cystadenoma (SCA) (n 1), or a neuroendocrine tumor (n 1). The histopathologic extent of epithelial ablation ranged from 0% to 100%, and a spectrum of histopathologic changes including epithelial denudation with fibrosis and an atrophied epithelium was observed (Fig. 3). A small cyst volume was predictive of complete resolution of the cyst by CT scanning. Two MCN cysts that were nearly resolved at 6-month follow-up demonstrated regrowth at 12 months. The return of the cyst may represent remnant epithelial regrowth. The resolution rate in this study (69%), greater than that in the previous study with ethanol alone, might be a result of the combination injection of ethanol and paclitaxel. In another follow-up report, 38 9 patients who had complete resolution as shown on a CT scan after 1 or 2 ethanol lavages were followed over a median of 26 months (range months). Cyst recurrence on CT scan was not observed in any patient. Imaging evidence of cyst resolution includes complete disappearance of cyst, small low-density focus on CT or EUS, or residual calcification. Imaging-based resolution Figure 2. A, B, A 36-mm unilocular cyst in the body of the pancreas. C, Dense calcification replaced the original cyst on follow-up CT scan at 30 months after cyst ablation. Volume 77, No. 4 : 2013 GASTROINTESTINAL ENDOSCOPY 529

5 EUS-guided pancreatic cyst ablation Oh & Brugge Figure 3. Spectrum of histopathologic changes after cyst ablation: atrophied epithelium (A), transitional area (B), persistent mucinous epithelium (C). may not correlate, however, with histologic ablation. Close monitoring should be continued even after complete resolution, but surveillance policy may be modified based on risk analysis. To improve the ablative effect of cyst injection therapy, procedural techniques including a second needle pass at a different angle and booster ablation have been tried. In 1 case series of 13 patients with branch-duct IPMN, 35 multiple sessions of cyst lavage were performed. Although cyst diameter and surface area showed no significant decrease after 1 ethanol lavage session, these parameters decreased after 2 ethanol lavage sessions. Complete resolution was achieved in 38% (5/13) only after 2 lavage sessions. 35 The presence and number of septations were not predictive of the response to injection therapy. When 2 needle injections with different needle angles were used, an 8-cm cyst was shown to be nearly eliminated on CT scanning. 33 Multiple cyst injection therapy may induce additional effects on the remnant epithelium or locules, but multiple injections have not consistently resulted in a better resolution rate. The relative effectiveness is probably related to the degree of contact between the ablative agent and the cyst epithelium. SAFETY OF CYST ABLATION The safety of an investigational treatment modality is a major concern when it is first applied clinically. Procedurerelated adverse events described in the 3 representative clinical trials are summarized in Table 2. Most adverse events were mild and self-limited. Abdominal pain just after cyst ablation was the most common acute complication. Contrary to initial concerns, the frequency of ablation-related pancreatitis was low (2%, 3/152). The risk of pancreatitis was increased if there was inadvertent injection of an ablative agent into the pancreatic parenchyma. Surprisingly, in cases of injection of branch-duct IPMN with main duct communication, pancreatitis was rare. Thick mucin in the communicating duct may prevent 530 GASTROINTESTINAL ENDOSCOPY Volume 77, No. 4 :

6 Oh & Brugge EUS-guided pancreatic cyst ablation Table 2. Cyst ablation related adverse events Adverse events, n* (%) Gan et al 34 (N 25) DeWitt et al 36 (N 75) Oh et al 6 (N 52) Overall (N 152)* Abdominal pain (7.9) Acute pancreatitis (2.0) Fever (0.7) Pericystic spillage (0.7) Splenic vein obliteration (0.7) *Total number of patients who underwent 1 session of EUS-guided cyst ablation. the leakage of the ablative agent into the main pancreatic duct. 35 Venous obliteration and thrombosis in the venous system adjacent to the cyst have been reported in 2 patients who underwent ethanol lavage and paclitaxel injection. 39 Extensive inflammation within and around the cyst induced by the injection itself or pericystic leak of the ablative agent may result in local extension of inflammation into the adjacent vessels. These adverse events may become serious because portal hypertension and collateral formation may develop. In addition, substantial difficulty may be encountered in subsequent surgical resection for the persistent cyst. For prevention of procedure-related adverse events, it is important to maintain the needle in the visual plane and within the cyst cavity during the entire procedure. The optimal volume of ablative agent needs to be cautiously titrated and an aggressive lavage procedure should be avoided, especially when a cyst is in close proximity to the portosplenic venous system. The ablative agent related systemic adverse events of intravenous administration have not been observed in patients undergoing local injection. Hypersensitivity reaction to paclitaxel, a worrisome and unexpected complication, has not occurred, even without premedication of a steroid and histamine antagonist. CONTROVERSIES IN PANCREATIC CYST ABLATION There are some concerns about ablation of benign cysts that meet the criteria for observation. Second, others have raised concerns of a false sense of success after cyst elimination seen on imaging. The possibility of residual viable epithelium undermines the hope of complete eradication. 40 An imaging surveillance policy for asymptomatic nonsurgical candidates has become widely accepted by surgeons and gastroenterologists. However, lifelong monitoring is burdensome economically and psychologically for the elderly. Cyst ablation of a benign cyst may be an attractive option if a cyst can be readily and successfully ablated by using a minimally invasive method. With successful elimination of a cyst shown by cross-sectional imaging, the subsequent imaging intervals could be prolonged, if not eliminated. Early treatment of premalignant diseases with lessinvasive modalities has resulted in paradigm shifts in the management of gastric and colon adenomas, as well as Barrett s esophagus. Although the role of EUS-guided pancreatic cyst ablation is still under evaluation and its potential benefits are theoretical, eradication of a premalignant cyst may also have a role in the prevention of malignant change. PROPOSED INDICATIONS EUS-guided pancreatic cyst ablation is still an investigational modality and should be judiciously used in select patients based on strict inclusion criteria that may predict high treatment efficacy while minimizing procedurerelated risks. Most patients in published clinical trials underwent cyst ablation at the time of diagnostic FNA. This practice resulted in the inclusion of a wide variety of cysts and types of epithelium. In the future, it would be ideal for the patient to have an established diagnosis before injection therapy. The ideal cyst candidate for ablation should have (1) a benign appearance without any malignant feature, (2) a diameter between 2 and 4 cm, (3) a unilocular or oligolocular morphology, and (4) no communication with the main pancreatic duct. The ideal size of the cyst for injection therapy is based on 2 competing factors, the risk of malignancy and the success rate, and both are related to the cyst diameter. It is generally accepted that a cyst larger than 3 to 4 cm in diameter may have an increased malignant potential. A cyst diameter less than 3.5 cm was predictive of cyst resolution after ablation therapy. On the other hand, a minimum cyst diameter of 2 cm may ensure the safety and feasibility of ablation therapy. Volume 77, No. 4 : 2013 GASTROINTESTINAL ENDOSCOPY 531

7 EUS-guided pancreatic cyst ablation Oh & Brugge Ideally, patient selection should be based on the specific type of cyst. MCN is the ideal target for EUSguided cyst ablation because it has malignant potential and is often unilocular. Cyst ablation should be considered only when the viscous mucinous cyst fluid can be effectively aspirated. There are some concerns about the treatment of a benign cyst such as SCA. Because SCAs may exhibit significant growth, they may ultimately lead to cyst-related symptom. 41,42 Cyst ablation may be considered for macrocystic SCAs that demonstrate a size increase during follow-up. Branch-duct IPMNs may also be good candidates because they may be unilocular, demonstrate malignant potential, and are highly prevalent in elderly patients. In terms of specific clinical indications, cyst ablation may be considered for the following clinical scenarios: (1) a 2- to 4-cm benign branch-duct IPMN or MCN located in the head or body of the pancreas, (2) a 2- to 4-cm benign branch-duct IPMN or MCN located in the tail of the pancreas in a high-risk surgical patient, (3) a 2- to 4-cm branch-duct IPMN or MCN with high-risk features (nodule or enlarging size) in a high-risk surgical patient. FUTURE PERSPECTIVES EUS-guided cyst ablation is a promising modality that may become an alternative to surgical resection, but should not be performed clinically at this time. Instead, cyst ablation therapy should be performed by using an institutional review board based protocol. For this paradigm shift, some limitations associated with cyst ablation need to be overcome. Procedural modifications may improve the treatment efficacy: (1) a second needle pass in septated cysts, (2) a booster ablation for a large cyst that demonstrates a plateau in response after initial ablation, and (3) maintenance ethanol concentration in the cyst during ethanol lavage. 43 Discovery and development of novel ablative agents that may exert durable activity by using slow-releasing formulations may provide improved ablation rates. 14 Long-term studies over 5 to 10 years after cyst ablation will provide the critical long-term outcomes including prevention of cancer development in premalignant cysts and procedure-related risk profile. The roles of emerging therapeutic modalities including radiofrequency ablation and photodynamic therapy need to be evaluated in future research. In radiofrequency ablation, the heating of the cyst fluid could deliver thermal injury not only directly to the exposed epithelium but also transmission through septations, resulting in complete ablation of septated cysts. In photodynamic therapy, the sensitization of the cyst epithelium by systemic injection of photosensitizer may limit its efficacy. Therefore, the development of locally injectable photosensitizer may enhance its clinical application in cyst ablation. REFERENCES 1. Laffan TA, Horton KM, Klein AP, et al. Prevalence of unsuspected pancreatic cysts on MDCT. AJR Am J Roentgenol 2008;191: de Jong K, Nio CY, Hermans JJ, et al. High prevalence of pancreatic cysts detected by screening magnetic resonance imaging examinations. Clin Gastroenterol Hepatol 2010;8: Brugge WR, Lauwers GY, Sahani D, et al. Cystic neoplasms of the pancreas. N Engl J Med 2004;351: Oh HC, Kim MH, Hwang CY, et al. Cystic lesions of the pancreas: challenging issues in clinical practice. 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8 Oh & Brugge EUS-guided pancreatic cyst ablation ultrasound-guided fine-needle injection in patients with advanced pancreatic carcinoma. Cancer 2000;88: Hecht JR, Bedford R, Abbruzzese JL, et al. A phase I/II trial of intratumoral endoscopic ultrasound injection of ONYX-015 with intravenous gemcitabine in unresectable pancreatic carcinoma. Clin Cancer Res 2003;9: Chang KJ, Lee JG, Holcombe RF, et al. Endoscopic ultrasound delivery of an antitumor agent to treat a case of pancreatic cancer. Nat Clin Pract Gastroenterol Hepatol 2008;5: Oh HC, Seo DW, Lee TY, et al. New treatment for cystic tumors of the pancreas: EUS-guided ethanol lavage with paclitaxel injection. Gastrointest Endosc 2008;67: Bean WJ, Rodan BA. Hepatic cysts: treatment with alcohol. AJR Am J Roentgenol 1985;144: Gelczer RK, Charboneau JW, Hussain S, et al. Complications of percutaneous ethanol ablation. J Ultrasound Med 1998;17: Okano A, Hajiro K, Takakuwa H, et al. Alcohol sclerotherapy of hepatic cysts: its effect in relation to ethanol concentration. Hepatol Res 2000; 17: Rowinsky EK, Donehower RC. Paclitaxel (taxol). N Engl J Med 1995;332: Song D, Wientjes MG, Au JL. Bladder tissue pharmacokinetics of intravesical taxol. Cancer Chemother Pharmacol 1997;40: Oh HC, Seo DW, Song TJ. Resolution of a septated pancreatic cyst by booster endoscopic ultrasonography-guided ablation. J Dig Dis 2011; 12: Gan SI, Thompson CC, Lauwers GY, et al. Ethanol lavage of pancreatic cystic lesions: initial pilot study. Gastrointest Endosc 2005;61: DiMaio CJ, DeWitt JM, Brugge WR. Ablation of pancreatic cystic lesions: the use of multiple endoscopic ultrasound-guided ethanol lavage sessions. Pancreas 2011;40: DeWitt J, McGreevy K, Schmidt CM, et al. EUS-guided ethanol versus saline solution lavage for pancreatic cysts: a randomized, double-blind study. Gastrointest Endosc 2009;70: Oh HC, Seo DW, Kim SC, et al. Septated cystic tumors of the pancreas: is it possible to treat them by endoscopic ultrasonography-guided intervention? Scand J Gastroenterol 2009;44: DeWitt J, DiMaio CJ, Brugge WR. Long-term follow-up of pancreatic cysts that resolve radiologically after EUS-guided ethanol ablation. Gastrointest Endosc 2010;72: Oh HC, Seo DW, Kim SC. Portal Vein thrombosis after EUS-guided pancreatic cyst ablation. Dig Dis Sci 2012;57: Fernandez-Del Castillo C. EUS treatment of pancreatic cysts: let s keep the alcohol (and the chemotherapy) locked in the cupboard. Gastroenterology 2011;140: Tseng JF, Warshaw AL, Sahani DV, et al. Serous cystadenoma of the pancreas: tumor growth rates and recommendations for treatment. Ann Surg 2005;242:413-9; discussion Khashab MA, Shin EJ, Amateau S, et al. Tumor size and location correlate with behavior of pancreatic serous cystic neoplasms. Am J Gastroenterol 2011;106: Xu XX, Du Y, Yang HF, et al. CT-guided sclerotherapy with ethanol concentration monitoring for treatment of renal cysts. AJR Am J Roentgenol 2011;196:W Received September 15, Accepted October 29, Current affiliations: Division of Gastroenterology, Chung-Ang University College of Medicine, Seoul, Korea (1), Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA (2). Reprint requests: William R. Brugge, MD, Gastrointestinal Unit, Massachusetts General Hospital, Blake 452c, 55 Fruit Street, Boston, MA Volume 77, No. 4 : 2013 GASTROINTESTINAL ENDOSCOPY 533