Alterations in cyst fluid genetics following endoscopic ultrasound-guided pancreatic cyst ablation with ethanol and paclitaxel
submitted 18 October 2013
accepted after revision 28 February 2014
25 April 2014 (online)
Background and study aims: Endoscopic ultrasound (EUS)-guided ethanol lavage with paclitaxel injection has been shown to be effective for the treatment of pancreatic cystic neoplasms; however, the evidence for effectiveness is based primarily on cyst resolution on imaging. The aim of this study was to evaluate changes in pancreatic cyst fluid DNA following EUS-guided pancreatic cyst ablation (PCA) with ethanol and paclitaxel.
Patients and methods: In a single-center, prospective study, patients with suspected benign pancreatic cysts (15 – 50 mm in diameter; ≤ 5 compartments) underwent EUS-PCA with ethanol and paclitaxel followed 3 months later by repeat EUS-FNA, cyst aspiration for repeat DNA analysis, and possible repeat EUS-PCA. Abdominal imaging was repeated 3 – 4 months and 12 months after the second EUS. Changes in baseline pancreatic cyst fluid DNA, procedural complications, and radiographic changes in cyst volume were evaluated.
Results: A total of 22 patients (median age 67 years; 15 women) with cysts in the head or uncinate (n = 10), body or neck (n = 8), and tail (n = 4), measuring a median diameter of 25 mm (range 15 – 43 mm), underwent one (n = 22) or two (n = 9) EUS-PCA procedures. Baseline cyst DNA included mutations in 11 patients (50 %). Postablation cyst fluid (n = 19) showed elimination of all baseline mutations in eight patients, new mutations in three, and no changes in eight without a baseline mutation. The largest per-protocol postablation image-defined volume change (n = 20) from either of the follow-up abdominal imaging studies (n = 20) demonstrated complete response ( < 5 % original volume) in 10 patients (50 %), partial response (5 % – 25 % original volume) in 5 (25 %), and a persistent cyst (> 25 % original volume) in 5 (25 %). During a median follow-up of 27 months (range 17 – 42 months), adverse events from all EUS-PCAs (n = 31) included abdominal pain alone in four patients (13 %), pancreatitis in three (10 %), peritonitis in one (3 %), and gastric wall cyst in one (3 %). The adverse events were classified as moderately severe in four patients (three with pancreatitis, one with peritonitis).
Conclusion: EUS-PCA with ethanol and paclitaxel may possibly eliminate mutant DNA in neoplastic pancreatic cysts. This technique leads to complete or partial image-defined resolution in 75 % of cysts but may lead to rare adverse events.
Clinical trial registration: ClinicalTrials.gov (NCT01643460)
- 1 Tanaka M, Fernández-del Castillo C, Adsay V et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology 2012; 12: 183-197
- 2 Al-Haddad M, Schmidt MC, Sandrasegaran K et al. Diagnosis and treatment of cystic pancreatic tumors. Clin Gastroenterol Hepatol 2011; 9: 635-648
- 3 DeWitt J. Endoscopic ultrasound-guided pancreatic cyst ablation. Gastrointest Endosc Clin N Am 2012; 22: 291-302
- 4 Oh HC, Brugge WR. EUS-guided pancreatic cyst ablation: a critical review (with video). Gastrointest Endosc 2013; 77: 526-533
- 5 Gan SI, Thompson CC, Lauwers GY et al. Ethanol lavage of pancreatic cystic lesions: initial pilot study. Gastrointest Endosc 2005; 61: 746-752
- 6 DeWitt J, McGreevy K, Schmidt CM et al. Endoscopic ultrasound-guided ethanol versus saline lavage for pancreatic cysts: a randomized double blinded study. Gastrointest Endosc 2009; 70: 710-723
- 7 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: 636-642
- 8 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: 242-247
- 9 Oh HC, Seo DW, Song TJ et al. Endoscopic ultrasonography-guided ethanol lavage with paclitaxel injection treats patients with pancreatic cysts. Gastroenterology 2011; 140: 172-179
- 10 Hruban RH, Adsay NV, Albores-Saavedra J et al. Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesions. Am J Surg Pathol 2001; 25: 579-586
- 11 Izeradjene K, Combs C, Best M et al. Kras(G12D) and Smad4/Dpc4 haploinsufficiency cooperate to induce mucinous cystic neoplasms and invasive adenocarcinoma of the pancreas. Cancer Cell 2007; 11: 229-243
- 12 Biankin AV, Biankin SA, Kench JG et al. Aberrant p16(INK4A) and DPC4/Smad4 expression in intraductal papillary mucinous tumours of the pancreas is associated with invasive ductal adenocarcinoma. Gut 2002; 50: 861-868
- 13 Jimenez RE, Warshaw AL, Z’graggen K et al. Sequential accumulation of K-ras mutations and p53 overexpression in the progression of pancreatic mucinous cystic neoplasms to malignancy. Ann Surg 1999; 230: 501-509
- 14 Sasaki S, Yamamoto H, Kaneto H et al. Differential roles of alterations of p53, p16, and SMAD4 expression in the progression of intraductal papillary-mucinous tumors of the pancreas. Oncol Rep 2003; 10: 21-25
- 15 Khalid A, Zahid M, Finkelstein SD et al. Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study. Gastrointest Endosc 2009; 69: 1095-1102
- 16 Cotton PB, Eisen GM, Asbakken L et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc 2010; 71: 446-454
- 17 Tanaka M, Chari S, Adsay V et al. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology 2006; 6: 17-32
- 18 Brugge WR, Lewandrowski K, Lee-Lewandrowski E et al. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology 2004; 126: 1330-1336
- 19 van der Waaij LA, van Dullemen HM, Porte RJ. Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis. Gastrointest Endosc 2005; 62: 383-389
- 20 Prasad GA, Bansal A, Sharma P et al. Predictors of progression in Barrett’s esophagus: current knowledge and future directions. Am J Gastroenterol 2010; 105: 1490-1502
- 21 Prasad GA, Wang KK, Halling KC et al. Correlation of histology with biomarker status after photodynamic therapy in Barrett esophagus. Cancer 2008; 113: 470-476
- 22 Prasad GA, Wang KK, Halling KC et al. Utility of biomarkers in prediction of response to ablative therapy in Barrett’s esophagus. Gastroenterology 2008; 135: 370-379