Alterations in cyst fluid genetics following endoscopic ultrasound-guided pancreatic cyst ablation with ethanol and paclitaxel.
OBJECTIVE
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.


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).


CONCLUSIONS
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.


BACKGROUND
ClinicalTrials.gov (NCT01643460).
Division of Gastroenterology and Hepatology, Indiana University Medical Center, Indianapolis, Indiana, USA.
John M
JM
DeWitt
Division of Gastroenterology and Hepatology, Indiana University Medical Center, Indianapolis, Indiana, USA.
Mohamad
M
Al-Haddad
Division of Gastroenterology and Hepatology, Indiana University Medical Center, Indianapolis, Indiana, USA.
Stuart
S
Sherman
Division of Gastroenterology and Hepatology, Indiana University Medical Center, Indianapolis, Indiana, USA.
Julia
J
LeBlanc
Division of General Surgery, Indiana University Medical Center, Indianapolis, Indiana, USA.
Christian M
CM
Schmidt
Division of Radiology, Indiana University Medical Center, Indianapolis, Indiana, USA.
Kumar
K
Sandrasegaran
RedPath Integrated Pathology, Pittsburgh, Pennsylvania, USA.
Sydney D
SD
Finkelstein
D055011:Ablation Techniques / Q000009:adverse effects* / Q000379:methods; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D020420:Cyst Fluid / Q000737:chemistry*; D004247:DNA / Q000032:analysis*; D004252:DNA Mutational Analysis; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration; D019160:Endosonography; D000431:Ethanol / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D010181:Pancreatic Cyst / Q000000981:diagnostic imaging / Q000235:genetics* / Q000601:surgery*; D011446:Prospective Studies; D011859:Radiography; D012997:Solvents / Q000008:administration & dosage
D000972:Antineoplastic Agents, Phytogenic; D012997:Solvents; D000431:Ethanol; D004247:DNA; D017239:Paclitaxel