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

John DeWitt, Mohamad Al-Haddad, Stuart Sherman, Julia Leblanc, C. Schmidt, Kumar Sandrasegaran, Sydney D. Finkelstein

Research output: Contribution to journalArticle

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Abstract

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).

Original languageEnglish
Pages (from-to)457-464
Number of pages8
JournalEndoscopy
Volume46
Issue number6
DOIs
StatePublished - 2014

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Pancreatic Cyst
Cyst Fluid
Paclitaxel
Ethanol
Cysts
DNA
Mutation
Peritonitis
Pancreatitis
Passive Cutaneous Anaphylaxis
Therapeutic Irrigation
Pancreatic Neoplasms
Abdominal Pain
Stomach
Neck
Head
Clinical Trials
Prospective Studies

ASJC Scopus subject areas

  • Gastroenterology
  • Medicine(all)

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Alterations in cyst fluid genetics following endoscopic ultrasound-guided pancreatic cyst ablation with ethanol and paclitaxel. / DeWitt, John; Al-Haddad, Mohamad; Sherman, Stuart; Leblanc, Julia; Schmidt, C.; Sandrasegaran, Kumar; Finkelstein, Sydney D.

In: Endoscopy, Vol. 46, No. 6, 2014, p. 457-464.

Research output: Contribution to journalArticle

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abstract = "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).",
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T1 - Alterations in cyst fluid genetics following endoscopic ultrasound-guided pancreatic cyst ablation with ethanol and paclitaxel

AU - DeWitt, John

AU - Al-Haddad, Mohamad

AU - Sherman, Stuart

AU - Leblanc, Julia

AU - Schmidt, C.

AU - Sandrasegaran, Kumar

AU - Finkelstein, Sydney D.

PY - 2014

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N2 - 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).

AB - 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).

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