Subscribe to RSS
DOI: 10.1055/s-0034-1390742
Integrated molecular pathology accurately determines the malignant potential of pancreatic cysts
Publication History
submitted 26 March 2014
accepted after revision 28 August 2014
Publication Date:
14 October 2014 (online)
Background and study aims: Current diagnostic testing is inadequate to determine the malignant potential of pancreatic cysts, resulting in overcautious patient management. Integrated molecular pathology (IMP) testing combines molecular analysis with first-line test results (cytology, imaging, and fluid chemistry) to assess the malignant potential of pancreatic cysts. This multicenter study aimed to determine the diagnostic accuracy of IMP for pancreatic adenocarcinoma, and the utility of IMP testing under current guideline recommendations for managing pancreatic cysts.
Patients and methods: Patients who had undergone previous IMP testing as prescribed by their physician and for whom clinical outcomes were available from retrospective record review were included (n = 492). Performance was determined by correlation between clinical outcome and previous IMP diagnosis (“benign”/“statistically indolent” vs. “statistically higher risk [SHR]”/ “aggressive”) or an International Consensus Guideline (Sendai 2012) criteria model for “surveillance” vs. “surgery.” The Cox proportional hazards model determined hazard ratios for malignancy.
Results: Benign and statistically indolent IMP diagnoses had a 97 % probability of benign follow-up for up to 7 years and 8 months from initial IMP testing. SHR and aggressive diagnoses had relative hazard ratios for malignancy of 30.8 and 76.3, respectively (both P < 0.0001). Sendai surveillance criteria had a 97 % probability of benign follow-up for up to 7 years and 8 months, but for surgical criteria the hazard ratio was only 9.0 (P < 0.0001). In patients who met Sendai surgical criteria, benign and statistically indolent IMP diagnoses had a > 93 % probability of benign follow-up, with relative hazard ratios for SHR and aggressive IMP diagnoses of 16.1 and 50.2, respectively (both P < 0.0001).
Conclusion: IMP more accurately determined the malignant potential of pancreatic cysts than a Sendai 2012 guideline management criteria model. IMP may improve patient management by justifying more relaxed observation in patients meeting Sendai surveillance criteria. IMP can more accurately differentiate between the need for surveillance or surgery in patients meeting Sendai surgical criteria.
-
References
- 1 Wu BU, Sampath K, Berberian CE et al. Prediction of malignancy in cystic neoplasms of the pancreas: a population-based cohort study. Am J Gastroenterol 2014; 109: 121-129
- 2 Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013; 63: 11-30
- 3 Khalid A, Brugge W. ACG practice guidelines for the diagnosis and management of neoplastic pancreatic cysts. Am J Gastroenterol 2007; 102: 2339-2349
- 4 Tanaka M, Fernandez-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
- 5 Del Chiaro M, Verbeke C, Salvia R et al. European experts consensus statement on cystic tumours of the pancreas. Dig Liver Dis 2013; 45: 703-711
- 6 Grobmyer SR, Cance WG, Copeland EM et al. Is there an indication for initial conservative management of pancreatic cystic lesions?. J Surg Oncol 2009; 100: 372-374
- 7 Allen PJ, D’Angelica M, Gonen M et al. A selective approach to the resection of cystic lesions of the pancreas: results from 539 consecutive patients. Ann Surg 2006; 244: 572-582
- 8 Gaujoux S, Brennan MF, Gonen M et al. Cystic lesions of the pancreas: changes in the presentation and management of 1,424 patients at a single institution over a 15-year time period. J Am Coll Surg 2011; 212: 590-600
- 9 Spinelli KS, Fromwiller TE, Daniel RA et al. Cystic pancreatic neoplasms: observe or operate. Ann Surg 2004; 239: 651-657
- 10 Huang ES, Turner BG, Fernandez-Del-Castillo C et al. Pancreatic cystic lesions: clinical predictors of malignancy in patients undergoing surgery. Aliment Pharmacol Ther 2010; 31: 285-294
- 11 Esserman LJ, Thompson Jr IM, Reid B. Overdiagnosis and overtreatment in cancer: an opportunity for improvement. JAMA 2013; 310: 797-798
- 12 Khalid A, McGrath KM, Zahid M et al. The role of pancreatic cyst fluid molecular analysis in predicting cyst pathology. Clin Gastroenterol Hepatol 2005; 3: 967-973
- 13 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
- 14 Shen J, Brugge WR, Dimaio CJ et al. Molecular analysis of pancreatic cyst fluid: a comparative analysis with current practice of diagnosis. Cancer 2009; 117: 217-227
- 15 Matthaei H, Norris AL, Tsiatis AC et al. Clinicopathological characteristics and molecular analyses of multifocal intraductal papillary mucinous neoplasms of the pancreas. Ann Surg 2012; 255: 326-333
- 16 Lee YH, Lee NJ, Kim JH et al. Sonographically guided fine needle aspiration of thyroid nodule: discrepancies between cytologic and histopathologic findings. J Clin Ultrasound 2008; 36: 6-11
- 17 Kosinski AS. A weighted generalized score statistic for comparison of predictive values of diagnostic tests. Stat Med 2013; 32: 964-977
- 18 Lawson R, Savides T, Kwong W et al. Natural history of pancreatic cystic lesions: validation of the 2012 Sendai criteria. Am J Gastroenterol 2013; 108: S91
-
Supplementary References
- 1 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
- 2 Shen J, Brugge WR, Dimaio CJ et al. Molecular analysis of pancreatic cyst fluid: a comparative analysis with current practice of diagnosis. Cancer 2009; 117: 217-227
- 3 Khalid A, McGrath KM, Zahid M et al. The role of pancreatic cyst fluid molecular analysis in predicting cyst pathology. Clin Gastroenterol Hepatol 2005; 3: 967-973
- 4 Khalid A, Brugge W. ACG practice guidelines for the diagnosis and management of neoplastic pancreatic cysts. Am J Gastroenterol 2007; 102: 2339-2349
- 5 Tanaka M, Fernandez-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
- 6 Klöppel G, Hruban RH, Klimstra DS et al. Solid-pseudopapillary tumor of pancreas. In: Bosman FT, Carneiro F, Hruban RH, et al, eds. World Health Organization Classification of Tumours of the Digestive System. Lyon: IARC; 2010: 327-330
- 7 Klöppel G, Hruban R, Luttges J et al. Solid-pseudopapillary neoplasm. In: Hamilton SR, Aaltonen LA, Theise ND, , eds. World Health Organization Classification of Tumours of the Digestive System. Lyon: IARC; 2000: 246-248
- 8 Papavramidis T, Papavramidis S. Solid pseudopapillary tumors of the pancreas: review of 718 patients reported in English literature. J Am Coll Surg 2005; 200: 965-972