Advertisement

Surgical Outcomes After Pancreatic Resection of Screening-Detected Lesions in Individuals at High Risk for Developing Pancreatic Cancer

  • Marcia Irene CantoEmail author
  • Tossapol Kerdsirichairat
  • Charles J. Yeo
  • Ralph H. Hruban
  • Eun Ji Shin
  • Jose Alejandro Almario
  • Amanda Blackford
  • Madeline Ford
  • Alison P. Klein
  • Ammar A. Javed
  • Anne Marie Lennon
  • Atif Zaheer
  • Ihab R. Kamel
  • Elliot K. Fishman
  • Richard Burkhart
  • Jin He
  • Martin Makary
  • Matthew J. Weiss
  • Richard D. Schulick
  • Michael G. Goggins
  • Christopher L. Wolfgang
Original Article

Abstract

Background

Screening high-risk individuals (HRI) can detect potentially curable pancreatic ductal adenocarcinoma (PDAC) and its precursors. We describe the outcomes of high-risk individuals (HRI) after pancreatic resection of screen-detected neoplasms.

Methods

Asymptomatic HRI enrolled in the prospective Cancer of the Pancreas Screening (CAPS) studies from 1998 to 2014 based on family history or germline mutations undergoing surveillance for at least 6 months were included. Pathologic diagnoses, hospital length of stay, incidence of diabetes mellitus, operative morbidity, need for repeat operation, and disease-specific mortality were determined.

Results

Among 354 HRI, 48 (13.6%) had 57 operations (distal pancreatectomy (31), Whipple (20), and total pancreatectomy (6)) for suspected pancreatic neoplasms presenting as a solid mass (22), cystic lesion(s) (25), or duct stricture (1). The median length of stay was 7 days (IQR 5–11). Nine of the 42 HRI underwent completion pancreatectomy for a new lesion after a median of 3.8 years (IQR 2.5–7.6). Postoperative complications developed in 17 HRI (35%); there were no perioperative deaths. New-onset diabetes mellitus after partial resection developed in 20% of HRI. Fourteen PDACs were diagnosed, 11 were screen-detected, 10 were resectable, and 9 had an R0 resection. Metachronous PDAC developed in remnant pancreata of 2 HRI. PDAC-related mortality was 4/10 (40%), with 90% 1-year survival and 60% 5-year survival, respectively.

Conclusions

Screening HRI can detect PDAC with a high resectability rate. Surgical treatment is associated with a relatively short length of stay and low readmission rate, acceptable morbidity, zero 90-day mortality, and significant long-term survival.

Clinical Trial Registration Number

NCT2000089

Keywords

Pancreatic cancer Early detection Screening Surgical outcomes 

Notes

Acknowledgments

CAPS 3 study participating centers and co-investigators (listed in alphabetical order) Dana Farber Cancer Institute, Boston, MA (Koenraad Mortele, John Saltzman, Sapna Syngal); The Mayo Clinic, Rochester, MN (Joel Fletcher, Gloria Petersen, Naoki Takahashi, Mark Topazian), MD Anderson Cancer Center, Houston, TX (Priya Bosale, Jeffrey Lee, Eric Tamm, Raghunandan Vikram), and University of California, Los Angeles, CA (James Farrell, Daniel Margolis).

Author Contributions

Conceived and designed the study: Marcia Canto and Michael Goggins.

Acquisition of data: Tossapol Kerdsirichairat, Madeline Ford, Ammar Javed, Marcia Canto, Anne Marie Lennon, Eun Ji Shin, Elliott Fishman, Ihab Kamel, Jin He, Richard Burkhart, Martin Makary, Richard Schulick, Charles Yeo, Matthew Weiss and Christopher Wolfgang.

Analysis and interpretation of data: Tossapol Kerdsirichairat, Amanda Blackford, Alison Klein, Marcia Canto, Michael Goggins, Ralph Hruban.

Drafted the manuscript: Tossapol Kerdsirichairat and Marcia Canto.

Statistical analysis: Tossapol Kerdsirichairat, Marcia Canto, Amanda Blackford.

Revised the manuscript and agreed with the manuscript’s results and conclusions: all authors.

Study support: Marcia Canto and Michael Goggins.

Obtained funding: Marcia Canto, Ralph Hruban, and Michael Goggins.

Study supervision: Marcia Canto, Michael Goggins.

Funding

This work was supported by the National Institutes of Health grants (CA210170, CA176828, CA62924, CA154823, CA132829), Susan Wojcicki and Dennis Troper, the Pancreatic Cancer Action Network, the Lustgarten Foundation for Pancreatic Cancer Research, the Rolfe Pancreatic Cancer Foundation, the John and Peter Hooven Memorial Endowment, Hugh and Rachel Victor, and ChiRhoCin, Inc.

References

  1. 1.
    Clancy TE. Surgery for pancreatic cancer. Hematol Oncol Clin North Am 2015;29:701–16.CrossRefPubMedGoogle Scholar
  2. 2.
    Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2019. CA Cancer J Clin 2019;69:7–34.CrossRefPubMedGoogle Scholar
  3. 3.
    Corral JE, Mareth KF, Riegert-Johnson DL, et al. Diagnostic yield from screening asymptomatic individuals at high risk for pancreatic cancer: a meta-analysis of cohort studies. Clin Gastroenterol Hepatol 2019.Google Scholar
  4. 4.
    Canto MI, Harinck F, Hruban RH, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut 2013;62:339–47.CrossRefPubMedGoogle Scholar
  5. 5.
    Canto MI, Almario JA, Schulick RD, et al. Risk of neoplastic progression in individuals at high risk for pancreatic cancer undergoing long-term surveillance. Gastroenterology 2018;155:740–51 e2.CrossRefPubMedGoogle Scholar
  6. 6.
    Vasen H, Ibrahim I, Ponce CG, et al. Benefit of surveillance for pancreatic cancer in high-risk individuals: outcome of long-term prospective follow-up studies from three European expert centers. J Clin Oncol 2016;34:2010–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Hruban RH, Canto MI, Goggins M, et al. Update on familial pancreatic cancer. Adv Surg 2010;44:293–311.CrossRefPubMedGoogle Scholar
  8. 8.
    Hu C, Hart SN, Polley EC, et al. Association between inherited germline mutations in cancer predisposition genes and risk of pancreatic cancer. JAMA 2018;319:2401–2409.CrossRefPubMedGoogle Scholar
  9. 9.
    Hruban RH, Pitman MB, Klimstra D. Tumors of the pancreas. Rockville, Maryland: American Registry of Pathology, 2007.Google Scholar
  10. 10.
    Hruban RH, Takaori K, Klimstra DS, et al. An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol 2004;28:977–87.CrossRefPubMedGoogle Scholar
  11. 11.
    Canto MI, Goggins M, Hruban RH, et al. Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study. Clin Gastroenterol Hepatol 2006;4:766–81; quiz 665.CrossRefPubMedGoogle Scholar
  12. 12.
    Canto MI, Goggins M, Yeo CJ, et al. Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach. Clin Gastroenterol Hepatol 2004;2:606–21.CrossRefPubMedGoogle Scholar
  13. 13.
    Canto MI, Hruban RH, Fishman EK, et al. Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. Gastroenterology 2012;142:796–804; quiz e14-5.CrossRefPubMedGoogle Scholar
  14. 14.
    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;12:183–97.CrossRefPubMedGoogle Scholar
  15. 15.
    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.CrossRefPubMedGoogle Scholar
  16. 16.
    Basturk O, Hong SM, Wood LD, et al. A revised classificaiton system and recommendations from the Baltimore consensus meeting for neoplastic precursor lesions in the pancreas. Am K Surg Pathol 2015;39:1730–41.CrossRefGoogle Scholar
  17. 17.
    Dusch N, Lietzmann A, Barthels F, et al. International study group of pancreatic surgery definitions for postpancreatectomy complications: applicability at a high-volume center. Scand J Surg 2017;106:216–223.CrossRefPubMedGoogle Scholar
  18. 18.
    Vollmer CM, Jr., Sanchez N, Gondek S, et al. A root-cause analysis of mortality following major pancreatectomy. J Gastrointest Surg 2012;16:89–102.CrossRefPubMedGoogle Scholar
  19. 19.
    Swanson RS, Pezzi CM, Mallin K, et al. The 90-day mortality after pancreatectomy for cancer is double the 30-day mortality: more than 20,000 resections from the national cancer data base. Ann Surg Oncol 2014;21:4059–67.CrossRefPubMedGoogle Scholar
  20. 20.
    Xourafas D, Pawlik TM, Cloyd JM. Independent predictors of increased operative time and hospital length of stay are consistent across different surgical approaches to pancreatoduodenectomy. J Gastrointest Surg 2018;22:1911–1919.CrossRefPubMedGoogle Scholar
  21. 21.
    Lassen K, Nymo LS, Olsen F, et al. Benchmarking of aggregated length of stay after open and laparoscopic surgery for cancers of the digestive system. BJS Open 2018;2:246–53.CrossRefPubMedGoogle Scholar
  22. 22.
    American Diabetes Association. Diagnosis and classifciation of diabetes mellitus. Diabetes Care 2010;33:S62–9.CrossRefGoogle Scholar
  23. 23.
    Wente MN, Bassi C, Dervenis MD, et al. Delayed gastric emptying after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 2007;142:761–8CrossRefPubMedGoogle Scholar
  24. 24.
    Bassi C, Marchegiani G, Dervenis C, et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery 2017;161:584–91.CrossRefPubMedGoogle Scholar
  25. 25.
    Wente MN, Veit JA, Bassi C, et al. Postpancreatectomy hemorrhage (PPH): an International Study Group of Pancreatic Surgery (ISGPS) definition. Surgery 2007;142:20–5.CrossRefPubMedGoogle Scholar
  26. 26.
    Burkhart RA, Gerber SM, Tholey RM, et al. Incidence and severity of pancreatogenic diabetes after pancreatic resection. J Gastrointest Surg 2015;19(2):217–25.CrossRefPubMedGoogle Scholar
  27. 27.
    Beger HG, Poch B, Mayer B, Siech M. New onset of diabetes and pancreatic exocrine insufficiency after pancreaticoduodenectomy for benign and malignant tumors: a systematic review and meta-analysis of long-term results. Ann Surg 2018;267(2):259–70.CrossRefPubMedGoogle Scholar
  28. 28.
    De Bruijin KM, van Eijck CH. New-onset diabetes after distal pancreatectomy: a systematic review. Ann Surg 2015;261(5):854–61.CrossRefGoogle Scholar
  29. 29.
    Brune K, Abe T, Canto M, et al. Multifocal neoplastic precursor lesions associated with lobular atrophy of the pancreas in patients having a strong family history of pancreatic cancer. Am J Surg Pathol 2006;30:1067–76.PubMedGoogle Scholar
  30. 30.
    Narayan KM, Boyle JP, Thompson TJ, et al. Lifetime risk for diabetes mellitus in the United States. JAMA 2003;290;1884–90.CrossRefPubMedGoogle Scholar
  31. 31.
    Harinck F, Konings IC, Kluijt I, et al. A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals. Gut 2016;65:1505–13.CrossRefPubMedGoogle Scholar
  32. 32.
    Al-Sukhni W, Borgida A, Rothenmund H, et al. Screening for pancreatic cancer in a high-risk cohort: an eight-year experience. J Gastrointest Surg 2012;16:771–83.CrossRefPubMedGoogle Scholar
  33. 33.
    Ludwig E, Olson SH, Bayuga S, et al. Feasibility and yield of screening in relatives from familial pancreatic cancer families. Am J Gastroenterol 2011;106:946–54.CrossRefPubMedGoogle Scholar
  34. 34.
    Poley JW, Kluijt I, Gouma DJ, et al. The yield of first-time endoscopic ultrasonography in screening individuals at a high risk of developing pancreatic cancer. Am J Gastroenterol 2009;104:2175–81.CrossRefPubMedGoogle Scholar
  35. 35.
    Schneider R, Slater EP, Sina M, et al. German national case collection for familial pancreatic cancer (FaPaCa): ten years experience. Fam Cancer 2011;10:323–30.CrossRefPubMedGoogle Scholar
  36. 36.
    Verna EC, Hwang C, Stevens PD, et al. Pancreatic cancer screening in a prospective cohort of high-risk patients: a comprehensive strategy of imaging and genetics. Clin Cancer Res 2010;16:5028–37.CrossRefPubMedGoogle Scholar
  37. 37.
    Springer S, Wang Y, Dal Molin M, et al. A combination of molecular markers and clinical features improve the classification of pancreatic cysts. Gastroenterology 2015;149:1501–10.CrossRefPubMedGoogle Scholar
  38. 38.
    Maker AV, Carrara S, Jamieson NB, et al. Cyst fluid biomarkers for intraductal papillary mucinous neoplasms of the pancreas: a critical review from the international expert meeting on pancreatic branch-duct-intraductal papillary mucinous neoplasms. J Am Coll Surg 2015;220:243–53.CrossRefPubMedGoogle Scholar
  39. 39.
    Suenaga M, Yu J, Shindo K, et al. Pancreatic Juice Mutation Concentrations Can Help Predict the Grade of Dysplasia in Patients Undergoing Pancreatic Surveillance. Clin Cancer Res 2018;24:2963–2974.CrossRefPubMedGoogle Scholar
  40. 40.
    Yu J, Sadakari Y, Shindo K, et al. Digital next-generation sequencing identifies low-abundance mutations in pancreatic juice samples collected from the duodenum of patients with pancreatic cancer and intraductal papillary mucinous neoplasms. Gut 2017;66:1677–1687.CrossRefPubMedGoogle Scholar
  41. 41.
    Kanda M, Sadakari Y, Borges M, et al. Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia. Clin Gastroenterol Hepatol 2013;11:719–30 e5.CrossRefPubMedGoogle Scholar
  42. 42.
    Cohen JD, Javed AA, Thoburn C, et al. Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers. Proc Natl Acad Sci U S A 2017;114:10202–7.CrossRefPubMedGoogle Scholar
  43. 43.
    Cohen JD, Li L, Wang Y, et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 2018;359:926–30.CrossRefPubMedGoogle Scholar
  44. 44.
    Poruk KE, Valero V, 3rd, He J, et al. Circulating epithelial cells in intraductal papillary mucinous neoplasms and cystic pancreatic lesions. Pancreas 2017;46:943–7.CrossRefPubMedGoogle Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2019

Authors and Affiliations

  • Marcia Irene Canto
    • 1
    Email author
  • Tossapol Kerdsirichairat
    • 1
  • Charles J. Yeo
    • 2
  • Ralph H. Hruban
    • 3
  • Eun Ji Shin
    • 1
  • Jose Alejandro Almario
    • 1
  • Amanda Blackford
    • 4
  • Madeline Ford
    • 3
  • Alison P. Klein
    • 4
  • Ammar A. Javed
    • 5
  • Anne Marie Lennon
    • 1
  • Atif Zaheer
    • 6
  • Ihab R. Kamel
    • 6
  • Elliot K. Fishman
    • 6
  • Richard Burkhart
    • 5
  • Jin He
    • 5
  • Martin Makary
    • 5
  • Matthew J. Weiss
    • 5
  • Richard D. Schulick
    • 7
  • Michael G. Goggins
    • 1
    • 3
  • Christopher L. Wolfgang
    • 5
  1. 1.Division of Gastroenterology and Hepatology, Department of Medicine, The Sol Goldman Pancreatic Cancer Research CenterJohns Hopkins Medical InstitutionsBaltimoreUSA
  2. 2.Department of SurgeryThomas Jefferson UniversityPhiladelphiaUSA
  3. 3.Department of Pathology, The Sol Goldman Pancreatic Cancer Research CenterJohns Hopkins Medical InstitutionsBaltimoreUSA
  4. 4.Department of Oncology, The Sol Goldman Pancreatic Cancer Research CenterJohns Hopkins Medical InstitutionsBaltimoreUSA
  5. 5.Department of Surgery, The Sol Goldman Pancreatic Cancer Research CenterJohns Hopkins Medical InstitutionsBaltimoreUSA
  6. 6.Department of Radiology, The Sol Goldman Pancreatic Cancer Research CenterJohns Hopkins Medical InstitutionsBaltimoreUSA
  7. 7.Department of Surgery, University of Colorado School of MedicineDenverUSA

Personalised recommendations