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Preoperative Diabetes Mellitus and Long-Term Survival After Resection of Pancreatic Adenocarcinoma

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

To assess clinicopathologic features and postresection survival of diabetes mellitus (DM)-associated pancreatic ductal adenocarcinoma (PDAC).

Methods

Records of resected PDAC patients from 2000 to 2007 were reviewed. DM was classified as new-onset (<24 months before PDAC) or longstanding (≥24 months). Clinicopathologic features were compared by univariate and multivariate analyses. Survival was assessed by Kaplan–Meier method and Cox regression.

Results

Of 209 patients, 93 (45%) met criteria for DM (35 longstanding DM, 55 new-onset DM, 3 duration unknown). DM patients were older (DM 66 ± 9 years, non-DM 63 ± 12 years, P = 0.06); a majority had additional preoperative comorbidities (DM 64.5%, non-DM 25.9%, P < 0.001). Tumor size was larger in patients with DM (DM 3.8 ± 1.7 cm, non-DM 3.2 ± 1.5 cm, P = 0.003). Groups were similar in terms of tumor location, perineural/lymphovascular invasion, and node and margin status. On logistic regression, tumor size ≥3.0 cm was independently associated with both overall DM (odds ratio [OR] 3.60; 95% confidence interval [1.79–7.26]) and new-onset DM (OR 3.69, [1.65–8.24]). Median survival was reduced in patients with DM compared with non-DM (15 versus 17 months, P = 0.015). Multivariate analysis controlling for prognostic variables including age, comorbidities, and tumor size demonstrated that DM was independently associated with reduced survival (hazard ratio [HR] 1.55, [1.02–2.35]). This association was more pronounced for patients with new-onset DM (HR 1.75 [1.10–2.78]) than those with longstanding DM (HR 1.30 [0.75–2.25]).

Conclusions

Preexisting DM is associated with reduced survival in patients undergoing resection for PDAC. PDAC with new-onset DM may exhibit increased tumor size and decreased postresection survival. Additional investigation is needed to clarify etiology and impact of PDAC-associated DM.

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References

  1. Bright R. Cases and observations connected with disease of the pancreas and duodenum. Med Chir Trans. 1833;18:1-56.

    Google Scholar 

  2. American Cancer Society: Cancer Facts and Figures 2008. http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_pancreatic_cancer_34.asp?sitearea=. Accessed February 11, 2009.

  3. Centers for Disease Control and Prevention: National Diabetes Fact Sheet, 2007. http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2007.pdf. Accessed February 12, 2009.

  4. King H, Aubert RE, Herman WH. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998;21(9):1414–31.

    Google Scholar 

  5. Wild S, Roglic G, Green A, et al. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27(5):1047–53.

    Article  PubMed  Google Scholar 

  6. Pannala R, Leirness JB, Bamlet WR, et al. Prevalence and clinical profile of pancreatic cancer-associated diabetes mellitus. Gastroenterology. 2008;134(4):981–7.

    Article  CAS  PubMed  Google Scholar 

  7. Chari ST, Leibson CL, Rabe KG, et al. Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology. 2008;134(1):95–101.

    Article  CAS  PubMed  Google Scholar 

  8. Wynder EL, Mabuchi K, Maruchi N, Fortner JG. Epidemiology of cancer of the pancreas. J Natl Cancer Inst. 1973;50(3):645–67.

    CAS  PubMed  Google Scholar 

  9. Hiatt RA, Klatsky AL, Armstrong MA. Pancreatic cancer, blood glucose and beverage consumption. Int J Cancer. 1988;41(6):794–7.

    Article  CAS  PubMed  Google Scholar 

  10. Kalapothaki V, Tzonou A, Hsieh CC, et al. Tobacco, ethanol, coffee, pancreatitis, diabetes mellitus, and cholelithiasis as risk factors for pancreatic carcinoma. Cancer Causes Control. 1993;4(4):375–82.

    Article  CAS  PubMed  Google Scholar 

  11. Stevens RJ, Roddam AW, Beral V. Pancreatic cancer in type 1 and young-onset diabetes: systematic review and meta-analysis. Br J Cancer. 2007;96(3):507–9.

    Article  CAS  PubMed  Google Scholar 

  12. Batty GD, Kivimaki M, Morrison D, et al. Risk factors for pancreatic cancer mortality: extended follow-up of the original Whitehall study. Cancer Epidemiol Biomarkers Prev. 2009.

  13. Ansary-Moghaddam A, Huxley R, Barzi F, et al. The effect of modifiable risk factors on pancreatic cancer mortality in populations of the Asia-Pacific region. Cancer Epidemiol Biomarkers Prev. 2006;15(12):2435–40.

    Article  PubMed  Google Scholar 

  14. Calle EE, Murphy TK, Rodriguez C, et al. Diabetes mellitus and pancreatic cancer mortality in a prospective cohort of United States adults. Cancer Causes Control. 1998;9(4):403–10.

    Article  CAS  PubMed  Google Scholar 

  15. Gullo L, Pezzilli R, Morselli-Labate AM. Diabetes and the risk of pancreatic cancer. N Engl J Med. 1994;331(2):81–4.

    Article  CAS  PubMed  Google Scholar 

  16. Wang F, Gupta S, Holly EA. Diabetes mellitus and pancreatic cancer in a population-based case-control study in the San Francisco Bay Area, California. Cancer Epidemiol Biomarkers Prev. 2006;15(8):1458–63.

    Article  PubMed  Google Scholar 

  17. Permert J, Ihse I, Jorfeldt L, et al. Improved glucose metabolism after subtotal pancreatectomy for pancreatic cancer. Br J Surg. 1993;80(8):1047–50.

    Article  CAS  PubMed  Google Scholar 

  18. Basso D, Plebani M, Fogar P, et al. Beta-cell function in pancreatic adenocarcinoma. Pancreas. 1994;9(3):332–5.

    Article  CAS  PubMed  Google Scholar 

  19. Litwin J, Dobrowolski S, Orlowska-Kunikowska E, Sledzinski Z. Changes in glucose metabolism after Kausch-Whipple pancreatectomy in pancreatic cancer and chronic pancreatitis patients. Pancreas. 2008;36(1):26–30.

    Article  CAS  PubMed  Google Scholar 

  20. Bell RH Jr, Place S, McCullough P, et al. Pancreatic insulin secretion in exocrine pancreatic cancer. J Surg Res. 1986;40(6):588–96.

    Article  CAS  PubMed  Google Scholar 

  21. Liu J, Knezetic JA, Strommer L, et al. The intracellular mechanism of insulin resistance in pancreatic cancer patients. J Clin Endocrinol Metab. 2000;85(3):1232–8.

    Article  CAS  PubMed  Google Scholar 

  22. Fogar P, Basso D, Panozzo MP, et al. C-peptide pattern in patients with pancreatic cancer. Anticancer Res. 1993;13(6):2577–80.

    CAS  PubMed  Google Scholar 

  23. Gullo L, Ancona D, Pezzilli R, et al. Glucose tolerance and insulin secretion in pancreatic cancer. Ital J Gastroenterol. 1993;25(9):487–9.

    CAS  PubMed  Google Scholar 

  24. Stolzenberg-Solomon RZ, Graubard BI, Chari S, et al. Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers. JAMA. 2005;294(22):2872–8.

    Article  CAS  PubMed  Google Scholar 

  25. Permert J, Adrian TE, Jacobsson P, et al. Is profound peripheral insulin resistance in patients with pancreatic cancer caused by a tumor-associated factor? Am J Surg. 1993;165(1):61–6; discussion 66–7.

    Google Scholar 

  26. Basso D, Brigato L, Veronesi A, et al. The pancreatic cancer cell line MIA PaCa2 produces one or more factors able to induce hyperglycemia in SCID mice. Anticancer Res. 1995;15(6):2585–8.

    CAS  PubMed  Google Scholar 

  27. Basso D, Greco E, Fogar P, et al. Pancreatic cancer-derived S-100A8 N-terminal peptide: a diabetes cause? Clin Chim Acta. 2006;372(1–2):120–8.

    Article  CAS  PubMed  Google Scholar 

  28. Barone BB, Yeh HC, Snyder CF, et al. Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA. 2008;300(23):2754–64.

    Article  CAS  PubMed  Google Scholar 

  29. van de Poll-Franse LV, Houterman S, Janssen-Heijnen ML, et al. Less aggressive treatment and worse overall survival in cancer patients with diabetes: a large population based analysis. Int J Cancer. 2007;120(9):1986–92.

    Article  PubMed  Google Scholar 

  30. Park SM, Lim MK, Shin SA, Yun YH. Impact of prediagnosis smoking, alcohol, obesity, and insulin resistance on survival in male cancer patients: National Health Insurance Corporation Study. J Clin Oncol. 2006;24(31):5017–24.

    Article  PubMed  Google Scholar 

  31. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.

    Article  CAS  PubMed  Google Scholar 

  32. Social Security Death Index, RootsWeb 2009. http://ssdi.rootsweb.ancestry.com/. accessed February 16, 2009.

  33. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2009;32(Suppl 1):S62–7.

    Article  Google Scholar 

  34. Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000;4(6):567–79.

    Article  CAS  PubMed  Google Scholar 

  35. Garcea G, Dennison AR, Pattenden CJ, et al 2008 Survival following curative resection for pancreatic ductal adenocarcinoma A systematic review of the literature. JOP. 9(2):99–132.

    PubMed  Google Scholar 

  36. Kleinbaum D, Klein M. Logistic regression: a self-learning text. New York: Springer; 2002.

    Google Scholar 

  37. Valerio A, Basso D, Mazza S, et al. Serum protein profiles of patients with pancreatic cancer and chronic pancreatitis: searching for a diagnostic protein pattern. Rapid Commun Mass Spectrom. 2001;15(24):2420–5.

    Article  CAS  PubMed  Google Scholar 

  38. Basso D, Millino C, Greco E, et al. Altered glucose metabolism and proteolysis in pancreatic cancer cell conditioned myoblasts: searching for a gene expression pattern with a microarray analysis of 5000 skeletal muscle genes. Gut. 2004;53(8):1159–66.

    Article  CAS  PubMed  Google Scholar 

  39. Basso D, Greco E, Fogar P, et al. Pancreatic cancer-associated diabetes mellitus: an open field for proteomic applications. Clin Chim Acta. 2005;357(2):184–9.

    Article  CAS  PubMed  Google Scholar 

  40. Meggiato T, Plebani M, Basso D, et al. Serum growth factors in patients with pancreatic cancer. Tumour Biol. 1999;20(2):65–71.

    Article  CAS  PubMed  Google Scholar 

  41. Isaksson B, Strommer L, Friess H, et al. Impaired insulin action on phosphatidylinositol 3-kinase activity and glucose transport in skeletal muscle of pancreatic cancer patients. Pancreas. 2003;26(2):173–7.

    Article  CAS  PubMed  Google Scholar 

  42. Fogar P, Pasquali C, Basso D, et al. Diabetes mellitus in pancreatic cancer follow-up. Anticancer Res. 1994;14(6):2827–30.

    CAS  PubMed  Google Scholar 

  43. Ishikawa O, Ohhigashi H, Wada A, et al. Morphologic characteristics of pancreatic carcinoma with diabetes mellitus. Cancer. 1989;64(5):1107–12.

    Article  CAS  PubMed  Google Scholar 

  44. Fisher WE, McCullough PJ, Ray MB, et al. Diabetes enhances growth of pancreatic carcinoma cells. Surgery. 1988;104(2):431–6.

    CAS  PubMed  Google Scholar 

  45. Fisher WE, Boros LG, Schirmer WJ. Insulin promotes pancreatic cancer: evidence for endocrine influence on exocrine pancreatic tumors. J Surg Res. 1996;63(1):310–3.

    Article  CAS  PubMed  Google Scholar 

  46. Fisher WE, Muscarella P, Boros LG, Schirmer WJ. Variable effect of streptozotocin-diabetes on the growth of hamster pancreatic cancer (H2T) in the Syrian hamster and nude mouse. Surgery. 1998;123(3):315–20.

    CAS  PubMed  Google Scholar 

  47. Stoeltzing O, Liu W, Fan F, et al. Regulation of cyclooxygenase-2 (COX-2) expression in human pancreatic carcinoma cells by the insulin-like growth factor-I receptor (IGF-IR) system. Cancer Lett. 2007;258(2):291–300.

    Article  CAS  PubMed  Google Scholar 

  48. Bergmann U, Funatomi H, Yokoyama M, et al. Insulin-like growth factor I overexpression in human pancreatic cancer: evidence for autocrine and paracrine roles. Cancer Res. 1995;55(10):2007–11.

    CAS  PubMed  Google Scholar 

  49. Ding X, Flatt PR, Permert J, Adrian TE. Pancreatic cancer cells selectively stimulate islet beta cells to secrete amylin. Gastroenterology. 1998;114(1):130–8.

    Article  CAS  PubMed  Google Scholar 

  50. Ganti AK, Potti A, Koch M, et al. Predictive value of clinical features at initial presentation in pancreatic adenocarcinoma: a series of 308 cases. Med Oncol. 2002;19(4):233–7.

    Article  PubMed  Google Scholar 

  51. Talar-Wojnarowska R, Gasiorowska A, Strzelczyk J, et al. Prognostic factors in the operative and palliative treatment of pancreatic cancer. Neoplasma. 2003;50(5):383–7.

    CAS  PubMed  Google Scholar 

  52. Wakasugi H, Funakoshi A, Iguchi H. Clinical observations of pancreatic diabetes caused by pancreatic carcinoma, and survival period. Int J Clin Oncol. 2001;6(1):50–4.

    Article  CAS  PubMed  Google Scholar 

  53. Coughlin SS, Calle EE, Patel AV, Thun MJ. Predictors of pancreatic cancer mortality among a large cohort of United States adults. Cancer Causes Control. 2000;11(10):915–23.

    Article  CAS  PubMed  Google Scholar 

  54. Bilimoria KY, Bentrem DJ, Ko CY, et al. Validation of the 6th edition AJCC Pancreatic Cancer Staging System: report from the National Cancer Database. Cancer. 2007;110(4):738–44.

    Article  PubMed  Google Scholar 

  55. Sperti C, Pasquali C, Piccoli A, Pedrazzoli S. Survival after resection for ductal adenocarcinoma of the pancreas. Br J Surg. 1996;83(5):625–31.

    Article  CAS  PubMed  Google Scholar 

  56. Pannala R, Basu A, Petersen GM, Chari ST. New-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer. Lancet Oncol. 2009;10(1):88–95.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA

    Carrie K. Chu MD, Ashley E. Mazo BS, Vasili Egnatashvili MD, Juan M. Sarmiento MD, Charles A. Staley MD, John R. Galloway MD & David A. Kooby MD

  2. Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA

    Michael Goodman MD, MPH

  3. Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA

    N. Volkan Adsay MD

  4. Division of Endocrinology, Emory University School of Medicine, Atlanta, GA, USA

    Sol Jacobs MD

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  1. Carrie K. Chu MD
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  2. Ashley E. Mazo BS
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  3. Michael Goodman MD, MPH
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Correspondence to David A. Kooby MD.

Additional information

Poster presentation at the 62nd annual meeting of the Society of Surgical Oncology, March 6th, 2009, Phoenix, AZ, USA.

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Chu, C.K., Mazo, A.E., Goodman, M. et al. Preoperative Diabetes Mellitus and Long-Term Survival After Resection of Pancreatic Adenocarcinoma. Ann Surg Oncol 17, 502–513 (2010). https://doi.org/10.1245/s10434-009-0789-6

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  • DOI: https://doi.org/10.1245/s10434-009-0789-6

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