Skip to main content
SpringerLink
Log in

Effect of the Duration of Chronic Pancreatitis on Pancreas Islet Yield and Metabolic Outcome Following Islet Autotransplantation

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Total pancreatectomy (TP) with islet autotransplantation (IAT) is a highly selected treatment for severe pain associated with chronic pancreatitis (CP) after exhausting medical and endoscopic therapies. The effect of duration of CP on TP-IAT has not been clarified.

Methods

Retrospective review of a consecutive cohort undergoing TP-IAT was performed. Patients were classified according to islet dose of <2500 IEQ/kg, 2500 to 5000 IEQ/kg, and >5000 IEQ/kg. Islet yield and metabolic outcomes were compared to disease duration of CP.

Results

A total of 76 CP patients underwent TP-IAT. Longer disease duration was associated with lower islet yield transplanted (Spearman’s correlation = −0.24; p = 0.04) for total cohort. Highest absolute value of the coefficient was found in patients with hereditary CP when study subjects were classified by the etiology of CP (correlation = −0.72; p = 0.02). Higher islet yields were significantly associated with better metabolic outcomes (7.6 ± 1.1 vs 6.6 ± 1.1 % of HbA1c post-TPIAT in patients with <2500 and >5000 IEQ/kg transplanted, respectively; p = 0.04).

Conclusions

The duration of CP could affect islet yield and metabolic outcomes. The time since the diagnosis of CP should be considered when selecting patients for islet autotransplantation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

BMI:

Body mass index

CP:

Chronic pancreatitis

CT:

Computed tomography

DM:

Diabetes mellitus

ERCP:

Endoscopic retrograde cholangiopancreatography

EUS:

Endoscopic ultrasonography

HbA1c:

Hemoglobin A1c

IAT:

Islet autotransplantation

IEQ:

Islet equivalent

MRI:

Magnetic resonance imaging

ROC:

Receiver operating characteristic

TP:

Total pancreatectomy

References

  1. Chari ST, Singer MV. The problem of classification and staging of chronic pancreatitis. Proposals based on current knowledge of its natural history. Scand J Gastroenterol 1994;29:949–60.

    Article  CAS  PubMed  Google Scholar 

  2. Stewart WF, Ricci JA, Chee E, et al. Lost productive time and cost due to common pain conditions in the US workforce. JAMA 2003;290:2443–54.

    Article  CAS  PubMed  Google Scholar 

  3. Russo MW, Wei JT, Thiny MT, et al. Digestive and liver diseases statistics, 2004. Gastroenterology 2004;126:1448–53.

    Article  PubMed  Google Scholar 

  4. Lowenfels AB, Sullivan T, Fiorianti J, et al. The epidemiology and impact of pancreatic diseases in the United States. Curr Gastroenterol Rep 2005;7:90–5.

    Article  PubMed  Google Scholar 

  5. Pezzilli R, Bini L, Fantini L, et al. Quality of life in chronic pancreatitis. World J Gastroenterol 2006;12:6249–51.

    PubMed Central  PubMed  Google Scholar 

  6. Garcea G, Weaver J, Phillips J, et al. Total pancreatectomy with and without islet cell transplantation for chronic pancreatitis: a series of 85 consecutive patients. Pancreas 2009;38:1–7.

    Article  PubMed  Google Scholar 

  7. Sutherland DE, Gruessner AC, Carlson AM, et al. Islet autotransplant outcomes after total pancreatectomy: a contrast to islet allograft outcomes. Transplantation 2008;86:1799–802.

    Article  PubMed  Google Scholar 

  8. Digon BJ, 3rd. History of islet transplantation. Curr Diab Rep 2009;9:312–6.

    Article  PubMed  Google Scholar 

  9. Andren-Sandberg A, Hoem D, Gislason H. Pain management in chronic pancreatitis. Eur J Gastroenterol Hepatol 2002;14:957–70.

    Article  PubMed  Google Scholar 

  10. Warnock GL, Thompson DM, Meloche RM, et al. A multi-year analysis of islet transplantation compared with intensive medical therapy on progression of complications in type 1 diabetes. Transplantation 2008;86:1762–6.

    Article  PubMed  Google Scholar 

  11. Rodriguez Rilo HL, Ahmad SA, D’Alessio D, et al. Total pancreatectomy and autologous islet cell transplantation as a means to treat severe chronic pancreatitis. J Gastrointest Surg 2003;7:978–89.

    Article  PubMed  Google Scholar 

  12. Sutherland DE, Radosevich DM, Bellin MD, et al. Total pancreatectomy and islet autotransplantation for chronic pancreatitis. J Am Coll Surg 2012;214:409–24.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Takita M, Naziruddin B, Matsumoto S, et al. Implication of pancreatic image findings in total pancreatectomy with islet autotransplantation for chronic pancreatitis. Pancreas 2011;40:103–8.

    Article  PubMed  Google Scholar 

  14. Matsumoto S, Rigley TH, Qualley SA, et al. Efficacy of the oxygen-charged static two-layer method for short-term pancreas preservation and islet isolation from nonhuman primate and human pancreata. Cell Transplant 2002;11:769–77.

    PubMed  Google Scholar 

  15. Ikemoto T, Noguchi H, Shimoda M, et al. Islet cell transplantation for the treatment of type 1 diabetes in the USA. J Hepatobiliary Pancreat Surg 2009;16:118–23.

    Article  PubMed  Google Scholar 

  16. Matsumoto S, Noguchi H, Naziruddin B, et al. Improvement of pancreatic islet cell isolation for transplantation. Proc (Bayl Univ Med Cent) 2007;20:357–62.

    Google Scholar 

  17. Siddiqi AJ, Miller F. Chronic pancreatitis: ultrasound, computed tomography, and magnetic resonance imaging features. Semin Ultrasound CT MR 2007;28:384–94.

    Article  PubMed  Google Scholar 

  18. Conwell DL, Zuccaro G, Purich E, et al. Comparison of endoscopic ultrasound chronic pancreatitis criteria to the endoscopic secretin-stimulated pancreatic function test. Dig Dis Sci 2007;52:1206–10.

    Article  PubMed  Google Scholar 

  19. DiMagno EP. A perspective on the use of tubeless pancreatic function tests in diagnosis. Gut 1998;43:2–3.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Chowdhury RS, Forsmark CE. Review article: Pancreatic function testing. Aliment Pharmacol Ther 2003;17:733–50.

    Article  CAS  PubMed  Google Scholar 

  21. Lara LF, Demarco DC. Double-balloon overtube-assisted endoscopic pancreas function test as a tool to rule out chronic pancreatitis in a patient with a previous Frey procedure. Gastrointest Endosc 2013;77:671–2.

    Article  PubMed  Google Scholar 

  22. Wiersema MJ, Hawes RH, Lehman GA, et al. Prospective evaluation of endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography in patients with chronic abdominal pain of suspected pancreatic origin. Endoscopy 1993;25:555–64.

    Article  CAS  PubMed  Google Scholar 

  23. Axon AT, Classen M, Cotton PB, et al. Pancreatography in chronic pancreatitis: international definitions. Gut 1984;25:1107–12.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Irisawa A, Katakura K, Ohira H, et al. Usefulness of endoscopic ultrasound to diagnose the severity of chronic pancreatitis. J Gastroenterol 2007;42 Suppl 17:90–4.

    Article  PubMed  Google Scholar 

  25. Kobayashi T, Manivel JC, Carlson AM, et al. Correlation of histopathology, islet yield, and islet graft function after islet autotransplantation in chronic pancreatitis. Pancreas 2011;40:193–9.

    Article  PubMed  Google Scholar 

  26. Bellin MD, Balamurugan AN, Pruett TL, et al. No islets left behind: islet autotransplantation for surgery-induced diabetes. Curr Diab Rep 2012;12:580–6.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Sawada T, Matsumoto I, Nakano M, et al. Improved islet yield and function with ductal injection of University of Wisconsin solution before pancreas preservation. Transplantation 2003;75:1965–9.

    Article  PubMed  Google Scholar 

  28. Ricordi C, Lacy PE, Finke EH, et al. Automated method for isolation of human pancreatic islets. Diabetes 1988;37:413–20.

    Article  CAS  PubMed  Google Scholar 

  29. Matsumoto S, Takita M, Shimoda M, et al. Impact of tissue volume and purification on clinical autologous islet transplantation for the treatment of chronic pancreatitis. Cell Transplant 2012;21:625–32.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Takita M, Naziruddin B, Matsumoto S, et al. Variables associated with islet yield in autologous islet cell transplantation for chronic pancreatitis. Proc (Bayl Univ Med Cent) 2010;23:115–20.

    Google Scholar 

  31. Layer P, Yamamoto H, Kalthoff L, et al. The different courses of early- and late-onset idiopathic and alcoholic chronic pancreatitis. Gastroenterology 1994;107:1481–7.

    Article  CAS  PubMed  Google Scholar 

  32. Lankisch PG. Progression from acute to chronic pancreatitis: a physician’s view. Surg Clin North Am 1999;79:815–27.

    Article  CAS  PubMed  Google Scholar 

  33. Steer ML, Waxman I, Freedman S. Chronic pancreatitis. N Engl J Med 1995;332:1482–90.

    Article  CAS  PubMed  Google Scholar 

  34. Webb MA, Illouz SC, Pollard CA, et al. Islet auto transplantation following total pancreatectomy: a long-term assessment of graft function. Pancreas 2008;37:282–7.

    Article  PubMed  Google Scholar 

  35. Benhamou PY, Watt PC, Mullen Y, et al. Human islet isolation in 104 consecutive cases. Factors affecting isolation success. Transplantation 1994;57:1804–10.

    Article  CAS  PubMed  Google Scholar 

  36. Brandhorst H, Brandhorst D, Hering BJ, et al. Body mass index of pancreatic donors: a decisive factor for human islet isolation. Exp Clin Endocrinol Diabetes 1995;103 Suppl 2:23–26.

    Article  PubMed  Google Scholar 

  37. Kobayashi T, Manivel JC, Bellin MD, et al. Correlation of pancreatic histopathologic findings and islet yield in children with chronic pancreatitis undergoing total pancreatectomy and islet autotransplantation. Pancreas 2010;39:57–63.

    Article  PubMed  Google Scholar 

  38. Shapiro AM, Ricordi C, Hering BJ, et al. International trial of the Edmonton protocol for islet transplantation. N Engl J Med 2006;355:1318–30.

    Article  CAS  PubMed  Google Scholar 

  39. Alejandro R, Barton FB, Hering BJ, et al. 2008 Update from the Collaborative Islet Transplant Registry. Transplantation 2008;86:1783–8.

    Article  PubMed  Google Scholar 

  40. Hirshberg B, Rother KI, Digon BJ, et al. Benefits and risks of solitary islet transplantation for type 1 diabetes using steroid-sparing immunosuppression: the National Institutes of Health experience. Diabetes Care 2003;26:3288–95.

    Article  PubMed  Google Scholar 

  41. Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000;343:230–8.

    Article  CAS  PubMed  Google Scholar 

  42. Takita M, Naziruddin B, Matsumoto S, et al. Body mass index reflects islet isolation outcome in islet autotransplantation for patients with chronic pancreatitis. Cell Transplant 2011;20:313–22.

    Article  PubMed  Google Scholar 

  43. Ahmad SA, Lowy AM, Wray CJ, et al. Factors associated with insulin and narcotic independence after islet autotransplantation in patients with severe chronic pancreatitis. J Am Coll Surg 2005;201:680–7.

    Article  PubMed  Google Scholar 

  44. Bellin MD, Beilman GJ, Dunn TB, et al. Islet autotransplantation to preserve beta cell mass in selected patients with chronic pancreatitis and diabetes mellitus undergoing total pancreatectomy. Pancreas 2013;42:317–21.

    Article  PubMed Central  PubMed  Google Scholar 

  45. Matsumoto S, Noguchi H, Hatanaka N, et al. SUITO index for evaluation of efficacy of single donor islet transplantation. Cell Transplant 2009;18:557–62.

    PubMed  Google Scholar 

  46. Blondet JJ, Carlson AM, Kobayashi T, et al. The role of total pancreatectomy and islet autotransplantation for chronic pancreatitis. Surg Clin North Am 2007;87:1477–501.

    Article  PubMed  Google Scholar 

  47. Gruessner RW, Sutherland DE, Dunn DL, et al. Transplant options for patients undergoing total pancreatectomy for chronic pancreatitis. J Am Coll Surg 2004;198:559–67; discussion 568–9.

    Article  PubMed  Google Scholar 

  48. Wang H, Desai KD, Dong H, et al. Prior surgery determines islet yield and insulin requirement in patients with chronic pancreatitis. Transplantation 2013;95:1051–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Yoshiko Tamura and Ana M. Rahman for technical support.

Grant Support

This study was supported in part by Baylor Health Care System Foundation and Juvenile Diabetes Research Foundation (JDRF 3-2011-447 to MT).

Conflict of Interest

The authors have no conflict of interest to disclose.

Contributions

Study concept and design: MT LFL. Acquisition of data: MT, LFL, BN, RS, MCL, PTK, NO, JSB, MFL. Analysis and interpretation of data: MT, LFL, BN, MFL. Drafting of the manuscript: MT, LFL. Critical revision of the manuscript for important intellectual content: BN, MFL, Statistical analysis: MT, LFL. Obtained funding: MT, LFL. Administrative, technical and material support: BN, LFL, Study supervision: LFL. All authors reviewed and approved of the final manuscript.

Writing Assistance

Cynthia Orticio (Scientific Publications Office of Baylor University Medical Center)

Author information

Author notes

    Authors and Affiliations

    1. Islet Cell Laboratory, Islet Cell Laboratory, Baylor Research Institute, 3410 Worth St. #950, Dallas, TX, 75246, USA

      Morihito Takita, Rauf Shahbazov & Michael C. Lawrence

    2. Department of Gastroenterology, Cleveland Clinic Florida, Weston, FL, USA

      Luis F. Lara

    3. Baylor Annette C. and Harold C. Simmons Transplant Institute, Dallas, TX, USA

      Bashoo Naziruddin, Peter T. Kim, Nicholas Onaca & Marlon F. Levy

    4. Department of Gastroenterology, Baylor University Medical Center, Dallas, TX, USA

      James S. Burdick

    5. Baylor Annette C. and Harold C. Simmons Transplant Institute at Baylor All Saints Medical Center, 1400 8th Ave, Fort Worth, TX, 76104, USA

      Marlon F. Levy

    Authors
    1. Morihito Takita
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Luis F. Lara
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Bashoo Naziruddin
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Rauf Shahbazov
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Michael C. Lawrence
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Peter T. Kim
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Nicholas Onaca
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. James S. Burdick
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Marlon F. Levy
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Morihito Takita or Marlon F. Levy.

    Additional information

    Morihito Takita and Luis F. Lara contributed equally to this work.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    Supplementary Table 1

    (DOCX 526 kb)

    Supplementary Table 2

    (DOCX 19 kb)

    Supplementary Table 3

    (DOCX 24 kb)

    Supplementary Table 4

    (DOCX 21 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Takita, M., Lara, L.F., Naziruddin, B. et al. Effect of the Duration of Chronic Pancreatitis on Pancreas Islet Yield and Metabolic Outcome Following Islet Autotransplantation. J Gastrointest Surg 19, 1236–1246 (2015). https://doi.org/10.1007/s11605-015-2828-x

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s11605-015-2828-x

    Keywords

    Search

    Navigation