Abstract
Purpose
To identify peri-operative risk factors and time to onset of pancreatic endocrine/exocrine insufficiency.
Methods
We retrospectively analyzed a single institutional series of patients who underwent pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) between 2000 and 2015. Endocrine/exocrine insufficiencies were defined as need for new pharmacologic intervention. Cox proportional modeling was used to identify peri-operative variables to determine their impact on post-operative pancreatic insufficiency.
Results
A total of 1717 patient records were analyzed (75.47% PD, 24.53% DP) at median follow-up 17.88 months. Average age was 62.62 years, 51.78% were male, and surgery was for malignancy in 74.35% of patients. Post-operative endocrine insufficiency was present in 20.15% (n = 346). Male gender (p = 0.015), increased body mass index (BMI) (p < 0.001), tobacco use (p = 0.011), family history of diabetes (DM) (p < 0.001), personal history of DM (p ≤ 0.001), and DP (p ≤ 0.001) were correlated with increased risk. Mean time to onset was 20.80 ± 33.60 (IQR: 0.49–28.37) months. Post-operative exocrine insufficiency was present in 36.23% (n = 622). Race (p = 0.014), lower BMI (p < 0.001), family history of DM (p = 0.007), steatorrhea (p < 0.001), elevated pre-operative bilirubin (p = 0.019), and PD (p ≤ 0.001) were correlated with increased risk. Mean time to onset was 14.20 ± 26.90 (IQR: 0.89–12.69) months.
Conclusions
In this large series of pancreatectomy patients, 20.15% and 36.23% of patients developed post-operative endocrine and exocrine insufficiency at a mean time to onset of 20.80 and 14.20 months, respectively. Patients should be educated regarding post-resection insufficiencies and providers should have heightened awareness long-term.
Similar content being viewed by others
References
Cameron JL. He J. Two thousand consecutive pancreaticoduodenectomies. J Am Coll Surg. 2015;220:530–536.
Fernández-del Castillo C, Morales-Oyarvide V, McGrath D, Wargo JA, Ferrone CR, Thayer SP, Lillemoe KD, Warshaw AL. Evolution of the Whipple procedure at the Massachusetts General Hospital. Surgery. 2012;152:S56–S63.
Venkat R, Edil BH, Schulick RD, Lidor AO, Makary MA, Wolfgang CL. Laparoscopic distal pancreatectomy is associated with significantly less overall morbidity compared to the open technique: A systematic review and meta-analysis. Ann Surg. 2012;255:1048–1059.
Huang JJ, Yeo CJ, Sohn TA, Lillemoe KD, Sauter PK, Coleman J, Hruban RH, Cameron JH. Quality of life and outcomes after pancreaticoduodenectomy. Ann Surg. 2000;231:890–898.
Cherif, R, Gaujoux S, Couvelard A, Dokmak S, Vuillerme MP, Ruszniewski P, Belghiti J, Sauvanet A. Parenchyma-sparing resections for pancreatic neuroendocrine tumors. J Gastrointest Surg. 2012;16:2045–2055.
Falconi M, Mantovani W, Crippa S, Masetta G, Salvia R, Pederzoli P. Pancreatic insufficiency after different resections for benign tumors. Br J Surg. 2008;95:85–91.
Crippa S, Bassi C, Warshaw AL, Falconi M, Stefano P, Thayer SP, Pederzoli P, Castillo CFD. Middle pancreatectomy. Ann Surg. 2007;246:69–76.
Falconi M, Zerbi A, Crippa S, Balzano G, Boninsegna L, Capitanio V, Bassi C, Di Carlo V, Pederzoli P. Parenchyma-preserving resections for small nonfunctioning pancreatic endocrine tumors. Ann Surg Oncol. 2010;17:1621–1627.
Whitcomb DC, Yadav D, Adam S, Hawes RH, Brand RE, Anderson MA, Money ME, Banks PA, Bishop MD, Baillie J, Sherman S, Disario J, Burton FR, Gardner TB, Amann ST, Gelrud A, Lo SK, DeMeo MT, Steinberg WM, Kockman ML, Etemad B, Forsmark CE, Elinoff B, Greer JB, O’Connell M, Lamb J, Barmada MM. Multicenter approach to recurrent acute and chronic pancreatitis in the United States: The North American Pancreatitis Study 2 (NAPS2). Pancreatology. 2008; 8:520–531.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Amer Statist Assn. 1958;53:457–481.
Mantel, N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966;50:163–170.
Cox, DR. Regression models and life-tables. Journal of the Royal Statistical Society, Series B. 1972;34:187–220.
Klein JP, Moeschberger ML. Semiparametric proportional hazards regression with fixed covariates. In: Klein JP, Moeschberger ML, eds. Survival Analysis: Techniques for Censored and Truncated Data. New York: Springer; 1997:229–263.
Lim PW, Dinh KH, Sullican M, Wassef WY, Zivny J, Whalen GF, LaFemina J. Thirty-day outcomes underestimate endocrine and exocrine insufficiency after pancreatic resection. HPB. 2016;18:360–366.
Phillips ME. Pancreatic exocrine insufficiency following pancreatic resection. Pancreatology. 2015;15:449–455.
Seiler CM, Izbicki J, Vargas-Szabo L, Czak L, Fiok J, Sperti C, Lerch MM, Pezzilli R, Vasileva G, Pap A, Varga M, Friess H. Randomised clinical trial: A 1-week, double-blinded, placebo-controlled study of pancreatin 25 000 Ph. Eur minimicrospheres (Creon 25000 MMS) for pancreatic exocrine insufficiency after pancreatic surgery, with a 1-year open-label extension. Aliment Pharmacol Ther. 2013;37:691–702.
Halloran CM, Cox TF, Chauhan S, Raraty MG, Sutton R, Neoptolemos JP, Ghaneh P. Partial pancreatic resection for pancreatic malignancy is associated with sustained pancreatic exocrine failure and reduced quality of life: A prospective study. Pancreatology. 2012;11:535–545.
American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes – 2018. Diabetes Care. 2018;41:S13.
Hirata K, Nakata B, Amano R, Yamazoe S, Kimura K, Hirakawa K. Predictive factors for change of diabetes mellitus status after pancreatectomy in preoperative diabetic and nondiabetic patients. J Gastrointest Surg. 2014;18:1597–1603.
White MA, Agle SC, Fuhr HM, Mehaffey JH, Waibel BH, Zervos EE. Impact of pancreatic cancer and subsequent resection on glycemic control in diabeteic and nondiabetic patients. Am Surg. 2011;77:1032–1037.
Dinorcia J, Ahmed L, Lee MK, Reavey PL, Yakaitis Ea, Lee JA, Schrope BA, Chabot JA, Allendorf JD. Better preservation of endocrine function after central versus distal pancreatectomy for mid-gland lesions. Surgery. 2010;148:1247–1254.
Kwon JH, Kim SC, Shim IK, Song KB, Lee JH, Hwang DW, Park KM, Lee YJ. Factors affecting the development of diabetes mellitus after pancreatic resection. Pancreas. 2015;44:1296–1303.
Gersell DJ, Gingerich RL, Greider MH. Regional distribution and concentration of pancreatic polypeptide in the human and canine pancreas. Diabetes. 1979;28:11–15.
Henquin JC, Ibrahim MM, Rahier J. Insulin, glucagon and somatostatin stores in the pancreas of subjects with type-2 diabetes and their lean and obese non-diabetic controls. Sci Rep. 2017;7:1–9.
Kachare SD, Fitzgerald TL, Schuth O, Vohra NA, Zervos EE. The impact of pancreatic resection on exocrine homeostasis. Am Surg. 2014;80:704–709.
Strasberg SM, Gao F, Sanford D, Linehan DC, Hawkins WG, Fields RC, Carpenter DH, Brunt EM, Phillips C. Jaundice: an important, porrly recognized risk factor for diminished survival with adenocarcinoma of the head of the pancreas. HPB. 2014;16:150–156.
Beger HG, Nakao A, Mayer B, Porch B. Duodenum-preserving total and partial pancreatic head resection for benign tumors – systematic review and meta-analysis. Pancreatology. 2015;15:167–178.
Vujasinovic M, Valente R, Del Chiaro M, Permert J, Lohr JM. Pancreatic exocrine insufficiency in pancreatic cancer. Nutrients. 2017;9:183.
Lemaire E, O’Toole D, Sauvanet A, Hammel P, Belghiti J, Ruszniewski P. Functional and morphological changes in the pancreatic remnant following pancreaticoduodenectomy with pancreaticogastric anastomosis. Br J Surg. 2000;87:434–438.
Gemici C, Sargin M, Uygur-Bayramicli O, Mayadagli A, Yaprak G, Dabak R, Kocak M. Risk of endocrine insufficiency in patients receiving adjuvant chemoradiation for resected gastric cancer. Radiother Oncol. 2013; 107, 195–199.
Wu JM, Ho TW, Kuo TC, Yang CY, Lai HS, Chiang PY, Hsieh SH, Lai F, Tien YW. Glycemic change after pancreaticoduodenectomy: A population-based study. Medicine (Baltimore). 2015l94:e1109.
Ferrara MJ, Lohse C, Kudva YC, Farnell MB, Que FG, Reid-Lombardo KM, Donohue JH, Nagorney DM, Chari ST, Vege SS, Kendrick ML. Immediate post-resection diabetes mellitus after pancreaticoduodenectomy: Incidence and risk factors. HPB. 2013;15:170–174.
Orfanidis NT, Loren DE, Santos C, Kennedy EP, Siddiqui AA, Lavu H, Yeo CJ, Kowalski TE. Extended follow-up and outcomes of patients undergoing pancreaticoduodenectomy for no-malignant disease. J Gastrointest Surg. 2012;16:80–88.
Elliott IA, Epelboym I, Winner M, Allendorf JD, Haigh PI. Population-level incidence and predictors of surgically induced diabetes and exocrine insufficiency after partial pancreatic resection. Perm J. 2017; 21:16–095.
Beger HG, Poch B, Mayer B, Siech M. New onset of diabetes and pancreatic exocrine insufficiency after pancreaticoduodenectomy fo benign and malignant tumors: A systematic review and meta-analysis of long-term results. Ann Surg. 2018;267:259–270.
Grant Support and Other Assistance
G.A.W. and J.L. supported by the SPORE grant 5P50CA196510-02. REDCap Supported by Clinical and Translational Science Award (CTSA) Grant [UL1 TR000448] and Siteman Comprehensive Cancer Center and NCI Cancer Center Support Grant P30 CA091842.
Author information
Authors and Affiliations
Contributions
J.K., B.A. participated in study conception and design, analysis, and drafting of the article.
J.L., G.A.W., W.C.C., M.M.B.D., A.S.K., D.E.S., C.W.H., S.M.S., W.G.H. participated in acquisition of data, analysis, and interpretation of data.
R.C.F. participated in study conception and design, acquisition of data, analysis, and interpretation of data, and critical revision of the manuscript.
Corresponding author
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Kusakabe, J., Anderson, B., Liu, J. et al. Long-Term Endocrine and Exocrine Insufficiency After Pancreatectomy. J Gastrointest Surg 23, 1604–1613 (2019). https://doi.org/10.1007/s11605-018-04084-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11605-018-04084-x