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Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Impact of the treatment of pancreatic exocrine insufficiency on survival of patients with unresectable pancreatic cancer: a retrospective analysis

Authors: Juan Enrique Domínguez-Muñoz, Laura Nieto-Garcia, Javier López-Díaz, Jose Lariño-Noia, Ihab Abdulkader, Julio Iglesias-Garcia

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Malnutrition and weight loss are commonly observed in patients with pancreatic cancer and contribute to poor survival. Pancreatic exocrine insufficiency (PEI), which can be caused by ductal obstruction by a tumor, causes maldigestion and malabsorption of nutrients, thus contributing to malnutrition in these patients. In this study, we evaluated the effects of pancreatic enzyme replacement therapy (PERT) on survival in patients with unresectable pancreatic cancer.

Methods

A retrospective analysis was conducted on a database of patients with unresectable, pathologically confirmed pancreatic cancer. All patients were evaluated for palliative chemotherapy and received the optimal palliative care. Patients were divided into two groups: Group 1 received standard therapy; Group 2 underwent additional evaluation of the pancreatic function and therapy with PERT, if needed. Survival (median and 95% confidence interval [CI]) was analyzed using Kaplan–Meier and Cox regression; groups were compared using the log-rank test.

Results

Overall, 160 patients with unresectable pancreatic cancer were included in the analysis (mean age: 70.5 years [range 28–100]; gender: 57.5% male; tumor stage: 78.7% Stage IV). Eighty-six patients (53.75%) were in Group 1 and 74 (46.25%) were in Group 2. Age, gender, tumor size, location and stage, weight loss, and serum CA 19–9 were similar between groups. Ninety-three (58.1%) patients received palliative chemotherapy; 46.5% in Group 1 and 71.6% in Group 2 (P < 0.001). Forty-nine (66.2%) patients in Group 2 and none in Group 1 received PERT. Survival in Group 2 (189 days, 95% CI 167.0–211.0 days) was significantly longer than in Group 1 (95.0 days, 95% CI 75.4–114.6 days) (HR 2.117, 95% CI 1.493–3.002; P < 0.001). Chemotherapy and PERT were significantly and independently associated with longer survival in a model controlled by age and tumor stage. In patients with significant weight loss at diagnosis (> 10% bodyweight within 6 months), PERT was associated with longer survival (HR 2.52, 95% CI 1.55–4.11; P < 0.001).

Conclusions

In patients with unresectable pancreatic cancer, PERT in patients with PEI was associated with longer survival compared with those not receiving PERT, especially in those experiencing significant weight loss. This finding should guide future prospective clinical trials of similar interventions.
Literature
1.
2.
go back to reference Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913–21.CrossRefPubMed Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913–21.CrossRefPubMed
3.
go back to reference Spanknebel K, Conlon KC. Advances in the surgical management of pancreatic cancer. Cancer J. 2001;7(4):312–23.PubMed Spanknebel K, Conlon KC. Advances in the surgical management of pancreatic cancer. Cancer J. 2001;7(4):312–23.PubMed
5.
go back to reference Bachmann J, Ketterer K, Marsch C, Fechtner K, Krakowski-Roosen H, Buchler MW, Friess H, Martignoni ME. Pancreatic cancer related cachexia: influence on metabolism and correlation to weight loss and pulmonary function. BMC Cancer. 2009;9:255.CrossRefPubMedPubMedCentral Bachmann J, Ketterer K, Marsch C, Fechtner K, Krakowski-Roosen H, Buchler MW, Friess H, Martignoni ME. Pancreatic cancer related cachexia: influence on metabolism and correlation to weight loss and pulmonary function. BMC Cancer. 2009;9:255.CrossRefPubMedPubMedCentral
6.
go back to reference Trede M, Schwall G, Saeger HD. Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality. Ann Surg. 1990;211(4):447–58.CrossRefPubMedPubMedCentral Trede M, Schwall G, Saeger HD. Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality. Ann Surg. 1990;211(4):447–58.CrossRefPubMedPubMedCentral
7.
go back to reference Geer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg. 1993;165(1):68–72.CrossRefPubMed Geer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg. 1993;165(1):68–72.CrossRefPubMed
8.
go back to reference Sener SF, Fremgen A, Menck HR, Winchester DP. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985-1995, using the National Cancer Database. J Am Coll Surg. 1999;189(1):1–7.CrossRefPubMed Sener SF, Fremgen A, Menck HR, Winchester DP. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985-1995, using the National Cancer Database. J Am Coll Surg. 1999;189(1):1–7.CrossRefPubMed
9.
go back to reference Carpelan-Holmstrom M, Nordling S, Pukkala E, Sankila R, Luttges J, Kloppel G, Haglund C. Does anyone survive pancreatic ductal adenocarcinoma? A nationwide study re-evaluating the data of the Finnish Cancer registry. Gut. 2005;54(3):385–7.CrossRefPubMedPubMedCentral Carpelan-Holmstrom M, Nordling S, Pukkala E, Sankila R, Luttges J, Kloppel G, Haglund C. Does anyone survive pancreatic ductal adenocarcinoma? A nationwide study re-evaluating the data of the Finnish Cancer registry. Gut. 2005;54(3):385–7.CrossRefPubMedPubMedCentral
10.
go back to reference Conlon KC, Klimstra DS, Brennan MF. Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg. 1996;223(3):273–9.CrossRefPubMedPubMedCentral Conlon KC, Klimstra DS, Brennan MF. Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg. 1996;223(3):273–9.CrossRefPubMedPubMedCentral
11.
go back to reference Harris GJ, Gaskill HV III, Cruz AB Jr. Carcinoma of the pancreas: a retrospective review. J Surg Oncol. 1990;45(3):184–9.CrossRefPubMed Harris GJ, Gaskill HV III, Cruz AB Jr. Carcinoma of the pancreas: a retrospective review. J Surg Oncol. 1990;45(3):184–9.CrossRefPubMed
12.
13.
go back to reference Golden DW, Novak CJ, Minsky BD, Liauw SL. Radiation dose >/=54 Gy and CA 19-9 response are associated with improved survival for unresectable, non-metastatic pancreatic cancer treated with chemoradiation. Radiat Oncol. 2012;7:156.CrossRefPubMedPubMedCentral Golden DW, Novak CJ, Minsky BD, Liauw SL. Radiation dose >/=54 Gy and CA 19-9 response are associated with improved survival for unresectable, non-metastatic pancreatic cancer treated with chemoradiation. Radiat Oncol. 2012;7:156.CrossRefPubMedPubMedCentral
14.
go back to reference Ridwelski K, Meyer F. Current options for palliative treatment in patients with pancreatic cancer. Dig Dis. 2001;19(1):63–75.CrossRefPubMed Ridwelski K, Meyer F. Current options for palliative treatment in patients with pancreatic cancer. Dig Dis. 2001;19(1):63–75.CrossRefPubMed
15.
go back to reference Ockenga J. Importance of nutritional management in diseases with exocrine pancreatic insufficiency. HPB (Oxford). 2009;11(Suppl 3):11–5.CrossRef Ockenga J. Importance of nutritional management in diseases with exocrine pancreatic insufficiency. HPB (Oxford). 2009;11(Suppl 3):11–5.CrossRef
16.
go back to reference Bruno MJ, Haverkort EB, Tijssen GP, Tytgat GN, van Leeuwen DJ. Placebo controlled trial of enteric coated pancreatin microsphere treatment in patients with unresectable cancer of the pancreatic head region. Gut. 1998;42(1):92–6.CrossRefPubMedPubMedCentral Bruno MJ, Haverkort EB, Tijssen GP, Tytgat GN, van Leeuwen DJ. Placebo controlled trial of enteric coated pancreatin microsphere treatment in patients with unresectable cancer of the pancreatic head region. Gut. 1998;42(1):92–6.CrossRefPubMedPubMedCentral
17.
go back to reference Saito T, Hirano K, Isayama H, Nakai Y, Saito K, Umefune G, Akiyama D, Watanabe T, Takagi K, Hamada T, Takahara N, et al. The role of pancreatic enzyme replacement therapy in unresectable pancreatic cancer: a prospective cohort study. Pancreas. 2017;46(3):341–6.CrossRefPubMed Saito T, Hirano K, Isayama H, Nakai Y, Saito K, Umefune G, Akiyama D, Watanabe T, Takagi K, Hamada T, Takahara N, et al. The role of pancreatic enzyme replacement therapy in unresectable pancreatic cancer: a prospective cohort study. Pancreas. 2017;46(3):341–6.CrossRefPubMed
18.
go back to reference Perez MM, Newcomer AD, Moertel CG, Go VL, DiMagno EP. Assessment of weight loss, food intake, fat metabolism, malabsorption, and treatment of pancreatic insufficiency in pancreatic cancer. Cancer. 1983;52(2):346–52.CrossRefPubMed Perez MM, Newcomer AD, Moertel CG, Go VL, DiMagno EP. Assessment of weight loss, food intake, fat metabolism, malabsorption, and treatment of pancreatic insufficiency in pancreatic cancer. Cancer. 1983;52(2):346–52.CrossRefPubMed
19.
go back to reference Davidson W, Ash S, Capra S, Bauer J. Weight stabilisation is associated with improved survival duration and quality of life in unresectable pancreatic cancer. Clin Nutr. 2004;23(2):239–47.CrossRefPubMed Davidson W, Ash S, Capra S, Bauer J. Weight stabilisation is associated with improved survival duration and quality of life in unresectable pancreatic cancer. Clin Nutr. 2004;23(2):239–47.CrossRefPubMed
20.
go back to reference Richter E, Denecke A, Klapdor S, Klapdor R. Parenteral nutrition support for patients with pancreatic cancer--improvement of the nutritional status and the therapeutic outcome. Anticancer Res. 2012;32(5):2111–8.PubMed Richter E, Denecke A, Klapdor S, Klapdor R. Parenteral nutrition support for patients with pancreatic cancer--improvement of the nutritional status and the therapeutic outcome. Anticancer Res. 2012;32(5):2111–8.PubMed
21.
go back to reference Freelove R, Walling AD. Pancreatic cancer: diagnosis and management. Am Fam Physician. 2006;73(3):485–92.PubMed Freelove R, Walling AD. Pancreatic cancer: diagnosis and management. Am Fam Physician. 2006;73(3):485–92.PubMed
22.
go back to reference Dominguez-Munoz JE. Pancreatic enzyme replacement therapy: exocrine pancreatic insufficiency after gastrointestinal surgery. HPB (Oxford). 2009;11(Suppl 3):3–6.CrossRefPubMedPubMedCentral Dominguez-Munoz JE. Pancreatic enzyme replacement therapy: exocrine pancreatic insufficiency after gastrointestinal surgery. HPB (Oxford). 2009;11(Suppl 3):3–6.CrossRefPubMedPubMedCentral
23.
go back to reference Dominguez-Munoz JE. Pancreatic enzyme therapy for pancreatic exocrine insufficiency. Curr Gastroenterol Rep. 2007;9(2):116–22.CrossRefPubMed Dominguez-Munoz JE. Pancreatic enzyme therapy for pancreatic exocrine insufficiency. Curr Gastroenterol Rep. 2007;9(2):116–22.CrossRefPubMed
24.
go back to reference Mossner J, Keim V. Pancreatic enzyme therapy. Dtsch Arztebl Int. 2010;108(34–35):578–82.PubMed Mossner J, Keim V. Pancreatic enzyme therapy. Dtsch Arztebl Int. 2010;108(34–35):578–82.PubMed
25.
go back to reference Toouli J, Biankin AV, Oliver MR, Pearce CB, Wilson JS, Wray NH. Management of pancreatic exocrine insufficiency: Australasian Pancreatic Club recommendations. Med J Aust. 2010;193(8):461–7.PubMed Toouli J, Biankin AV, Oliver MR, Pearce CB, Wilson JS, Wray NH. Management of pancreatic exocrine insufficiency: Australasian Pancreatic Club recommendations. Med J Aust. 2010;193(8):461–7.PubMed
26.
go back to reference Partelli S, Frulloni L, Minniti C, Bassi C, Barugola G, D'Onofrio M, Crippa S, Falconi M. Faecal elastase-1 is an independent predictor of survival in advanced pancreatic cancer. Dig Liver Dis. 2012;44(11):945–51.CrossRefPubMed Partelli S, Frulloni L, Minniti C, Bassi C, Barugola G, D'Onofrio M, Crippa S, Falconi M. Faecal elastase-1 is an independent predictor of survival in advanced pancreatic cancer. Dig Liver Dis. 2012;44(11):945–51.CrossRefPubMed
27.
go back to reference 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. 2011;11(6):535–45.CrossRefPubMed 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. 2011;11(6):535–45.CrossRefPubMed
28.
go back to reference Seiler CM, Izbicki J, Varga-Szabó L, Czakó L, Fiók J, Sperti C, Lerch MM, Pezzilli R, Vasileva G, Pap A, Varga M, et al. Randomised clinical trial: a 1-week, double-blind, 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(7):691–702.CrossRefPubMedPubMedCentral Seiler CM, Izbicki J, Varga-Szabó L, Czakó L, Fiók J, Sperti C, Lerch MM, Pezzilli R, Vasileva G, Pap A, Varga M, et al. Randomised clinical trial: a 1-week, double-blind, 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(7):691–702.CrossRefPubMedPubMedCentral
29.
go back to reference Landers A, Muircroft W, Brown H. Pancreatic enzyme replacement therapy (PERT) for malabsorption in patients with metastatic pancreatic cancer. BMJ Support Palliat Care. 2016;6(1):75–9.CrossRefPubMed Landers A, Muircroft W, Brown H. Pancreatic enzyme replacement therapy (PERT) for malabsorption in patients with metastatic pancreatic cancer. BMJ Support Palliat Care. 2016;6(1):75–9.CrossRefPubMed
31.
go back to reference Vera R, Dotor E, Feliu J, Gonzalez E, Laquente B, Macarulla T, Martinez E, Maurel J, Salgado M, Manzano JL. SEOM Clinical Guideline for the treatment of pancreatic cancer (2016). Clin Transl Oncol. 2016;18(12):1172–8.CrossRefPubMedPubMedCentral Vera R, Dotor E, Feliu J, Gonzalez E, Laquente B, Macarulla T, Martinez E, Maurel J, Salgado M, Manzano JL. SEOM Clinical Guideline for the treatment of pancreatic cancer (2016). Clin Transl Oncol. 2016;18(12):1172–8.CrossRefPubMedPubMedCentral
32.
go back to reference Wigmore SJ, Plester CE, Richardson RA, Fearon KC. Changes in nutritional status associated with unresectable pancreatic cancer. Br J Cancer. 1997;75(1):106–9.CrossRefPubMedPubMedCentral Wigmore SJ, Plester CE, Richardson RA, Fearon KC. Changes in nutritional status associated with unresectable pancreatic cancer. Br J Cancer. 1997;75(1):106–9.CrossRefPubMedPubMedCentral
33.
go back to reference Dintinjana RD, Redzovic A, Cubranic A, Dintinjana M, Vanis N. Nutrition in cancer patients. Coll Antropol. 2014;38(4):1271–5.PubMed Dintinjana RD, Redzovic A, Cubranic A, Dintinjana M, Vanis N. Nutrition in cancer patients. Coll Antropol. 2014;38(4):1271–5.PubMed
34.
go back to reference Vujasinovic M, Valente R, Del Chiaro M, Permert J, Löhr JM. Pancreatic exocrine insufficiency in pancreatic cancer. Nutrients. 2017;9(3):183.CrossRefPubMedCentral Vujasinovic M, Valente R, Del Chiaro M, Permert J, Löhr JM. Pancreatic exocrine insufficiency in pancreatic cancer. Nutrients. 2017;9(3):183.CrossRefPubMedCentral
35.
go back to reference Gooden HM, White KJ. Pancreatic cancer and supportive care--pancreatic exocrine insufficiency negatively impacts on quality of life. Support Care Cancer. 2013;21(7):1835–41.CrossRefPubMed Gooden HM, White KJ. Pancreatic cancer and supportive care--pancreatic exocrine insufficiency negatively impacts on quality of life. Support Care Cancer. 2013;21(7):1835–41.CrossRefPubMed
36.
go back to reference Thorat V, Reddy N, Bhatia S, Bapaye A, Rajkumar JS, Kini DD, Kalla MM, Ramesh H. Randomised clinical trial: the efficacy and safety of pancreatin enteric-coated minimicrospheres (Creon 40000 MMS) in patients with pancreatic exocrine insufficiency due to chronic pancreatitis - a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2012;36(5):426–36.CrossRefPubMedPubMedCentral Thorat V, Reddy N, Bhatia S, Bapaye A, Rajkumar JS, Kini DD, Kalla MM, Ramesh H. Randomised clinical trial: the efficacy and safety of pancreatin enteric-coated minimicrospheres (Creon 40000 MMS) in patients with pancreatic exocrine insufficiency due to chronic pancreatitis - a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2012;36(5):426–36.CrossRefPubMedPubMedCentral
37.
go back to reference Trang T, Chan J, Graham DY. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21(st) century. World J Gastroenterol. 2014;20(33):11467–85.CrossRefPubMedPubMedCentral Trang T, Chan J, Graham DY. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21(st) century. World J Gastroenterol. 2014;20(33):11467–85.CrossRefPubMedPubMedCentral
38.
go back to reference Case CL, Henniges F, Barkin JS. Enzyme content and acid stability of enteric-coated pancreatic enzyme products in vitro. Pancreas. 2005;30(2):180–3.CrossRefPubMed Case CL, Henniges F, Barkin JS. Enzyme content and acid stability of enteric-coated pancreatic enzyme products in vitro. Pancreas. 2005;30(2):180–3.CrossRefPubMed
39.
go back to reference Layer P, Groger G. Fate of pancreatic enzymes in the human intestinal lumen in health and pancreatic insufficiency. Digestion. 1993;54(Suppl 2):10–4.CrossRefPubMed Layer P, Groger G. Fate of pancreatic enzymes in the human intestinal lumen in health and pancreatic insufficiency. Digestion. 1993;54(Suppl 2):10–4.CrossRefPubMed
40.
go back to reference Dominguez-Munoz JE, Iglesias-Garcia J, Iglesias-Rey M, Vilarino-Insua M. Optimising the therapy of exocrine pancreatic insufficiency by the association of a proton pump inhibitor to enteric coated pancreatic extracts. Gut. 2006;55(7):1056–7.CrossRefPubMedPubMedCentral Dominguez-Munoz JE, Iglesias-Garcia J, Iglesias-Rey M, Vilarino-Insua M. Optimising the therapy of exocrine pancreatic insufficiency by the association of a proton pump inhibitor to enteric coated pancreatic extracts. Gut. 2006;55(7):1056–7.CrossRefPubMedPubMedCentral
41.
go back to reference Woo SM, Joo J, Kim SY, Park SJ, Han SS, Kim TH, Koh YH, Chung SH, Kim YH, Moon H, Hong EK, et al. Efficacy of pancreatic exocrine replacement therapy for patients with unresectable pancreatic cancer in a randomized trial. Pancreatology. 2016;16(6):1099–105.CrossRefPubMed Woo SM, Joo J, Kim SY, Park SJ, Han SS, Kim TH, Koh YH, Chung SH, Kim YH, Moon H, Hong EK, et al. Efficacy of pancreatic exocrine replacement therapy for patients with unresectable pancreatic cancer in a randomized trial. Pancreatology. 2016;16(6):1099–105.CrossRefPubMed
Metadata
Title
Impact of the treatment of pancreatic exocrine insufficiency on survival of patients with unresectable pancreatic cancer: a retrospective analysis
Authors
Juan Enrique Domínguez-Muñoz
Laura Nieto-Garcia
Javier López-Díaz
Jose Lariño-Noia
Ihab Abdulkader
Julio Iglesias-Garcia
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4439-x

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