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

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

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.

Keywords: Malnutrition; Pancreatic carcinoma; Pancreatic enzyme replacement therapy; Pancreatic exocrine insufficiency; Survival; Unresectable pancreatic cancer.

Conflict of interest statement

Authors’ information

J.E.D.-M. is expert pancreatologist, Director of the Department of Gastroenterology and Hepatology and Professor of Medicine at the University Hospital of Santiago de Compostela, Spain. J.L.-N. and J.I.-G. are experts endosonographers and clinical pancreatologists. I.A. is an expert cytopathologist for EUS-guided FNA-FNB samples of pancreatic lesions.

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki and its amendments, and with Good Clinical Practice guidelines. Ethical approval for this study was obtained from the Ethics and Clinical Research Committee of Santiago de Compostela-Lugo, Spain. The need for consent for this study was waived by the institutional review board (Ethics and Clinical Research Committee of Santiago de Compostela-Lugo, Span) due to its retrospective design.

Competing interests

J.E.D.-M. has worked as advisor and speaker for Mylan and Abbott. J.L.-N. and J.I.-G. have worked as speaker for Mylan and Abbott. The remaining authors declare that they have nothing to disclose.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Kaplan–Meier survival curves of patients with unresectable pancreatic cancer in Group 1 (standard oncologic therapy, n = 86) and Group 2 (evaluation of symptoms of pancreatic exocrine insufficiency [PEI] and the need for pancreatic enzyme replacement therapy [PERT] in addition to standard oncologic therapy, n = 74). The hazard ratio (HR) and 95% confidence interval (CI) associated with Group 2 are shown. Log-rank test (Mantel–Cox) P < 0.001
Fig. 2
Fig. 2
Kaplan–Meier survival curves of patients with unresectable pancreatic cancer and a significant weight loss (> 10% bodyweight within 6 months) at diagnosis (n = 95) according to administration of pancreatic enzyme replacement therapy (PERT). The hazard ratio (HR) and 95% confidence interval (CI) associated with PERT are shown. Log-rank test (Mantel–Cox) P < 0.001

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