Effect of Hypercapnia, an Element of Obstructive Respiratory Disorder, on Pancreatic Cancer Chemoresistance and Progression.

Authors

• Avinoam Nevler
• Samantha Z Brown
• David Nauheim
• Carla Portocarrero
• Ulrich Rodeck
• Jonathan Bassig
• Christopher W Schultz
• Grace A McCarthy
• Harish Lavu
• Theresa P Yeo
• Charles J Yeo
• Jonathan R Brody

Publication/Presentation Date

4-1-2020

Abstract

BACKGROUND: Chronic obstructive respiratory disorders (ORDs) are linked to increased rates of cancer-related deaths. Little is known about the effects of hypercapnia (elevated CO

STUDY DESIGN: Two PDAC cell lines were exposed to normocapnic (5% CO

RESULTS: Exposure to hypercapnia resulted in increased colony formation and proliferation rates in vitro in both cell lines (MIA-PaCa-2: 111% increase and Panc-1: 114% increase; p < 0.05). Hypercapnia exposure induced a 2.5-fold increase in oxaliplatin resistance (p <  0.05) in both cell lines and increased resistance to ionizing radiation in MIA-PaCa-2 cells (p < 0.05). Five hundred and seventy-eight patients were included (52% were male, median age was 68.7 years [interquartile range 60.6 to 76.8 years]). Cox regression analysis, assessing TNM staging, age, sex, and ORD status, identified ORD as an independent risk factor for both overall survival (hazard ratio 1.64; 95% CI, 1.2 to 2.3; p < 0.05) and disease-free survival (hazard ratio 1.68; 95% CI, 1.06 to 2.67).

CONCLUSIONS: PDAC cells exposed to hypercapnic environments, which is common in patients with ORD, showed tumor proliferation, radioresistance, and chemoresistance. Patients with a history of ORD had a worse overall prognosis, suggesting that hypercapnic conditions play a role in the development and progression of PDAC and stressing the need for patient-tailored care.

Volume

230

Issue

4

First Page

659

Last Page

667

ISSN

1879-1190

Published In/Presented At

Nevler, A., Brown, S. Z., Nauheim, D., Portocarrero, C., Rodeck, U., Bassig, J., Schultz, C. W., McCarthy, G. A., Lavu, H., Yeo, T. P., Yeo, C. J., & Brody, J. R. (2020). Effect of Hypercapnia, an Element of Obstructive Respiratory Disorder, on Pancreatic Cancer Chemoresistance and Progression. Journal of the American College of Surgeons, 230(4), 659–667. https://doi.org/10.1016/j.jamcollsurg.2019.12.033

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

32058016

Department(s)

Administration and Leadership

Document Type

Article