Pancreatic steatosis promotes dissemination and lethality of pancreatic cancer.
BACKGROUND
Obesity is a worldwide epidemic. Clinical and basic studies have shown obesity to be associated with an increased incidence and progression of pancreatic cancer. The precise role that pancreatic fat plays in this process has remained undefined. We tested the hypothesis that pancreatic steatosis would be associated with increased dissemination and reduced survival in patients with resected pancreatic cancer.


METHODS
A case-control analysis was conducted in patients who had undergone resection for pancreatic adenocarcinoma. Twenty lymph node-positive patients and 20 node-negative patients were matched for age (59 versus 63 years), gender (70% male versus 60% male), body mass index (24.5 versus 25.6), medical comorbidities (hypertension, diabetes, hyperlipidemia), tumor size (2.8 versus 2.6 cm), and resection status (Ro 80% versus 85%). Pancreatic neck margins were reviewed in a blinded fashion by two trained investigators. Pancreatic fat (number of cells/5 high power field) and degree of fibrosis (0 to 4+) were recorded.


RESULTS
Node-positive patients had significantly more fat cells in the pancreas compared with node-negative patients (46.4 +/- 8.7 versus 21.4 +/- 4.8; p < 0.02). Node-positive patients also demonstrated decreased fibrosis compared with node-negative patients (1.7 +/- 0.3 versus 2.7 +/- 0.3; p < 0.02). Mean survival was reduced in node-positive patients (18.9 +/- 2.7 versus 30.8 +/- 4.8 months; p < 0.04).


CONCLUSIONS
These data show that increased pancreatic fat promotes dissemination and lethality of pancreatic cancer. We conclude that pancreatic steatosis alters the tumor microenvironment, enhances tumor spread, and contributes to the early demise of patients with pancreatic adenocarcinoma.
Mathur
Abhishek
A
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Zyromski
Nicholas J
NJ
Pitt
Henry A
HA
Al-Azzawi
Hayder
H
Walker
Julia J
JJ
Saxena
Romil
R
Lillemoe
Keith D
KD
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000273:Adipose Tissue / Q000473:pathology*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010179:Pancreas / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D016577:Pancreaticoduodenectomy; D016019:Survival Analysis