title: Parasympathetic neurogenesis is strongly associated with tumor budding and correlates with an adverse prognosis in pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  To investigate the frequency of parasympathetic neurogenesis and determine its association with tumor budding and prognosis in pancreatic ductal adenocarcinoma (PDAC).
  
  
  METHODS
  Parasympathetic neurogenesis was defined as the distribution of abnormal parasympathetic nerves in the stroma tissue. Staining of vesicular acetylcholine transporter (VAChT), as a marker for parasympathetic neurogenesis, was performed on a representative specimen of the tumor for 59 PDAC patients with available clinical, pathologic, and follow-up information. Three specimens containing normal pancreatic tissues were stained in parallel. The number of parasympathetic nerve fibers was counted in five high-power microscopic fields (5×0.785 mm(2)). Cut-off values were calculated by receiver operating characteristic curve analysis.
  
  
  RESULTS
  VAChT-positive parasympathetic nerve fibers were not seen in the stroma of 3 cases of normal pancreatic tissues. In 59 PDAC cases, the range of parasympathetic neurogenesis was 4-38 fibers/(5×0.785) mm(2), with a median of 18 fibers/(5×0.785) mm(2). Patients with parasympathetic neurogenesis >15 fibers/(5×0.785) mm(2) were defined as the high-density group (39 patients, 66.1%), and those with parasympathetic neurogenesis 15 fibers/(5×0.785) mm(2) as the low-density group (20 patients, 33.9%). The high-density group had a higher occurrence of tumor budding (P=0.001) and a higher rate of early recurrence (P=0.035). Parasympathetic neurogenesis appeared to be an independent adverse prognostic factor [hazard ratio (HR)=2.45, 95% confidence interval (95% CI): 1.25-4.81, P=0.009], in addition to American Joint Committee on Cancer (AJCC) stage (P=0.010) and tumor budding (P=0.009).
  
  
  CONCLUSIONS
  Parasympathetic neurogenesis is strongly associated with tumor budding and correlates with an adverse prognosis in PDAC.
authors.affiliation: 1Department of General Surgery;
authors.forename: Lingfu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 2Department of Pathology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Limei
authors.initials: L
authors.lastname: Guo
authors.affiliation: 1Department of General Surgery;
authors.forename: Ming
authors.initials: M
authors.lastname: Tao
authors.affiliation: 1Department of General Surgery;
authors.forename: Wei
authors.initials: W
authors.lastname: Fu
authors.affiliation: 1Department of General Surgery;
authors.forename: Dianrong
authors.initials: D
authors.lastname: Xiu
keywords: Pancreatic ductal adenocarcinoma; parasympathetic neurogenesis; prognosis; recurrence; tumor budding