title: Association between pathologic features of peripheral nerves and postoperative anal function after neoadjuvant therapy for low rectal cancer.
abstract: OBJECTIVE
  Neoadjuvant chemoradiotherapy (CRT) for rectal cancer improves local control but also induces severe postoperative anal dysfunction that may be related to neural degeneration. The aims of the study were to identify pathological features of neural degeneration caused by neoadjuvant CRT or neoadjuvant chemotherapy (NAC) and to evaluate the association between neural degeneration and anal function.
  
  
  METHODS
  A retrospective study using chronologically different groups was performed in 95 patients with rectal cancer treated with curative resection with neoadjuvant CRT (n = 47), NAC (n = 27), or surgery alone (no neoadjuvant therapy) (n = 21) at National Cancer Center Hospital East from 2001 to 2014. Peripheral nerve degeneration was evaluated histopathologically using H&E stained sections, based on karyopyknosis, vacuolar or acidophilic degeneration, denucleation, adventitial neuron change, and fibrosis. Morphological analysis of peripheral nerves was compared among the three groups. The association between pathological features and anal function (Wexner Score) was evaluated.
  
  
  RESULTS
  After CRT, the degree of fibrosis around the tumor was severe, and neural degeneration was found in peripheral neurons. With NAC and surgery alone, there was little fibrosis and neural degeneration. Pathological changes after CRT were more pronounced than those after NAC, indicating greater tissue degeneration due to CRT. There was an association between anal function and degeneration score in the CRT group, but not in the other groups.
  
  
  CONCLUSIONS
  Peripheral nerves in patients who received neoadjuvant CRT showed characteristic pathological features indicating greater degeneration, compared with patients who received NAC. Neural degeneration is associated with anal function and several pathological factors after CRT.
authors.affiliation: Division of Surgical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.|Juntendo University Graduate School of Medicine Advanced Clinical Research of Cancer, Tokyo, Japan.
authors.forename: Keinchi
authors.initials: K
authors.lastname: Koushi
authors.affiliation: Division of Surgical Oncology, National Cancer Center Hospital East, Kashiwa, Japan. yunishiz@east.ncc.go.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishizawa
authors.affiliation: Division of Pathology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kojima
authors.affiliation: Division of Pathology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Division of Surgical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Saito
authors.affiliation: Juntendo University Graduate School of Medicine Advanced Clinical Research of Cancer, Tokyo, Japan.|Division of Head and Neck surgery, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Hayashi
authors.affiliation: Division of Pathology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
authors.affiliation: Division of Surgical Oncology, National Cancer Center Hospital East, Kashiwa, Japan. maito@east.ncc.go.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ito
mesh_terms: D000328:Adult; D000368:Aged; D001003:Anal Canal / Q000503:physiopathology* / Q000601:surgery*; D059186:Chemoradiotherapy, Adjuvant; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010525:Peripheral Nerves / Q000473:pathology* / Q000503:physiopathology; D011182:Postoperative Care; D012004:Rectal Neoplasms / Q000503:physiopathology* / Q000601:surgery / Q000628:therapy*
keywords: Neoadjuvant therapy; Pathological evaluation; Perineural nerve; Rectal cancer