title: The Ki-67 labeling index and lymphatic/venous permeation predict the metastatic potential of rectal neuroendocrine tumors.
abstract: Endoscopic resection has been used to treat small rectal neuroendocrine tumors (NETs). However, the indication for additional surgery after endoscopic resection is unclear. The aim of this study was to identify risk factors for rectal NET metastasis and to determine the indication for additional surgery.
  
  
  
  Fifty-five patients with a total of 57 rectal NETs, treated between October 2003 and January 2013, were retrospectively divided into metastatic (11 lesions) and non-metastatic (46 lesions) groups. Tumor size, central depression, invasion depth, lymphatic and venous permeation, mitotic activity, nuclear abnormality, Ki-67 labeling index, and World Health Organization grading classification (G1 or G2) were compared between the groups. Patients underwent endoscopic submucosal resection with a ligation device, transanal full-thickness surgical resection, or radical surgery.
  
  
  
  By univariate analysis, the odds ratios (OR) for a Ki-67 labeling index >3.0 %, positive lymphatic or venous permeation, World Health Organization grading classification G2, tumor size >10 mm, submucosal invasion >4000 μm, and central depression were 120 (P < 0.001), 67.6 (P < 0.001), 58.7 (P < 0.001), 9.8 (P = 0.0037), 6.8 (P = 0.012), and 5.7 (P = 0.018), respectively. Multivariate logistic regression analyses showed that vascular permeation (OR 111; P = 0.006) and a Ki-67 labeling index >3.0 % (OR 88; P = 0.012) were independent risk factors for metastasis.
  
  
  
  The Ki-67 labeling index and lymphatic/venous permeation were reliable predictors of rectal NET metastases.
authors.affiliation: Division of Endoscopy, Shizuoka Cancer Center, 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka, 411-8777, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Sugimoto
authors.affiliation: Division of Endoscopy, Shizuoka Cancer Center, 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka, 411-8777, Japan. k.hotta@scchr.jp.
authors.forename: Kinichi
authors.initials: K
authors.lastname: Hotta
authors.affiliation: Divisions of Pathology, Shizuoka Cancer Center, Suntogun, Shizuoka, Japan.
authors.forename: Tadakazu
authors.initials: T
authors.lastname: Shimoda
authors.affiliation: Division of Endoscopy, Shizuoka Cancer Center, 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka, 411-8777, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Imai
authors.affiliation: Division of Endoscopy, Shizuoka Cancer Center, 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka, 411-8777, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Divisions of Pathology, Shizuoka Cancer Center, Suntogun, Shizuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Divisions of Pathology, Shizuoka Cancer Center, Suntogun, Shizuoka, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Oishi
authors.affiliation: Divisions of Clinical Trials, Shizuoka Cancer Center, Suntogun, Shizuoka, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Mori
authors.affiliation: Division of Endoscopy, Shizuoka Cancer Center, 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka, 411-8777, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Takizawa
authors.affiliation: Division of Endoscopy, Shizuoka Cancer Center, 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka, 411-8777, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kakushima
authors.affiliation: Division of Endoscopy, Shizuoka Cancer Center, 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka, 411-8777, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Division of Endoscopy, Shizuoka Cancer Center, 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka, 411-8777, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Kawata
authors.affiliation: Division of Endoscopy, Shizuoka Cancer Center, 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka, 411-8777, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsubayashi
authors.affiliation: Division of Endoscopy, Shizuoka Cancer Center, 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka, 411-8777, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ono
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D000069916:Endoscopic Mucosal Resection; D004724:Endoscopy; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008113:Liver Neoplasms / Q000556:secondary; D016015:Logistic Models; D008197:Lymph Node Excision; D042601:Lymphatic Vessels / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016017:Odds Ratio; D011379:Prognosis; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D012189:Retrospective Studies; D012307:Risk Factors; D000067368:Transanal Endoscopic Surgery; D047368:Tumor Burden; D014680:Veins / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
keywords: Ki-67 labeling index; Lymphatic permeation; Metastasis; Predictor; Rectal NET; Venous permeation