title: Actual status of distribution and prognostic impact of extramural discontinuous cancer spread in colorectal cancer.
abstract: OBJECTIVE
  To clarify the prognostic impact of tumor nodules without residual lymph node (LN) structure (ND) in colorectal cancer and to determine optimal categorization of ND in tumor staging.
  
  
  METHODS
  A multicenter, retrospective pathologic review was performed for 1716 patients with stages I to III curatively resected colorectal cancer treated at 11 institutions between 1994 and 1998. An additional 2242 patients from nine institutions were enrolled between 1999 and 2003 as a second cohort to validate the results.
  
  
  RESULTS
  LN metastasis (LNM) and ND were observed in 33.7% and 16.0% (smooth-contour nodule [S-ND], 8.2%; irregular-contour nodule [I-ND], 10.7%) of patients in the first cohort. S-ND and I-ND were similarly distributed in the regional area. There was no considerable difference in the impact on survival between S-ND (hazard ratio [HR], 2.7; 95% CI, 1.9 to 3.8) and I-ND (HR, 4.3; 95% CI, 3.3 to 5.8) or between LNM (HR, 4.5; 95% CI, 3.4 to 6.0) and ND (HR, 4.0; 95% CI, 3.1 to 5.3). LNM and ND were similarly associated with the mode of recurrence. Tumor nodules ≥ 5 mm growing with venous/perineural invasion (ND [v/pni+]), judged with 0.61 κ value among 11 observers, had an independent prognostic value for 5-year survival of 42%; similar results were observed in the second cohort.
  
  
  CONCLUSIONS
  These results do not support the TNM system in which S-ND is treated differently from I-ND in tumor staging; LNM and ND should be considered together in the same category. The presence of ND (v/pni+) has a considerable adverse prognostic effect.
authors.affiliation: Department of Surgery, National Defense Medical College, 3-2, Namiki, Tokorozawa, Saitama 359-8513, Japan. ueno@ndmc.ac.jp
authors.forename: Hideki
authors.initials: H
authors.lastname: Ueno
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shirouzu
authors.forename: Takaya
authors.initials: T
authors.lastname: Kusumi
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Yamada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ikegami
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
authors.forename: Shingo
authors.initials: S
authors.lastname: Kameoka
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohkura
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Masaki
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kushima
authors.forename: Keiichi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ajioka
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hase
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
authors.forename: Ryo
authors.initials: R
authors.lastname: Wada
authors.forename: Keiichi
authors.initials: K
authors.lastname: Iwaya
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging / Q000379:methods*; D015588:Observer Variation; D011379:Prognosis; D012189:Retrospective Studies; D055815:Young Adult