title: The effect of neoadjuvant chemotherapy on lymph node micrometastases in squamous cell carcinomas of the thoracic esophagus.
abstract: BACKGROUND
  Neoadjuvant chemotherapy (NACT) has been postulated but not yet proven to eradicate micrometastases and improve the prognosis of patients with advanced esophageal squamous cell carcinomas (ESCC). Cytokeratin immunohistochemistry of the lymph nodes of ESCC revealed immunohistochemical micrometastases (IHM) and cytokeratin deposits (CD), which are hyalinized denucleated particles considered to be cadavers of carcinoma cells. Successful chemotherapy should convert cancer cells from IHM to CD and improve the status of ESCC patients from systemic disease to regional disease.
  
  
  METHODS
  Cytokeratin immunostaining of surgically removed lymph nodes was performed for 107 patients with node-positive ESCC, including 32 patients without preoperative treatment (Surgery group) and 75 patients undergoing NACT using CDDP, doxorubicin hydrochroride, and 5-fluorouracil (NACT group). Cytokeratin-positive staining was done for serial hematoxylin-eosin-stained sections and classified as pathologic metastasis, IHM, or CD.
  
  
  RESULTS
  CD was observed less frequently in the Surgery group than in the NACT group (6% vs 43%, P < .0001), whereas IHM was more frequent in the former (47% vs 24%, P = .019). IHM was a poor prognostic factor in both groups, whereas CD was a favorable one in the NACT group. The effect of chemotherapy on IHM was classified as eradicated, IHM(-)/CD(+); persistent, IHM(+)/CD(+); no effect, IHM(+)/CD(-); or not informative, IHM(-)/CD(-). This classification correlated well with the clinical response of the primary neoplasm, number of pathologic metastases, and postoperative survival (3-year survival rates: 78%, 18%, 0%, and 38%). IHM/CD was found to be an independent prognostic factor together with the number of pathologic metastases in the multivariate analysis.
  
  
  CONCLUSIONS
  Disappearance of IHM and the emergence of CD suggest the eradication of micrometastases by NACT. The clinical benefit of NACT was apparent for IHM(-)/CD(+) patients with node-positive ESCC.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Jin
authors.initials: J
authors.lastname: Matsuyama
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Takushi
authors.initials: T
authors.lastname: Yasuda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyata
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Shuji
authors.initials: S
authors.lastname: Takiguchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Makari
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Mano
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use*; D004317:Doxorubicin / Q000627:therapeutic use*; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D008207:Lymphatic Metastasis / Q000175:diagnosis; D020360:Neoadjuvant Therapy; D011379:Prognosis
chemical_list: D007633:Keratins; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil