title: Tumor budding in tumor invasive front predicts prognosis and survival of patients with esophageal squamous cell carcinomas receiving neoadjuvant chemotherapy.
abstract: BACKGROUND
  In neoadjuvant chemotherapy for advanced esophageal cancers, complete tumor regression has been difficult to achieve, and tumor often remained after chemotherapy. However, the best method for evaluating the response to chemotherapy based on histopathologic examination of residual tumors has not been established.
  
  
  METHODS
  Studied were 74 patients who received neoadjuvant chemotherapy (5-fluorouracil, cisplatin, and doxorubicin), followed by surgery for advanced esophageal squamous cell carcinoma. The correlation between various histopathologic factors and clinical response with survival was examined, including the importance of tumor budding in the invasive front of tumors on clinical response and survival.
  
  
  RESULTS
  Among 74 patients, 3 achieved a pathologic complete response, and 29 (41%) of 71 residual tumors demonstrated high-grade budding in the invasive front. The 5-year survival rate of patients with low-grade budding tumors was 49%, compared with 17% for those with high-grade budding (P < .001). Budding correlated inversely with good response, which was observed in 44 (60%) of 74 patients. Univariate analysis showed that pathologic tumor depth, number of lymph node metastases, pathologic stage, lymphatic invasion, budding and clinical response were significant prognostic factors. Multivariate analysis identified budding as the most important prognostic factor followed by number of lymph node metastases.
  
  
  CONCLUSIONS
  The results of the current study indicated that tumor budding in the invasive front of tumors correlated significantly with clinical response and prognosis of patients with esophageal squamous cell carcinomas who received neoadjuvant chemotherapy. However, the mechanism of tumor budding in the invasion front of esophageal squamous cell carcinomas treated with chemotherapy was not clarified.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan. hmiyata@gesrug.med.osaka-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyata
authors.forename: Akiko
authors.initials: A
authors.lastname: Yoshioka
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Nushijima
authors.forename: Shuji
authors.initials: S
authors.lastname: Takiguchi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Toshiro
authors.initials: T
authors.lastname: Nishida
authors.forename: Masayuki
authors.initials: M
authors.lastname: Mano
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000401:mortality; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil