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Int J Clin Exp Pathol 2012;5(4):308-314

Original Article
Histologic evaluation of intrahepatic micrometastases in patients treated with or without
neoadjuvant chemotherapy for colorectal carcinoma liver metastasis

Toshifumi Wakai, Yoshio Shirai, Jun Sakata, Hitoshi Kameyama, Hitoshi Nogami, Tsuneo Iiai, Yoichi Ajioka, Katsuyoshi Hatakeyama

Division of Digestive and General Surgery, 1Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and
Dental Sciences, Niigata, Japan

Received March 13, 2012; accepted April 3, 2012; Epub April 16, 2012; Published May 30, 2012

Abstract: In the present retrospective study, we tested the hypothesis that neoadjuvant chemotherapy (NAC) as a treatment for patients with
colorectal carcinoma liver metastases (CRLM) may reduce intrahepatic micrometastases. The incidence and distribution of intrahepatic
micrometastases were determined in specimens resected from 63 patients who underwent hepatectomy for CRLM (21 treated with NAC and
42 without). In addition, the therapeutic efficacy of NAC was evaluated histologically. Intrahepatic micrometastases were defined as
microscopic lesions spatially separated from the gross tumor. The distance from these lesions to the border of the hepatic tumor was
measured on histological specimens and the density of intrahepatic micrometastases (number of lesions/mm2) was determined in regions
close to (<1 cm) the gross hepatic tumor. Of the 21 patients treated with NAC, 13 were identified as having a partial response according to the
Response Evaluation Criteria in Solid Tumors (RECIST) guidelines; thus, the overall response rate was 62%. Histologic evaluation of the
therapeutic efficacy of NAC was significantly associated with tumor response to NAC according to the RECIST guidelines (p=0.048). In all, 260
intrahepatic micrometastases were detected in 39 patients (62%). Intrahepatic micrometastases were less frequently detected in NAC-treated
patients than in untreated patients (5/21 [24%] vs. 34/42 [81%], respectively; p<0.001). There were no significant differences in the distance and
density of intrahepatic micrometastases between the two groups (p=0.313 and p=0.526, respectively). In conclusion, NAC reduces the
incidence of intrahepatic micrometastases in patients with CRLM, but NAC has no significant effect on their distribution when intrahepatic
micrometastases are present.

Keywords: Liver neoplasms, colorectal metastases, intrahepatic micrometastases, immunohistochemistry, surgical resection, hepatectomy

Address all correspondence to:
Dr. Toshifumi Wakai
Division of Digestive and General Surgery
Niigata University Graduate School of Medical and Dental Sciences
1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan.
Tel: +81-25-227-2228; Fax: +81-25-227-0779
E-mail: wakait@med.niigata-u.ac.jp