Prognostic significance of intrahepatic lymphatic invasion in colorectal liver metastases

Colorectal cancer is the third most common cancer worldwide in incidence and second in mortality in both sexes [1]. Prognosis in patients with colorectal cancer has improved; however, about half of these patients might present recurrent disease after curative resection [2]. The most frequent organ with recurrent tumor is the liver, and the incidence of synchronous or metachronous liver metastasis is about 30 % [3]. Liver resection for colorectal liver metastases (CLMs) has been performed since the late 1960s [4]. Due to the progression of surgical management, diagnostic and surgical modalities, and chemotherapeutic agents, survival after liver resection for CLMs has improved [5]. The median overall survival (OS) and disease-free survival (DFS) after liver resection in an adjuvant chemotherapy setting have been reported about 50 % and 70 %, respectively, in a recent report [6].

Many authors have reported prognostic factors after liver resection for CLMs before the era of FOLFOX/FIRI-based chemotherapy [[7], [8], [9]]. The major prognostic factors reported are short intervals between primary colorectal cancer and CLMs [7,9], elevation of preoperative serum carcinoembryonic antigen (CEA) [[7], [8], [9]], larger size [8] or number [[7], [8], [9]] of CLMs, positive surgical margin of hepatic tumor [8], and positive lymph node metastasis [7]. In 2002, we reported the prognostic significance of intrahepatic lymphatic invasion in CLMs [10]. After our first report, many authors confirmed the prognostic impact of intrahepatic lymphatic invasion after liver resection for CLMs [[11], [12], [13], [14], [15]]. However, the periods of surgical treatment in these investigations varied from 1982 to 2011 [[10], [11], [12], [13], [14], [15]].

Oxaliplatin is a platinum complex with diaminocyclohexane developed in 1976 that has proven antitumor activity against colon cancer cell lines [16]. After several phase II clinical trials for efficacy [17,18], oxaliplatin was approved in European countries in 1996, in the United Stated in 2002, and in Japan in 2005. After that, a randomized study of FOLFOX therapy was published in 1997 by de Gramont et al. [19]. Those of FOLFIRI therapy in 2000 by Saltz et al. [20] and Douillard et al. [21]. Therefore, postoperative chemotherapy may vary according to the period of liver resection and the country. The efficacy of adjuvant chemotherapy after liver resection for CLMs has been controversial. Several recent randomized studies demonstrated no difference in OS with the addition of perioperative chemotherapy with FOLFOX compared with surgery alone for patients with resectable CLMs [6.22]. However, the survival of patients has improved due to the development of chemotherapeutic agents in patients with unresectable disease [5].

This study, retrospectively analyzed consecutive patients with CLMs who underwent liver resection with a curative intent to clarify the prognostic significance of intrahepatic lymphatic invasion in the era of FOLFOX/FIRI-based chemotherapy.

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