No abstract

Objective: The microenvironment of cancer plays a critical role in its progression. However, the molecular features of cancer-associated fibroblasts (CAFs) are less well understood than those of cancer cells. We investigated the clinicopathological significance of podoplanin expression in stromal fibroblasts in patients with colorectal cancer (CRC). Methods: We selected podoplanin as an upregulated marker in CAF from a DNA microarray experiment. Consequently, podoplanin was identified as an upregulated gene. Immunohistochemical podoplanin expression was investigated at the National Cancer Center Hospital, Tokyo, Japan, in 120 patients with advanced CRC, and its clinicopathological significance was examined. The biological function of podoplanin expression was also assessed by a coculture invasion assay with CRC cell lines such as HCT116 and HCT15. Results: Podoplanin expression was exclusively confined to stromal fibroblasts and absent in tumor cells. Podoplanin is absent in normal stroma except for lymphatic vessels. Staining was considered positive when over 30% of the cancer stroma was stained. Positive podoplanin expression was significantly correlated with a more distal tumor localization (p = 0.013) and a shallower depth of tumor invasion (p = 0.011). Univariate analysis revealed that negative podoplanin expression in stromal fibroblasts was significantly associated with reduced disease-specific survival (p = 0.0017) and disease-free survival (p < 0.0001). Multivariate analysis revealed that negative podoplanin expression (p = 0.016) and lymph node metastasis (p = 0.027) were significantly associated with disease-free survival. CRC cell invasion was augmented by co-culture with CAFs that were treated with siRNA for podoplanin. Conclusions: Our results suggest that a positive podoplanin expression in stromal fibroblasts could have a protective role against CRC cell invasion and is a significant indicator of a good prognosis in patients with advanced CRC, supported by biological analysis showing that podoplanin expression in CAFs is associated with decreased CRC cell invasion.

We have shown that using Interceed in laparoscopic colorectal surgery is valid and technically safe.

PurposeFor locally advanced pathological T4 (pT4) colon cancer, the safety and feasibility of laparoscopic procedures remain controversial. Therefore, this study aimed to assess short-term and long-term outcomes and to identify the prognostic factors in laparoscopic surgery for pT4 colon cancer.MethodsThe study group included 130 patients who underwent laparoscopic radical resection for pT4 colon and rectosigmoid cancer from January 2004 through December 2012. The short-term outcomes, long-term outcomes, and prognostic factors in pT4 colon cancer were analyzed.ResultsThe median operative time was 205 min, with a median blood loss of 10 ml. The conversion rate was 3.8%, and 13 patients (10.0%) had postoperative complications. The radial resection margin was positive in 1 patient (0.8%). The median follow-up time was 73 months. The 5-year overall survival (OS) and recurrence-free survival (RFS) were 77.2 and 63.5%, respectively. On a multivariate analysis, a male sex [hazard ratio (HR) 3.09, p < 0.001], lymph node ratio ≥ 0.06 (HR 2.35, p = 0.021), tumor diameter < 38 mm (HR 2.57, p = 0.007), and right-sided colon cancer (HR 2.11, p = 0.047) were significantly related to a poor OS.ConclusionsThese results suggest that laparoscopic surgery for pT4 colon cancer is safe and feasible, and the oncological outcomes are acceptable. Based on the present findings, select patients with locally advanced colon cancer should not be excluded from laparoscopic surgery.

To prevent SSI after laparoscopic surgery for colon cancer, triclosan-coated PDS Plus sutures should be used for abdominal closure.