Systemic Immune-Inflammation Index Predicts Tumor Recurrence after Radical Resection for Colorectal Cancer.

The systemic inflammatory response is associated with tumor promotion and suppression. Accumulating evidence shows that peripheral blood markers of inflammatory response predict clinical outcomes in various human cancers. The aim of this study was to investigate the prognostic relevance of the inflammation-based biomarkers in colorectal cancer (CRC). We retrospectively analyzed 118 CRC patients who underwent curative resection between 2012 and 2017. The inflammation-based biomarkers were evaluated by using preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), prognostic nutritional index (PNI), and Glasgow prognostic score (GPS). Prognostic values were assessed by the Kaplan-Meier analysis for cancer-specific recurrence-free survival (RFS) and Cox proportional-hazards model. There were significant differences in the levels of NLR, PLR, SII, and SIRI between recurrence and non-recurrence group. The area under the curve (AUC) for SII was 0.710, which showed the highest value in the inflammation-based biomarkers. Multivariate analysis identified that SII (p = 0.0031) and lymph node metastasis (p = 0.0168) were independent prognostic factors for recurrence. High SII exhibited more dismal RFS than low SII in CRC patients with non-metastatic lymph node (p = 0.0002). Our study suggests that SII and lymph node metastasis could be useful indicators in predicting the recurrence of CRC patients. Additionally, SII could accurately stratify CRC patients with tumor recurrence by combining with lymph node metastasis. This result would be beneficial for determining the optimal therapeutic strategies after surgical resection for CRC.

Comparison of long-term outcome of laparoscopic and conventional surgery for advanced colon and rectosigmoid cancer.

BACKGROUND/AIMS: Although after laparoscopic surgery for colorectal cancer postoperative recovery is better than after open surgery, oncologic outcome after this minimally invasive technique remains unclear. In this study we tested the null hypothesis that there is no difference in the outcome of advanced colorectal cancer according to whether it is treated by laparoscopic or conventional open resection. METHODOLOGY: The long-term outcome of 79 patients with advanced colorectal cancer who underwent laparoscopic surgery between 1996 and 2002 was compared with that of 79 who underwent open surgery during the same period, being well-matched patients for age, gender, tumor site, and pathological TNM stage (II or III). Adjuvant therapy and postoperative follow-up were the same in both groups. RESULTS: The median follow-up time after laparoscopic and open surgery was 36 months and 47 months, respectively (p = 0.0756). No significant difference was found between the groups in overall or disease-free survival rates (96% versus 88%, p = 0.12; 96% versus 86%, p = 0.09, respectively). The recurrence rate was 23% in both groups, and liver metastasis was the most frequent form of recurrence. No port site recurrence was observed in the laparoscopic surgery group. CONCLUSIONS: The laparoscopic approach is an acceptable alternative to open surgery for advanced colorectal cancer because of the comparable medium-term outcome. Longer follow-up and large scale RCT is needed to fully assess the oncologic outcome.

Evaluation of the usefulness of tumor budding on the prediction of metastasis to the lung and liver after curative excision of colorectal cancer.

BACKGROUND/AIMS: We evaluated the usefulness of tumor budding, defined as the morphology of infiltration by small clusters of undifferentiated adenocarcinoma into the invasive front of the lesion, for the prediction of metastasis to the lung and liver after curative excision of colorectal cancer. METHODOLOGY: The subjects were 491 patients with a single colorectal cancer lesion, in whom follow-up observation was performed for more than 5 years, consisting of 278 patients without recurrence, 155 patients with the first metastasis to the liver alone, and 58 patients with the first metastasis to the lung alone. The invasive front was histologically re-examined using sections with the largest diameter of the primary colorectal cancer lesion, and the tumor budding was classified into 3 grades based on the morphology of infiltration. The usefulness of this factor for the prediction of metastasis to the lung and liver was examined by multivariate analysis together with conventional clinicopathological factors such as age, sex, tumor location, tumor size, histological type, tumor depth, invasion of lymph ducts, venous invasion, and metastasis to lymph nodes. RESULTS: Comparisons of the no-recurrence and lung metastasis groups by multivariate analysis indicated that moderate to severe tumor budding (odds ratio=0.1291, P<0.0001) and positive metastasis to lymph nodes (odds ratio=0.1142, P<0.0001) were extracted as the independent prediction factors of metastasis to the lung. Comparisons of the no-recurrence and liver metastasis groups indicated that infiltration over the proper muscular tunics (odds ratio=0.0284, P<0.0001) and positive metastasis to lymph nodes (odds ratio=0.3289, P=0.0002) were extracted as the independent prediction factors of metastasis to the liver. CONCLUSIONS: Tumor budding in the invasive front of the lesion was considered to be a simple and useful pathohistological factor for the prediction of metastasis to the lung in patients with colorectal cancer after curative excision. It was suggested that this factor is important for the prediction of metastasis to the lung after surgery and for the planning of treatment methods.

Enzyme histochemical analysis of lymphatic vessels in colon carcinoma: occurrence of lymphangiogenesis within the tumor.

BACKGROUND/AIMS: While it is generally recognized that the lymph vessel is absent in solid carcinoma, a few papers have reported the presence of intratumoral lymph vessels. The present study was carried out to clarify whether or not intratumoral lymphangiogenesis occurs. METHODOLOGY: To identify lymphatics in colon carcinomas, tumor-adjoining and normal submucosa, we tried using an enzymatic histochemistry procedure to examine the specific high activity of 5'-nucleotidase that is seen in lymphatic endothelial cells. Additionally, arterioles and venules were identified by alkaline phosphatase and dipeptidyl (amino) peptidase IV staining, respectively. RESULTS: Intratumoral lymphatic vessels were observed in 30 of 34 colon carcinomas (91%), and arterioles were found in all cases. However, no venules were identified within the tumor. The lymphatic density (mean +/- SD vessels/mm2) increased in the order of the submucosa near the tumor (21.9 +/- 9.5), normal submucosa (27.9 +/- 13.8) and tumor tissue (33.9 +/- 25.1). Intratumoral lymphatic density was significantly higher than that in the submucosa near the tumor (P<0.05). Intratumoral lymphatic density is related to arteriolar density (r=0.284, P=0.0012). The ratio of lymphatic/arteriolar density in the tumor was significantly higher than that seen in the submucosa near the tumor (0.78 +/- 0.76 vs. 0.51 +/- 0.36, P<0.05). Intratumoral lymphatic density was relatively higher in cases with lymph node metastasis than in those without metastasis, but was not related to tumor size, depth of tumor invasion, distant metastasis and TNM stage. CONCLUSIONS: Enzyme histochemistry revealed active lymphangiogenesis and the absence of venules within the tumor. Intratumoral lymphatic density was relatively correlated to arteriolar density. Enzyme histochemistry is a simple and quickly processed method that can be used to differentiate lymphatics from arterioles and venules.

High apoptotic activity and low epithelial cell proliferation with underexpression of p21(WAF1/CIP1) and p27Kip1 of mucinous carcinomas of the colorectum: comparison with well-differentiated type.

We comparatively assessed 41 mucinous colorectal carcinomas (MUCs) and 620 non-MUC (well-, moderately, and poorly differentiated adenocarcinoma) cases for clinicopathologic findings; and 41 MUCs and 115 randomly selected non-MUCs also were studied for the following: (1) apoptotic activity and Ki-67 immunoreactivity; (2) immunohistochemical expression of p21(WAF1/CIP1), p27Kip1, p53, and bcl-2; and (3) c-Ki-ras mutations. The rates for lymph node involvement and peritoneal dissemination were higher in MUCs than in non-MUCs. Multivariate analysis showed MUCs to have a worse prognosis than well-differentiated adenocarcinomas. The Ki-67 labeling for MUCs was significantly lower than that for non-MUCs, whereas the apoptotic index was significantly higher than for the well-differentiated type. The labeling for p21(WAF1/CIP1) and p27Kip1 was lower in MUCs (2.7% and 35.3%, respectively) than in well-differentiated adenocarcinomas (4.2% and 48.6%, respectively). MUCs can be considered a different tumor from the well-differentiated type, with a poor prognosis owing to frequent lymph node metastasis and peritoneal dissemination, and characterized by high apoptotic and low proliferative activities associated with low p21(WAF1/CIP1) and p27Kip1 expression.