Prognostic significance of lymph node status in patients with metastatic colorectal carcinoma treated with lymphadenectomy.

BACKGROUND AND OBJECTIVES: To test prognostic significance of lymph node status in patients with metastatic colorectal carcinoma (mCRC). METHODS: Four hundred ninety six patients diagnosed with synchronous mCRC and treated with lymphadenectomy between 1995 and 2008 were identified and divided into groups pN0, pN1, and pN2 (140 (28.2%) in pN0, 223 (45.0%) in pN1, and 133 (26.8%) in pN2 group) according to their lymph node status. The Kaplan-Meier and Cox regression analyses were used to test associations and independent predictor status of lymph node involvement. RESULTS: The Cox proportional hazards regression showed pN as significantly associated with disease-specific survival (DSS) both in univariate (HR = 1.609, 95% CI 1.411 to 1.835, P < 0.001) and multivariate (HR = 1.630, 95% CI 1.422 to 1.868, P < 0.001) analyses. The Kaplan-Meier analysis demonstrated that patients with pN2 and pN1 had a significantly worse DSS compared with patients with pN0 tumors (respectively, 17.273 ± 1.020 and 27.145 ± 1.715 vs. 34.992 ± 2.143 months; P < 0.001). In accuracy analyses based on AUC values, nodal status demonstrated the highest accuracy (65.1%) out of all the variables. CONCLUSIONS: Our findings indicate that optimal TNM staging for mCRC should incorporate lymph node status to provide a more effective and predictive model.

Microsatellite-based analysis of genetic structure and gene flow of Mythimna separata (Walker) (Lepidoptera: Noctuidae) in China.

The oriental armyworm, Mythimna separata, is a serious agricultural pest in China. Seasonal and roundtrip migration has recently led to sudden, localized outbreaks and crop losses. To evaluate genetic differentiation between populations in eastern and western China and elucidate gene flow, the genetic structure of 20 natural populations from nine provinces was examined using seven microsatellite markers. The results indicated high genetic diversity. However, little to moderate (0 < F ST < 0.15) genetic differentiation was detected, and there was no correlation between genetic distance and geographical distance. Bayesian clustering analysis identified three groups whereas discriminant analysis of principal components identified ten clusters that were considered as two clear-cut clusters and one admixed group. Gene flow occurred frequently in most population pairs, and an asymmetrical migration rate was detected in several pairwise population comparisons. The bottleneck test showed that few populations had experienced recent bottlenecks. Correspondingly, large-scale and long-distance migration of M. separata has caused low genetic differentiation and frequent gene exchange. Our findings are important for studying genetic evolution and help to improve predictions of M. separata outbreaks in China.

USP22 acts as an oncogene by the activation of BMI-1-mediated INK4a/ARF pathway and Akt pathway.

Recent studies provided strong support for the view that ubiquitin-specific protease 22 (USP22) plays a central role in cell-cycle progression and also in pathological processes such as oncogenesis. We have recently shown that USP22 levels are elevated in colorectal carcinoma with associated increase in the expression of several cell-cycle-related genes. However, the precise mechanism for these functions of USP22 at molecular level has not been fully elucidated. Currently, we investigated the role of USP22 in human colorectal cancer (CRC). We observed that USP22 expression was statistically significantly correlated positively with that of BMI-1, c-Myc and both, pAkt (Ser473), and pAkt (Thr308), in primary tumor tissues from 43 CRC patients. Down-regulation of USP22 expression in HCT116 colorectal cancer cells by siRNA resulted in the accumulation of cells in the G1 phase of the cell cycle. RNAi-knockdown of USP22 in HCT16 cells also led to the repression of BMI-1 and was accompanied by the up-regulation of p16INK4a and p14ARF, with a consequent decrease in E2F1 and p53 levels. In addition, down-regulation of c-Myc-targeted cyclin D2 was also noticed in cells treated with USP22-siRNA. Furthermore, our results showed that USP22 deletion also caused down-regulation of Akt/GSK3ß activity, which can also contribute to the reduction of cyclin D2. Collectively, our current results suggest that USP22 may act as an oncogene in CRC as it positively regulates cell cycle via both BMI-1-mediated INK4a/ARF pathway and Akt signaling pathway.

The role of para-aortic lymphadenectomy in surgical management of patients with stage N+ rectal cancer below the peritoneal reflection.

The goal of this retrospective study was to determine the effect of para-aortic lymphadenectomy on clinical outcome in patients with stage N+ rectal adenocarcinoma below the peritoneal reflection. A retrospective analysis was performed on the clinical outcome of 181 patients with stage N+ rectal adenocarcinoma below the peritoneal reflection who underwent total mesorectal excision (TME) with total pelvic lymph node (PLN) adenectomy, with or without para-aortic lymph node (PAN) adenectomy. Independent prognostic factors were determined by multivariate Cox regression analysis. Disease-free survival (DFS) was analyzed using Kaplan-Meier curves and the log-rank test. The incidence of PLN metastases was 39.2% (71/181) in all the patients, and the incidence of PAN metastases was 12% (12/100) in patients who received PLN + PAN adenectomies. The patients were divided into two groups: PLN adenectomy (n = 81) and PLN + PAN adenectomy (n = 100). There were no statistically significant differences in clinicopathological factors between the PLN adenectomy and PLN + PAN adenectomy groups. On univariate analysis, the gross tumor type (P = 0.012), histological differentiation (P = 0.013), CEA level (P = 0.019), T stage (P = 0.019), N stage (P < 0.0001), and the number of positive PLN sites (P < 0.0001) were associated with poor DFS. Gross tumor type (P = 0.031), N stage (P = 0.001), and the number of positive PLN sites (P < 0.0001) were independent prognostic factors for DFS as identified by multivariate Cox regression analysis. PLN + PAN adenectomy significantly improved DFS compared to PLN adenectomy alone in patients with noninfiltrating type (P = 0.001), but not in patients with infiltrating type (P = 0.075). PLN + PAN adenectomy significantly improved DFS compared to PLN adenectomy alone in patients with 0 or 1 positive PLN site (P = 0.001, P = 0.009 respectively), but not in patients with ≥2 positive PLN sites (P = 0.095). In the N1 and N2 stage groups, PLN + PAN adenectomy significantly improved DFS compared with PLN adenectomy alone (P = 0.001; P < 0.0001, respectively). Furthermore, mean DFS was longer in the absence of PAN metastasis (P < 0.0001). PAN metastases appear to be associated with reduced DFS. Total PAN adenectomy may improve DFS in patients with noninfiltrating type, stage III rectal cancer below the peritoneal reflection, who have <2 positive PLN sites.

Adhesion pattern and prognosis studies of T4N0M0 colorectal cancer following en bloc multivisceral resection: evaluation of T4 subclassification.

In current TNM stage system, T4 lesions represent a complex group and should be considered to further optimize the classification. This study evaluates the significance of adhesion pattern in T4 subclassification based on prognostic analysis of T4N0M0 colorectal cancer following en bloc multivisceral resection (MVR). Prospectively collected data (1992-2004) were analyzed for 278 patients with stage T4N0M0 lesions following MVR for colorectal cancer. Patients were divided into inflammatory adhesion (IA) and malignant invasion (MI) groups based on adhesion to adjacent organs. Survival was evaluated by Kaplan-Meier and Cox proportional hazards regression analyses. MI was detected in 249 of 460 (54.1%) resected organs and in 159 of 287 (55.40%) patients undergoing MVR. Compared with IA group, patients in MI group showed no significant difference in clinicopathological data except tumor differentiation (P = 0.0376). Cox proportional hazards regression showed that MI was independently associated with overall survival among both colon (HR = 2.028; P = 0.0001) and rectal (HR = 0.451; P = 0.0002) cancer patients. Kaplan-Meier analysis showed that MI patients had a significantly higher MVR compared with IA patients (colon cancer: P = 0.0018; rectal cancer: P = 0.0116). In conclusion, MI was validated as an adverse prognostic factor for stage T4N0M0 colorectal cancer following MVR suggesting that it may be classified as a T4-subgroup in order to reinforce practice guidelines.

Altering trend of clinical characteristics of colorectal cancer: a report of 3,607 cases.

BACKGROUND AND OBJECTIVE: Incidence of colorectal cancer in China has increased since 1980s. The epidemiologic character of colorectal cancer in China is similar to that in high prevalence districts. The distributions among different regions are different, with high incidence in the Eastern coastal regions and low incidence in the Western inland. This study was to explore the clinical characteristics of colorectal cancers in Heilongjiang province in 1981-2005. METHODS: A total of 3607 patients with pathologically confirmed colorectal cancer who were hospitalized to Tumor Hospital of Harbin Medical University, Heilongjiang province, in 1981-2005 were divided into 5-year groups. Their clinical data were analyzed. RESULTS: The annual hospitalization number of colorectal cancer patients in 1985-2005 was increased by 8.5%. The median age increased by seven years. There was no significant change in the male to female ratio of the patients. The proportion of rectal cancer decreased by 13.6%, while the proportions of both right and left hemi-colon cancers increased by 6.8%; the proportion of colorectal cancer at Dukes' A increased by 3.8%, while the proportion of colorectal cancer at Dukes' D decreased by 8.1%. CONCLUSIONS: In the past 25 years, the incidence of colorectal cancer has increased in Heilongjiang province with an increase in median age; the male to female ratio has no significant change. The incidence of rectal cancer and proportion of Dukes' A cancer have increased.

[Study on retrograde metastasis rule of middle-low rectal cancer].

OBJECTIVE: To investigate the resection range of mesorectum and rectum below the inferior margin of tumor for the total mesorectum excision (TME) in middle-low rectal cancer. METHODS: Sixty patients were enrolled in the study. After TME operation, serial 5 mm interval sections were made in specimens of middle-low rectal cancer. The retrograde metastasis of rectal cancer was observed by routine HE staining. RESULTS: The phenomena of retrograde metastasis in mesorectum were found in 15 cases, and the distance of retrograde metastasis was 0.5-4.0(2.47+/-1.06) cm, which was correlated with Dukes stage, lymph node metastasis and histological differentiation. The retrograde metastases in bowel were found in 11 cases, and the distance of retrograde metastasis was 0.5-4.0 (1.64+/-1.16) cm, which was correlated with histological differentiation. CONCLUSIONS: The distal mesorectum should be resected at least 4 cm when TME is carried out, and the distal bowel at least 2.5 cm. More than 5 cm mesorectum and bowel should be resected when advanced Dukes stage, extensive lymph node metastasis and poor histological differentiation occurred.