Purpose: The expression of chemokine receptors CXCR4 and CCR7 has been associated with tumor dissemination and poor prognosis in a limited number of tumor entities. However, no data are currently available on the impact of chemokine receptor expression on disease progression and prognosis in human colorectal cancer.Experimental Design: The expression of CXCR4 and CCR7 was evaluated in 96 patients with histologically confirmed colorectal cancers and in four colorectal cancer cell lines by immunohistochemical staining. Furthermore, cell migration assays were done with SW480, SW620, and LS174T cancer cells to confirm the effect of the CXCR4 ligand stromal cell -derived factor 1A on migration.Results: Human colorectal cancer specimens and cell lines displayed a CXCR4 and CCR7 expression with variable intensities. Interestingly, strong expression of CXCR4, but not of CCR7, was significantly associated with higher Union International Contre Cancer stages 3/4 (P = 0.0017), lymph node metastasis (P = 0.00375), and distant metastasis (P = 0.00003) and further correlated with a reduced 3-year survival rate (P = 0.1). Strong CXCR4 and CCR7 expression positively correlated with the location of the primary tumor in the rectum (P < 0.01). Furthermore, activation of CXCR4-expressing cancer cells by stromal cell -derived factor 1A resulted in a significant increase of cell migration (P < 0.014).Conclusion: Strong expression of CXCR4 by colorectal cancer cells is significantly associated with lymphatic and distant dissemination in patients with colorectal cancer as well as with cancer cell migration in vitro.
Despite of a highly selected patient collective, an extended indication for LE of cT2-3 rectal cancer after nCRT may be considered. The strongest prognostic factors were a CR (ypT0) or responses on submucosa level (ypT1). These first results will have to be confirmed in a prospective trial with an appropriate sample size to ensure high statistical power.
Sessile adenomas are predominantly localized in the rectum and lower sigma. Surgical removal is indicated but often implies an invasive surgical procedure. Using conventional transanal surgical techniques, only the lower rectum can be reached and there are high rates of recurrence. The new technique combines an endoscopic view of the rectum under gas insufflation via a stereoscopic telescope with conventional surgical preparation and suturing. Adenomas can be excised using the mucosectomy technique or full-thickness-excision, whereas carcinomas should be excised using full-thickness excision with a sufficient border of healthy mucosa. In carcinomas of the sacral cavity, we remove the retrorectal fat up to the fascia of Waldeyer, including the regional lymph nodes. Transanal endoscopic microsurgery is the most economical and tissue-saving surgical technique for the removal of rectal adenomas and early rectal carcinomas.
Local R0-resection in cases with low-risk pT1 carcinomas represents an oncologically adequate therapy, which results in similar survival rates compared with primary radical surgery of pT1N0M0 rectal carcinomas. High recurrence rates are observed in tumors with unfavorable histologic result (Group B) requiring further treatment. In these cases immediate reoperation reduces the recurrence rate to 6 percent.
In different tumour entities, expression of the chemokine receptor 4 (CXCR4) has been linked to tumour dissemination and poor prognosis. Therefore, we evaluated, if the expression of CXCR4 exerts similar effects in human hepatocellular carcinoma (HCC). Expression analysis and functional assays were performed in vitro to elucidate the impact of CXCL12 on human hepatoma cells lines. In addition, expression of CXCR4 was evaluated in 39 patients with HCC semiquantitatively and correlated with both, tumour and patients characteristics. Human HCC and hepatoma cell lines displayed variable intensities of CXCR4 expression. Loss of p53 function did not impact on CXCR4 expression. Exposure to CXCL12 mediated a perinuclear translocation of CXCR4 in Huh7/ Hep3B cells and increased the invasive potential of Huh7 cells. In HCC patients, CXCR4 expression significantly correlated with progressed local tumours (T-status; P ¼ 0.006), lymphatic metastasis (N-status; P ¼ 0.005) and distant dissemination (M-status; P ¼ 0.009), as well as with a decreased 3-year-survival rate (P ¼ 0.01). In summary, strong expression of CXCR4 is significantly associated with progressed hepatocellular cancer.
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