Disseminated tumour cells in bone marrow in experimental colon cancer: metastatic or resident?

AIM: There are conflicting data on the biological and prognostic significance of disseminated tumour cells (DTCs) in the bone marrow of colorectal cancer patients since bone metastasis is rare in this disease. The study aimed to determine the origin of bone marrow DTCs using human colorectal cancer cells in in vivo and in vitro experimental settings. METHOD: CD1 nude female mice were xenotransplanted with SW620 cells (a colorectal cancer cell line isolated from a male patient) injected in the colon wall. At autopsy, the presence of SW620 in the bone marrow (BM), colon and other organs/tissues was recognized by detection of the epithelial marker cytokeratin-19 (CK19) and Y chromosome. In addition SW620 cells or their conditioned medium were cultured with human BM cells. RESULTS: Macroscopically evident CK19+/Y-chromosome-positive tumours developed only in five mice receiving SW620 cells while putative DTCs (CK19+) were found in the bone marrow of all treated mice. Most of these CK19+ cells were Y chromosome negative, only few being Y chromosome positive. In vitro SW620 cells or their conditioned medium induced CK19 expression in cultured human bone marrow cells. CONCLUSION: Experimental colorectal cancer can induce the appearance of two distinct CK19+ cell populations in the bone marrow, one of metastatic origin and the other of murine origin. These findings suggest that bone marrow cells may undergo phenotypic modifications induced by cancer cells.

Anti-tumor necrosis factor treatment in occult hepatitis B virus infection: a retrospective analysis of 62 patients with psoriatic disease.

One of the problems possibly related to the use of biological agents targeting tumor necrosis factor (TNF)-alpha is the increased risk of infections, including the activation of hepatitis B virus (HBV). HBV activation can occur in carriers of hepatitis B surface antigen (HBsAg), but the risk may also involve the HBsAg-negative (anti-HBc ± anti-HBs) occult carriers. Precise data on the safety of anti-TNF and/or other immunosuppressive drugs in HBV occult carriers are not available. We performed a retrospective analysis of 62 psoriatic patients with occult HBV infection treated with anti-TNF biological agents over a period of approximately 4 years: 44 subjects were treated with etanercept, 8 with infliximab and 10 with adalimumab. During the observational treatment period, no signs of HBV activation were observed. Only in one patient the reappearance of HBsAg, without detectable HBV-DNA, was noted before retreatment with etanercept and after 10 months from discontinuation of the previous course. In this patient etanercept was re-administered in association with lamivudine without any adverse event. Our results suggest the overall safety of treatment with anti-TNF drugs in HBV occult carriers, although a careful and constant monitoring of virological markers is required in such patients during treatment with anti-TNF drugs in order to have an early recognition of viral reactivation.