De novo gastrointestinal tumours after renal transplantation: Role of CMV and EBV viruses

Abstract

The development of new and more effective immunosuppressive agents has provided long-term survival for transplant recipients, thereby increasing the risk of de novo malignancy in chronic immunocompromised hosts. While de novo post-transplant lymphoproliferative diseases and skin cancer has been shown to have an increased incidence in long-term surviving solid organ transplant recipients, the association with gastrointestinal (GI) cancer is controversial. Over 12 yr, 20 patients (5%) out of 395 renal transplant recipients developed 23 de novo tumours; 11 skin cancer and 12 non-skin cancer. Four patients (1%) developed de novo tumours of the GI tract (three colon, and one gastric cancer). Immediately after tumour's diagnosis, immunosuppressive therapy was reduced; all patients were shifted from cyclosporine to Rapamicine within 30 d. The tumour was surgically resected with curative intent in three cases, while one patient had only palliative surgery because of metastatic disease. The post-operative courses was uneventful. All patients maintained normal graft function. However, three out of four patients (75%) died of progression of the neoplasm, within a median time from the diagnosis of 12 months. Further, we investigated a possible correlations between de novo GI cancer and HCV, HBV status, infections, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation, episodes of rejection, and blood transfusions. All cases with GI de novo cancers reported in this paper developed CMV and EBV reactivation within three months after transplantation. Thereafter we suggest a closer follow-up for de novo GI cancer in renal transplants with early CMV and EBV reactivation in order to avoid delayed diagnosis.

Gastrointestinal cytomegalovirus disease in the immunocompromised patient

“…Reactivation of CMV and the Epstein-Barr virus (EBV) is an established risk factor in developing malignancies after transplantation, but only EBV, as the etiologic agent of posttransplantation lymphoproliferative disorder, has been directly associated with malignancies [ 46 ]. A recent case series by Adani et al [ 47 ] reported four patients who developed gastrointestinal tumors following transplantation; all had CMV and EBV reactivation within 3 months after the procedure.…”

How virus persistence can initiate the tumorigenesis process

“…For example the analysis of DNA damage could be associated with HPV isolation at the time of pap test screening, or with EBV viral load determination in the follow-up of transplant patients [28] . Retrospective and prospective studies could be implemented, analyzing possible correlation between frequency of different virus reactivations, severity of these reactivations, evidence of genetic damage in cells that harbor latent viruses and development of malignancies, in order to better define the importance of evocative findings [56] : ideal candidates for these studies would be populations of immunocompromised patients such as those in post-transplant settings [57] . Chronic infections, clinically manifest or subclinical, are an additional interesting condition for virus related DNA damage investigation [37] .…”