Chapter 29: Malignancies

NOTES

• We detail malignancies in organ transplant recipients as a whole.

• Observations that apply exclusively to liver recipients are specifically mentioned.

DE NOVO MALIGNANCIES AFTER LIVER TRANSPLANTATION

• Skin cancers account for the largest nonlymphoid class of de novo malignancies after liver transplantation.¹

• 2-7 fold higher risk.²

• Incidence:²

  • Reported 2.2% to 26% overall

  • 10%-14.6% at 5 years

  • 20%-32% at 10 years

• 37% of de novo malignancies after transplantation are nonmelanoma skin cancers (NMSC).²

• More likely to be diagnosed with American Joint Commission on Cancer (AJCC) stage 2 or greater.²

• Worse survival.²

• 2.9 relative risk (RR) relative risk of cancer-related mortality (with respect to general population).²

• Lower standardized incidence ratio (SIR 2.2) of de novo malignancies among liver transplant recipients when compared to heart (2.5) and to lung (3.6) recipients.²

• Recurrent and de novo malignancies are the second most frequent cause of late death after liver transplantation, only surpassed by cardiovascular-associated mortality.¹

• When compared to the general population, liver transplantation recipients have a greater incidence of de novo malignancies.¹

• De novo malignancies attributable to chronic viral infections have the greatest incidence.¹

• The development of de novo malignancies after liver transplantation has been estimated to range from 4% to 16%.¹

• The overall frequency of nonlymphoid de novo cancers increases proportionally to the length of follow-up.¹

• Malignancy is one of the leading causes of mortality after transplantation, especially in the long term.³

• Some of the cancers with higher frequency in transplant recipients include:³

  • Non-Hodgkin lymphoma

  • NMSC (non melanoma skin cancer)

  • Kaposi sarcoma

  • Cervical cancer

• Although a viral oncogenic association has been observed in the transplant population, it is likely to involve multifactorial components.³

• The greater incidence of cardiovascular disease, chronic kidney disease, and infections among transplant recipients increases the risk of potential complications, morbidity, and mortality associated with medical and surgical oncologic interventions.³

• Immunosuppressive agents may have a direct carcinogenic power that associates them with malignancies rather than an indirect effect via immunosuppression.³

• Skin cancers are aggressive and may have a poor response to established treatments.⁴

IMMUNOSUPPRESSION

• Immunosuppression has been implicated in increasing the cancer risk associated with latent oncogenic viral infections.²

• Rejection episodes were not associated with a greater risk of malignancies after liver transplantation.²

  • Calcineurin inhibitors

    • Inhibit T lymphocytes and increase tumor proliferation in animal models of colon cancer (especially cyclosporine).³

    • Tacrolimus associated with a lower relative risk of skin cancers when compared to cyclosporine.⁴

      • Cyclosporine is associated with resistance to apoptosis in ultraviolet light (UV)–exposed keratinocytes.⁴

      • Tacrolimus is not associated with resistance to apoptosis in UV-exposed keratinocytes.⁴

  • Mammalian target of rapamycin (mTOR) inhibitors:

    • Some nonprospective studies report lower rates of hepatocellular carcinoma (HCC) recurrence and de novo malignancies in liver and kidney recipients treated with mTOR inhibitors.²

    • Increasing evidence to ...