General Demographic, Clinical and Operative Characteristics of The Patients
In total, 23 patients had de novo malignancy in the present study. The median age of the patients was 59 (1-66)years. Most of the indications for liver transplantation was hepatitis B virus [HBV] related cirrhosis [n=12; 52.2%]. Twenty patients received a living donor liver graft and 3 patients [13%] received deceased donor liver graft. In 18 recipients (90%), the donor was first degree relative. Median age of the living donors were 28 (20-45) years and for the deceased donors it was 75.5 (20-78) years. Table-1 summarizes the demographic and clinical parameters of the patients included in the study.
Characteristics of The De-Novo Malignancies
The type of de novo malignancies varied widely. Non-melanoma skin cancer developed in 5 patients (21.7%), gynecological cancers developed in 4 patients (17.3%), post-transplant lymphoproliferative disorders (PTLD) developed in 2 patients (8.7%), myeloproliferative disorder in 2 patients (8.7%), colon cancer in 2 patients (8.7%) and non-Hodgkin lymphoma in 1 patient (4.3%). Other rare malignancies that were observed in our cohort were malignant melanoma (n=1), small bowel neuroendocrine tumor (n=1), renal cell carcinoma (n=1), parotid carcinoma (n=1), nasopharyngeal carcinoma (n=1), lung cancer (n=1), and Kaposi’s sarcoma (n=1) .
The median interval between the time of transplantation until the development of de novo malignancy was 36 (6-75) months. Solid organ tumors developed at a median of 31 (5-101) months and lymphoproliferative disorders developed at a median of 38.5 (13-40) months. Six patients had distant metastasis at the time of diagnosis and 5 of them died from their tumor. Therefore, the most frequent de novo malignancy observed in the present study was non-melanoma skin cancer.
Characteristics of Patients with Non-Melanoma Skin Cancer
In total, 5 patients had non-melanoma skin cancer. 3 were male and 2 were female. The median interval between the transplant procedure and the diagnosis of skin cancer was 37 (6-75) months. The median age of the patients with non-melanoma skin cancers were 59 (36-66) years. There was only one pediatric patient. In this patient a squamous cell carcinoma developed at the wound edge. The closure of the incision was performed by Bogota bag. In the remaining 4 patients 2 had squamous cell carcinoma and the remaining two patients had basal cell carcinoma. Only one patient in this group died 3 months after the diagnosis, the cause of death was very aggressive cancer  (Figure 1).
Characteristics of Patients with Malignancies of the Reproductive System
Malignancies of the reproductive system developed in 4 patients. Three of these patients had breast cancer and the remaining one patient had ovarian cancer. Median age of the patients were 52 (36-60) years. All patients were female. Median interval between the transplant procedure and the diagnosis of cancer was 31 (6-75) months. Breast cancer developed at median of 55 (5-75) months following LT. One patient with breast cancer had distant metastasis at initial diagnosis. Only in two patients with breast cancer, the disease was diagnosed at 5th and 8th months following the transplant procedure. None of the patients in this group dies due to cancer.
Characteristics of Patients with Lymphoproliferative Disorders
PTLD developed in 2 patients. Both were male and their ages were 49 and 52 years. The indications for liver transplantation were alcoholic cirrhosis (n=1) and HBV related HCC (n=1). One patient developed B cell lymphoma of the lungs and the other patient developed T cell lymphoma. B cell lymphoma of the lungs were diagnosed at post-transplant 37 months. The patient T cell lymphoma died 2.5 months after the diagnosis and patient with B cell lymphoma of the lungs died 41.2 months after the initial diagnosis. Both patients succumbed to their malignancies.
Characteristics of 2 Patients with Myeloproliferative Disorders and Non-Hodgkin Lymphoma
The patient with non-Hodgkin lymphoma was 61 years old male patient who received liver transplantation for HBV related cirrhosis and HCC. The disease was diagnosed 40 months after the transplant procedure and the patient is still alive.
One of the patients with lymphoproliferative disorders was a 1-year-old girl who received liver transplantation for progressive familial intrahepatic cholestasis (PFIC). She was diagnosed with acute lymphoblastic leukemia 24 months after the transplant procedure. Her polymerase chain reaction (PCR) was positive for both cytomegalovirus (CMV) and Epstein-Barr Virus (EBV). She is still in remission 63 months after the diagnosis, after receiving appropriate treatment. The other patient with myeloproliferative disorder was a 59-year-old male patient who was transplanted for cryptogenic cirrhosis. He developed multiple myeloma 13 months after the transplant procedure and died 12.8 months after the diagnosis.
The Impact of De-Novo Malignancies on Post-Transplant Prognosis and Survival.
In the present study, 10 patients (43.5%) are still alive after the diagnosis of de novo malignancy. Furthermore, 6 (26%) of the patients had metastatic disease and 5 have died due their malignancies. The median post-transplant follow-up of the patients were 7.75 years and median follow-up period after the diagnoses of the de novo malignancies was 4.11 years. The overall, 1-, 3- and 5-year survival rate of the total cohort of patients after transplantation were 91.3%, 78.3% and 62.9%; respectively. Whereas 1-, 3- and 5-year survival rate of the patients after the diagnosis of de novo malignancies were 69.6%, 56.5% and 41.9%; respectively (Figure 2).
The meansurvival duration of the patients with different types of de novo malignancies and the 1-, 3- and 5-year survival rates of the patients with different de-novo malignancies are summarized in Figure 3A and B. The difference that is observed between different malignancies did not reach statistical significance; however best prognosis and survival periods were observed in patients with non-melanoma skin cancer, whereas poor prognosis and survival intervals were observed in patients with hematologic malignancies.