Posttransplant lymphoproliferative disorder (PTLD) is a heterogeneous disease group of benign and malignant entities. The new World Health Organisation classification introduced in 2008 distinguishes early lesions, polymorphic, monomorphic and classical Hodgkin lymphoma-type PTLD. Based on the time of appearance, early and late forms can be identified.PTLDs are the second most frequent posttransplantation tumors in adulthood, and the most frequent ones in childhood. The incidence varies with the transplanted organ-from 1%-2% following kidney transplantation to as high as 10% following thoracic organ transplantation-due to different intensities in immunosuppression. Immunocompromised state and Epstein-Barr virus (EBV) infection are the two major risk factors.In Europe and the US approximately 85% of PTLDs are of B-cell origin, and the majority are EBV-associated. Symptoms are often unspecific; extranodal, organ manifestations and central nervous system involvement is common. Early lesions respond well to a decrease in immunosuppression. Malignant entities are treated with rituximab, chemotherapy, radiotherapy and surgical therapy. Adoptive T-cell transfer represents a promising therapeutic approach. The prognosis is favorable in early PTLD, and poor in late PTLD. Five-year survival is 30% for high-grade lymphomas. The prognosis of EBV-negative lymphomas is worse.Lowering the risk of PTLD may be achieved by low dose maintenance immunosuppression, immunosuppressive drugs inhibiting cell proliferation, and special immunotherapy (e.g. interleukin-2 inhibitors). Early detection is especially important for high risk-e.g. EBV-negative-patients, where the appearance of EBV-DNA and the increase in its titer may help.
The objective of the study was to examine proliferation and apoptosis associated gene expression in the whole sequence parathyroid lesions to reveal specific features of carcinoma. This study was based on surgically removed parathyroid tissues, gene expression analysis was performed both at gene and protein level. First, mRNA isolation was performed from deep-frozen tissue samples, and further apoptosis pathway-specific cDNA macroarray analysis was carried out. The results were validated with real-time PCR. Subsequently, protein expression was analyzed with immunhistochemistry on Tissue Micro Array multi-blocks derived from several paraffin-embedded samples. cDNA macroarrays revealed elevated expression of both pro-apoptotic (FAS receptor, TRAIL ligand, CASPASE8, and -4) and anti-apoptotic (cIAP1, APOLLON) genes in benign proliferative lesions compared to that in normal gland. TMA studies showed overexpression of KI67, P53, SURVIVIN and APOLLON protein and failure of expression of P27, BCL2, BAX, CHROMOGRANIN-A, SYNAPTOPHYSIN, CYCLIND1, FLIP, TRAIL, CK8, CK18, CK19 in parathyroid carcinoma was detected. These alterations in gene expression of the investigated products could be used in differentiation between beningn and malignant proliferative processes of the parathyroid gland. Authors conclude that a series of alterations in gene expression such as overexpression of APOLLON, P53, KI67 and suppression of P27, BCL2, BAX lead to uncontrolled cell proliferation, but still not leading to increased apoptotic activity in parathyroid carcinoma.
This study provides an analysis of incidence and characteristics of malignant tumors of 2535 patients who underwent renal transplantation between 1973 and 2007 at the Transplantation Center in Budapest. One hundred ninety-three malignant diseases were found in 188 patients (7.6%). The incidence of thyroid-, renal- hepatic-, skin- and gastric cancers as well as of Kaposi sarcoma and lymphomas increased in our transplant patient cohort compared to the figures of the general population based on the data of our Cancer Registry. On the other hand, colorectal-, oralprostate and lung cancers were underrepresented in our patient cohort. The mean time of diagnosis of malignancies following kidney transplantation was 58.5+/-44.8 months. One fifth of the tumors were detected within the first year. Patients with malignancies were distributed into four groups based on the immunosuppressive regimen: group I (8.5%), azathioprine + prednisone; group II (59.0%), cyclosporine + prednisone; group III (26.6%), cyclosporine + mycophenolate mofetil + prednisone; group IV (5.9%), tacrolimus + mycophenolate mofetil + prednisone. The mean age of patients was 47.3, 53.5, 55.5 and 58.1 years in group I, II, III and IV, respectively. Oncologic and immunosuppressive therapy was decided individually. Immunosuppression was switched to rapamycin-containing regimens in 63 cases. We lost 92 patients (48.9%) with a mean survival time of 25.8+/-39.4 months. Cumulative 1- and 5-year survivals were 69.5% and 52%, respectively. The increasing number of cancers seen early after transplantation and the increased risk of developing a cancer due to the older age of recipients draw attention to the importance of regular oncologic screening in patients on the waiting list and after transplantation.
According to our observation, we can state that RCC of the kidney allograft diagnosed at an early stage can be successfully treated with RFA instead of graft removal. A longer follow-up is needed to assess the effectivity of the RFA treatment in these cases.
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