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      Donor-Transmitted Malignancies in Organ Transplantation: Assessment of Clinical Risk : Donor Malignancy Transmission Risk Assessment

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          Abstract

          The continuing organ shortage requires evaluation of all potential donors, including those with malignant disease. In the United States, no organized approach to assessment of risk of donor tumor transmission exists, and organs from such donors are often discarded. The ad hoc Disease Transmission Advisory Committee (DTAC) of the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) formed an ad hoc Malignancy Subcommittee to advise on this subject. The Subcommittee reviewed the largely anecdotal literature and held discussions to generate a framework to approach risk evaluation in this circumstance. Six levels of risk developed by consensus. Suggested approach to donor utilization is given for each category, recognizing the primacy of individual clinical judgment and often emergent clinical circumstances. Categories are populated with specific tumors based on available data, including active or historical cancer. Benign tumors are considered in relation to risk of malignant transformation. Specific attention is paid to potential use of kidneys harboring small solitary renal cell carcinomas, and to patients with central nervous system tumors. This resource document is tailored to clinical practice in the United States and should aid clinical decision making in the difficult circumstance of an organ donor with potential or proven neoplasia. ©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

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          Most cited references23

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          Donor-derived disease transmission events in the United States: data reviewed by the OPTN/UNOS Disease Transmission Advisory Committee.

          Donor-derived disease transmission is increasingly recognized as a source of morbidity and mortality among transplant recipients. Policy 4.7 of the Organ Procurement and Transplantation Network (OPTN) currently requires reporting of donor-derived events. All potential donor-derived transmission events (PDDTE) reported to OPTN/UNOS were reviewed by the Disease Transmission Advisory Committee (DTAC). Summary data from January 1, 2005-December 31, 2007, were prepared for presentation. Reports of PDDTE have increased from 7 in 2005, the first full year data were collected, to 60 in 2006 and to 97 in 2007. More detailed information is available for 2007; a classification system for determining likelihood of donor-derived transmission was utilized. In 2007, there were four proven and one possible donor-derived malignancy transmissions and four proven, two probable and six possible donor-derived infectious diseases transmissions. There were nine reported recipient deaths attributable to proven donor transmissions events arising from eight donors during 2007. Although recognized transmission events resulted in significant morbidity and mortality, transmission was reported in only 0.96% of deceased donor donations overall. Improved reporting, through enhanced recognition and communication, will be critical to better estimate the transmission risk of infection and malignancy through organ transplantation.
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            Tumor size does not predict risk of metastatic disease or prognosis of small renal cell carcinomas.

            We characterized the clinicopathological features and the prognosis of small solid renal tumors defined as tumors 4 cm or smaller. We identified 1,208 patients who were treated with nephrectomy at 5 international academic centers for small solid renal tumors. Clinicopathological parameters and outcome data were collected for each patient and analyzed. Of the tumors 88% were renal cell carcinoma and 12% were benign. Of those with renal cell carcinoma 995 (93%) were localized (N0M0) and 72 (7%) presented with metastatic disease. Tumor size did not predict synchronous metastatic disease. The incidence of metastatic disease in the tumor size ranges 0.1 to 1.0, 1.1 to 2.0, 2.1 to 3.0 and 3.1 to 4.0 cm was 7%, 6%, 5% and 8%, respectively (p = 0.322). Survival rates were excellent. The majority of patients who died of renal cell carcinoma (54%) presented with synchronous metastatic disease, but 3% of patients with localized disease also died of renal cell carcinoma. In patients with localized disease there was a 7% chance of recurrence post nephrectomy at 5 years. Progression-free survival (28 months) was better than for patients with metastatic disease having a primary tumor greater than 4 cm (8 months). Tumor size was not retained as an independent prognostic factor of survival in multivariate analyses. The University of California Integrated Staging System and the Karakiewicz nomogram were the best predictors of cancer specific survival for all renal cell carcinoma stages (c-index 0.87). More than 85% of small solid renal tumors are renal cell carcinoma. The majority of localized small renal tumors can be cured with existing surgical approaches. However, there is a small but not insignificant risk of synchronous and metachronous metastatic disease and cancer associated death. Patients considering experimental therapies such as ablation and surveillance should be aware of this. Tumor size alone is not sufficient to distinguish renal cell carcinoma with benign behavior from aggressive small renal cell carcinoma. Survival of patients with small metastatic renal cell carcinoma is better then expected. The biology of these unique tumors should be further studied.
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              Ultra-late recurrence (15 years or longer) of cutaneous melanoma.

              Melanoma can remain clinically quiescent for decades before regional or distant recurrence appears. This protracted disease free interval challenges the concept of a "cure" for melanoma. To understand this prolonged dormancy better, the authors retrospectively studied patients who developed recurrent melanoma 15 years or longer after their initial diagnosis ("ultra-late" recurrence). These cases were identified from 2766 melanoma diagnoses available in the Cancer Registry at the Massachusetts General Hospital (MGH). Histologic features of the primary lesion were also included when possible. Twenty cases were retrieved from the MGH database. There were equal numbers of women and men, although women were younger at the time of initial diagnosis (mean age of women: 29.8 years vs. 43.0 years for men). No patients had more than one primary cutaneous melanoma. The trunk was the most common primary site (35%), although there was no predominant anatomic localization. The average disease free interval was 17.3 years for women, 20.0 years for men, 18.1 years for patients with regional recurrence, and 19.0 years for patients with distant metastases. Distant recurrence was the most common type of recurrence (50% of women and 60% of men). The estimated probability of survival (5 years after recurrence) was 0.8 for regional disease and 0.2 for distant disease. With the available histologic records, it appears that almost all tumors were Clark Level III or IV with thicknesses ranging from 0.8-2.3 mm. In contrast to the published cases, this study did not find that women with lower extremity melanomas were at higher risk for developing ultra-late recurrence. Ultra-late recurrence of melanoma, although uncommon, can occur in any patient without identifiable risk factors. Because many prognostically favorable melanomas (thin melanomas on extremities) can recur after prolonged disease free intervals, the possibility of delayed recurrence remains and must be kept in mind.
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                Author and article information

                Journal
                American Journal of Transplantation
                Wiley
                16006135
                June 2011
                June 2011
                June 06 2011
                : 11
                : 6
                : 1140-1147
                Article
                10.1111/j.1600-6143.2011.03565.x
                21645251
                d8623c29-3eee-4450-90d9-9ff630804a1f
                © 2011

                http://doi.wiley.com/10.1002/tdm_license_1

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