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Biomedical subjects

I Penn

Publications and source records attributed to I Penn.

At least 37 records · Page 2Linked to original sources

Transmission of cancer from organ donors.

One hundred and seventeen of 270 (43%) recipients of organs obtained from donors with malignancies had evidence of transmitted cancers. In 9 instances these were removed from renal allografts immediately prior to transplantation. Including these cases there were 45 recipients of organs in which a neoplasm involved the allograft, 6 others in whom adjacent structures were invaded, and another 66 patients who had distant metastases. Precautions to prevent cancer transmission include meticulous preoperative screening of donors, careful examination of all organs at the time of harvesting, biopsy of any suspicious lesions, and routine donor autopsy, if possible.

Cadaver↗

Evaluation of transplant candidates with pre-existing malignancies.

A retrospective study was done of the recurrence rates of 1297 preexisting tumors in renal transplant recipients. Of 1137 neoplasms that were treated prior to transplantation, the recurrence rate was 21%, and it was 33% in 99 cancers treated after transplantation. Fifty-four percent of recurrences in the pretransplant-treated group occurred among malignancies treated within 2 years of transplantation, 33% in those treated 2-5 years before transplantation, and 13% among those treated more than 5 years pretransplantation. Among the 31 neoplasms in the last group 52% of recurrences occurred within 2 years after transplantation. Among those cancers treated pretransplantation the highest recurrence rates occurred with breast carcinomas (23%), symptomatic renal carcinomas (27%), sarcomas (29%), bladder carcinomas (29%), nonmelanoma skin cancers (53%) and multiple myeloma (67%). In the tumors treated posttransplantation 39% of recurrences were from nonmelanoma skin cancers. The bulk of evidence suggests that immunosuppressive therapy facilitates the growth of residual cancers. With some exceptions a minimum waiting period of 2 years between treatment of a neoplasm, with a favorable prognosis, and undertaking renal transplantation is desirable. A waiting period of approximately 5 years is desirable for lymphomas, most carcinomas of the breast, prostate or colon, or for large (> 5 cm) symptomatic renal carcinomas. No waiting period is necessary for incidentally discovered renal carcinomas, in situ carcinomas, and possibly tiny focal neoplasms. As it is highly unlikely that most candidates for nonrenal transplantation can be kept alive for a two year waiting period nonrenal transplantation can be undertaken in patients who have been treated for major cancers, provided that the disease appears to have been adequately controlled, and that the stage of the malignancy does not have a poor prognosis.

Female↗

Renal transplantation exposes patients with previous Kaposi's sarcoma to a high risk of recurrence.

It is currently estimated that about 0.5% of patients will develop Kaposi's sarcoma (KS) after kidney transplantation. Tapering of immunosuppression often leads to KS remission, but also results in graft loss in more than 50% of cases. Whether retransplantation is safe in these patients is unknown. We here report on eight patients who developed KS recurrence after kidney transplantation-(A) Patients with previously treated KS: There were 4 patients who had clinical remission of KS (including three posttransplantation) for periods ranging from 5 months up to 19 years before transplantation. All 4 developed KS recurrence within months after transplantation. In 3 patients, KS regressed only when all immunosuppression was discontinued, at the price of allograft removal. Partial remission occurred in the fourth patient following reduction of immunosuppression and gancyclovir administration; (B) Patients with recurrent KS during a single transplant: 4 patients developed KS after transplantation that regressed following reduction of immunosuppressive therapy. Increased immunosuppression, in the form of steroid pulses in 3 patients was associated with recurrence of KS. Subsequent reduction of immunosuppression caused regression of KS in all 4 patients, but 2 recipients lost their allografts. These data emphasize the high risk of recurrence of KS after renal transplantation. If physicians decide to transplant patients with a history of KS, they should inform the future recipient of the possibility of KS recurrence.

Adult↗

Oral presentation of posttransplantation lymphoproliferative disorders. An unusual manifestation.

Cyclosporine, an immunosuppressive agent widely used in organ transplantation, has several undesirable side effects, including gingival hyperplasia, which occurs in up to 70% of patients. Another complication associated with use of cyclosporine and other immunosuppressants is an increased incidence of malignancies. Long-term use of cyclosporine also is associated with a spectrum of hyperproliferative disorders ranging from reactive lymphoid hyperplasia to aggressive malignant lymphomas. While cyclosporine-related lymphoproliferative disorders have been widely reported, they have not been described in the oral cavity as the first manifestation of this disease. We report on two cardiac transplantation patients with a history of cyclosporine use who presented initially with oral symptoms of lymphoproliferative disorder. Both had erythematous to cyanotic and hyperplastic gingiva. On gingivectomy, the fixed tissue was soft, glistening, and tan colored, in contrast to the usual firm, white, cyclosporine-associated, benign gingival fibrous hyperplasia. Histologically, a dense, diffuse infiltrate of lymphoplasmacytoid cells with vesicular nuclei, prominent nucleoli, a moderate amount of cytoplasm, and high mitotic activity was observed. Immunocytochemical studies confirmed that the cells were monoclonal for lambda light chains in one patient and kappa light chains in the other. The cells from one patient were positive for CD45, while both patients were negative for CD20 and all nonhematopoietic antigens tested. Both tissues were strongly positive for Epstein-Barr virus. Morphology and immunocytochemistry findings are consistent with a posttransplant lymphoproliferative disorder. These are the first two reported cases of cyclosporine-associated posttransplant lymphoproliferative disorders presenting as gingival hyperplasia.

Adult↗

Malignant melanoma in organ allograft recipients.

Three groups of tumors were studied. The first group was melanomas inadvertently transmitted from donors. Brain metastases from melanoma were often misdiagnosed in the donors as primary brain tumors or cerebral hemorrhage. Eleven donors provided organs to 20 recipients of whom 3 never manifested evidence of melanoma, 1 showed local spread of tumor beyond the allograft, and 16 had metastases. Of the last group 11 died from melanoma, but 4 patients had complete remissions following transplant nephrectomy and discontinuation of immunosuppressive therapy. The second group was Melanomas treated pretransplantation. Thirty patients had cutaneous melanomas and one an ocular melanoma. Six patients (19%) had recurrences posttransplantation. Three were treated < 2 years pretransplantation, 2 between 2-5 years pretransplantation, and one 120 months pretransplantation. The third group was De novo melanomas. Cutaneous melanomas occurred in 164 patients, melanomas of unknown origin in 8, and ocular melanomas in 5. Melanomas constituted 5.2% of posttransplant skin cancers compared with 2.7% in the general population. Unusual features of cutaneous melanomas were that 6 (4%) occurred in children, and 9 (5%) occurred in bone marrow recipients who were treated for leukemia. Forty-four patients (27%) who had cutaneous melanomas also had other skin cancers. Forty-seven of 68 patients (69%) had thick skin lesions (Clark's level III or greater or > 0.76 mm by Breslow's technique). Lymph node metastases occurred in 32 patients (20%) with cutaneous melanomas. Fifty patients (30%) with cutaneous melanomas died of their malignancies, as did 5 with melanomas of unknown origin, and 1 with ocular melanoma. The risks of melanoma may be reduced by stringent selection of donors; by waiting at least 5 years between treatment of melanoma and undertaking transplantation; and, perhaps, by reducing sunlight exposure and by early excision of suspicious dysplastic lesions.

Humans↗

Posttransplantation de novo tumors in liver allograft recipients.

De novo cancers occurred after transplantation in 8,008 organ allograft recipients, who developed 8,531 different types of malignancy. Three hundred twenty-four liver recipients developed 329 cancers. There were striking differences in the patterns of neoplasms observed when these were compared with 7,200 tumors that occurred in renal allograft recipients. Lymphomas were much more common in liver allograft recipients (57% v 12% of all tumors), whereas skin cancers (39% v 15%), carcinomas of the cervix (4% v 1%), renal tumors (4% v 1%), and vulvar carcinomas (3% v 0.6%) were more common in renal allograft recipients. The high incidence of lymphomas is related partly to the more intense immunosuppressive therapy administered to hepatic allograft recipients and partly to the large percentage of pediatric patients among them. The intense immunosuppression also accounts for the much shorter induction times of lymphomas (mean, 15 v 46 months; P < .001) and nonlymphomatous tumors (mean, 27 v 72; P < .001) in liver compared with kidney recipients. The longer follow-up of renal recipients probably accounts for the higher incidence of the other tumors that tend to appear relatively late after transplantation. A remarkable feature was the high incidence of allograft involvement by lymphoma (44%). Complete remissions after treatment occurred in 11 of 28 patients in whom the lymphoma was confined to the allograft. A few tumors in liver recipients were related to the underlying disease for which transplantation was performed: hepatomas in patients who underwent transplantation for hepatitis B cirrhosis and colon carcinomas or cholangiocarcinomas in patients who underwent transplantation for chronic ulcerative colitis with sclerosing cholangitis. A surprising finding was the development of four leiomyosarcomas, three occurring in the allograft itself, in pediatric liver recipients.

Adolescent↗

Testicular seminoma originating in an undescended testis in a renal allograft recipient.

Immunosuppressed transplant recipients are at significantly increased risk for developing neoplasms than are nonimmunosuppressed individuals. However, only six cases of pure testicular seminoma following renal transplantation have been reported in the English literature. This case report represents the first description of a seminoma arising in an undescended testis post-transplantation. We propose that it may be prudent to remove atrophic undescended testes when lifelong immunosuppressive therapy is anticipated, because accelerated tumor growth can occur.

Adult↗

Sarcomas in organ allograft recipients.

In a review of 8724 de novo malignancies that occurred in 8191 organ allograft recipients sarcomas were 7.4% of cancers. Kaposi's sarcoma (KS) made up 5.7%, and other sarcomas (OS) 1.7% a much higher proportion than in the general population. KS was most common in Arab, black, Italian, Jewish, or Greek patients. In 60% of patients with KS the lesions were confined to the skin and/or oropharynx while 40% involved internal organs and/or lymph nodes. Complete remissions following various treatments occurred in 53% of the former group and 27% of the latter. In both groups 32% and 60% of remissions, respectively, occurred when the only treatment was reduction or cessation of immunosuppressive therapy. However, this treatment caused impaired function or allograft loss from rejection in 22 of 34 kidney recipients. Recurrent KS occurred in 5% of patients in remission when immunosuppressive therapy was resumed. Nine of 114 patients (8%) tested for human immunodeficiency virus were positive. Most OS arose in internal organs or soft tissues. The major types were fibrous histiocytoma (20 patients), leiomyosarcoma (15), fibrosarcoma (12), rhabdomyosarcoma (9), hemangiosarcoma (8), undifferentiated sarcoma (7) and mesothelioma (6). Several unusual features were noted. Remarkably, 10 of 105 (10%) sarcomas occurred adjacent to or in a renal (6) or hepatic (4) allograft. Leiomyosarcomas are rare in children, yet 5 of 15 (33%) occurred in pediatric patients. Three hemangiosarcomas occurred in forearms at sites of arteriovenous fistulas used for pretransplant hemodialysis access. One leiomyosarcoma and one fibrosarcoma occurred in previously irradiated areas. One patient with mesothelioma had a history of asbestos exposure and two others had possible exposure.

Humans↗

Primary kidney tumors before and after renal transplantation.

Three groups of patients were reviewed. Primary carcinomas were found in donors kidneys of 47 recipients. In 30 instances a tumor was present at harvesting. When a neoplasm was removed immediately pretransplantation or early posttransplantation there were no recurrences in 14 recipients. In another two instances, a tumor was not removed or was incompletely excised pretransplantation and both recipients died of metastases. Fourteen other patients received kidneys from donors in whom the opposite kidney had a malignancy. Thirteen remained tumor-free and one had allograft nephrectomy for rejection 3 months posttransplantation when a carcinoma was found. In 17 recipients an allograft neoplasm was not recognized at harvesting. In 9 it was discovered at graft nephrectomy an average of 3 months posttransplantation. In a tenth patient a hypoechogenic area, found on routine posttransplant ultrasonography, progressively increased in size and proved to be malignant. Another 7 patients developed metastases from renal carcinomas an average of 12 months posttransplantation. Preexisting carcinomas were found in 350 recipients. Seventy-one patients with incidentally discovered tumors had no recurrences no matter when nephrectomy was performed in relationship to transplantation. Of 279 patients with symptomatic renal tumors, 70 (25%) had recurrences, 63% of which occurred in patients treated < or = 2 years pretransplantation. De novo cancers were found posttransplantation in 256 recipients. Renal carcinomas were 4.6% of posttransplant cancers compared with 3% of tumors in the general population. In 222 patients their own diseased kidneys were involved, in 24 tumors occurred in the allograft, and in 10 cases the site was not stated. Development of neoplasia seemed to be related not to the immunosuppressive therapy but to the underlying cause of renal failure, especially analgesic nephropathy. A disproportionate number of carcinomas (15%) involved the renal pelvis, most likely because of prior analgesic abuse.

Carcinoma↗

Central nervous system lymphomas in organ allograft recipients.

Central nervous system (CNS) involvement occurred in 289 of 1332 patients (22%) with posttransplant non-Hodgkins lymphomas. The average time of appearance was 33 months (range 3 weeks to 248.5 months) posttransplantation. Lesions were confined to the CNS in 159 patients (55%), while 130 (45%) had involvement of other organs. Lesions involved the brain in 254 patients (88%), the brain and spinal cord in 5 (2%), the spinal cord in 2 (1%), unspecified locations in the CNS in 13 (4%), the meninges in 8 (3%), and the cerebrospinal fluid (CSF) in 7 (2%). All patients whose only involvement of the CNS was of the meninges or CSF had lymphomas involving multiple organs. Many tumors (48%) appeared within one year after transplantation. Brain lesions were frequently multicentric in distribution. Ninety-one (31%) of the 289 patients had no treatment and died, 70 (77%) of their malignancies and 21 (23%) from other causes. Of 198 patients who received treatment 124 (63%) died of their malignancies; 40 (20%) died of other causes, including 17 patients who had had complete remissions following treatment; 22 (11%) are currently alive and in complete remission; and 12 (6%) are alive and still undergoing therapy. The treatment of choice is local radiotherapy to the brain, which either alone (18 patients) or in combination with other modalities (14 patients) caused 32 of the 39 (82%) complete remissions. Ten of 30 patients with disease localized to the CNS survived more than 5 years, including 6 who survived more than 10 years. CNS lymphomas should be suspected whenever a transplant patient has neurologic symptoms however minor, and prompt work-up is essential to eliminate other possible causes. The dismal prognosis can be improved only by early diagnosis and prompt therapy.

Adolescent↗

A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators.

BACKGROUND: Coronary-stent placement is a new technique in which a balloon-expandable, stainless-steel, slotted tube is implanted at the site of a coronary stenosis. The purpose of this study was to compare the effects of stent placement and standard balloon angioplasty on angiographically detected restenosis and clinical outcomes. METHODS: We randomly assigned 410 patients with symptomatic coronary disease to elective placement of a Palmaz-Schatz stent or to standard balloon angioplasty. Coronary angiography was performed at base line, immediately after the procedure, and six months later. RESULTS: The patients who underwent stenting had a higher rate of procedural success than those who underwent standard balloon angioplasty (96.1 percent vs. 89.6 percent, P = 0.011), a larger immediate increase in the diameter of the lumen (1.72 +/- 0.46 vs. 1.23 +/- 0.48 mm, P < 0.001), and a larger luminal diameter immediately after the procedure (2.49 +/- 0.43 vs. 1.99 +/- 0.47 mm, P < 0.001). At six months, the patients with stented lesions continued to have a larger luminal diameter (1.74 +/- 0.60 vs. 1.56 +/- 0.65 mm, P = 0.007) and a lower rate of restenosis (31.6 percent vs. 42.1 percent, P = 0.046) than those treated with balloon angioplasty. There were no coronary events (death; myocardial infarction; coronary-artery bypass surgery; vessel closure, including stent thrombosis; or repeated angioplasty) in 80.5 percent of the patients in the stent group and 76.2 percent of those in the angioplasty group (P = 0.16). Revascularization of the original target lesion because of recurrent myocardial ischemia was performed less frequently in the stent group than in the angioplasty group (10.2 percent vs. 15.4 percent, P = 0.06). CONCLUSIONS: In selected patients, placement of an intracoronary stent, as compared with balloon angioplasty, results in an improved rate of procedural success, a lower rate of angiographically detected restenosis, a similar rate of clinical events after six months, and a less frequent need for revascularization of the original coronary lesion.

Angioplasty, Balloon, Coronary↗