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Biomedical subjects

I Penn

Publications and source records attributed to I Penn.

At least 19 recordsLinked to original sources
PubMed1998

Primary malignancies of the hepato-biliary-pancreatic system in organ allograft recipients.

In a series of 10151 organ allograft recipients who developed 10813 de novo malignancies after transplantation, 755 involved the hepato-biliary-pancreatico-duodenal (HBPD) area. If nonmelanoma skin cancers and in situ carcinomas of the uterine cervix were excluded (as they are from most cancer statistics), then the HBPD area was affected by 10% of neoplasms. Many of the tumors encountered were uncommon in the general population. The largest group of neoplasms was 474 lymphomas, which comprised 63% of the total. Other major malignancies were hepatocellular carcinomas (HCC; 15%), pancreatic carcinomas (11%), cholangiocarcinomas (3%), Kaposi's sarcomas (3%), and other sarcomas (1%). Lymphomas occurred at a younger age than other tumors (average, 39 versus 50 years), appeared earlier after transplantation (average, 24 versus 77 months), and were more frequently associated with immunosuppressive therapy with the antilymphocytic agents (ALG/ATG) and/or (OKT3) (59% versus 28%). Lymphomas were localized to the HBPD area in only 18% of patients, whereas in 82% there was involvement of other organs or sites. The liver was involved in 95% of lymphomas. Lymphomas frequently involved allografts, the liver in 84%, and the pancreas in 59%. Of 292 patients treated for lymphomas 67 (23%) had complete remissions lasting 6 months or more. HCC was frequently associated with hepatitis B or C infection. Kaposi's sarcomas were rarely confined to the HBPD area, and in 25% of cases there were no associated skin lesions. An unusual subset of tumors were leiomyosarcomas involving hepatic allografts of pediatric patients. The poor prognosis of most tumors in this series may be related to delays or problems in making the diagnosis in these immunosuppressed patients and, perhaps, it may also be related to the unusually aggressive behavior of some tumors.

Adolescent↗
PubMed1998

Efficacy of coronary stenting versus balloon angioplasty in small coronary arteries. Stent Restenosis Study (STRESS) Investigators.

OBJECTIVES: The goal of this study was to compare the efficacy of elective stent implantation and balloon angioplasty for new lesions in small coronary arteries. BACKGROUND: Palmaz-Schatz stents have been designed and approved by the Food and Drug Administration for use in coronary arteries with diameters > or = 3.0 mm. The efficacy of elective stent placement in smaller vessels has not been determined. METHODS: By quantitative coronary angiography, 331 patients in the Stent Restenosis Study (STRESS) I-II were determined to have a reference vessel < 3.0 mm in diameter. Of these, 163 patients were randomly assigned to stenting (mean diameter 2.69 +/- 0.21 mm), and 168 patients were assigned to angioplasty (mean diameter 2.64 +/- 0.24 mm). The primary end point was restenosis, defined as > or = 50% diameter stenosis at 6-month follow-up angiography. Clinical event rates at 1 year were assessed. RESULTS: Baseline clinical and angiographic characteristics were similar in the two groups. Procedural success was achieved in 100% of patients assigned to stenting and in 92% of patients assigned to angioplasty (p < 0.001). Abrupt closure within 30 days occurred in 3.6% of patients in both groups. Compared with angioplasty, stenting conferred a significantly larger postprocedural lumen diameter (2.26 vs. 1.80 mm, p < 0.001) and a larger lumen at 6 months (1.54 vs. 1.27 mm, p < 0.001). Restenosis (> or = 50% diameter stenosis at follow-up) occurred in 34% of patients assigned to stenting and in 55% of patients assigned to angioplasty (p < 0.001). At 1 year, event-free survival was achieved in 78% of the stent group and in 67% of the angioplasty group (p = 0.019). CONCLUSIONS: These findings suggest that elective stent placement provides superior angiographic and clinical outcomes than balloon angioplasty in vessels slightly smaller than 3 mm.

Angioplasty, Balloon, Coronary↗
PubMed1998

Intravascular ultrasound-guided optimized stent deployment. Immediate and 6 months clinical and angiographic results from the Multicenter Ultrasound Stenting in Coronaries Study (MUSIC Study)

OBJECTIVES: A study was set up to validate the safety and feasibility of intravascular ultrasound-guided stenting without subsequent anticoagulation, and its impact on the 6 months restenosis rate. METHODS: The study was designed to be multicentred, prospective, and observational. RESULTS: One hundred and sixty-one patients with stable angina and a de novo coronary artery lesion were enrolled. In four patients, the implantation of a Palmaz-Schatz (with spiral bridge) stent had failed. One of these four patients died 3 days following bypass surgery. In two other patients, intravascular ultrasound assessment was not performed. One hundred and twenty-five of the remaining 155 patients (81%) were treated with aspirin (100 mg x day(-1)), because all three criteria for optimized stent expansion were met. Twenty-two of the remaining 38 patients (25%), in whom at least one criterion was not met were treated with aspirin and acenocoumarol (3 months, INR 2.5-3.5), while 16 patients only received aspirin. Stent thrombosis was documented in two patients (1.3%) for which repeat angioplasty was performed. During the hospital stay, there were no deaths or Q-wave myocardial infarctions. Five patients (3.2%) sustained a non-Q-wave myocardial infarction. During the follow-up period (198+/-38 days, complete for all patients, except one), one patient (0.6%) sustained a Q-wave myocardial infarction, one (0.6%) underwent bypass surgery, and repeat angioplasty was performed in nine patients (5.7%). In two of the nine patients, repeat angioplasty involved another lesion. Therefore, the target lesion revascularization rate during follow-up was 4.5% (seven patients). At quantitative coronary angiography, the minimal lumen diameter (mean+/-SD) increased from 1.12+/-0.34 mm before to 2.89+/-0.35 mm after stenting. Repeat angiography at 6 months was performed in 144 patients (92%). The minimal lumen diameter at follow-up was 2.12+/-0.67 mm. Restenosis (diameter stenosis of 50% or more) was documented in 12 patients or 8.3%. When the two patients with documented stent thrombosis are included, the restenosis rate amounts to 97%. CONCLUSIONS: These data confirm that, in selected patients, stents can safely be implanted without the use of systemic anticoagulation, provided optimal stent expansion is achieved. The exact role of intravascular ultrasound in the achievement of these results needs to be established by appropriately designed studies. In the meantime, intravascular ultrasound coupled with the Palmaz-Schatz stent incorporating a spiral bridge, may have contributed considerably to the immediate angiographic outcome, which in turn may explain the favourable clinical and angiographic outcome at 6 months.

Aged↗
PubMed1998

Peritoneal metastasis of intracranial glioblastoma via a ventriculoperitoneal shunt preventing organ retrieval: case report and review of the literature.

The case of patient with glioblastoma metastatic to the peritoneal cavity 9 months after ventriculoperitoneal shunt surgery precluding cadaver organ procurement is presented. Even though central nervous tumors rarely metastasize spontaneously, the literature indicates that systemic metastases are related to previous surgical procedures and especially shunt surgery. Central nervous tumors have been known to metastasize to lungs, liver, and kidneys and could be transmitted through transplanted organs as shown in the Cincinnati tumor registry. The transplant surgeon should be alerted to this possibility and thorough search for metastases should be undertaken before considering primary brain tumor patients as donors.

Adolescent↗
PubMed1997

Results of renal transplantation in patients with renal cell carcinoma and von Hippel-Lindau disease.

BACKGROUND: Patients with von Hippel-Lindau (VHL) disease are at risk for the development of end-stage renal failure from the treatment of localized renal cell carcinoma. Transplantation with its attendant immunosuppression may predispose patients to tumor recurrence; however, there is little information regarding the outcome with this approach. In this article, we review the North American and European experience with renal transplantation in this patient population. METHODS: The study group comprises 32 patients who have VHL rendered anephric secondary to localized renal cell carcinoma and who have undergone renal transplantation. Patients were identified from North American (n=18) and European (n=14) registries. The outcome of the study group is compared with a cohort of 32 renal transplant recipients without VHL from the Cleveland Clinic Unified Transplant Data Base, who were matched for donor source, gender, age, transplant status (primary vs. regraft), and date of transplantation. RESULTS: The 23 men and 9 women in the study group received transplants between 1974 and 1996. The average age at transplantation was 36 years, and the average duration of dialysis before transplantation was 26 months. Patients have been followed for 48+/-35 months. There was no statistically significant difference in graft survival, patient survival, or renal function between the study and control groups. There were five deaths in both the study and control groups. In the study group, three patients died with metastatic disease. There was no difference in the duration of dialysis before transplantation between patients who developed metastatic disease and those who did not. CONCLUSION: These data support the utility of renal transplantation as an effective form of renal replacement therapy in this unique population, with a limited risk of recurrent cancer.

Carcinoma, Renal Cell↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗