David P. O’Brien

Microchimerism and rejection in clinical transplantation

BACKGROUNDnHaemopoietic microchimerism has been identified in recipients of solid-organ transplants and is thought by some to be critical for the development and maintenance of immunological tolerance. The aim of this study was to correlate prospectively the persistence of donor cells with clinical outcome in recipients of kidney, kidney and pancreas, and liver transplants.nnnMETHODSnPersistence of donor cells in recipient peripheral blood was assessed at 3 days, and at 1, 3, 6, and 12 months after transplantation by a two-stage nested PCR technique to detect donor MHC HLA DR gene specifically. A pretransplant blood sample was collected from each patient to serve as an individual negative control. Seven liver, six kidney and pancreas, and 17 kidney patients were enrolled. 12 of the 17 kidney patients and all of the kidney and pancreas, and liver recipients were suitable for analysis. Exact matches for donors and recipients at the HLA DR loci (n = 1) or inability to obain primer pair specificity among similar HLA DR types (n = 4), meant that we were unable to analyse five patients.nnnFINDINGSnDonor DNA was detected in 20 (80%) of 25, ten (40%) of 25, seven (30%) of 23, five (22%) of 23, and six (32%) of 19 recipients at 3 days, and 1, 3, 6 and 12 months post-transplant, respectively. Within individuals, the detection of donor DNA varied over time; only two patients had detectable donor DNA at all times. Analysis of the whole group of transplant patients showed a similar frequency and severity of rejection episodes in patients with and without microchimerism as defined by detectable donor DR genes.nnnINTERPRETATIONnThese data suggest that a significant percentage of the recipients had persistent donor class II DNA in the peripheral circulation for at least 1 year after transplantation. We showed that a pretransplant blood sample is critical to avoid a false-positive result, and suggest that detectable chimerism may vary over time in individual patients. Therefore, analysis of microchimerism with a single, post-transplant analysis may not help in making clinical decisions for individual patients.

Comparison of Fine-Needle Aspiration Biopsy, Doppler Ultrasound, and Radionuclide Scintigraphy in the Diagnosis of Acute Allograft Dysfunction in Renal Transplant Recipients: Sensitivity, Specificity, and Cost Analysis

150 episodes of allograft dysfunction in 128 renal transplant recipients, 77 due to acute rejection, 32 secondary to acute-on-chronic rejection, 33 due to either prerenal factors, acute tubular necrosis, or ciclosporin A nephrotoxicity, and 8 secondary to multiple causes, were evaluated by fine-needle aspiration biopsy (FNAB), Doppler ultrasound (DUS), and radionuclide scintigraphy (RS), each performed within a 24-hour period and prior to any specific therapeutic intervention. Tests were interpreted by appropriate specialists in a large transplant center without access to clinical information. The final diagnosis was based primarily upon response to therapeutic maneuvers with histological (core biopsy) confirmation in 123 episodes. RS was the most sensitive (70%) test for the diagnosis of acute rejection during the early posttransplant period, exceeding both FNAB (52%) and DUS (43%). The predictive accuracy of either FNAB, DUS, RS, or core biopsy in the detection of a steroid-responsive component to acute rejection when superimposed upon chronic rejection was low at approximately 50%. When the underlying cause of renal dysfunction was either prerenal, acute tubular necrosis, or ciclosporin A nephrotoxicity, FNAB, DUS, and RS each gave an erroneous diagnosis of acute rejection in about 50% of the episodes. Cost analysis revealed that core biopsy was the most expensive test, but only 9% more than RS, with FNAB the least costly. In conclusion, the lack of ideal sensitivity and specificity combined with the expense of present-day FNAB, DUS, RS, and core biopsy in the diagnosis of a therapeutically reversible component to acute-on-chronic rejection and of FNAB, DUS, and RS in the diagnosis of acute rejection during the early posttransplant period should prompt research into ways to improve their diagnostic yield or alternate modalities.

Gunshot Wounds of the Ureter: A 15-Year Review of 63 Consecutive Cases

We reviewed 63 consecutive cases of gunshot wounds of the ureter seen during a 15-year period. The importance of prompt recognition and aggressive surgical management is emphasized, with particular attention being placed on adequate debridement and spatulated splinted watertight ureteroureterostomy. Our philosophy of management for individual injuries is discussed along with our complications and results. This series is the largest reported to date of ureteral gunshot wounds.

Experience with the Horton-Devine Dermal Graft in the Treatment of Peyronie’s Disease

We treated 15 patients with Peyronies disease surgically with the dermal graft technique described by Horton and Devine. Details of the preoperative management and surgical technique are provided. Return of normal sexual function without residual chordee or pain was achieved in more than 75 per cent of the patients, suggesting that this is the procedure of choice in the management of severe Peyronies disease.

Simple Renal Cyst and High Renin Hypertension Cured by Cyst Decompression

A case of renin elevated hypertension cured by cyst decompression is presented. The proposed mechanism is segmental renal ischemia produced by the cyst. Renal cyst evaluation should include renin studies if hypertension is present.

Unsuspected Renal Tumors Associated with Renal Cysts

A series of renal tumors associated with renal cysts is presented. Prior to surgical exploration appropriate diagnostic studies failed to indicate evidence of the presence of neoplastic lesions. The importance of surgical exploration of avascular benign renal masses is emphasized.

Condylomata Acuminata and Verrucous Carcinoma of the Bladder: Case Report and Literature Review

Condylomata acuminata and verrucous carcinoma are 2 lesions rarely seen in the bladder. Condylomata of the bladder can be treated successfully by local therapy but underlying carcinoma must be considered if the lesion is extensive or progressive in nature. Vigorous biopsies of the base of the lesions are necessary to eliminate the possibility of malignancy. If verrucous carcinoma is found the patient should be treated surgically. A case of condylomata acuminata of the bladder undergoing malignant change to verrucous carcinoma is reported.

Bilateral Clear Cell Papillary Cystadenoma of the Epididymides Presenting as Infertility: An Early Manifestation of Von Hippel-lindau’s Syndrome

Papillary cystadenoma of the epididymis is a rare benign tumor, accounting for only 4 per cent of all epididymal tumors. Histologically, it can be confused with metastatic renal cell carcinoma. We report a case of bilateral involvement of the epididymides and infertility. Its diagnostic significance is its association with the von Hippel-Lindau syndrome, necessitating close surveillance.

A 37-Pound Scrotal Leiomyosarcoma: A Case Report and Literature Review

We report a case of a 37-pound scrotal leiomyosarcoma. The literature is reviewed, and the presentation, diagnosis, treatment and survival of patients with scrotal leiomyosarcoma are discussed.

Nonmetastatic Bladder Cancer Associated with Hypercalcemia, Thrombocytosis and Leukemoid Reaction

We reviewed 4 patients with urothelial bladder cancer and hypercalcemia but without evidence of bony metastasis. Of the patients 2 presented with a leukemoid reaction (1 also had thrombocytosis). None of the patients had evidence of bone metastases or other causes of hypercalcemia, such as hyperparathyroidism, sarcoidosis or vitamin D intoxication. All 4 patients received aggressive therapy for the tumors. In each instance the serum calcium returned to normal following radiation therapy or tumor removal, lending support to the theory of humoral hypercalcemia of cancer. A diagnostic and therapeutic approach to such patients is outlined.