Nicholas R. Brook

Outcomes of transplants from patients with small renal tumours, live unrelated donors and dialysis wait-listed patients

We report the outcomes of renal transplant patients (n = 43) who received grafts from donors (n = 41) with small (<3 cm) renal tumours removed before transplantation covering the period from May 1996 to September 2007. Patient and graft survival were compared with the outcomes of conventional live unrelated transplants (LURTs) (n = 120) and to patient survival on the transplant waiting list for those who did not receive a kidney during this period (n = 153). Patient survival at 1, 3 and 5 years were 92%, 88% and 88% for recipients of tumourectomized kidneys (TKs), 99%, 97% and 97% for LURTs, and 98%, 92% and 74% for dialysis patients waiting for a deceased donor kidney (log rank score 10.4, P = 0.005). One patient experienced a local tumour recurrence at 9 years following transplantation. This patient declined intervention and is currently under active surveillance. Transplantation of tumourectomized kidneys from patients with small, localized, incidentally detected renal tumours results in similar outcomes to conventional LURTs and confers a significant survival advantage for patients who would otherwise be unable to receive a transplant.

Desensitization for renal transplantation: depletion of donor-specific anti-HLA antibodies, preservation of memory antibodies, and clinical risks

Desensitization protocols reduce donor‐specific anti‐HLA antibodies (DSA) and enable renal transplantation in patients with a positive complement‐dependent cytotoxic cross‐match (CDC‐CXM). The effect of this treatment on protective antibody and immunoglobulin levels is unknown. Thirteen patients with end‐stage renal disease, DSA and positive CDC‐CXM underwent desensitization. Sera collected pre‐ and post‐transplantation were analysed for anti‐tetanus and anti‐pneumococcal antibodies, total immunoglobulin (Ig) levels and IgG subclasses and were compared to healthy controls and contemporaneous renal transplant recipients treated with standard immunosuppression alone. Ten patients developed negative CDC‐CXM and enzyme‐linked immunosorbent assay (ELISA) and underwent successful transplantation. Eight recipients achieved good graft function without antibody‐mediated or late rejection, BK virus or cytomegalovirus infection. One patient had primary non‐function due to recurrent oxalosis, and one patient with immediate graft function died from septicaemia. Seven recipients required post‐operative transfusion and three developed septicaemia. DSA remained negative by ELISA at 12 months, but were detectable by Luminex®. Anti‐tetanus and anti‐pneumococcal antibodies, total Ig and IgG subclasses were below the normal range but comparable to levels in renal transplant recipients who had not undergone desensitization. Desensitization protocols effectively reduce DSA and allow successful transplantation. Post‐operative bleeding and short‐term infectious risk is increased. Protective antibody and serum immunoglobulin levels are relatively preserved.

Stereotactic Ablative Body Radiotherapy for Inoperable Primary Kidney Cancer: A Prospective Clinical Trial

To assess the feasibility and safety of stereotactic ablative body radiotherapy (SABR) for renal cell carcinoma (RCC) in patients unsuitable for surgery. Secondary objectives were to assess oncological and functional outcomes.

Open and laparoscopic donor nephrectomy: Activity and outcomes from all Australasian transplant centers

Background. Laparoscopic donor nephrectomy (LapDN) has been widely adopted despite a lack of randomized trials comparing recipient outcomes with open surgery. Review of registry data now seems the most realistic mechanism to compare outcomes. The Australia and New Zealand Dialysis and Transplant Registry prospectively captures data on all renal transplants performed in Australia and New Zealand including long-term follow-up of recipients. Aim. To compare graft outcomes among recipient of kidneys from donors undergoing nephrectomy using open and laparoscopic techniques, through analysis of the Australia and New Zealand Dialysis and Transplant Registry after the introduction of laparoscopic donor surgery in Australia and New Zealand in 1997. Methods. Operative technique data for live donor transplants were collected from all surgeons performing live kidney donation procedures from May 1997 to December 2003; the outcomes of all live donor transplants were examined with follow-up to December 2007. Donor and recipient demographic variables and graft outcomes were compared between the laparoscopic and the open donor groups. Results. One thousand four hundred seventy-four live donor transplants were performed in 27 transplant centers. Of these, 315 (21%) were performed laparoscopically in 11 centers. Nineteen laparoscopic cases (6%) were converted to open. Total ischemic time was longer in the LapDN group (3.16 hr) than in the open donor group (1.61 hr, P<0.0001). The LapDN group experienced a lower incidence of rejection episodes (29.2% vs. 38.6%, P=0.002). Delayed graft function and technical failure rates were statistically equal across the groups. There were a total of 242 graft failures (175 graft losses and 67 deaths with a functioning graft, NS). Among surviving grafts, there was no consistent difference in serum creatinine at any time point. Graft and patient survivals were similar in both groups during 10-year follow-up. Conclusion. This study suggests that there is no difference in short- or long-term recipient outcomes for open and laparoscopic live donor nephrectomy.

Ureteroiliac Artery Fistula Caused by a Metallic Memokath Ureteral Stent in a Radiation-Induced Ureteral Stricture

Abstract Background: Memokath 051™ stents are increasingly used for management of benign and malignant ureteral strictures refractory to management with single or tandem polymeric Double-J ureteral stents. Migration, encrustation, and difficulty in extraction during stent exchange are the chief problems reported so far with these thermoexpandable metallic stents. We report an unusual complication of ureteroexternal iliac artery fistula (UEAF) caused by Memokath stent inserted for radiation-induced ureteral stricture. Case Presentation: A 71-year-old male with history of colorectal cancer (underwent extirpative surgery + chemoradiotherapy) and subsequently radiation-induced ureteral stricture had bilateral Memokath ureteral stents inserted. Three months later, he presented with sepsis and hemodynamic instability secondary to UEAF, confirmed on angiography. A covered vascular stent was inserted as an immediate management. Conclusion: Memokath stent insertion in radiation-induced ureteral strictures may be associated with an increased risk of erosion and the rare potential complication of UEAF. This potential risk needs to be considered in the overall setting of such strictures and the difficulty in treating them. Prompt imaging (angiography) and placement of an endovascular stent are the ideal immediate options in such cases.

High-grade transitional cell carcinoma masquerading as a xanthogranulomatous pyelonephritis and perinephric abscess

Xanthogranulomatous pyelonephritis (XGPN) is an atypical long-term pyelonephritis with destruction of renal parenchyma and a long-term inflammatory infiltrate of macrophages. Reported presentations of transitional cell carcinoma (TCC) are different. A 73-year-old woman presented with loin pain, prostration, and fever. Computed tomography scan revealed poor cortical enhancement of the kidney, but some of the images bore resemblance to the characteristic “bears paw” sign, consistent with XGPN with a 7-cm perinephric collection. She was provisionally diagnosed as severe acute pyelonephritis, possibly XGPN, with abscess. In view of the poor clinical condition, decision was made to perform nephrectomy. Histology revealed a G3pT4 high grade TCC with perineural and vascular invasion and reactive xanthogranulomatous inflammatory response. There are few reports of concomitant XGPN and TCC affecting the kidney. However, there has not been any mention of XGPN and TCC presenting as acute pyelonephritis and perinephric abscess so far.

Current status of live-donor renal transplantation

Live kidney donation is assuming an increasingly prominent role in kidney transplantation programs. The traditional operative approach has been through an incision in the upper quadrant of the abdomen or in the loin, with potential postoperative complications associated with a large surgical wound. These problems may act as disincentives to prospective donors. The introduction of laparoscopic donor surgery in 1995 heralded a new era, offering reduced postoperative pain and improved cosmetic result. It is hoped that these benefits may counter some disincentives and thereby increase donation rates. Three minimal-access approaches, along with their advantages and disadvantages are described, including; classical laparoscopic, hand-assisted laparoscopic and retroperitoneoscopic surgery. All three approaches present specific challenges in the context of retrieving an organ that is fit for transplantation and safe for the donor. For minimal-access surgery to be accepted as the procedure of choice for live kidney donors, it must be demonstrated that morbidity is not transferred from donor to recipient when these techniques are used. Some concerns about these procedures are addressed. It appears that, with appropriate modifications, these techniques are safe for both the donor and the allograft. This review also covers other contemporary approaches to overcoming donor shortage by utilizing blood group-incompatible donor and recipient pairs.

Disseminated Intravascular Coagulation After Embolization to Treat Acutely Bleeding Bilateral Massive Angiomyolipoma: A Case Report

Abstract Background: Hemorrhage from an angiomyolipoma (AML) of the kidney can be life threatening and arterial embolization is the primary treatment. Embolization is less invasive than surgery, is well tolerated, and major complications are rare. We describe a case of disseminated intravascular coagulation (DIC) after embolization of a bleeding renal AML in a 44-year-old man with massive bilateral AMLs. This report aims to highlight the possibility that acute DIC could be a major complication of embolization itself and so should be considered and screened for because, if present, it requires early and aggressive management. Case Presentation: A 44-year-old man with a history of large bilateral renal AMLs associated with tuberous sclerosis complex presented with visible hematuria and abdominal pain. Renal CT revealed bleeding from the right kidney. Embolization with polyvinyl alcohol and lipiodol was urgently performed. The following day he required multiple blood transfusions and repeat embolization, this time with gelfoam and “tornado” coils. He suddenly developed DIC, cardiovascular collapse and acute renal failure requiring many days in the intensive care unit for inotropic support and renal replacement therapy. Conclusion: Arterial embolization may be associated with increased risk of DIC in the setting of treating large bleeding renal AMLs. DIC may be a direct or indirect complication of this. The clinician must act quickly to identify this and treat this complication aggressively.

MP47-08 COMPARISON OF ONCOLOGICAL AND FUNCTIONAL OUTCOMES FOLLOWING RADICAL PROSTATECTOMY IN CLINICAL T2 AND CLINICAL T3 PROSTATE CANCERS: FINDINGS FROM THE SA-PCOCC DATABASE.

INTRODUCTION AND OBJECTIVES: With improved surgical technique and understanding of the disease, radical prostatectomy (RP) is increasingly offered for locally advanced prostate cancer. RP in T3 prostate cancer may be associated with incomplete local tumour control, and functional outcomes may be worse because of the need for wider resection margins. We examined the oncological and functional outcomes in of patients undergoing RP in T2 and T3 prostate cancer. METHODS: A retrospective review was conducted including all patients listed in the SA-PCCOC database who underwent RP with stage pT2a-c or pT3a-b prostate cancer (any PSA, and any biopsy Gleason score). Demographics, PSA values, imaging characteristics, pathological details, intraoperative blood loss and length of stay were recorded. Oncological outcome was assessed by final histology report, margin status, and presence of and time to biochemical recurrence. Functional outcomes were assessed using the EPIC 26 questionnaire (urinary incontinence and erectile dysfunction domains). RESULTS: 1254 patients underwent RP for pT2, and 1297 patients for pT3 prostate cancer. In the patients with pT2 prostate cancer PSA values were <4 in 9.4%, 4-10 in 45.8%, 10-20 in 10.7% and > 20 in 1.4%. The patients with pT3 prostate cancer PSA values were <4 in 5.6%, 4-10 in 37.2%, 10-20 in 14.3% and > 20 in 3.6%. The Gleason scores in patients with pT2 were Gleason 3þ3 in 51.9%, 3þ4 in 30.3%, 4þ3 in 9.4%, 4þ4 in 5.2%, 5þ4 in 3.2% patients. The Gleason scores in patients with pT3 were Gleason 3þ3 in 25.8%, 3þ4 in 35.1%, 4þ3 in 21.7%, 4þ4 in 16.1%, 5þ4 in 1.3% patients. No significant difference was observed in blood loss and length of stay between the groups (p1⁄40.85 and 0.83, respectively). Nerve sparing surgery was more frequently performed in patients with pT2 disease compared with pT3 (85.7% vs 75.8%, p<0.001). Despite this, the erectile dysfunction and urinary continence rates were comparable in the two groups. pT3 patients were at higher risk of biochemical recurrence (BCR) than pT2 patients (HR 1.96, 95% CI 1.6-2.5, p<0.001). Factors influencing biochemical recurrence were PSA >20 at presentation (HR 1.9, 95% CI 1.7-5.3, p<0.001), positive margin (HR 2.9, 95% CI 2.4-3.5, p<0.001), high Gleason scoresGleason 4þ3 (HR 4.2, 95% CI 3.0-5.9, p<0.001) and Gleason >7(HR 5.2, 95% CI 3.6-7.7, p<0.001). CONCLUSIONS: Although T3 patients have an increased risk of BCR than T2 patients, the functional outcomes are comparable. This is despite a difference in the rate of nerve-sparing surgery in the groups.

MP81-03 ERECTILE DYSFUNCTION IS INDEPENDENTLY ASSOCIATED WITH APNEA HYPOPNEA INDEX & OXYGEN DESATURATION INDEX IN ELDERLY, BUT NOT YOUNGER, COMMUNITY-DWELLING MEN

INTRODUCTION AND OBJECTIVES: Sexual dysfunction, including decreased libido, sexual behavior disorder and erectile dysfunction (ED), is common in male patients with diabetes mellitus (DM). We previously demonstrated that increased peripheral tumor necrosis factor alpha (TNF-a) expression, associated with inflammation in DM, contributes to ED in the rat corpus cavernosum. However, the role of TNF-a in the central pathophysiology of DM-associated male sexual dysfunction is unknown. In this study, we examined the effects of TNF-a inhibition, i.e. etanercept (ETN) via chronic intra-cerebroventricular (ICV) infusion on neuronal nitric oxide synthase (nNOS) expression in the hypothalamic paraventricular nucleus (PVN) and sexual behavior disorder in male diabetic rats. METHODS: Type II male DM rats were divided into 4 groups (G), n1⁄4 12/G, and subjected to chronic ICV infusion of artificial cerebrospinal fluid (aCSF) or ETN (10 mg/kg/day) by Osmotic Pumps, with and without induction of DM: G1: non-diabetic+ICV aCSF as control; G2: non-diabetic+ICV ETN; G3: DM+ICV aCSF; and G4: DM+ICV ETN. After 4 weeks of treatments, sexual behavior, expression of TNF-a, TNFR-1, and nNOS proteins, nNOS activity, and reactive oxygen species (ROS) generation within the PVN were assessed. RESULTS: Male diabetic rats with ICV aCSF treatment displayed significantly severe sexual disorder accompanied with blunted nNOS expression and activity in the PVN in addition to local upregulated TNF-a and TNFR-1 expression, and increased ROS generation compared with non-diabetic controls. The sexual behavioral parameters including mounting latency, intromission latency, the number of mountings and the number of intromissions until ejaculation, induced by the introduction of receptive females, were significantly improved in the treated group with ETN. ICV ETN significantly inhibited TNF-a and TNFR-1 expression and reduced ROS generation in the PVN in diabetic rats. In addition, ICV ETN appeared to induce marked increased in nNOS expression in the PVN of diabetic animals compared with ICV aCSF-treated diabetic rats. Activity of nNOS in the PVN was also significantly increased in ICV ETN-treated versus ICV aCSF-treated diabetic rats. CONCLUSIONS: Increased TNF-a and TNFR1 expression in the hypothalamic PVN associated with DM contributes to male sexual disorder by centrally inhibiting nNOS expression and activity in the PVN via promoting local ROS generation. Central TNF-a blockade may have beneficial effects on the male sexual disorder in diabetes through improvement of NO pathway within the PVN.