A prospective multicentre phase III validation study of AZGP1 as a biomarker in localized prostate cancer.

BACKGROUND: Prostate cancers (PCs) with similar characteristics at the time of diagnosis can have very different disease outcomes. Conventional biomarkers of PC still lack precision in identifying individuals at high risk of PC recurrence. While many candidate biomarkers are proposed in the literature, few are in clinical practice as they lack rigorous validation. This study prospectively enrolled an independent phase III cohort to evaluate the clinical utility of zinc-alpha 2-glycoprotein (AZGP1) as a prognostic biomarker in localized PC. PATIENTS AND METHODS: In our multicentre, prospective phase III study, AZGP1 status in 347 radical prostatectomy specimens was assayed by immunohistochemistry in a NATA-accredited laboratory. The AZGP1 score was assessed in a multivariable model incorporating established prognostic factors. We also report extended outcomes from our previous phase II study. The primary endpoint was biochemical relapse-free survival (BRFS). Secondary endpoints were metastasis-free survival (MFS) and PC-specific survival (PCSS). RESULTS: In the phase II cohort, with a median follow-up of 15.8 years, low/absent AZGP1 expression was an independent predictor of poor BRFS (HR, 1.4; 95% CI, 1.1-1.9; P = 0.03), MFS (HR, 2.8; 95% CI, 1.2-6.6; P = 0.02) and PCSS (HR, 3.8; 95% CI, 1.5-9.5; P = 0.005). These results were validated in our prospective phase III cohort. Low/absent AZGP1 expression independently predicted for BRFS (HR, 1.9; 95% CI, 1.1-3.3; P = 0.02), with shorter MFS (HR, 2.0; 95% CI, 1.1-3.4; P = 0.02). AZGP1 improved the discriminatory value when incorporated into existing prognostic risk models. CONCLUSION: Our study provides prospective phase III validation that absent/low AZGP1 expression provides independent prognostic value in PC. This study provides robust evidence for the incorporation of this biomarker into clinical practice.

Evaluation of the loin pain/hematuria syndrome treated by renal autotransplantation or radical renal neurectomy.

Some patients with the loin pain/hematuria syndrome suffer incapacitating flank pain. No effective therapy has been reported. Uncertainty persists concerning the authenticity of the pain and the role of surgery in treatment. Forty-six patients with loin pain/hematuria syndrome and intractable pain were evaluated following treatment either by renal autotransplantation (30 patients, 10 bilaterally) or by renal denervation (20 patients, four bilaterally) over a 13-year period. All patients had concomitant renal nerve excision and ligation and capsulotomy. There were 37 (80%) women and nine men aged 18 to 61 years (mean age, 33 years). Excretion urography and angiography were normal in all patients. Nineteen of 25 (76%) patients in whom renal autotransplantation was successfully accomplished and who completed a follow-up questionnaire were free of pain, including eight of 10 with bilateral procedures. The follow-up periods ranged from 1 to 13 years (mean, 8.4 years). Six patients have been free of pain for 10 to 13 years. Of 18 patients treated with renal neurectomy who were available for follow-up examination, 12 (67%) developed recurrent renal pain, including four who had pain relief on the other side following previous renal autotransplantation. The follow-up period for these patients ranged from 6 to 9.9 years (mean, 8.0 years). Three of four patients with recurrent renal pain following neurectomy were treated successfully by renal autotransplantation. The loin pain/hematuria syndrome is a rare cause of incapacitation, predominantly of relatively young females. The pain of the syndrome is organic. Renal autotransplantation achieves pain relief in three quarters of patients, but the procedure is often (30%) required bilaterally and has significant complications. Renal neurectomy is followed by an excessive incidence of recurrent renal pain.

Nephrogenic adenoma of the bladder in renal transplant and non-renal transplant patients: a review of 22 cases.

OBJECTIVES: To review diagnoses of nephrogenic adenoma and in particular to evaluate its association with transitional cell carcinoma (TCC) of the bladder and its relationship to renal transplantation. METHODS: A retrospective review of 22 cases of nephrogenic adenoma (NA) diagnosed between 1989 and 1996 was conducted, 7 of which were in renal transplant patients. Data collected in each case included demographic details, predisposing factors, associated urologic pathology, mode of presentation, cystoscopic finding, management, and follow-up. RESULTS: There was a 3:1 predominance of men. Mean follow-up was 21.4 months (range 3 to 50). Six patients (27%) had one or more recurrences. All 22 patients had some form of previous bladder insult or surgery, including recurrent urine infections, urinary tract instrumentation, placement of ureteric stents, cystodiathermy, and open bladder surgery. Six cases were associated with TCC of the bladder, of which 4 had NA lesions directly over or close to the site of previous fulguration. In 4 patients, there was a temporal relationship between the administration of intravesical doxorubicin hydrochloride or bacille Calmette-Guérin (BCG) and the onset of NA lesions. One case was associated with an inverted papilloma that had not been described before. In 7 renal transplant cases, 3 lesions were found contralateral to the side of the ureterovesical anastomosis. All 22 cases were benign histologically, but one NA was found within a low-grade baldder TCC. Nineteen cases were followed up regularly with no malignant transformation. Three patients were lost to follow-up. CONCLUSIONS: This study has demonstrated an association between NA and bladder cancer. Patients with NA, especially those treated with intravesical chemotherapy or BCG, should have regular cystoscopies. Fulguration or transurethral resection appear to be sufficient treatment. No renal transplant patients had vesical TCC and NA simultaneously. Neither immunosuppression nor ureterovesical anastomosis appeared to be a significant predisposing factor in the transplant patients.

Renal parenchyma-sparing surgery in carcinoma.

BACKGROUND: There is controversy regarding the role of renal-sparing surgery in patients with kidney cancer who have a functioning contralateral kidney. METHODS: The present study aimed to review the recent experience of renal-sparing surgery at Royal Prince Alfred Hospital (RPAH), Sydney. Eighteen consecutive patients undergoing conservative surgery for kidney tumours at RPAH between February 1987 and January 1995, were reviewed. Eleven patients had imperative indications for conservative surgery and the remaining seven patients had elective indications. Ten patients had modified enucleation with a margin of normal parenchyma. Six patients underwent partial nephrectomy and two had wedge resections. Patients were followed up at 1, 6 and 12 months, and thence every 6-12 months. Follow-up ranged from 9 to 104 months (mean: 46.2 months, median: 48 months). RESULTS: Sixteen of the 18 patients were still alive at the end of the follow-up (October 1995), with no clinical evidence of local or distant metastasis. The two deaths were not related to the fact that these patients had conservative surgery. The average tumour dimensions were 43 mm x 49 mm, with an average volume of 194 mm3. All resections were complete, with margins ranging between 1.0 and 20.0 mm (mean: 8.7 mm). The survival rate in the present study is comparable to those found by other researchers. CONCLUSIONS: Conservative surgery is indicated in renal tumours where radical surgery would render the patient anephric. Conservative surgery, however, is controversial in a patient with a normal contralateral kidney. The present study has shown that renal parenchyma-preserving surgery for localized tumours provides a feasible treatment option.

["Reposition-flap" technique in amputation of the finger tip. Apropos of a series of 21 cases]. / La technique de "reposition-lambeau" dans les amputations digitales distales. A propos d'une série de vingt et un cas.

The authors review 21 cases of a so-called "reposition-flap" technique for finger tip injuries consisting of simple reposition when no vessels can be found for replantation. This technique is combined with palmar soft tissue excision and advancement of a local flap to cover the bone providing blood supply and good sensitivity. The mean age in the 19 patients was 34 years. The Weber test was an average of 6 mm in the 17 patients with more than 2 years of follow-up. A moderate nail hook deformity was noted in 24% and cold intolerance in 28.5%.

Neo-adjuvant (pre-emptive) cisplatin therapy in invasive transitional cell carcinoma of the bladder.

Following 2 pilot studies which showed 57 and 61% response rates to intravenous cisplatin for transitional cell carcinoma of the bladder prior to definitive treatment, the West Midlands Urological Research Group (WMURG) and the Australian Bladder Cancer Study Group (ABCSG) independently began randomised trials to test the survival benefit of neo-adjuvant intravenous cisplatin prior to radiotherapy in T2-T4 M0 transitional cell carcinoma of the bladder. Both trials failed to recruit their target numbers of 250 patients in the West Midlands and 320 in Australia. Since they had similar treatment protocols and eligibility criteria, they were combined in an overview analysis, achieving a total number of 255 patients. Each treatment group was compared with its own control group and the differences were pooled to give an overall result. There was no difference in survival between treated and control patients. The odds ratio was 1.13 with the control groups faring marginally better than the chemotherapy groups. Even with 255 patients the 95% confidence interval of the odds ratio was wide (0.80-1.57). Although there is no clear evidence of a clinically worthwhile benefit from neo-adjuvant cisplatin, this approach must be tested in a larger study using combination treatments with greater activity in metastatic disease.

End-stage renal failure in children: 16 years' experience at one Australian centre.

Sixty-five children over one year and under 15 years of age began treatment for end-stage renal failure between 1973 and 1988. Sixty-one renal transplants were performed in 53 children, 39 of these were from living donors (38 were first-degree relatives and one was an emotionally related volunteer). Thirteen children, of whom seven had received transplants and six had not, died, including three children with functioning transplants; nine deaths occurred in the first eight years of the programme. Cumulative five-year and 10-year patient survival rates were 78% and 75%, respectively. Eighteen transplants failed, 12 as a result of rejection, five as a result of disease recurrence and one due to primary non-function. Cumulative five-year and 10-year transplant survival rates for first grafts were 66% and 53%, respectively. For living donor transplants these rates were 85% and 68%, respectively. Growth rates fell by 0.4 +/- 0.05 standard deviation score (SDS) per year in children undergoing dialysis, were normal in children with renal transplants receiving prednisone (change in SDS per year, -0.02 +/- 0.08) and increased by 0.36 +/- 0.07 SDS per year in children with transplants receiving cyclosporin A alone. Currently, 32 (82%) of 39 transplant recipients and 7 (58%) of 12 patients undergoing dialysis attend school or work full time. Although both dialysis and transplantation are acceptable therapies for children with end-stage renal failure, successful transplantation provides the best opportunity for satisfactory growth and development.

Danazol treatment of advanced prostate cancer: clinical and hormonal effects.

Danazol was administered to 19 patients with advanced prostate cancer. These patients were treated for periods ranging from 3 days to 18 weeks. There were no objective remissions, but three patients (15.8%) had objectively stable disease (N.P.C.P. criteria) with complete pain control for periods ranging 15-18 weeks. Seven patients experienced tumor flare reactions, one requiring withdrawal of treatment and one resulting in rapid clinical deterioration and death. Four other patients died within 3 weeks and, although they were already in the terminal phase of disease when treatment commenced, it is possible that the deaths were treatment related. This study indicates that danazol has only limited activity in the treatment of advanced prostate cancer and is associated with a high incidence of tumor flare reactions with the risk of rapid clinical deterioration.

Initial intravenous cis-platinum therapy: improved management for invasive high risk bladder cancer?

Between August 1981 and December 1983, 50 patients with invasive high risk bladder cancer were treated initially with 100 mg. per m.2 cis-platinum intravenously in 2 doses with a 3-week interval, which was followed by definitive treatment (radiotherapy and/or cystectomy). High risk disease was defined on the basis of at least 2 of the following: invasion into or beyond the muscle (stages B2 to D1), grade III histology, large tumors and ureteral obstruction. Major symptomatic improvement was noted in 38 patients (76 per cent) after 1 to 2 doses of cis-platinum and 30 (60 per cent) had an objective response to cis-platinum. An objective response (complete or partial remission) was noted in 43 patients (86 per cent) after cis-platinum plus definitive treatment. The 12-month actuarial survival was 86 per cent and the 2-year actuarial survival was 80 per cent (although only 14 patients were entered in the study more than 2 years ago). The protocol was well tolerated, with nausea and vomiting being the most common side effects. There were no deaths related to treatment. Ten patients (20 per cent) died of cancer. The relevance of initial cis-platinum therapy in this management program is now being evaluated in a multicenter randomized trial.

Small arterial reconstruction using modified cadaveric saphenous veins.

Human saphenous veins removed from cadaver donors were subjected to proteolytic enzymatic digestion, cross bonding, and heparin bonding. They were tested as small arterial substitutes in dogs. Eight of eleven were successful, persisting without development of stenosis or aneurysm, the longest for eighteen months. In humans, similarly prepared veins were used as arterial bypasses to revascularize ischemic limbs in eleven patients and aneurysmal degeneration of an earlier unmodified allograft bypass in one patient. Distal arterial anastomoses were to the tibial and peroneal arteries. Nine patients who had not undergone previous reconstructive surgery involving the vessel used for distal anastomosis were treated successfully; all remain with healed limbs between three and twelve months after surgery, eight with functioning bypasses. In three patients who had undergone previous operations on the same artery used for distal anastomosis, long bypasses failed, although amputation was avoided in one patient by additional bypass with modified vein to the profunda femoris artery. We conclude that modified saphenous vein allografts are suitable small arterial substitutes. It remains to be seen whether veins will maintain patency for long periods without development of complications.

A controlled clinical trial of machine perfusion of cadaveric donor renal allografts.

Outcome in eighty-eight recipients of cadaveric donor renal allografts preserved before implantation by machine perfusion with a solution of human albumin was compared to that for eighty-three recipients of similar kidneys implanted after simple cold storage. Average total ischaemic intervals for machine-perfused and cold-stored kidneys were 18 and 4 1/4 hours, respectively. Machine-perfused kidneys were implanted regardless of perfusion characteristics. Initial function and 1-month and 1-year graft survivals for the machine-perfused group (58%, 85%, 68%, respectively) were either similar or improved compared to those of cold-stored kidneys (58%, 81%, 52%, respectively). Improved 1-year survival for machine-perfused grafts was dependent upon reduced rejection. Careful donor selection and management ensured good machine perfusion of kidneys on 90% of occasions. In the other 10%, despite poor perfusion characteristics, outcome for kidneys was similar to those with good perfusion characteristics. Antilymphocyte globulin treatment reduced rejection whether allografts were machine perfused or not. In the absence of antilymphocyte globulin treatment, machine-perfused kidneys did much better than cold-stored kidneys. Machine perfusion had important advantages and improved the results in kidney-graft recipients.