Preconditioning against renal ischaemia reperfusion injury: the failure to translate to the clinic.

Acute kidney injury (AKI) as a result of ischaemia-reperfusion represents a major healthcare burden worldwide. Mortality rates from AKI in hospitalized patients are extremely high and have changed little despite decades of research and medical advances. In 1986, Murry et al. demonstrated for the first time the phenomenon of ischaemic preconditioning to protect against ischaemia-reperfusion injury (IRI). This seminal finding paved the way for a broad body of research, which attempted to understand and ultimately harness this phenomenon for human application. The ability of preconditioning to limit renal IRI has now been demonstrated in multiple different animal models. However, more than 30 years later, a safe and consistent method of protecting human organs, including the kidneys, against IRI is still not available. This review highlights agents which, despite strong preclinical data, have recently failed to reduce AKI in human trials. The multiple reasons which may have contributed to the failure to translate some of the promising findings to clinical therapies are discussed. Agents which hold promise in the clinic because of their recent efficacy in preclinical large animal models are also reviewed.

Renal colic: current protocols for emergency presentations.

Flank pain caused by renal colic is a common presentation to emergency departments. This paper reviews the acute clinical assessment of these patients, outlines appropriate diagnostic strategies with labwork and imaging and updates the reader on conservative treatments, suitable choices for analgesia and indications for surgical intervention. Prompt diagnosis and appropriate treatment instituted in the Emergency Department can rapidly and effectively manage this excruciatingly painful condition.

Active surveillance for prostate cancer: an Australian experience.

OBJECTIVE: To assess the patient and cancer characteristics as well as outcomes of a large cohort of Australian men who chose active surveillance (AS) as initial management of their low-risk prostate cancer. PATIENTS AND METHODS: Men treated by one surgeon who had chosen AS as the primary management for prostate cancer were identified from the records. The patient and cancer data recorded included: patient age, prostate-specific antigen (PSA) concentration at diagnosis, mode of prostate cancer detection. For prostate cancer diagnosed at prostate biopsy, data were collected for the number of cores taken as well as positive core number, cancer burden, and Gleason grade. Survival analysis was used to determine the duration of AS. RESULTS: In all, 154 men with low-risk prostate cancer with a median (range) age 63.0 (36-81) years and a mean (range) PSA concentration of 6.5 (0.3-22) ng/mL underwent AS. The median (range) duration of AS was 1.9 (0.1-16.6) years. AS was ceased in 29 patients (19%) after a mean (range) of 2.4 (0.2-7.9) years. Of these, 26 were upstaged, one chose curative treatment despite stable disease, and two died from disease not related to prostate cancer. Actuarial analysis on the probability of still being on AS after 5 years was 61.9% (95% confidence interval [CI] 46.2-74.2%) and after 10 years was 45.0% (95% CI 21.3-66.2%). While the period of follow-up is short, there were no biochemical recurrences in men who underwent curative treatment and no deaths from prostate cancer. CONCLUSION: AS is an acceptable mode of initial treatment in Australian men with low-risk prostate cancer.

Is a cystogram necessary after radical prostatectomy?

BACKGROUND: Improvements in the surgical technique of radical prostatectomy have allowed the length of postoperative catheterization to be reduced dramatically over the past 20 years. Today, many surgeons perform a cystogram to ensure the anastomosis is watertight before an 'early' (day 7 or less) trial of void (TOV). We aim to show that achieving an intraoperative watertight anastomosis may preclude the need for routine cystogram prior to TOV. METHODS: Between 31 May 1999 and 29 February 2004, we performed a prospective study of 68 consecutive patients who underwent radical prostatectomy by a single surgeon. We tested the vesicourethral anastomosis for watertightness intraoperatively by instilling 250 mL of normal saline in to the bladder and compared this with evidence of extravasation on the cystogram on day 7. RESULTS: Fifty-four (79.4%) of the 68 patients had a watertight anastomosis intraoperatively. All men had a cystogram on day 7 (6-9 days). Sixty (88.2%) of these cystograms showed no evidence of extravasation. Three men (4.4%) who had evidence of a leak on their cystogram had achieved a watertight anastomosis intraoperatively. However, one of these men had suffered a postoperative septicaemia which may have jeopardized the anastomosis. Only two (2.9%) of the 68 patients had unsuspected extravasation at their day 7 cystogram. Therefore, 97.1% of patients (95% Confidence Interval: 95.1%-99.2%) could be suitably managed by our proposed protocol. CONCLUSION: Achieving an intraoperative watertight anastomosis is a very good predictor of a watertight cystogram on day 7. It seems feasible to avoid routine cystograms prior to TOV in the absence of other postoperative complications.