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.

An examination of prostate cancer trends in Australia, England, Canada and USA: Is the Australian death rate too high?

PURPOSE: To compare prostate cancer incidence and mortality rates in Australia, USA, Canada and England and quantify the gap between observed prostate cancer deaths in Australia and expected deaths, using US mortality rates. METHODS: Analysis of age-standardised prostate cancer incidence and mortality rates, using routinely available data, in four similarly developed countries and joinpoint regression to quantify the changing rates (annual percentage change: APC) and test statistical significance. Expected prostate cancer deaths, using US mortality rates, were calculated and compared with observed deaths in Australia (1994-2010). RESULTS: In all four countries, incidence rates initially peaked between 1992 and 1994, but a second, higher peak occurred in Australia in 2009 (188.9/100,000), rising at a rate of 5.8 % (1998-2008). Mortality rates in the USA (APC: -2.9 %; 2004-2010), Canada (APC: -2.9 %; 2006-2011) and England (APC: -2.6 %; 2003-2008) decreased at a faster rate compared with Australia (APC: -1.7 %; 1997-2011). In 2010, mortality rates were highest in England and Australia (23.8/100,000 in both countries). The mortality gap between Australia and USA grew from 1994 to 2010, with a total of 10,895 excess prostate cancer deaths in Australia compared with US rates over 17 preceding years. CONCLUSIONS: Prostate cancer incidence rates are likely heavily influenced by prostate-specific antigen testing, but the fall in mortality occurred too soon to be solely a result of testing. Greater emphasis should be placed on addressing system-wide differences in the management of prostate cancer to reduce the number of men dying from this disease.

The pertussis epidemic: informing strategies for prevention of severe disease.

To assess the impact of Bordetella pertussis infections in South Australia during an epidemic and determine vulnerable populations, data from notification reports for pertussis cases occurring between July 2008 and December 2009 were reviewed to determine the distribution of disease according to specific risk factors and examine associations with hospitalizations. Although the majority (66%) of the 6230 notifications for pertussis occurred in adults aged >24 years, the highest notification and hospitalization rate occurred in infants aged <1 year. For these infants, factors associated with hospitalization included being aged <2 months [relative risk (RR) 2·3, 95% confidence interval (CI) 1·60-3·32], Indigenous ethnicity (RR 1·7, 95% CI 1·03-2·83) and receiving fewer than two doses of pertussis vaccine (RR 4·1, 95% CI 1·37-12·11). A combination of strategies aimed at improving direct protection for newborns, vaccination for the elderly, and reducing transmission from close contacts of infants are required for prevention of severe pertussis disease.

An initial melanoma diagnosis may increase the subsequent risk of prostate cancer: Results from the New South Wales Cancer Registry.

Emerging evidence suggests that a diagnosis of cutaneous melanoma (CM) may be associated with prostate cancer (PC) incidence. We examined if the incidence of CM was associated with an increased subsequent risk of PC. We used data from the New South Wales Cancer Registry for all CM and PC cases diagnosed between January 1972 and December 2008. We calculated the age standardized incidence ratio (SIR) and 95% confidence intervals (95% CI) for PC incidence following a CM diagnosis, applying age- and calendar- specific rates to the appropriate person years at risk. We determined rate ratio (RR) and 95% CI of PC incidence according to specified socio-demographic categories and disease related characteristics, using a negative binomial model. There were 143,594 men diagnosed with PC or CM in the study period and of these 101,198 and 42,396 were diagnosed with PC and CM, respectively, as first primary cancers. Risk of PC incidence increased following CM diagnosis (n = 2,114; SIR = 1.25; 95% CI:1.20.8-1.31: p < 0.0001), with the increased risk apparent in men diagnosed with localised CM (n = 1,862;SIR = 1.26; 95% CI:1.20-1.32). CM diagnosis increased the subsequent risk of PC incidence. This raises the potential for future PC risk to be discussed with newly diagnosed males with CM.

A novel method of bladder neck imbrication to improve early urinary continence following robotic-assisted radical prostatectomy.

Early return of continence forms an important component of quality of life for patients after robotic-assisted radical prostatectomy (RALP). Here we describe the steps of bladder neck imbrication and vesico-urethral anastomosis improving early continence after RALP. Between April 2008 and July 2009, 202 consecutive patients underwent RALP for clinically localised prostate cancer in a tertiary referral centre by a single surgeon. One hundred and thirty-two (65 %) of these patients agreed to participate in the study. Prior to November 2008, 51 patients underwent standard RALP as described by Patel et al. From November 2008, 81 patients underwent a novel method of bladder neck imbrication. The robotic urethro-vesical anastomosis commences on the posterior wall of the urethra and proceeds anteriorly. In our technique the anastomosis is halted with the suture arms fixed to the anterior abdominal wall. A new suture is used to perform a two-layer repair, anchoring proximally then continuing anteriorly to the level of the urethral stump, where it returns upon itself. The aim is to narrow the urethra to 16 Fr and tighten the second layer to create an imbrication effect. Posterior reconstruction was performed in all patients. Outcome measures were recorded prospectively using the Expanded Prostate Cancer Index Composite tool. Our technique shows significant improvement at all stages of follow-up in urinary summary and incontinence scores. Absolute continence rates increased from 8.2 to 20.5 %, 26.7 to 44.3 %, and 47.7 to 62.3 % at 1.5, 3 and 6 months, respectively. These results support the use of our technique in patients undergoing RALP.

Laparoscopic repair of a traumatic diaphragmatic hernia.

The laparoscopic diagnosis and repair of an unusual diaphragmatic hernia are described. Extensive radiological assessment failed to demonstrate the injury, which was diagnosed by laparoscopy 5 weeks after the initial presentation. The diaphragmatic tear was adjacent to the costal margin and was repaired using a novel percutaneous technique. The place of laparoscopy in blunt abdominal trauma is discussed.

Melanoma of the nose.

BACKGROUND: Melanoma of the nose is rare and management guidelines are poorly defined. In the past, excision margins have often been much narrower than for melanoma elsewhere. METHODS: The study was a retrospective clinicopathological study of 34 patients with cutaneous melanoma of the nose treated in a single unit. RESULTS: Desmoplastic neurotropic melanoma and lentigo maligna melanoma were the most common histological tumour types. Local recurrence occurred in eight patients, and in six cases appeared to be a result of inadequate excision margins. Regional lymph node metastases were associated with a very poor prognosis. CONCLUSION: Adequate surgical excision is the mainstay of successful treatment for melanoma of the nose. Excision margins for nasal melanoma should not be any less than for melanoma elsewhere. Careful planning is required, not only to gain local disease control and the best chance of cure, but also to achieve functionally and aesthetically acceptable results. Excision margins need not be compromised in view of the variety of local flaps that can be employed to close the primary defect.