Christopher Woodhouse

Multiple newly identified loci associated with prostate cancer susceptibility

Prostate cancer is the most common cancer affecting males in developed countries. It shows consistent evidence of familial aggregation, but the causes of this aggregation are mostly unknown. To identify common alleles associated with prostate cancer risk, we conducted a genome-wide association study (GWAS) using blood DNA samples from 1,854 individuals with clinically detected prostate cancer diagnosed at ≤60 years or with a family history of disease, and 1,894 population-screened controls with a low prostate-specific antigen (PSA) concentration (<0.5 ng/ml). We analyzed these samples for 541,129 SNPs using the Illumina Infinium platform. Initial putative associations were confirmed using a further 3,268 cases and 3,366 controls. We identified seven loci associated with prostate cancer on chromosomes 3, 6, 7, 10, 11, 19 and X (P = 2.7 × 10−8 to P = 8.7 × 10−29). We confirmed previous reports of common loci associated with prostate cancer at 8q24 and 17q. Moreover, we found that three of the newly identified loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK3.

Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002)

The British Society of Gastroenterology (BSG) and the Association of Coloproctology for Great Britain and Ireland (ACPGBI) commissioned this update of the 2002 guidance. The aim, as before, is to provide guidance on the appropriateness, method and frequency of screening for people at moderate and high risk from colorectal cancer. This guidance provides some new recommendations for those with inflammatory bowel disease and for those at moderate risk resulting from a family history of colorectal cancer. In other areas guidance is relatively unchanged, but the recent literature was reviewed and is included where appropriate.

Multiple loci on 8q24 associated with prostate cancer susceptibility

Previous studies have identified multiple loci on 8q24 associated with prostate cancer risk. We performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We confirmed associations at three previously reported loci and identified additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 × 10−8; rs620861: OR = 0.90, P = 4.8 × 10−8). Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility.

Long-term Outcome After Percutaneous Treatment of Transitional Cell Carcinoma of the Renal Pelvis

PURPOSE The application of conservative surgery has been established in the treatment of transitional cell tumors of the renal pelvis. We reviewed retrospectively the long-term outcome after percutaneous treatment of select patients referred to a tertiary center with transitional cell tumors of the renal pelvis. MATERIALS AND METHODS We studied 28 patients referred with a presumptive diagnosis of transitional cell carcinoma of the renal pelvis based on filling defects noted on excretory urograms. At percutaneous endoscopy tumor was resected in 26 patients, while no tumor was found in 2. All 19 men and 7 women smoked, and mean age at presentation was 65 years. Of the patients 18 presented with hematuria and 6 had bilateral upper tract tumors. After percutaneous resection, the access tract was irradiated either with iridium wire in 12 patients or a commercial high dose rate radiation delivery system in 12. Thiotepa was instilled into the nephrostomy tube without brachytherapy in 1 patient and 1 received no adjuvant treatment in all. All patients were followed by excretory urography and urine cytology. Cystoscopy and retrograde pyelography were performed when technically possible. RESULTS After percutaneous tumor resection 6 patients (23%) had local recurrence in the treated renal pelvis, including 3 at 44, 55 and 60 months, respectively. Further conservative treatment was initially possible in 4 of these patients but ultimately only 2 (both of whom had late recurrences) retained the treated kidney. Of the 11 patients with recurrence elsewhere in the urinary tract the bladder was invariably involved (11), while synchronous or metachronous ureteral recurrence was less common (3). Nine patients remained free of any urothelial recurrence in the upper or lower tract. No patient had recurrent tumor in the nephrostomy tract. Of the patients 7 suffered from procedure-related complications, including 1 who had a persistent urinary fistula that failed to heal after brachytherapy and required nephroureterectomy. There have been 6 deaths during followup, of which 2 were disease related. The 3-year estimated local recurrence-free survival rate was 86% (95% confidence interval 63 to 95%), cause-specific survival rate 91% (95% confidence interval 67 to 98%) and overall survival rate 78% (95% confidence interval 55 to 90%). Differences in recurrence-free survival, comparing those with recurrence in the treated renal pelvis or elsewhere in the urothelium and those remaining disease-free, did not translate to a significant overall survival difference (p < 0.5) between these groups. CONCLUSIONS Our results suggest that the combination of percutaneous local resection and tract irradiation offers an effective long-term alternative to radical extirpation in the management of select patients with superficial transitional cell carcinoma confined to the renal pelvis. When the postoperative nephrostogram demonstrates a leaking renal pelvis, tract irradiation should not be given.

Anatomy of the Penis and its Deformities in Exstrophy and Epispadias

The anatomy and erectile deformities of the penis in patients with exstrophy and epispadias are described. The information was derived from cavernosograms in 17 patients, an operation in 12, a pelvic computerized tomography scan in 1 and a cystectomy for carcinoma in 1. The inferior pubic ramus and, therefore, the corpora cavernosa are parallel to the floor when the patient is standing. Although the penis loses some of its length through the separation of pubic bones the corpora are shorter than in normal men. Ten corpora were rudimentary in 6 patients, perhaps because of vascular damage during a neonatal operation. The most common erectile deformity was tight dorsal chordee owing to intrinsic curvature of the corpora. The deformity is not caused by scar tissue or shortness of the reconstructed urethra. Patients with 1 rudimentary corpus have lateral deviation on erection.

Processing of radical prostatectomy specimens for correlation of data from histopathological, molecular biological, and radiological studies : a new whole organ technique

Aims: To develop a method of processing non-formalin fixed prostate specimens removed at radical prostatectomy to obtain fresh tissue for research and for correlating diagnostic and molecular results with preoperative imaging. Methods/Results: The method involves a prostate slicing apparatus comprising a tissue slicer with a series of juxtaposed planar stainless steel blades linked to a support, and a cradle adapted to grip the tissue sample and receive the blades. The fresh prostate gland is held in the cradle and the blades are moved through the cradle slits to produce multiple 4 mm slices of the gland in a plane perpendicular to its posterior surface. One of the resulting slices is preserved in RNAlaterTM. The areas comprising tumour and normal glands within this preserved slice can be identified by matching it to the haematoxylin and eosin stained sections of the adjacent slices that are formalin fixed and paraffin wax embedded. Intact RNA can be extracted from the identified tumour and normal glands within the RNAlater preserved slice. Preoperative imaging studies are acquired with the angulation of axial images chosen to be similar to the slicing axis, such that stained sections from the formalin fixed, paraffin wax embedded slices match their counterparts on imaging. Conclusions: A novel method of sampling fresh prostate removed at radical prostatectomy that allows tissue samples to be used both for diagnosis and molecular analysis is described. This method also allows the integration of preoperative imaging data with histopathological and molecular data obtained from the prostate tissue slices.

Identification of new genetic risk factors for prostate cancer.

There is evidence that a substantial part of genetic predisposition to prostate cancer (PCa) may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.

The management of cyclophosphamide-induced haematuria

Haemorrhagic cystitis is a frequent complication of treatment with cyclophosphamide. It remains a difficult clinical problem to treat, compounded by the frailty of patient. Furthermore, the preventative measures and treatments available for CP‐induced haematuria have their own benefits and disadvantages.

Destruction of the bladder by single dose Mitomycin C for low-stage transitional cell carcinoma (TCC)--avoidance, recognition, management and consent.

To identify a cohort of patients under our care who have had significant and in some cases irreparable damage to their bladders after Mitomycin C (MMC) instillation. To highlight the importance of avoidance and recognition of bladder perforations during transurethral resection of bladder tumour (TURBT) and explore the issue of consent regarding MMC given the serious complications that may occur after its instillation.

Penile anomalies in adolescence.

This article considers the impact and outcomes of both treatment and underlying condition of penile anomalies in adolescent males. Major congenital anomalies (such as exstrophy/epispadias) are discussed, including the psychological outcomes, common problems (such as corporal asymmetry, chordee, and scarring) in this group, and surgical assessment for potential surgical candidates. The emergence of new surgical techniques continues to improve outcomes and potentially raises patient expectations. The importance of balanced discussion in conditions such as micropenis, including multidisciplinary support for patients, is important in order to achieve appropriate treatment decisions. Topical treatments may be of value, but in extreme cases, phalloplasty is a valuable option for patients to consider. In buried penis, the importance of careful assessment and, for the majority, a delay in surgery until puberty has completed is emphasised. In hypospadias patients, the variety of surgical procedures has complicated assessment of outcomes. It appears that true surgical success may be difficult to measure as many men who have had earlier operations are not reassessed in either puberty or adult life. There is also a brief discussion of acquired penile anomalies, including causation and treatment of lymphoedema, penile fracture/trauma, and priapism.