J. A. Thornhill

Keratinising squamous metaplasia of the bladder: natural history and rationalization of management based on review of 54 years experience.

OBJECTIVE To review our experience of keratinising squamous metaplasia of the bladder as a predictor for the development of cancer and other complications, and formulate a policy for its management. MATERIALS AND METHODS A retrospective review (1945-1999) identified 34 patients with histologically proven keratinising squamous metaplasia (27 males and 7 females, average age 50 years, range 13-80 years). The histological criteria used to diagnose keratinising squamous metaplasia were squamous metaplasia of the urothelium with keratinisation and/or hyperkeratosis and/or acanthosis. Female patients with non-keratinising squamous metaplasia (vaginal metaplasia) were excluded. RESULTS Four patients had synchronous bladder carcinoma (three advanced with early death; one localised, cured by cystectomy). Another 14 patients had extensive metaplasia (Group A, >50% of mucosal involvement). Three cases had cystectomy and cure. Six cases (out of 11) developed subsequent cancer (4 advanced and early death, two localised and cured by cystectomy). One other case died of obstructive uropathy secondary to squamous metaplasia. Two cases died of unrelated causes. Sixteen patients had limited squamous metaplasia (Group B, <50% involvement mucosal surface). Twelve patients had endoscopic resection, extraction bladder calculus etc. with no further complications. Another two patients underwent urinary diversion. Two patients (out of 16) developed subsequent cancer both with advanced disease and early death. CONCLUSION Keratinising squamous metaplasia of the bladder is a significant risk factor for vesical carcinoma and complications, such as bladder contracture and ureteral obstruction. This risk of complications increases with more extensive bladder mucosal involvement. The wide variation in lag time to the development of complications necessitates indefinite follow-up. Selected patients with extensive bladder involvement and long life expectancy should be offered cystectomy.

The connective tissue framework in the normal prostate, B.P.H and prostate cancer: analysis by scanning electron microscopy after cellular digestion

Abstract The objective of this study was twofold: (1) to determine if a cellular digestion process can facilitate examination of the morphology of the connective tissue framework of the prostate, and (2) to examine the connective tissue framework in normal prostate tissue, benign prostatic hyperplasia (BPH) and prostate cancer. Ten prostate glands were examined. Using the Ohtani method of digestion, the cellular elements were removed. This enabled scanning electron microscopy analysis of the connective tissue framework within the prostatic tissue. Light microscopy of tissue blocks determined the histology of specimens. The prostate is supported by a highly structured network of collagen fibres. This network of fibres varies in normal and diseased states. In benign prostatic hyperplasia, the collagen network is dense, with an increased number of fibres. In prostatic adenocarcinoma, there is non-uniform swelling with a loss and disintegration of collagen fibres. In conclusion, sodium hydroxide cellular digestion provides an excellent method for demonstrating the connective tissue framework of prostatic tissue. The morphological changes in collagen fibres in normal prostate, benign prostatic hyperplasia and prostatic adenocarcinoma have implications for prostate growth in normal and diseased states.

An audit of 2273 ureteroscopies — a focus on intra-operative complications to justify proactive management of ureteric calculi

BACKGROUND At the national Stone Centre we have adopted a proactive management approach involving early ureteroscopy for ureteric calculi. As the efficacy of ureteroscopy is known this study focuses on the low intra-operative complication rate as justification for a proactive management protocol. PATIENTS AND METHODS A retrospective study (1987-1997) identified 1936 patients undergoing 2273 ureteroscopies. A database was created from inpatient hospital records. The male to female ratio was 3 to 1, age range was 25 to 84 years. RESULTS Twenty-three patients (1%) had an intra-operative complication during ureteroscopy. Immediate ureteric JJ stenting was performed in 16 cases with ureteric injury. Two cases underwent percutaneous drainage and delayed antegrade ureteric stenting, ureteroscopy was terminated because of poor visibility. Five patients (0.22%) underwent open surgery for: ureteric perforation (n = 2); Dormia basket ureteric avulsion (n = 1); impacted Dormia basket and stone (n = 1); and impacted balloon dilator and stone (n = l). Ureteroscopic complications were not related to the level of ureteric calculus. CONCLUSION A protocol of proactive management of ureteric calculi facilitates rapid turnover of large patient numbers. This approach is supported by the low intra-operative complication rate, most of which can be managed by further endoscopic procedures. In the event of corrective open surgery a favourable outcome has resulted.

Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer.

Aberrant activation of Wnts is common in human cancers, including prostate. Hypermethylation associated transcriptional silencing of Wnt antagonist genes SFRPs (Secreted Frizzled‐Related Proteins) is a frequent oncogenic event. The significance of this is not known in prostate cancer. The objectives of our study were to (i) profile Wnt signaling related gene expression and (ii) investigate methylation of Wnt antagonist genes in prostate cancer. Using TaqMan Low Density Arrays, we identified 15 Wnt signaling related genes with significantly altered expression in prostate cancer; the majority of which were upregulated in tumors. Notably, histologically benign tissue from men with prostate cancer appeared more similar to tumor (r = 0.76) than to benign prostatic hyperplasia (BPH; r = 0.57, p < 0.001). Overall, the expression profile was highly similar between tumors of high (≥ 7) and low (≤ 6) Gleason scores. Pharmacological demethylation of PC‐3 cells with 5‐Aza‐CdR reactivated 39 genes (≥ 2‐fold); 40% of which inhibit Wnt signaling. Methylation frequencies in prostate cancer were 10% (2/20) (SFRP1), 64.86% (48/74) (SFRP2), 0% (0/20) (SFRP4) and 60% (12/20) (SFRP5). SFRP2 methylation was detected at significantly lower frequencies in high‐grade prostatic intraepithelial neoplasia (HGPIN; 30%, (6/20), p = 0.0096), tumor adjacent benign areas (8.82%, (7/69), p < 0.0001) and BPH (11.43% (4/35), p < 0.0001). The quantitative level of SFRP2 methylation (normalized index of methylation) was also significantly higher in tumors (116) than in the other samples (HGPIN = 7.45, HB = 0.47, and BPH = 0.12). We show that SFRP2 hypermethylation is a common event in prostate cancer. SFRP2 methylation in combination with other epigenetic markers may be a useful biomarker of prostate cancer.

A comparison of the functional durability of the AMS 800 artificial urinary sphincter between cases with and without an underlying neurogenic aetiology

AbstractAim To compare the efficacy and functional durability of the American Medical Systems 800 (AMS 800) artificial urinary sphincter (AUS) device for patients with neurogenic and non-neurogenic incontinence. Methods From 1985 to 2000, 38 patients underwent implantation of an AMS 800 AUS at our institution. Thirty of these patients had complete records and follow-up data available. The mean follow-up for these two groups of patients was six years. Seventeen devices (57%) were implanted for non-neurogenic indications including incontinence after prostatectomy or hysterectomy. Thirteen devices (43%) were implanted for neurogenic conditions including spina bifida, spinal cord injury or severe pelvic trauma. The primary end point measured was continence. Secondary end points included mechanical and non-mechanical device failure, re-operation and complication rates between the two groups. Results In the neurogenic group, only two patients (15%) have their original device in situ without revisions. Only three patients (23%) in this group are entirely dry. In contrast, seven patients (41%) in the non-neurogenic group are completely dry with their original device in situ. A further four (23%) are entirely dry after device revision or replacement surgery. The rates of mechanical failure were not statistically different between the two groups. The rate of non-mechanical failure (NMF) was statistically greater in the neurogenic group in comparison to that in the non-neurogenic group (p<0.05). Conclusions Insertion of an AMS 800 artificial sphincter remains a durable means of regaining urinary continence. Patients who are incontinent as a result of an underlying neurological deficit should be counselled that they might have a higher risk of non-mechanical device failure, requirement for re-operation and that their overall long-term continence rates may be poor.

Public awareness of testis cancer and the prevalence of testicular self-examination-changing patterns over 20 years.

OBJECTIVES Delay in treatment of testis cancer (TC) has a proven negative impact on disease stage, treatment outcome, and mortality. Poor public awareness of the disease and lack of testis self-examination (TSE) may account for late presentation. The aim of this study was to examine the knowledge of TC and performance of TSE in a group of men over 2 time periods 20 years apart. METHODS In the current study, 677 men from a banking institution were surveyed on their knowledge of TC and their performance of TSE. Comparisons were made from the current data and those from the original study in 1986. RESULTS This study demonstrates an increase in public awareness and modest concomitant increase in TSE since first studied in this country in 1986. There was no difference in knowledge across age groups in this study. Furthermore, men who demonstrate a superior degree of knowledge were more likely to perform TSE. Limitations included possible selection bias in the 2 studies conducted in a banking institution. CONCLUSIONS Increased testicular cancer knowledge combined with TSE may have a role in improving detection of significant testicular pathology.

IGFBP7 promoter methylation and gene expression analysis in prostate cancer.

PURPOSE IGFBP7 belongs to a family of insulin-like growth factor-1 regulatory binding proteins. IGFBP7 hypermethylation is associated with its down-regulation in various carcinomas. In prostate cancer IGFBP7 down-regulation has been widely reported but to our knowledge the mechanisms behind this event are unknown. We performed a denaturing high performance liquid chromatography screening and validation strategy to profile the methylation status of IGFBP7 in prostate cancer. MATERIALS AND METHODS We combined denaturing high performance liquid chromatography and bisulfite sequencing to examine IGFBP7 methylation in a panel of prostate cancer cell lines. Quantitative methylation specific polymerase chain reaction was used to determine methylation levels in prostate tissue specimens of primary prostate cancer, histologically benign prostate adjacent to tumor, high grade prostatic intraepithelial neoplasia and benign prostatic hyperplasia. IGFBP7 gene expression was measured by quantitative methylation specific polymerase chain reaction in cell lines and tissue specimens. RESULTS IGFBP7 was methylated in the 4 prostate cancer cell lines DU145, LNCaP, PC-3 and 22RV1. Quantitative methylation specific polymerase chain reaction analysis revealed that promoter methylation was associated with decreased IGFBP7 expression. Quantitative methylation specific polymerase chain reaction showed that IGFBP7 methylation was more frequently detected in prostate cancer (60% (31/52)) and high grade prostatic intraepithelial neoplasia (40% (6/15)) samples compared to histologically benign prostate adjacent to tumor (10%) and benign prostatic hyperplasia (0%) samples. CONCLUSIONS To our knowledge this is the first report of aberrant IGFBP7 promoter hypermethylation and concurrent IGFBP7 gene silencing in prostate cancer cell lines. Results demonstrate that CpG methylation of IGFBP7 may represent a novel biomarker of prostate cancer and pre-invasive neoplasms. Thus, future examination of IGFBP7 methylation and expression in a larger patient cohort, including bodily fluids, is justified to further evaluate its role in a diagnostic and prognostic setting.

Scrotal signs and symptoms in the general population, the value of testis self-examination and the pitfalls of a scrotal screening programme: is the two-week rule relevant?

PurposeTesticular symptoms/lumps are a cause of concern, anxiety and possible diagnostic dilemma for patient and general practitioner. The majority of scrotal pathology is benign in nature and results in a huge workload. The main aim of this study was to determine the relationship between scrotal symptoms, previous scrotal surgery, testicular self-examination and awareness of scrotal abnormalities. Secondarily, we sought to determine the scrotal findings in men enrolled in a consultant urologist-directed screening programme.MethodsThere were 677 men surveyed on their performance of TSE. They were also asked about scrotal symptoms and prior surgery, before undergoing blinded physical examination by one of four consultant urologists.ResultsAmong the participants, 9.8% of men had scrotal symptoms with 55% of these having a normal scrotal examination and the rest having benign pathology. A number of men who had undergone previous scrotal surgery (13%) had no clinical findings detected on scrotal examination. No subject was found to have testis cancer; 20.9% had a benign scrotal or inguinal condition detected with the majority (65%) not aware of the abnormality. Men who demonstrate a superior awareness of their scrotal abnormalities were more likely to perform TSE.ConclusionsIncreased awareness of scrotal abnormalities combined with TSE may have a role in improving detection of significant testicular pathology. However, the high prevalence of benign scrotal conditions, of which most men were unaware, may serve to raise anxiety in the patient and general practitioner. We believe there is no role for a one-stop scrotal anxiety clinic, as the costs do not justify the benefits.

Pelvic recurrence in stage I seminoma: A new phenomenon that questions modern protocols for radiotherapy and follow‐up

Abstract  Objective:  To highlight the increased risk for pelvic relapse in patients with stage 1 seminoma treated with adjuvant radiotherapy limited to para‐aortic template alone.

Anaplastic large cell lymphoma: a unique presentation with urinary bladder involvement: a case report.

Anaplastic large cell lymphoma (ALCL) is a T-cell lymphoma composed of large pleomorphic CD30-positive cells. While systemic ALCL frequently involves extranodal sites, involvement of the urinary bladder is extremely rare. We report a case of systemic ALCL presenting with bladder involvement. A 28-year-old man presented with hematuria, dysuria, and lower abdominal pain. Imaging revealed pelvic lymphadenopathy and a thickened bladder wall. Bladder biopsies showed diffuse infiltration of the lamina propria by large pleomorphic cells, with preservation of the overlying urothelium. Immunohistochemistry demonstrated cell membrane and Golgi region staining for CD30 and epithelial membrane antigen. This is the first documented instance of systemic ALCL presenting with bladder symptoms.