Ketamine-associated lower urinary tract destruction: a new radiological challenge.

AIM: Ketamine is a short-acting dissociative anaesthetic whose hallucinogenic side effects have led to an increase in its illicit use amongst club and party goers. There is a general misconception amongst users that it is a safe drug with few long term side effects, however ketamine abuse is associated with severe urinary tract dysfunction. Presenting symptoms include urinary frequency, nocturia, dysuria, haematuria and incontinence. MATERIALS AND METHODS: We describe the radiological findings found in a series of 23 patients, all with a history of ketamine abuse, who presented with severe lower urinary tract symptoms (LUTS). Imaging techniques used included ultrasonography (US), intravenous urography (IVU), and computed tomography (CT). These examinations were reviewed to identify common imaging findings. All patients with positive imaging findings had also undergone cystoscopy and bladder wall biopsies, which confirmed the diagnosis. The patients in this series have consented to the use of their data in the ongoing research into ketamine-induced bladder pathology. RESULTS: Ultrasound demonstrated small bladder volume and wall thickening. CT revealed marked, generalized bladder wall thickening, mucosal enhancement, and perivesical inflammation. Ureteric wall thickening and enhancement were also observed. In advanced cases ureteric narrowing and strictures were identified using both CT and IVU. Correlation of clinical history, radiological and pathological findings was performed to confirm the diagnosis. CONCLUSION: This case series illustrates the harmful effects of ketamine on the urinary tract and the associated radiological findings. Delayed diagnosis can result in irreversible renal tract damage requiring surgical intervention. It is important that radiologists are aware of this emerging clinical entity as early diagnosis and treatment are essential for successful management.

Bicalutamide vs cyproterone acetate in preventing flare with LHRH analogue therapy for prostate cancer--a pilot study.

OBJECTIVE: To evaluate the efficacy of bicalutamide vs cyproterone acetate in preventing PSA flare (as a surrogate for tumour flare) for patients requiring luteinizing hormone-releasing hormone (LHRH) analogue therapy for prostate cancer. PATIENTS AND METHODS: In this pilot study, 40 men were randomized 1 : 1 to bicalutamide 50 mg o.d. or cyproterone acetate 100 mg t.i.d. 5 days prior to goserelin acetate and continued for 21 days thereafter. PSA, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone were obtained before treatment and on days 6, 8, 10, 16, 21 and 28. Primary end point was PSA. Hormone profile and clinical features including urinary symptoms and bone pain were secondary end points. RESULTS: Both groups were equally matched apart from serum creatinine and ALP. The speed and magnitude of the percentage change in median PSA from baseline was increased for the CPA group but there was no statistically significant difference in the two groups. Although those receiving bicalutamide all showed a testosterone peak, this remained within the normal range. No difference in the frequency of drug-specific adverse events was found. None of the patients died or developed cord compression during the study period. CONCLUSION: Bicalutamide is able to suppress the initial PSA surge as effectively as cyproterone acetate albeit slightly delayed. A statement whether bicalutamide is equally good at preventing clinical flare cannot be made and should be assessed in an appropriately powered study.

PSA recurrence following radical prostatectomy is comparable for all age groups in the UK.

UNLABELLED: Increasing numbers of men are being diagnosed with prostate cancer and undergo operative curative treatment. It has been suggested that outcome after radical prostatectomy (RP) may vary for different age groups. OBJECTIVE: To investigate whether PSA recurrence-free survival after RP is related to age at operation for a cohort of English men. METHODS: A total of 854 patients notes from four Urology units were audited for preoperative staging parameters and follow-up data obtained. The relationship of PSA, age, biopsy Gleason grade, clinical stage, era and institution on PSA recurrence-free survival was competitively assessed with a multivariate model. RESULTS: Only preoperative PSA (P<0.0001) and biopsy Gleason grade (P < 0.0001) were found to be strongly associated with PSA recurrence-free survival on multivariate analysis. PSA recurrence-free survival probabilities at 5 y for patients aged 45-55 y, 55.1-60 y, 60.1-65 y, 65.1-70 y and 70.1-75 y were 0.59 (CI 0.47-0.71), 0.74 (CI 0.64-0.784), 0.56 (CI 0.44-0.68), 0.61 (CI 0.53-0.69) and 0.60 (CI 0.46-0.74), respectively. No significant difference of PSA recurrence-free survival between any of the age groups was found (Log-rank, P = 0.8567). CONCLUSION: No significant difference of pathological variables or biochemical recurrence across the age groups was found. The widely held belief of poorer outcome in younger men selected for RP does not seem to be borne out by this study.

Serine-arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted therapeutic strategy in prostate cancer.

Angiogenesis is required for tumour growth and is induced principally by vascular endothelial growth factor A (VEGF-A). VEGF-A pre-mRNA is alternatively spliced at the terminal exon to produce two families of isoforms, pro- and anti-angiogenic, only the former of which is upregulated in prostate cancer (PCa). In renal epithelial cells and colon cancer cells, the choice of VEGF splice isoforms is controlled by the splicing factor SRSF1, phosphorylated by serine-arginine protein kinase 1 (SRPK1). Immunohistochemistry staining of human samples revealed a significant increase in SRPK1 expression both in prostate intra-epithelial neoplasia lesions as well as malignant adenocarcinoma compared with benign prostate tissue. We therefore tested the hypothesis that the selective upregulation of pro-angiogenic VEGF in PCa may be under the control of SRPK1 activity. A switch in the expression of VEGF165 towards the anti-angiogenic splice isoform, VEGF165b, was seen in PC-3 cells with SRPK1 knockdown (KD). PC-3 SRPK1-KD cells resulted in tumours that grew more slowly in xenografts, with decreased microvessel density. No effect was seen as a result of SRPK1-KD on growth, proliferation, migration and invasion capabilities of PC-3 cells in vitro. Small-molecule inhibitors of SRPK1 switched splicing towards the anti-angiogenic isoform VEGF165b in PC-3 cells and decreased tumour growth when administered intraperitoneally in an orthotopic mouse model of PCa. Our study suggests that modulation of SRPK1 and subsequent inhibition of tumour angiogenesis by regulation of VEGF splicing can alter prostate tumour growth and supports further studies for the use of SRPK1 inhibition as a potential anti-angiogenic therapy in PCa.

Her-2/neu oncogene amplification in clinically localised prostate cancer.

AIM: To examine the incidence of Her-2/neu oncogene amplification in clinically localised prostate cancer using in situ hybridisation. METHODS: One hundred and seventeen patients, who had undergone radical prostatectomy, were identified and in situ hybridisation was performed on formalin fixed, paraffin wax embedded tissue using the Quantum Appligene probe for Her-2/neu. The enzyme peroxidase was used to detect the probe because this enabled a permanent record to be kept. Tumours in which there were five or more signals in each nucleus in > 20% of the tumour cells were considered to have a significantly increased copy number. A serial section from these tumours was then hybridised with the chromosome 17 alpha satellite probe. The ratio of the percentage of cells showing an increase in Her-2/neu copy number to the number showing polysomy for chromosome 17 was calculated. A ratio above 2 was considered amplified. RESULTS: Biochemical recurrence occurred in 50 (43%) patients and 24 (21%) had clinical recurrence. In situ hybridisation for Her-2/neu was accessible in 114 (97%) patients. A significant increase in copy number was present in two patients (1.75 %), but chromosome 17 hybridisation showed that the increase was the result of polysomy rather than true amplification. Both these patients had a Gleason score of 7 and stage T3; they also had recurrent clinical disease with distal metastasis within two and 19 months. CONCLUSIONS: Increased Her-2/neu oncogene copy number appears to be rare in clinically localised prostatic adenocarcinoma and is related to chromosome 17 polysomy rather than true amplification. As a result, it would not be a useful biomarker for identifying those patients who will have recurrences after radical prostatectomy.

Pseudo-pseudocysts of the pancreas.

Pancreatic pseudocyst was erroneously diagnosed in three patients aged 52-57 years. Two patients had acute epigastric pain, hyperamylasemia (approximately 4,000 IU/L), and a retrogastric collection of fluid demonstrated by early ultrasonography. Laparotomy undertaken within 48 h of admission revealed the correct diagnosis in each case. One patient had perforation of a gastric ulcer into the lesser sac, and the other patient (who died) had perforation of an obstructed afferent loop 25 years after Polya partial gastrectomy. The third patient with renal failure, back pain, and marginal hyperamylasemia had a cystic mass in the lesser sac. Two internal drainage operations were performed before the correct diagnosis of epithelioid leiomyoma was established 6 years later.

PC-SPES: a herbal therapy for the treatment of hormone refractory prostate cancer.

In this review the authors consider the commercially available herbal product PC-SPES. This is a combination of eight different herbs marketed for its effects of reducing prostate specific antigen (PSA) levels, improving pain, and enhancing the quality of life of those with hormone refractory prostate cancer. The evidence for these claims does not appear to be as conclusive as reported by the manufactures of this product. There also appears to be a significant risk of deep vein thrombosis (DVT) in those treated with PC-SPES. There have been 116 clinical and laboratory based studies of PC-SPES published to date, but there have been no randomised controlled trials conducted. Many of these studies contain very few patients, thus making the drawing of conclusions difficult. Despite this lack of information, there still remains a large patient group taking this supplement, therefore caution should be advised in the usage of PC-SPES in the treatment of hormone refractory prostate cancer.

Learning curve and stage migration of a radical retropubic prostatectomy series over a 10-y period.

OBJECTIVE: To show the impact of learning curve and patient selection on complication rate and biochemical recurrence-free survival of a UK radical prostatectomy series for localised prostate cancer and to model the influence of common preoperative variables on biochemical recurrence after controlling for learning curve. PATIENTS AND METHODS: From 1989 to 1999, 280 of 350 patients who underwent anatomical radical retropubic prostatectomy (RRP) at our institution had complete records and follow-up of at least 1 y. After exclusions of preoperative staging, factors reflecting the learning curve, early complications and prostate-specific antigen (PSA) outcome were recorded on 217 patients. Procedures before 1995 were compared with procedures after 1995. RESULTS: Comparison of the two groups showed a significant decrease in operating time (mean 152 vs 130 min), blood loss (mean 1500 vs 1000 ml), transfusion rate (83 vs 42%) and hospital stay (mean 7 vs 6 days). Median preoperative PSA changed significantly from 13.2 to 11.5 ng/ml. Only 17% were diagnosed by rectal examination compared to 27% in the early years. The number of clinical T1 tumours increased from 33 to 47%. This did lead to an increase of organ-confined tumours on pathological staging by 25%. Biochemical recurrence-free survival improved significantly after 1995. After controlling for the learning curve PSA and clinical stage were significant predictors of PSA recurrence. CONCLUSION: Time trends of case selection, stage migration and a steep learning curve are shown over a 10-y period. Factors associated with the learning curve as well as case selection have a significant impact on outcome. There may be other as yet not specified factors over time, which have a significant impact on PSA recurrence-free survival. Patients with a PSA of 20 ng/ml and above have a poor outcome and do not appear to be suitable candidates for RRP.

Squamous cell carcinoma of the anus arising within condyloma acuminatum.

Condyloma acuminatum are 'warty' lesions of viral aetiology. Four cases of squamous carcinoma arising within such condyloma are reported and discussed.

Magnetic resonance imaging in the staging of renal cell carcinoma.

A prospective study has been carried out to examine the role of magnetic resonance imaging (MRI) in the investigation of renal cell carcinoma in 24 patients. In all cases the inferior vena cava (IVC) was well demonstrated with MRI. In 14 out of 15 patients where surgical correlation was available, the MRI and operative staging were in agreement. Magnetic resonance imaging and computed tomographic (CT) staging were in agreement in 16 out of the 17 patients where both were performed. In one case, CT suggested hepatic invasion but this was found not to be present on MRI and at operation. Magnetic resonance imaging also provided substantial additional information in three patients, including two cases where MRI demonstrated a patent IVC that appeared occluded on CT (one of which also had vertebral metastases seen on MRI but missed on CT) and one case where CT failed to demonstrate minimal involvement of the IVC. Magnetic resonance imaging is an accurate means of staging renal cell carcinoma with clear advantages over CT. In no case in this series was inferior vena cavography found to be necessary.

Complications of T-tube drainage of the common bile duct.

The complications associated with T-tube drainage of the common bile duct following biliary surgery were studied prospectively. A high rate of complications especially associated with T-tube removal was found. Biliary leakage and bacteraemia were the two main problems though in most cases caused minimal clinical upset. Alternatives to T-tube drainage are discussed. It is suggested that if T-tubes are to be used broad spectrum antibiotic cover should be employed at the time of removal.

Polydioxanone suture in the gastrointestinal tract.

A randomized prospective trial was undertaken of polydioxanone suture (PDS) versus conventional suture material in 98 patients undergoing anastomoses in the gastrointestinal tract. Nine patients died within 6 months of surgery, one of these being related to an anastomotic leak. All other patients were followed up for between one and three and a half years. In 57 colonic anastomoses, 30 were randomized to a single layer of 2/0 (BPC) interrupted PDS and 27 to a single of 2/0 (BPC) interrupted silk. Follow up sigmoidoscopy and barium enemas were used to confirm the clinical suspicion of 6 benign anastomotic strictures, 5 of which occurred in the PDS group. At this stage, the colonic arm of the trial was discontinued because the 19% stricture rate with PDS was deemed unacceptable. In a second limb of the study, patients were randomized to two layers of 2/0 (BPC) continuous PDS or 2/0 (BPC) continuous chromic catgut. There were no significant differences in 32 gastric or small bowel anastomoses and in particular, no anastomotic strictures were apparent. The reasons for the high rate of stricture formation when using PDS for large bowel anastomoses are unclear. However, it would seem to be a suitable alternative to chromic catgut when confined to the stomach and small intestine.

Haematuria analysed--a prospective study.

One hundred consecutive cases of haematuria were studied prospectively. The results showed a high proportion (52%) of serious urological disease. The need for thorough investigation of even minor degrees of haematuria is again emphasized.

Intracorporeal papaverine injection in androgen deprived men.

The intracorporeal injection of papaverine (ICP) is now a well recognized therapeutic option in the management of impotence. The current treatment of advanced prostatic carcinoma causes erectile failure. Although intracorporeal papaverine can induce erections in these men, libido is also reduced so that the role of ICP is limited to those men complying with the wishes of a highly motivated partner.

Histological and environmental changes in longstanding ileal conduits.

Seventeen patients with urinary diversions present for between 10 and 17 years were examined endoscopically. The region of the anastomosis was successfully biopsied in 13 cases. Biopsy specimens were examined both histologically and cytologically. Urine was aspirated from the conduits under sterile conditions and sent for qualification of bacterial flora. Histology revealed a variable degree of villous atrophy, mucosal metaplasia, crypt hyperplasia and in one case, antral type gland metaplasia. The finding of hyperplasia was corroborated by flow cytometry which demonstrated a high percentage of cells in G2 and metaphase. The majority of cases showed a colonic type of bacterial colonization and mucin histochemistry demonstrated a colonic type of mucin.

Magnetic resonance imaging of spinal metastases.

Sixty-six patients with spinal metastatic disease secondary to urological malignancy underwent magnetic resonance imaging. Twenty-eight patients had clinical evidence of spinal cord compression. MRI demonstrated metastatic cord compression in 16 cases, a benign cause in two cases, nerve root involvement in five cases. In seven patients MRI demonstrated spinal metastases which were not visible on plain radiographs and isotope bone scans. Nine patients had metastatic deposits involving the cauda equina and in a further 22 patients spinal metastases were an incidental finding during MRI for staging of the primary tumour. MRI is a sensitive method of imaging spinal metastases and provides a non-invasive means of assessing patients with spinal cord compression.

Pathological analysis of lymph nodes in anterior prostatic fat excised at robot-assisted radical prostatectomy.

AIMS: To assess the lymph node content of anterior prostatic fat (APF) sent routinely at robot-assisted laparoscopic radical prostatectomy (RALP) and the incidence of positive nodes in the extended pelvic lymph node dissection. METHODS: Between September 2008 and April 2012, APF excised from 282 patients who underwent RALP was sent for pathological analysis. This tissue was completely embedded and lymph nodes counted. RESULTS: In total, 49/282 (17%) patients had lymph nodes in the APF, median lymph node yield in this tissue was 1 (range 1­5). In four patients, the lymph nodes contained metastatic deposits. These patients did not have positive nodes elsewhere in the extended lymph node dissection. CONCLUSIONS: APF contains lymph nodes in 1 in 6 patients and infrequently these may be malignant. APF should always be removed at radical prostatectomy. APF should be routinely sent for pathological analysis.