Histological outcome of delayed orchidectomy after primary chemotherapy for metastatic germ cell tumour of the testis.

AIMS: To identify the incidence of viable local tumour in the testis of patients undergoing delayed orchidectomy after initial presentation with advanced germ cell tumour (GCT) treated by primary chemotherapy. PATIENTS AND METHODS: Thirty-three patients presenting with advanced metastatic GCT were reviewed. The median age at presentation was 34 years. All received chemotherapy without previous orchidectomy. The decision to initiate chemotherapy without orchidectomy was based on a heavy tumour load and the patient's condition at initial presentation. A histological diagnosis was available from a biopsy of metastases in 23 patients; treatment in the remaining 10 patients was initiated after diagnosis based on a combination of elevated serum tumour markers, testicular findings and the presence of a retroperitoneal mass. RESULTS: Seminomatous GCT (SGCT) was diagnosed in 13 patients, non-seminomatous GCT (NSGCT) in 17 patients and mixed GCT (MGCT) in the remaining three patients. Bleomycin/etoposide/cisplatin-based chemotherapy was the principle regimen. After initial chemotherapy, all patients with pure SGCT had only scar tissue in the orchidectomy specimen, with no residual tumour. Nine of 17 patients (52.9%) with NSGCT had viable tumour remaining in the orchidectomy specimen. All three cases of MGCT had persistent viable invasive seminoma. Twenty-seven patients (81.8%) were recurrence free and alive after a median of 49 months of follow-up. CONCLUSIONS: Thirty-six per cent of patients had residual tumour locally in the testis after primary chemotherapy for metastatic GCT of the testis. However, in the cases with pure seminomatous disease, there was no residual tumour present. It may not be necessary to undertake delayed orchidectomy in these patients.

Development of a novel rapid assay to assess the fidelity of DNA double-strand-break repair in human tumour cells.

Cellular survival following ionising radiation-mediated damage is primarily a function of the ability to successfully detect and repair DNA double-strand breaks (DSBs). Previous studies have demonstrated that radiosensitivity, determined as a reduction in colony forming ability in vitro, may be related to the incorrect repair (misrepair) of DSBs. The novel rapid dual fluorescence (RDF) assay is a plasmid-based reporter system that rapidly assesses the correct rejoining of a restriction-enzyme produced DSBs within transfected cells. We have utilised this novel assay to determine the fidelity of DSB repair in the prostate tumour cell line LNCaP, the bladder tumour cell line MGH-U1 and a radiosensitive subclone S40b. The two bladder cell lines have been shown in previous studies to differ in their ability to correctly repair plasmids containing a single DSB. Using the RDF assay we found that a substantial portion of LNCaP cells [80.4 +/- 5.3(standard error)%] failed to reconstitute reporter gene expression; however, there was little difference in this measure of DSB repair fidelity between the two bladder cell lines (48.3 +/- 3.5% for MGH-U1; 39.9 +/- 8.2% for S40b). The RDF assay has potential to be developed to study the relationship between DSB repair fidelity and radiosensitivity as well as the mechanisms associated with this type of repair defect.

Estimated glomerular filtration rate is unreliable in detecting renal function loss during follow-up after cystectomy and urinary diversion.

PURPOSE: To evaluate the accuracy of estimated glomerular filtration rate (eGFR) against the reference standard of isotopic GFR (iGFR) in monitoring renal function during follow-up after cystectomy and urinary diversion. METHODS: Patients who had undergone cystectomy and ileal conduit urinary diversion at two centres between August 2001 and August 2006 were identified. eGFR calculated using the MDRD formula was compared to (51)Cr EDTA measured iGFR values measured at similar time-points during follow-up. RESULTS: Six hundred and fourteen paired iGFR and eGFR results were analysed from 166 patients (18% female, median age 70 years). There was a significant difference between paired iGFR and eGFR measurements (p < 0.0001) with a mean bias of +1.8 mls/min/1.73 m(2) (SD 18.0) and a 95% limit of agreement of -33.5 to 37.2 mls/min/1.73 m(2). iGFR and eGFR values converged at a GFR of approximately 45 mls/min/1.73 m(2). 70.6% of patients experienced a loss of renal function greater than expected (>0.58 mls/min/1.73 m(2)/year). In 22.4% of these patients, a decline of greater than 10% in iGFR occurred that was undetected by eGFR measurements, which overestimated GFR. There was no significant relationship between patient height, weight or body mass index and the accuracy of eGFR measurements. CONCLUSIONS: iGFR measurement is recommended following ileal conduit urinary diversion if early signs of renal function loss are to be detected. eGFR overestimates GFR in critically relevant ranges and fails to detect loss in a clinically significant proportion of patients.

Balloon Cell Urethral Melanoma: Differential Diagnosis and Management.

Introduction. Primary malignant melanoma of the urethra is a rare tumour (0.2% of all melanomas) that most commonly affects the meatus and distal urethra and is three times more common in women than men. Case. A 76-year-old lady presented with vaginal pain and discharge. On examination, a 4 cm mass was noted in the vagina and biopsy confirmed melanoma of a balloon type. Preoperative CT showed no distant metastases and an MRI scan of the pelvis demonstrated no associated lymphadenopathy. She underwent anterior exenterative surgery and vaginectomy also. Histology confirmed a urethral nodular malignant melanoma. Discussion. First-line treatment of melanoma is often surgical. Adjuvant treatment including chemotherapy, radiotherapy, or immunotherapy has also been reported. Even with aggressive management, malignant melanoma of the urogenital tract generally has a poor prognosis. Recurrence rates are high and the mean period between diagnosis and recurrence is 12.5 months. A 5-year survival rate of less than 20% has been reported in balloon cell melanomas along with nearly 20% developing local recurrence. Conclusion. To the best of our knowledge, this case is the first report of balloon cell melanoma arising in the urethra. The presentation and surgical management has been described and a literature review provided.

Diagnosis of a liver abscess with Ga-67 and radiocolloid tomography.

A 46 year-old white male with fever of unknown origin demonstrated a multiloculated hepatic cyst on abdominal CT. Persistent fever and leukocytosis prompted Tc-99m Sulfur colloid liver-spleen and gallium-67 citrate imaging to identify a possible liver abscess. SPECT imaging provided pertinent clinical information that allowed the diagnosis of abscess to be made.

A 15-year longitudinal analysis of trends in elective urological surgery - an evidence base for Modernising Medical Careers.

INTRODUCTION: The impact of Modernising Medical Careers on the differential need for consultant urologists and urological surgeons is as yet unknown. This study's aim was to determine what changes there had been in operative urological activity so as to predict the need for urological surgeons in the future. MATERIALS AND METHODS: A retrospective study of all elective operative urological surgery over a 15-year period was performed. The absolute numbers of patients presenting for different grades of surgery were aggregated and analysed using the Spearman's rank correlation test. RESULTS: Aggregated data from 27,839 procedures demonstrated no change in the number of operations (r 0.01; NS) or the number of diagnostic endoscopic procedures (r 0.21; NS) carried out over the study period. There was a decrease in endoscopic surgery related to a 70% reduction in trans-urethral resection of the prostate (TURP) (r -0.89; P = <0.0001) and an increase in ureteroscopic interventions (r 0.82; P = 0.0002) for stone disease. There was no change in the amount of major surgery carried out (r -0.43; NS) over the 15 years. CONCLUSIONS: There have been changes to the pattern of surgery urologists have provided over the last 15 years but the need for complex surgical interventions has not altered. This suggests there will be as great a need for operating surgeons in the future, as currently exists.

Differential radiosensitisation by ZD1839 (Iressa), a highly selective epidermal growth factor receptor tyrosine kinase inhibitor in two related bladder cancer cell lines.

The epidermal growth factor receptor (EGFR) is expressed in a wide variety of epithelial tumours including carcinoma of the bladder. Stimulation of the EGFR pathway is blocked by ZD1839 (Iressa), a highly selective EGFR tyrosine kinase inhibitor. Radical radiotherapy is an established organ sparing treatment option for muscle invasive bladder cancer and this study has explored the possibility for the use of ZD1839 as a radiosensitiser in this scenario. The effect of combination treatment with ZD1839 (0.01 microM) and ionising radiation in the established bladder cancer cell lines MGH-U1 and its radiosensitive mutant clone S40b was measured by clonogenic assays. A highly significant radiosensitising effect was seen in both cell lines (P < 0.001 for MGH-U1 and S40b cell lines). This effect was independent of the concentration of the drug and the duration of exposure prior to treatment with ionising radiation. Cell cycle kinetics of both cell lines was not significantly altered with ZD1839 (0.01 microM) as a single agent. A modest induction of apoptosis was observed with ZD1839 (0.01 microM) as a single agent, but a marked induction was observed with the combination treatment of ZD1839 and ionising radiation. These results suggest a potentially important role for ZD1839 in combination with radiotherapy in the treatment of muscle invasive bladder cancer.

Polysaccharide produced by Anacystis nidulans: its ecological implication.

An extracellular polysaccharide from Anacystis nidulans was extracted from cell-free medium. Analysis showed that the polysaccharide consisted of glucose, galactose, and mannose in the ratio of 60:14:20. The production of polysaccharide depends on the age of culture, the growth temperature, and the form of nitrogen available.

Acid phosphatase production as an aid in rapid characterization of Candida species.

Yeast isolates were tested for phosphatase activity, using p-nitrophenyl phosphate substrate. Several Candida species displayed characteristic patterns. The enzyme activity was absent in all except one of the 78 isolates of Candida albicans tested. C. tropicalis, C. pseudotropicalis, and C. krusei were the most consistent and active enzyme producers. Enzyme production by these yeasts was not influenced by the amount of growth or a decrease in the pH of the culture media. The characteristic enzyme activity of these three yeasts was demonstrated in the presence of concentrations of inorganic phosphate which inhibited the enzyme activity of other Candida species. The activity of isolates of C. gullermondii, C. parapsilosis, and C. stellatoidea was variable, although none of these were strong enzyme producers. It seems feasible to use phosphatase activity as a simple and rapid additional method for the separation of C. albicans from closely related species of the genus.

An evaluation of gemcitabines differential radiosensitising effect in related bladder cancer cell lines.

The aim of this study was to establish the radiosensitising properties of gemcitabine in a pair of related bladder tumour cell lines with differential radiosensitivity. The radioresistant bladder tumour cell line MGH-U1 and its radiosensitive mutant clone, S40b (both p53 mutant), had SF(2) values (surviving fraction at 2 Gy) of 0.98 and 0.64, respectively (P<0.001). Colony-forming assays showed that at 0.01 microM gemcitabine radiosensitisation occurred only in the S40b cell line (dose-modifying factor (DMF)=1.4). At 0.3 microM (killing 50% of cells), both cell lines were radiosensitised; DMF=2.25 and 1.2 for MGH-U1 and S40b, respectively. These data suggest that gemcitabine is an effective radiosensitiser in bladder cancer cell lines, with greater sensitisation in the radioresistant parental line-a feature that should be useful in a clinical setting.