M.C. Hayes

Percutaneous cryoablation of renal tumours: outcomes from 171 tumours in 147 patients

To evaluate the technical and oncological efficacy of an image‐guided cryoablation programme for renal tumours.

Evolution of the Southampton Enhanced Recovery Programme for radical cystectomy and the aggregation of marginal gains

To describe and assess the evolution of an enhanced recovery programme (ERP) for open radical cystectomy.

Estramustine Reversal of Resistance to Intravesical Epirubicin Chemotherapy

Objective: Failure of epirubicin treatment of superficial bladder cancer implies multidrug resistance (MDR) which is common. MDR is characterised by decreased cellular levels of drug. TCC cell lines sensitive to epirubicin and resistant to both epirubicin and mitomycin C were used to investigate augmented therapy by adding the MDR reversing agent estramustine to an in vitro model. Methods: Cells were cultured as monolayers. Fluorescence analysis was performed by flow cytometry and confocal microscopy. Cells were exposed to epirubicin 20 µg/ml for 2 h and increasing amounts of estramustine. Cytotoxicity was determined under similar exposure conditions and MTT culture (dye reduction by live cells) allowed viable biomass to be read optically. Results: Resistant cells accumulated eight times less epirubicin than sensitive cells. Confocal microscopy confirmed this for nuclear uptake. Accumulation in resistant cells can be increased to near-sensitive cell levels using 40 µg/ml estramustine. Image analysis of confocal fluorescence showed a shift from cytoplasm to nucleus. This correlated with increased cytotoxicity. Conclusion: Estramustine plus epirubicin chemotherapy can overcome MDR and may achieve more successful tumour killing in vivo. It may also prevent emergence of resistance. Primary TCC culture examination permits detection of sensitive and resistant cells and may predict outcome allowing a more logical treatment selection.

Cellular resistance to mitomycin C is associated with overexpression of MDR‐1 in a urothelial cancer cell line (MGH‐U1)

Objective To compare multidrug resistance (MDR)‐1 and MDR‐3 gene expression in a new urothelial cancer cell line (MGHU‐1, with resistance to mitomycin C) against controls and the established (epirubicin‐resistant) MDR clone, and to correlate MDR with cytotoxicity data.

The nuclear membrane in multidrug resistance: microinjection of epirubicin into bladder cancer cell lines

To assess whether microinjecting epirubicin into cells showing multidrug resistance (MDR, common to many cancers, including bladder cancer, with resistance to, e.g. anthracyclines and mitomycin C) spares the nucleus, as when these drugs accumulate, distribution in MDR cells characteristically spares the nucleus, suggesting that the nuclear membrane is responsible for excluding cytotoxic drugs from MDR nuclei.

Sex Cord Stromal Testicular Tumors: A Clinical Series—Uniformly Stage I Disease

PURPOSE Sex cord stromal testicular tumors are rare. Historically 10% of lesions are said to be malignant but to our knowledge there are no clinical or histological features that can accurately predict potential malignant behavior. Because of this, groups at some centers have advocated prophylactic retroperitoneal lymph node dissection in patients with clinical stage I disease. We reviewed our experience with these tumors to determine whether this policy is justified. MATERIALS AND METHODS We retrospectively reviewed the records of all 38 men older than 18 years with sex cord stromal testicular tumors who were referred to the Wessex regional cancer center for treatment or pathological review during the 25-year period of 1982 to 2006. We then compared our series with a malignant sex cord stromal testicular tumor database generated from the world literature. RESULTS All Wessex patients were treated with excision of the primary tumor alone and metastatic disease developed in none. All remained disease-free with an overall median survival of 6.8 years (range 1.4 to 25). Features in the literature favoring malignant behavior, ie metastatic disease, included larger tumors (mean 6.43 vs 1.71 cm), a high mitotic rate, tumor necrosis, angiolymphatic invasion, infiltrative margins and extratesticular extension (each p <0.0001). The malignant group had an overall median survival of 2.3 years (range 0.02 to 17.3). CONCLUSIONS No patient had disease progression in our study, which is to our knowledge the largest reported United Kingdom series of sex cord stromal testicular tumors. Our data suggest that malignancy is uncommon and prophylactic retroperitoneal lymph node dissection is unjustified for clinical stage I disease.

Intravesical pH: a potentially important variable affecting efficacy and the further development of anthracycline chemotherapy for superficial bladder cancer.

Objective  To assess, using epirubicin‐sensitive and multidrug resistant (MDR) derivatives of human bladder cancer cell lines in vitro, the probable effect of intravesical pH changes, with and without the MDR antagonist verapamil, on the uptake, intracellular distribution and cytotoxicity of epirubicin during intravesical chemotherapy.

The clinical features and management of testicular germ cell tumours in patients aged 60 years and older.

Study Type – Therapy (case series)

Time-lapse live cell imaging and flow analysis of multidrug resistance reversal by verapamil in bladder cancer cell lines

OBJECTIVES To examine the effects of verapamil on the intracellular drug pharmacokinetics of epirubicin using alternative dosing schedules. The results might inform the choices for optimizing clinical chemotherapy. METHODS Sensitive parental (MGH-U1) and multidrug resistant (MDR) (MGH-U1R and MGH-U1-MMC) bladder cancer cell lines were used. Fluorescence time-lapsed studies were performed on cells incubated with epirubicin alone or combined with verapamil. Flow cytometry was performed after the alternative dosing regimens. RESULTS Verapamil reversed the epirubicin localization patterns in MDR cells. Time-lapse imaging showed that nuclear epirubicin accumulation in MDR cells with verapamil followed the parental curve. The maximal reversal took >60 minutes. Flow cytometry showed increased epirubicin uptake in MDR cells co-incubated with verapamil. Preincubation was not as effective as co-incubation. CONCLUSIONS The results of our model indicate that longer exposure to MDR-class drugs, exemplified by epirubicin, increases uptake and the MDR reversing action of co-treatment with verapamil. The present results highlight the need for additional clinical trials of drug dosing and scheduling for combination intravesical chemotherapy regimens.

Case series - adult testicular dermoid tumours--mature teratoma or pre-pubertal teratoma?

Adult testicular dermoid tumours are rare tumours with no reported potential for recurrent or metastatic spread. Despite this they are currently classified as mature teratoma and managed as if they have equivalent malignant potential. This report describes two cases of adult mature teratoma of dermoid type and questions the classification and pathogenesis of this disease. In one of the cases there was a clear history of a testicular lump arising pre-pubertally, raising the possibility that some adult dermoid tumours may in fact be pre-pubertal teratomas that have persisted into adulthood. Classification as a mature teratoma carries with it a follow-up regimen that includes numerous radiological investigations with their attendant radiation exposure. A positive histological diagnosis and separate classification of adult dermoid tumours would allay clinical fears of recurrence and metastasis and negate the need for repeated radiological investigations.