Radical nephrectomy and intracaval thrombectomy for advanced renal cancer with extensive inferior vena cava involvement utilising cardiopulmonary bypass and hypothermic circulatory arrest: Is it worthwhile?

OBJECTIVE: To report our long-term outcomes of surgical treatment of renal tumours with inferior vena cava (IVC) tumour thrombus above the hepatic veins, utilising cardiopulmonary bypass (CBP) and hypothermic circulatory arrest (HCA), as surgical resection remains the only effective treatment for renal cancers with extensive IVC tumour thrombus. PATIENTS AND METHODS: We retrospectively reviewed 48 consecutive patients (median age 58 years) who underwent surgical treatment for non-metastatic renal cancer with IVC tumour thrombus extending above the hepatic veins. Perioperative, histological, disease-free (DFS) and overall survival (OS) data were recorded. RESULTS: Tumour thrombus was level III in 23 patients and level IV in 25 patients. The median (range) CBP and HCA times were 162 (120-300) min and 35 (9-64) min, respectively. Three patients underwent synchronous cardiac surgical procedures. There were three (6.3%) perioperative deaths. American Society of Anesthesiologists grade and perioperative blood transfusion requirement were significant factors associated with perioperative death (P < 0.05). Despite extensive preoperative screening for metastases the median (range) DFS was only 10.2 (1.2-224.4) months. The median (range) OS was 23 (0-224.4) months. Cox regression analysis revealed that perinephric fat invasion conferred a significantly poorer DFS (P = 0.005). CONCLUSIONS: Radical surgery for patients with extensive IVC tumour thrombus has acceptable operative morbidity and mortality. It provides symptom palliation and the possibility of long-term survival. Improvements in preoperative detection of occult metastasis may improve case selection and newer adjuvant therapies may improve survival in this high-risk group.

Claudin-11 decreases the invasiveness of bladder cancer cells.

The expression of claudin-11 in benign and malignant bladder tissue and the effect of forced expression of claudin-11 on tight junction function and invasiveness of bladder cancer cells were studied. Claudin-11 expression was tested in bladder cancer cell lines (T24/83, RT 112/84 and EJ138) using reverse transcription-polymerase chain reaction (RT-PCR) and in benign and malignant bladder tissue by quantitative RT-PCR and immunohistochemistry. T24/83 cells were transfected with the pcDNA.1/NT-GFP-TOPO vector containing full-length human claudin-11 sequence. Stable-transfected cells overexpressing claudin-11 (T24Cl-11Ex), wild-type cells (T24WT) and the empty plasmid control clone (T24GFP) were compared using transurothelial resistance (TUR), in vitro adhesion, invasion and growth assays. Claudin-11 was strongly expressed in the non-invasive RT112/84 cell line compared to the invasive T24/83 and EJ138 TCC cell lines. Benign bladder tissue demonstrated equal expression of claudin-11 mRNA as carcinoma, but displayed more intense staining than malignant tissue on immunohistochemistry. Forced-expression of claudin-11 in T24/83 cells was confirmed by PCR, immunoprecipitation and by immunofluorescence, which demonstrated increased perinuclear claudin-11 staining. Forced expression of claudin-11 did not affect TUR (p = 0.243), but significantly reduced invasion (p = 0.001) while increasing cell matrix adhesion (p = 0.001) and growth rates (p = 0.001). The greater expression of claudin-11 in benign vs. malignant tissue and non-invasive vs. invasive cell lines, and its effect in reducing bladder cancer cell invasiveness suggests that claudin-11 may have a role in preventing cancer progression and may serve as a therapeutic target in reducing metastasis.

Tight junctions and bladder cancer (review).

Tight junctions play a critical role in the maintenance of the urine-blood barrier creating a physiological barrier to the passage of ions and solutes between the urine and blood. Alterations in this urine-blood barrier function have been demonstrated in some diseases and regulation of the tight junction function has been recognised as an important aspect of the cell biology of cancer in terms of disease progression and as a potential therapeutic target. Although tight junctions play an important role in the physiological control of bladder function, there is little published on their molecular composition or regulation in the normal or diseased bladder. The purpose of this review is to summarise current understanding on the role and regulation of tight junction function in the normal and diseased bladder.

A phase-1 study of sequential mitomycin C and 5-aminolaevulinic acid-mediated photodynamic therapy in recurrent superficial bladder carcinoma.

OBJECTIVE: To report a phase-1 study of patients with recurrent superficial bladder cancer treated with photodynamic therapy (PDT) using sequential mitomycin C and 5-aminolaevulinic acid (ALA). PATIENTS AND METHODS: Twenty-four patients were treated, the primary endpoint being the safety and tolerability of combined therapy at increasing doses of ALA and light. RESULTS: Mitomycin C instillation was followed by ALA concentrations of 6%, 8% or 10%; there was no effect on toxicity. The light dose, at a wavelength of 635 nm, was increased from zero to 25 J/cm(2), with the upper fluences producing transient symptoms. There were no episodes of skin photosensitivity or systemic toxicity. A total fluence of 25 J/cm(2) represented the upper light dose for the tolerability of this procedure by patients. There were no persistently high urinary symptom scores or reduction in functional bladder capacity up to > or =24 months of follow-up. In this group, cumulative tumour recurrences were none at 4, two at 8, six at 12, nine at 18 and 11 at 24 months after PDT, respectively. CONCLUSION: Sequential mitomycin C and ALA-PDT is a safe and well tolerated treatment, with potential for managing difficult-to-control superficial transitional cell carcinoma and carcinoma in situ of the bladder.