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1.  Oncolytic Viruses in the Treatment of Bladder Cancer 
Advances in Urology  2012;2012:404581.
Bladder carcinoma is the second most common malignancy of the urinary tract. Up to 85% of patients with bladder cancer are diagnosed with a tumor that is limited to the bladder mucosa (Ta, T1, and CIS). These stages are commonly termed as non-muscle-invasive bladder cancer (NMIBC). Although the treatment of NMIBC has greatly improved in recent years, there is a need for additional therapies when patients fail bacillus Calmette-Guérin (BCG) and chemotherapeutic agents. We propose that bladder cancer may be an ideal target for oncolytic viruses engineered to selectively replicate in and lyse tumor cells leaving normal cells unharmed. In support of this hypothesis, here we review current treatment strategies for bladder cancer and their shortcomings, as well as recent advancements in oncolytic viral therapy demonstrating encouraging safety profiles and antitumor activity.
PMCID: PMC3414001  PMID: 22899907
2.  Surgical management of stage T1 renal tumours at Canadian academic centres 
The proportion of patients with stage 1 renal tumours receiving partial nephrectomy is considered a quality of care indicator. The objective of this study was to characterize surgical practice patterns at Canadian academic institutions for the treatment of these tumours.
The Canadian Kidney Cancer Information System (CKCis) is a multicentre collaboration of 13 academic institutions in Canada. All patients with pathologic stage T1 renal tumours in CKCis were identified. Descriptive statistics were performed to characterize practice patterns over time. Associations between patient, tumour, and treatment factors with the use of partial nephrectomy were determined.
From 1988 to April 2014, 1453 patients with pathologic stage 1 renal tumours were entered in the CKCis database. Of these, 977 (67%) patients had pT1a tumours; of these, 765 (78%) received partial nephrectomy. Of the total number of patients (1453), 476 (33%) had pT1b tumours; of these, 204 (43%) received partial nephrectomy. The use of partial nephrectomy increased over time from 60% to 90% for pT1a tumours and 20% to 60% for pT1b tumours. Stage pT1b (relative risk [RR] 0.56, 95% confidence interval [CI] 0.50–0.63) and minimally invasive surgical approach (RR 0.78, 95% CI 0.73–0.84 for pT1a and RR 0.23, 95% CI 0.17–0.30 for pT1b) were associated with decreased use of partial nephrectomy. Most patient factors including age, gender, body mass index, hypertension, and renal function were not significantly associated with use of partial nephrectomy (p > 0.05).
Almost all pT1a and most pT1b renal tumours managed surgically at academic centres in Canada receive partial nephrectomy. The use of partial versus radical nephrectomy appears to occur independently of patient age and comorbid status, which may indicate that urologists are performing partial nephrectomy whenever technically feasible based on tumour factors. Although the ideal proportion patients receiving partial nephrectomy cannot be determined, treatment distribution observed in this cohort may indicate an achievable case distribution among experienced surgeons.
PMCID: PMC4455632  PMID: 26085866
3.  Detecting functional changes with [18F]FAZA in a renal cell carcinoma mouse model following sunitinib therapy 
EJNMMI Research  2014;4:27.
The multitargeting tyrosine kinase inhibitor (TKI) sunitinib is currently the first-line drug therapy for metastasizing renal cell carcinoma (RCC). TKIs have profound effects on tumor angiogenesis, leading to modifications of the tumor microenvironment. The goal of this study was to determine whether these treatment-induced changes can be detected with [18F]FAZA.
The present study utilized positron emission tomography (PET) to analyze tumor oxygenation status during and after sunitinib therapy in the murine Caki-1 RCC tumor model. Dynamic and static scans were performed, as well as ex vivo biodistributions at 3 h post injection (p.i.). Immunohistochemical analysis of tumor tissue was carried out for the quantification of pimonidazole binding and the hypoxia-associated factors CD-31, Ki-67, and Von Willebrand factor (VWF). In addition, in vitro cellular uptake studies were done to analyze the direct effects of sunitinib on the Caki-1 cells.
During therapy with sunitinib (40 mg/kg/day), uptake of [18F]FAZA into Caki-1 mice decreased by 46 ± 5% (n = 4; 5 days) at 3 h post injection (p.i.) during the first study and 22 ± 5% (n = 8; 9 days) during the long-term study, indicating a decrease in the tumor's hypoxia level. However, when drug therapy was stopped, this effect was reversed completely, and the tumor [18F]FAZA uptake increased to 126 ± 6% (n = 6) of the control tumor uptake, indicative of an even higher level of tumor hypoxia compared to the therapy starting point. Sunitinib had no direct effect on [18F]FAZA uptake into Caki-1 cells in vitro.
[18F]FAZA PET could be used to monitor drug response during sunitinib therapy in RCC and may guide combination therapies based on the tumor's hypoxia status.
PMCID: PMC4451188  PMID: 26116107
Renal cell carcinoma; Tyrosine kinase inhibitor; Sunitinib; [18F]FAZA
5.  Antitumor Efficacy of Intravesical BCG, Gemcitabine, Interferon-α and Interleukin-2 as Mono- or Combination-Therapy for Bladder Cancer in an Orthotopic Tumor Model 
To reduce adverse effects and improve efficacy of intravesical BCG for bladder cancer, alternative treatment options were investigated in an orthotopic rat tumor model.
Superficial bladder cancer was established in syngeneic female rat bladders by instillation of AY-27 cells. Animals were randomly assigned to treatment groups including dose escalation of intravesical BCG with or without interferon-α (IFN-α) or interleukin-2 (IL-2); or graded doses of gemcitabine alone; or BCG plus gemcitabine. Treatments were given twice weekly for 3 weeks. Rats in control groups received saline instillations. Treatment response was monitored by animals’ well-being, survival days, tumor growth inhibition, and histological examination at necropsy.
Rats receiving monotherapy with intravesical BCG, gemcitabine, or IFN-α, attained significantly better survival and tumor reduction compared with control (P = 0.002; 0.001; 0.002, respectively, Log-rank Test). A dose-dependent treatment response was observed in animals with established bladder tumor receiving escalated BCG instillations. Only high-dose BCG significantly improved animal survival. Although high-dose BCG plus gemcitabine or IFN-α did not increase benefit over monotherapies, low-dose BCG plus IL-2 did show improved efficacy (P = 0.01).
Intravesical monotherapies with gemcitabine and IFN-α were as effective as BCG for treatment of early non-muscle-invasive urothelial bladder cancer in this immune competent rat model. Combining these agents with high-dose BCG did not further increase efficacy. However, combining low-dose BCG with IL-2 enhanced BCG effectiveness.
PMCID: PMC3201113  PMID: 22084620
BCG; bladder cancer; gemcitabine; interferon-α; intravesical therapy
6.  Laser photoablation of renal pelvic tumours 
We evaluated the clinical effects of the Zeiss OPMILAS (Oberkochen, Germany) multi–yttrium–aluminum–garnet (YAG) laser in the treatment of renal pelvic tumours as an alternative to nephroureterectomy. Four patients with evidence of transitional cell carcinoma (TCC) in the renal pelvis and a previous history of TCC of the bladder or opposite renal pelvis were treated with the Zeiss OPMILAS multi-YAG laser. Three patients underwent a retrograde ureteroscopic approach and 1 patient required percutaneous resection. Two wavelengths were used: 1060 nm continuous coagulative mode and 1440 nm pulsed ablative mode. The patients were followed for 12, 24, 76 and 84 months, respectively. Two patients showed no evidence of recurrence as determined by cystoscopy, retrograde pyelography and selective pelvic urine cytology. One patient experienced a recurrence of TCC requiring subsequent treatment. The ureteroscopic approach was associated with fewer complications and a more rapid recovery, compared with the percutaneous approach. All patients with solitary kidneys avoided dialysis.
PMCID: PMC2532556  PMID: 18781220
7.  Rhabdomyolysis following renal autotransplantation 
A 26-year-old male body builder diagnosed with renal artery stenosis and middle aortic syndrome underwent an autotransplantation with bench reconstruction and end-to-end anastomosis using the hypogastric artery. Shortly after the procedure, the patient developed rhabdomyolysis and renal insufficiency, possibly related to his increased muscle mass, potentially greater susceptibility to hypertrophic skeletal muscle cells or his unique vascular condition. We review the risk factors, diagnosis, management and outcome of a case of rhabdomyolysis in a male patient who underwent autotransplantation for renal vascular hypertension.
PMCID: PMC2422887  PMID: 18542734
8.  Malignant spinal cord compression secondary to testicular seminoma at the time of initial presentation and at relapse while on surveillance 
We report cases of 2 pure seminoma patients who developed metastatic spinal cord compressions. One patient was diagnosed at age 33 years with stage 1 seminoma and, after undergoing an orchidectomy, chose to be followed on a surveillance protocol. He was lost to follow-up and presented again 22 months later with back pain, leg weakness and sensory loss when his disease recurred as a spinal cord compression. He was treated with urgent surgical decompression and subsequent standard chemotherapy. More than 2 years posttreatment, he is disease-free with normal neurologic function in his lower extremities. The second patient presented at age 44 years with back pain and rapid loss of leg strength and sensation. Investigations revealed a malignant cord compression with lymphatic and vertebral body metastases. On physical examination, the patient was found to have a 6-cm left testicular mass. He was treated with emergency radiotherapy to the region of his cord compression followed by a left inguinal orchidectomy. Pathology confirmed a pure classic seminoma. Postoperatively, he received standard chemotherapy and eventually regained neurologic function in his legs. Although it is rare for malignant spinal cord compression to occur in seminoma patients—either as the initial presentation of disease or as a site of disease recurrence in stage 1 patients on surveillance—it is crucial to consider seminoma as a possible etiology in young men diagnosed with malignant spinal cord compression because timely contemporary treatments for seminoma will cure most of these patients and offer them excellent functional recovery.
PMCID: PMC2422929  PMID: 18542765

Results 1-8 (8)