Faculty Bibliography

BACKGROUND: A 64-year-old man with a history of hypertension and type II diabetes mellitus presented to his primary care physician for his annual health examination. Renal ultrasonography revealed a solid right renal mass, which was confirmed by MRI. The initial consultant recommended laparoscopic radical nephrectomy. The patient sought a second opinion. INVESTIGATIONS: Physical examination, baseline serum creatinine level, urine cytology, CT urogram and renal ultrasonography. DIAGNOSIS: Centrally located subcortical tumor arising from the renal parenchyma. MANAGEMENT: Open partial nephrectomy. There were no intraoperative complications and the patient's postoperative course was uneventful

Aberrant expression of vascular endothelial growth factor (VEGF) is associated with human prostate cancer (PCa) metastasis and poor clinical outcome. We found that both phosphorylation of cyclic AMP-responsive element-binding protein (CREB) and VEGF levels were significantly elevated in patient bone metastatic PCa specimens. A PCa ARCaP progression model demonstrating epithelial-to-mesenchymal transition exhibited increased CREB phosphorylation and VEGF expression as ARCaP cells became progressively more mesenchymal and bone-metastatic. Activation of CREB induced, whereas inhibition of CREB blocked, VEGF expression in ARCaP cells. CREB may regulate VEGF transcription via a hypoxia-inducible factor-dependent mechanism in normoxic conditions. Activation of CREB signaling is involved in the coordinated regulation of VEGF and may pre-dispose to PCa bone metastasis

With the widespread use of abdominal imaging, there has been a substantial increase in the detection of incidental, small renal masses. This change has resulted in a downward trend in the size and stage of tumors being detected, and a corresponding increase in the number of renal cortical tumors amenable to partial nephrectomy. Based solely on a size criterion of 7 cm or less (pT1), nearly 70% of all patients with newly diagnosed kidney tumors are eligible for partial nephrectomy. Here, we briefly review the current rationale for partial nephrectomy and provide insight into advances in the technique of open partial nephrectomy. In addition to describing in detail the surgical techniques used at our institution, we also report the outcomes of our series of open partial nephrectomies performed via a mini-flank incision above the 11th rib. We believe that this approach offers a safe, practical and easily adoptable alternative to traditional open partial nephrectomy and laparoscopic partial nephrectomy

A significant number of men with prostate cancer will experience biochemical failure following treatment with primary radiation therapy. For patients with biopsy-proven recurrent cancer confined to the prostate, local salvage therapy may be a potentially curative treatment option. Most men, however, do not undergo local salvage therapy owing to difficulties in diagnosis as well as concerns over treatment-related complications in the salvage setting. Recently, improvements in technique and technology have substantially reduced the morbidity associated with locally ablative therapies, resulting in an increased interest in the use of minimally invasive therapies such as brachytherapy, cryotherapy, and high-intensity focused ultrasound in the salvage setting. Although these treatments are well tolerated, concerns remain over incomplete and inadequate treatment with locally ablative therapies. Future studies are required to appropriately select candidates for salvage ablative therapies and to determine the long-term oncologic efficacy of these treatments

PURPOSE: Recurrent or radioresistant prostate cancer occurs in approximately 30% of men receiving primary radiotherapy. For men who are candidates for local salvage therapy, the oncological efficacy of ablative therapies may be affected by the anatomical and pathological features of cancers within irradiated prostate glands. We characterized and mapped the prostate cancers in our series of whole mount salvage radical prostatectomy specimens. MATERIALS AND METHODS: A total of 47 salvage radical prostatectomies were performed at our institution between 2000 and 2004. Detailed pathological data, including the anatomical distribution of cancers, were obtained from 46 whole mount salvage radical prostatectomy specimens. RESULTS: A total of 70 cancer foci were identified in 46 specimens. Of the specimens 93% had cancer foci at the apex. The median minimum cancer-to-urethra distance was smallest at the apex (4.1 mm) and greatest at the base (13.8 mm). More than 65% of patients had cancer 5 mm or less from the urethra and 7% of patients had cancer directly involving the urethra. Nearly half of all patients had evidence of extraprostatic disease. CONCLUSIONS: The anatomical and pathological features in our study demonstrate that a significant portion of irradiated cancers are pathologically advanced and distributed in regions of the prostate (apical and periurethral) which are at risk for undertreatment using current ablative therapies. Our findings raise serious concerns regarding the oncological efficacy of such treatment modalities. Long-term studies without the use of hormonal therapy are needed to determine the oncological efficacy of salvage ablative therapies in patients with radiorecurrent or resistant prostate cancer

Since the advent of effective chemotherapeutic regimens for treating transitional cell carcinoma, multimodal therapy has become part of the contemporary management of patients with muscle-invasive bladder cancer. However, radical cystectomy with pelvic lymphadenectomy remains the cornerstone of treatment for patients with localized and regionally advanced muscle-invasive disease. The effectiveness of chemotherapy models in bladder cancer can depend greatly on the quality of surgery. Unfortunately, without sufficient level I data, the boundaries of lymphadenectomy and the diagnostic and therapeutic ramifications of variations in the pelvic lymph node dissection remain undetermined. This article examines the role of pelvic lymph node dissection during perioperative chemotherapy and discusses the current challenges in establishing standards for lymphadenectomy in patients undergoing treatment for muscle-invasive bladder cancer

PURPOSE: The emergence of laparoscopic nephron sparing surgery has rekindled interest in the impact of warm renal ischemia on renal function. To provide data with which warm renal ischemia can be compared we analyzed short-term and long-term changes in the glomerular filtration rate after temporary cold renal ischemia. MATERIALS AND METHODS: In patients undergoing open nephron sparing surgery the estimated glomerular filtration rate was assessed preoperatively, early in the postoperative hospital stay, and 1 and 12 months after surgery using the abbreviated Modification of Diet in Renal Disease Study equation. We separately analyzed 70 patients with a solitary kidney and 592 with 2 functioning kidneys. The end point was the percent change from the baseline glomerular filtration rate. A linear regression model was used to test the association between the glomerular filtration rate change, and ischemia time, patient age, tumor size, estimated blood loss and intraoperative fluid administration. RESULTS: Median cold ischemia time was 31 minutes in patients with a solitary kidney and 35 minutes in those with 2 kidneys. Compared to patients with 2 kidneys those with a solitary kidney had a significantly lower preoperative estimated glomerular filtration rate (p < 0.001), which decreased a median of 30% during the early postoperative period, and 15% and 32% 1 and 12 months after surgery, respectively. In patients with 2 kidneys the corresponding glomerular filtration rate decreases were 16%, 13% and 14%, respectively. On multivariate analyses in each group cold ischemia duration and intraoperative blood loss were significantly associated with early glomerular filtration rate changes. However, 12 months after surgery age was the only independent predictor of a glomerular filtration rate decrease in patients with 2 kidneys. CONCLUSIONS: Cold renal ischemia during nephron sparing surgery is a significant determinant of the short-term postoperative glomerular filtration rate. Longer clamping time is particularly detrimental in patients with a solitary kidney but it does not appear to influence long-term renal function. Patients of advanced age may be less likely to recover from acute ischemic renal injury

BACKGROUND: Chronic kidney disease is a graded and independent risk factor for substantial comorbidity and death. We aimed to examine new onset of chronic kidney disease in patients with small, renal cortical tumours undergoing radical or partial nephrectomy. METHODS: We did a retrospective cohort study of 662 patients with a normal concentration of serum creatinine and two healthy kidneys undergoing elective partial or radical nephrectomy for a solitary, renal cortical tumour (</=4 cm) between 1989 and 2005 at a referral cancer centre. Glomerular filtration rate (GFR) was estimated with the abbreviated Modification in Diet and Renal Disease Study equation. Separate analysis was undertaken, with chronic kidney disease defined as GFR lower than 60 mL/min per 1.73 m(2) and GFR lower than 45 mL/min per 1.73 m(2). FINDINGS: 171 (26%) patients had pre-existing chronic kidney disease before surgery. After surgery, the 3-year probability of freedom from new onset of GFR lower than 60 mL/min per 1.73 m(2) was 80% (95% CI 73-85) after partial nephrectomy and 35% (28-43; p<0.0001) after radical nephrectomy; corresponding values for GFRs lower than 45 mL/min per 1.73 m(2) were 95% (91-98) and 64% (56-70; p<0.0001), respectively. Multivariable analysis showed that radical nephrectomy remained an independent risk factor for patients developing new onset of GFR lower than 60 mL/min per 1.73 m(2) (hazard ratio 3.82 [95% CI 2.75-5.32]) and 45 mL/min per 1.73 m(2) (11.8 [6.24-22.4]; both p<0.0001). INTERPRETATION: Because the baseline kidney function of patients with renal cortical tumours is lower than previously thought, accurate assessment of kidney function is essential before surgery. Radical nephrectomy is a significant risk factor for the development of chronic kidney disease and might no longer be regarded as the gold standard treatment for small, renal cortical tumours