Faculty Bibliography

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

OBJECTIVE: To present the complications and early outcomes in a small series of men infected with human immunodeficiency virus (HIV) and treated with radical prostatectomy (RP) for prostate cancer, and to review reports on surgery in HIV-positive patients. PATIENTS AND METHODS: During 2002-2005, seven men infected with HIV underwent RP at our institution. For the five patients whose HIV status was known before surgery, we retrospectively examined preoperative variables, including HIV-specific data (clinical category, CD4+ lymphocyte count, viral load, duration of HIV diagnosis, and opportunistic infections), and the complications and early outcomes after RP. RESULTS: Before RP all the patients were in the Center for Disease Control clinical category A (asymptomatic HIV infection). The CD4+ counts before RP ranged from 269-870 cells/microL and viral loads ranged from <50-18 700 copies/mL. Three patients were on highly active anti-retroviral therapy (HAART) at the time of surgery. After RP, two patients had incisional wound infections, including one requiring re-hospitalization for intravenous antibiotics. During the follow-up (median 26 months) none of the patients progressed to acquired immunodeficiency syndrome or developed biochemical recurrence of prostate cancer. One healthcare worker was exposed to contaminated urine and placed on prophylactic therapy, but has not sero-converted. CONCLUSIONS: The risk of peri-operative complications in HIV-positive patients can be minimized by carefully selecting the patient and procedure, and by measuring routine and HIV-specific preoperative variables. The two infectious complications in this series were in patients with less favourable preoperative factors, i.e. the lowest CD4+ count and the highest viral load. Further experience is needed to determine whether the risk of surgical infections is higher in this cohort. However, our results are consistent with reports from other surgical specialities that surgery in asymptomatic HIV-positive patients is safe and effective

PURPOSE: Pelvic lymph node dissection at the time of radical cystectomy is a crucial component of the surgical management of invasive bladder cancer. No established therapeutic or diagnostic guidelines regarding pelvic lymph node dissection are, however, currently available. We reviewed the past and contemporary literature to clarify the current role of pelvic lymph node dissection both as a staging modality as well as potential therapeutic intervention. RECENT FINDINGS: The role of pelvic lymph node dissection has evolved over the past 60 years. Although the added benefits of radical cystectomy over simple cystectomy alone are accepted, an optimal template for pelvic lymph node dissection has not been established. Increasing evidence suggesting therapeutic and diagnostic benefits by extending the boundaries of lymphadenectomy or by increasing the number of nodes excised has been reported. Much of the recent literature, however, is based on retrospective studies, and is influenced by factors such as node count variability, inconsistencies in the quality of the surgery, and the biases in patient selection. Currently, the optimal boundaries of pelvic lymph node dissection and the minimum number of nodes to be pathologically examined remain undetermined. SUMMARY: The diagnostic and therapeutic benefits obtained by extending the limits of lymphadenectomy are compelling but inconclusive. Establishing standards for pelvic lymph node dissection will not only increase the consistency of staging and improve the design and interpretation of clinical trials in invasive bladder cancer but also help to identify and optimize the therapeutic benefits of lymphadenectomy. Prospective, randomized trials will be needed to properly establish the extent of lymphadenectomy required to obtain such benefits

The classification of urothelial neoplasms of the kidney traditionally has been similar to that of urinary bladder tumors. Several years ago, the classification of papillary urothelial neoplasms was revised. The current study focuses on the application of the 1998 World Health Organization (WHO)/International Society of Urological Pathology classification system to 102 renal pelvic urothelial neoplasms and compares it to the 1973 WHO classification scheme. In this study, all tumors were classified as urothelial carcinomas, and the majority (85%) were papillary. Most patients with papillary tumors presented with 'superficial' disease (< or = pT1). With the 1998 system, most papillary carcinomas were high grade, and were more often invasive as compared to low-grade tumors. Only 34% were low-grade papillary tumors and, of these, most (93%) were noninvasive. With the 1973 system, most papillary tumors were grade 2 or 3, with invasion more common in grade 3 tumors. By 1973 criteria, grade 2 tumors were a heterogeneous group; with 1998 criteria, nearly one-half were high grade and the other half low grade. The grade of papillary urothelial carcinomas with both the 1973 and 1998 grading methods was associated with stage (P=0.001). Our study reveals that papillomas and papillary urothelial neoplasms of low malignant potential are uncommon tumors in the kidney. Renal pelvic papillary urothelial neoplasms are most often carcinomas and are more commonly high grade than low grade. Although both the 1973 and 1998 systems showed a significant association with tumor stage, grade 2 papillary carcinomas are a heterogeneous group by 1973 criteria. The 1998 system provides useful information in that it more clearly defines a papillary tumor's grade and selects for a group of tumors, namely low-grade papillary urothelial carcinomas, for which a low likelihood of invasion can be predicted

PURPOSE: The standard of care for muscle invasive transitional cell carcinoma of the bladder is radical cystectomy. Definitive therapy may often be delayed for various reasons. We assessed whether pathological stage and survival correlated with the length of time between diagnosis of muscle invasion and cystectomy. MATERIALS AND METHODS: The records of 290 consecutive patients who underwent radical cystectomy between February 1987 and July 2000 were reviewed. Of 265 (91.4%) cystectomies performed for transitional cell carcinoma data were available for 247 (85.2%) and 189 (65.2%) patients were identified who underwent surgery for muscle invasive disease (T2 or greater). The interval between diagnosis of muscle invasion and cystectomy was calculated for each patient. Patients were divided into groups based on time to surgery as group 1-less than 4 weeks, 2-4 to 6 weeks, 3-7 to 9 weeks, 4-10 to 12 weeks, 5-13 to 16 weeks, and 6-greater than 16 weeks. Exploratory univariate and multivariate analyses were performed to test the association of time lag with clinical features and postoperative survival. RESULTS: Mean patient age was 66 years (range 37 to 84) and overall 3-year Kaplan-Meier estimated survival was 59.1% +/- 4% (median followup 36 months). For all patients mean interval from diagnosis to cystectomy was 7.9 weeks (range 1 to 40). Extravesical disease (P3a or greater) or positive nodes were identified in 84% (16 of 19) of patients when the delay was longer than 12 weeks, compared with 48.2% (82 of 170) in those with a time lag of 12 weeks or less (p < 0.01). Similarly 3-year estimated survival was lower (34.9% +/- 13.5%) for patients with a surgery delay longer than 12 weeks compared to those with a shorter interval 62.1% +/- 4.5% (hazards ratio 2.51, 95% CI 1.30-4.83, p = 0.006). When adjusted for nodal status, and clinical and pathological stages the interval was still statistically significant (adjusted hazards ratio 1.93, 95% CI 0.99-3.76, p = 0.05). CONCLUSIONS: In patients undergoing radical cystectomy a delay in surgery of greater than 12 weeks was associated with advanced pathological stage and decreased survival. Although this relationship persisted after adjusting for nodal status, and clinical and pathological stages, the presence of lymph node metastasis remained the strongest predictor of patient outcome

Chromosomal gain on 1q23-24 is a cytogenetic finding found in approximately 30% of bladder tumors. Currently, no defined or candidate tumor-associated genes from this region have been identified. The objective of this study was to identify and quantitate the expression of putative cancer genes located at this chromosome locus in normal urothelium, superficial, and muscle invasive bladder tumors. We examined both normal and bladder cancer tissue specimens (N = 40-80 RNA, DNA, and protein) by semiquantitative RT/PCR, genomic PCR, and by Western blotting. The KIAA1096 gene is located at 1q23-24 with no overexpression or amplification in normal urothelium, but was significantly upregulated in 30% of tumors (P = 0.0001). There was a trend towards increased expression in invasive compared to superficial lesions (P = 0.06). A significant increase in gene copy was also found in a 38% of TCC of the bladder compared to normal bladder mucosa or peripheral blood lymphocytes. Immunohistochemistry (IHC) demonstrated KIAA1096 expression in nonmalignant bladder mucosa tissue but apparent upregulation in invasive transitional cell carcinoma. Two other genes, CH1 and RGS5, which are situated in the same region of chromosome 1q, demonstrated disparate patterns of expression. In summary, KIAA1096 is a gene situated at 1q23-24, which demonstrated a pattern of RNA and DNA expression consistent with the 38% expression of cytogenetic amplification noted on previous studies. This gene may, therefore, be a putative marker for this cytogenetic phenomenon and provide an opportunity to evaluate the clinical significance of previous cytogenetic findings