Faculty Bibliography

This article presents the oncological and medical rationale for partial nephrectomy as the treatment of choice whenever possible for T1 renal tumors. The value of partial nephrectomy in the management of small renal cortical tumors is gaining wider recognition thanks to (1) enhanced understanding of the biology of renal cortical tumors; (2) better knowledge about tumor size and stage migration to small tumors at the time of presentation; (3) studies indicating the oncologic efficacy of kidney-sparing surgery, and (4) increasing awareness of the wide prevalence of chronic kidney disease. The overzealous use of radical nephrectomy for small renal tumors must now be considered detrimental to the long-term health and safety of the patient with a small renal cortical tumor

BACKGROUND.: Mortality rates from kidney cancer have continued to rise despite increases in the detection of smaller renal tumors and rates of renal surgery. To explore the factors associated with this treatment-outcome discrepancy, the authors evaluated how changes in tumor size have affected disease progression in patients after nephrectomy for localized kidney cancer, and they sought to identify the factors associated with disease progression and overall patient survival after resection for localized kidney cancer. METHODS.: In total, 1618 patients with localized kidney cancer were identified who underwent nephrectomy at Memorial Sloan-Kettering Cancer Center from 1989 to 2004. Patients were categorized by year of surgery: from 1989 to 1992, from 1993 to 1996, from 1997 to 2000, and from 2001 to 2004. Tumor size was classified according to the following strata: <2 cm, from 2 cm to 4 cm, from 4 cm to 7 cm, and >7 cm. Disease progression was defined as the development of local recurrence or distant metastases. Five-year progression-free survival (PFS) was calculated for patients in each tumor size strata according to the year of operation using the Kaplan-Meier method. The patient-, tumor-, and surgery-related characteristics associated with PFS and overall survival (OS) were explored using univariate analysis, and all significant variables were retained in a multivariate Cox regression analysis. RESULTS.: Overall, the number of nephrectomies increased for all tumor size categories from 1989 to 2004. A tumor size migration was evident during this period, because the proportion of patients with tumors <2 cm and with tumors from 2 cm to 4 cm increased, whereas the proportion of patients with tumors >7 cm decreased. One hundred seventy-nine patients (11%) developed disease progression after nephrectomy. Sixteen patients (1%) developed local recurrences, and 163 patients (10%) developed distant metastases. When 5-year PFS was calculated for each tumor size strata according to 4-year cohorts, trends in PFS did not improve or differ significantly over time. Compared with historic cohorts, patients in more contemporary cohorts were more likely to undergo partial nephrectomy rather than radical nephrectomy and were less likely to undergo concomitant lymph node dissection and adrenalectomy. Multivariate analysis demonstrated that pathologic stage and tumor grade were associated with disease progression, whereas patient age and tumor stage were associated with overall patient survival. CONCLUSIONS.: Despite an increasing number of nephrectomies and a size migration toward smaller tumors, trends in 5-year PFS and OS did not improve or differ significantly over time. These findings require further research to identify causative mechanisms, and they argue for the consideration of active surveillance for patients who have select renal tumors and a re-evaluation of the current treatment paradigm of surgically removing solid renal masses on initial detection. Cancer 2008. (c) 2008 American Cancer Society

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