Faculty Bibliography

BACKGROUND: Nephroureterectomy alone fails to adequately treat many patients with advanced upper tract urothelial carcinoma (UTUC). Perioperative platinum-based chemotherapy has been proposed but requires adequate renal function. OBJECTIVE: Our aim was to determine whether the ability to deliver platinum-based chemotherapy following nephroureterectomy is affected by postoperative changes in renal function. DESIGN, SETTINGS, AND PARTICIPANTS: We retrospectively reviewed data on 388 patients undergoing nephroureterectomy for UTUC between 1991 and 2009. Four institutions were included. INTERVENTION: All patients underwent nephroureterectomy. MEASUREMENTS: All patients had serum creatinine measured before and after surgery. The value closest to 3 mo after surgery was taken as the postoperative value (range: 2-52 wk). Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease study equation. eGFR values before and after surgery were compared using the paired t test. We chose an eGFR of 45 and 60 ml/min per 1.73 m(2) as possible cut-offs for chemotherapy eligibility and compared eligibility before and after surgery using the chi-square test. RESULTS AND LIMITATIONS: Our cohort of 388 patients included 233 men (60%) with a median age of 70 yr. Mean eGFR decreased by 24% after surgery. Using a cut-off of 60 ml/min per 1.73 m(2), 49% of patients were eligible for chemotherapy before surgery, but only 19% of patients remained eligible postoperatively. Using a cut-off of 45 ml/min per 1.73 m(2), 80% of patients were eligible preoperatively, but only 55% remained eligible after surgery. This distribution persisted when we limited the analysis to patients with advanced pathologic stage (T3 or higher). Patients older than the median age of 70 yr were more likely to be ineligible for chemotherapy both pre- and postoperatively by either definition, and they were significantly more likely to have an eGFR <45 ml/min per 1.73 m(2) postoperatively, regardless of their starting eGFR. This study is limited by its retrospective nature, and there was some variability in the timing of postoperative serum creatinine measurements. CONCLUSIONS: eGFR is significantly diminished after nephroureterectomy, particularly in elderly patients. These changes in renal function likely affect eligibility for adjuvant cisplatin-based therapy. Accordingly, we suggest strong consideration of neoadjuvant regimens

The surgical management of kidney tumors has significantly evolved over the past decade. Partial nephrectomy and nephron sparing surgery have emerged as the treatments of choice for most newly diagnosed kidney tumors at tertiary care centers. The trend towards an organ sparing approach is largely due to an improved understanding of the global importance of kidney function as well as the impact that kidney surgery may have on non-oncologic morbidity and mortality. In addition to reviewing the methods of evaluating kidney function, this article discusses the effectiveness of various nephron sparing techniques in preserving kidney function and improving non-oncologic outcomes

BACKGROUND:: Most small renal tumors are amenable to partial nephrectomy (PN). Studies have documented the association of radical nephrectomy (RN) with an increased risk of comorbid conditions, such as chronic kidney disease. Despite evidence of equivalent oncologic outcomes, PN remains under used within the United States. In this study, the authors identified the most recent trends in kidney surgery for small renal tumors and determined which factors were associated with the use of PN versus RN within the United States. METHODS:: A population-based patient cohort was analyzed using the Surveillance, Epidemiology and End Results cancer registry (SEER 1999-2006). The authors identified 18,330 patients ages 40 to 90 years who underwent surgery for kidney tumors </=4 cm in the United States between 1999 and 2006. RESULTS:: In total, 11,870 patients (65%) underwent RN, and 6460 patients (35%) underwent PN. The ratio of PN to RN increased yearly (P < .001), representing 45% of kidney surgeries in 2006 for small tumors. There were significant differences in the cohort of patients who underwent PN versus RN, including age, sex, tumor location, marital status, year of treatment, and tumor size. When adjusting for these variables, being a man, age </=70 years, urban residence, smaller tumor size, and more recent treatment year were predictors of PN. CONCLUSIONS:: Although the total numbers of PN procedures increased in the United States between 1999 and 2006, there remains a significant under use of PN, particularly among women, the elderly, and those living in rural locations. Further investigation will be required to determine the reasons for these disparities, and strategies to optimize access to PN need to be developed. Cancer 2010. (c) 2010 American Cancer Society

BACKGROUND:: Procedures performed in the office offer potential cost savings. Recent analyses suggest, however, that a fee-for-service system may incentivize subscale operations and, thus, contribute to excessive spending. The authors of this report sought to characterize changes in the practice of office-based and hospital-based endoscopic bladder surgery after 2005 increases in Medicare reimbursement. METHODS:: All office and hospital-based endoscopic surgeries that were performed in a faculty practice from 2002 through 2007 were identified using billing codes for procedures, diagnoses, and procedure locations and then analyzed using the chi-square test and logistic regression. Costs were estimated based on published Medicare reimbursements for office and hospital-based surgeries. RESULTS:: In total, 1341 endoscopic bladder surgeries were performed, including 764 in the office and 577 in the hospital. After 2005, the odds ratio (OR) for office surgery occurring among all cystoscopies and for surgery occurring in the office versus the hospital was 2.01 (95% confidence interval [CI], 1.71-2.37) and 2.29 (95% CI, 1.83-2.87), respectively. Among all treated lesions that were associated with a diagnosis of bladder cancer and nonbladder cancer, the OR for a procedure occurring in the office versus the hospital was 1.36 (95% CI, 1.07-1.73) and 1.99 (95% CI, 1.52-2.60), respectively. The likelihood of repeat surgery on the same lesion increased after 2005 (OR, 2.86; 95% CI, 1.46-5.62), and the likelihood of an office surgery leading to a bladder cancer diagnosis at the next visit declined (OR, 0.29; 95% CI, 0.16-0.51). The overall estimated expenditure increased by 50%. CONCLUSIONS:: After 2005, more bladder lesions were identified and treated in the office. In a single group practice, office treatment of bladder cancer did not fully explain this new practice pattern, suggesting a lowered threshold for office intervention. Cancer 2010. (c) 2010 American Cancer Society

BACKGROUND: MLH1 is one of six known genes responsible for DNA mismatch repair (MMR), whose inactivation leads to HNPCC. It is important to develop genotype-phenotype correlations for HNPCC, as is being done for other hereditary cancer syndromes, in order to guide surveillance and treatment strategies in the future. CASE PRESENTATION: We report a 47 year-old male with hereditary nonpolyposis colorectal cancer (HNPCC) associated with a novel germline mutation in MLH1. This patient expressed a rare and severe phenotype characterized by three synchronous primary carcinomas: ascending and splenic flexure colon adenocarcinomas, and ureteral carcinoma. Ureteral neoplasms in HNPCC are most often associated with mutations in MSH2 and rarely with mutations in MLH1. The reported mutation is a two base pair insertion into exon 10 (c.866_867insCA), which results in a premature stop codon. CONCLUSION: Our case demonstrates that HNPCC patients with MLH1 mutations are also at risk for ureteral neoplasms, and therefore urological surveillance is essential. This case adds to the growing list of disease-causing MMR mutations, and contributes to the development of genotype-phenotype correlations essential for assessing individual cancer risk and tailoring of optimal surveillance strategies. Additionally, our case draws attention to limitations of the Amsterdam Criteria and the need to maintain a high index of suspicion when newly diagnosed colorectal cancer meets the Bethesda Criteria. Establishment of the diagnosis is the crucial first step in initiating appropriate surveillance for colorectal cancer and other HNPCC-associated tumors in at-risk individuals

PURPOSE: Compared with partial nephrectomy, radical nephrectomy increases the risk of chronic kidney disease, which is a significant risk factor for cardiovascular events and death. Given equivalent oncological efficacy in patients with small renal tumors, radical nephrectomy may result in overtreatment. We analyzed a population based cohort of patients to determine whether radical nephrectomy is associated with an increase in cardiovascular events and mortality compared with partial nephrectomy. MATERIALS AND METHODS: Using Surveillance, Epidemiology and End Results cancer registry data linked with Medicare claims we identified 2,991 patients older than 66 years who were treated with radical or partial nephrectomy for renal tumors 4 cm or less between 1995 and 2002. The primary end points of cardiovascular events and overall survival were assessed using Kaplan-Meier survival estimation, Cox proportional hazards regression and negative binomial regression. RESULTS: A total of 2,547 patients (81%) underwent radical nephrectomy and 556 (19%) underwent partial nephrectomy. During a median followup of 4 years 609 patients experienced a cardiovascular event and 892 died. When adjusting for preoperative demographic and comorbid variables, radical nephrectomy was associated with an increased risk of overall mortality (HR 1.38, p <0.01) and a 1.4 times greater number of cardiovascular events after surgery (p <0.05). However, radical nephrectomy was not significantly associated with time to first cardiovascular event (HR 1.21, p = 0.10) or with cardiovascular death (HR 0.95, p = 0.84). CONCLUSIONS: Radical nephrectomy, which is currently the most common treatment for small renal tumors, may be associated with significant, adverse treatment effects compared with partial nephrectomy. Partial nephrectomy should be considered in most patients with small renal tumors

Nephron preservation has been increasingly prioritized in the treatment of small renal tumors. Radical nephrectomy is now understood as a risk factor for development of chronic kidney disease, which is known to increase the risk of cardiovascular events and all-cause mortality. Indications for nephron-sparing surgery (NSS) have broadened from solitary kidney, bilateral tumors, and hereditary tumor syndromes to essentially all small renal tumors. Laparoscopic NSS has demonstrated excellent cancer control as well as good functional preservation despite the need for warm ischemia. There has been ongoing debate regarding safe parameters for warm ischemia, which are thought to vary with patient factors. Focal ablative therapies have been developed for use in high-risk surgical candidates (eg, radiofrequency ablation, cryoablation) to minimize renal and other treatment-related morbidity. Emphasis on minimally invasive approaches and advances in preventing renal dysfunction and other morbidity after NSS will guide the future of these therapies