Faculty Bibliography

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

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