Igor Frank

An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: The SSIGN score

PURPOSE Currently outcome prediction in renal cell carcinoma is largely based on pathological stage and tumor grade. We developed an outcome prediction model for patients treated with radical nephrectomy for clear cell renal cell carcinoma, which was based on all available clinical and pathological features significantly associated with death from renal cell carcinoma. MATERIALS AND METHODS We identified 1,801 adult patients with unilateral clear cell renal cell carcinoma treated with radical nephrectomy between 1970 and 1998. Clinical features examined included age, sex, smoking history, and signs and symptoms at presentation. Pathological features examined included 1997 TNM stage, tumor size, nuclear grade, histological tumor necrosis, sarcomatoid component, cystic architecture, multifocality and surgical margin status. Cancer specific survival was estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to test associations between features studied and outcome. The selection of features included in the multivariate model was validated using bootstrap methodology. RESULTS Mean followup was 9.7 years (range 0.1 to 31). Estimated cancer specific survival rates at 1, 3, 5, 7 and 10 years were 86.6%, 74.0%, 68.7%, 63.8% and 60.0%, respectively. Several features were multivariately associated with death from clear cell renal cell carcinoma, including 1997 TNM stage (p <0.001), tumor size 5 cm. or greater (p <0.001), nuclear grade (p <0.001) and histological tumor necrosis (p <0.001). CONCLUSIONS In patients with clear cell renal cell carcinoma 1997 TNM stage, tumor size, nuclear grade and histological tumor necrosis were significantly associated with cancer specific survival. We present a scoring system based on these features that can be used to predict outcome.

Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up

B7-H1 participates in T-cell costimulation functioning as a negative regulator of immunity. Recent observations suggest that B7-H1 is expressed by renal cell carcinoma (RCC) tumor cells and is associated with poor prognosis. However, outcome analyses have been restricted to patients with fresh-frozen tissue and limited follow-up. We report the clinical effect of B7-H1 in RCC patients with a median of 10 years of follow-up. Between 1990 and 1994, 306 patients underwent nephrectomy for clear cell RCC and had paraffin tissue available for review. We did immunohistochemistry with anti-B7-H1 and conducted outcome analyses. Among the 306 patients, 73 (23.9%) harbored tumors with B7-H1 expression. Patients with tumor B7-H1 were at a significantly increased risk of both death from RCC [risk ratio (RR), 3.92; P < 0.001] and overall mortality (RR, 2.37; P < 0.001). The 5-year cancer-specific survival rates were 41.9% and 82.9% for patients with and without tumor B7-H1, respectively. In a multivariate model, tumor B7-H1 remained associated with cancer-specific death even after adjusting for tumor-node-metastasis stage, grade, and performance status (RR, 2.00; P = 0.003). In the subset of 268 patients with localized RCC, tumor B7-H1 was significantly associated with metastatic cancer progression (RR, 3.46; P < 0.001) and death from RCC (RR, 4.13; P < 0.001) even after adjusting for stage, grade, and performance status (RR, 1.78, P = 0.036). RCC patients with tumor B7-H1 are at significant risk of rapid cancer progression and accelerated rates of mortality. B7-H1 may function as a key determinant in RCC, abrogating immune responses directed against this immunogenic tumor.

Every Minute Counts When the Renal Hilum Is Clamped During Partial Nephrectomy

BACKGROUND The safe duration of warm ischemia during partial nephrectomy remains controversial. OBJECTIVE Our aim was to evaluate the short- and long-term renal effects of warm ischemia in patients with a solitary kidney. DESIGN, SETTING, AND PARTICIPANTS Using the Cleveland Clinic and Mayo Clinic databases, we identified 362 patients with a solitary kidney who underwent open (n=319) or laparoscopic (n=43) partial nephrectomy using warm ischemia with hilar clamping. MEASUREMENTS Associations of warm ischemia time with renal function were evaluated using logistic or Cox regression models first as a continuous variable and then in 5-min increments. RESULTS AND LIMITATIONS Median tumor size was 3.4 cm (range: 0.7-18.0 cm), and median ischemia time was 21 min (range: 4-55 min). Postoperative acute renal failure (ARF) occurred in 70 patients (19%) including 58 (16%) who had a glomerular filtration rate (GFR) <15 ml/min per 1.73 m(2) within 30 d of surgery. Among the 226 patients with a preoperative GFR >or=30 ml/min per 1.73 m(2) and followed >or=30 d, 38 (17%) developed new-onset stage IV chronic kidney disease during follow-up. As a continuous variable, longer warm ischemia time was associated with ARF (odds ratio: 1.05 for each 1-min increase; p<0.001) and a GFR<15 (odds ratio: 1.06; p<0.001) in the postoperative period, and it was associated with new-onset stage IV chronic kidney disease (hazard ratio: 1.06; p<0.001) during follow-up. Similar results were obtained adjusting for preoperative GFR, tumor size, and type of partial nephrectomy in a multivariable analysis. Evaluating warm ischemia in 5-min increments, a cut point of 25 min provided the best distinction between patients with and without all three of the previously mentioned end points. Limitations include the retrospective nature of the study. CONCLUSIONS Longer warm ischemia time is associated with short- and long-term renal consequences. These results suggest that every minute counts when the renal hilum is clamped.

Sarcomatoid renal cell carcinoma: an examination of underlying histologic subtype and an analysis of associations with patient outcome.

A sarcomatoid component can occur in all histologic subtypes of renal cell carcinoma (RCC) and indicates an aggressive tumor. We studied 2381 patients treated with radical nephrectomy for RCC between 1970 and 2000. A urologic pathologist reviewed the microscopic slides from all tumor specimens for the presence of a sarcomatoid component, defined as a RCC with any malignant spindle cell component. All tumors with a sarcomatoid component were classified as nuclear grade 4. A total of 120 (5.0%) patients had RCC with a sarcomatoid component, including 94 who died of RCC at a mean of 1.4 years following nephrectomy (median 8 months; range 44 days to 10 years). Cancer-specific survival rates at 2 and 5 years following nephrectomy were 33.3% and 14.5%, respectively. The presence of distant metastases at the radical nephrectomy and histologic tumor necrosis were significantly associated with death from RCC among patients with sarcomatoid RCC. Patients with clear cell (conventional) RCC and chromophobe RCC were more likely to have tumors with a sarcomatoid component (5.2% and 8.7%, respectively) compared with patients with papillary RCC (1.9%). The presence of a sarcomatoid component was significantly associated with death from RCC for all three subtypes (P < 0.001). Even among patients with grade 4 clear cell RCC, the presence of a sarcomatoid component was significantly associated with outcome, both univariately (risk ratio 1.59; P = 0.010) and after adjusting for TNM stage, tumor size, and histologic tumor necrosis (risk ratio 1.46; P = 0.037).

PD-L1 (B7-h1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: Associations with localized stage progression

PD‐L1 (programmed death ligand 1, B7‐H1) is a cell surface glycoprotein that can impair T‐cell function. PD‐L1 is aberrantly expressed by multiple human malignancies and has been shown to carry a highly unfavorable prognosis in patients with kidney cancer. The role of PD‐L1 was evaluated as a mechanism for local stage progression in urothelial carcinoma (UC) of the bladder.

Renal Function After Partial Nephrectomy: Effect of Warm Ischemia Relative to Quantity and Quality of Preserved Kidney

OBJECTIVE To evaluate the effects of warm ischemia time (WIT) and quantity and quality of kidney preserved on renal functional recovery after partial nephrectomy (PN). The effect of WIT relative to these other parameters has recently been challenged. METHODS We identified 362 consecutive patients with a solitary kidney who had undergone PN using warm ischemia. Multivariate models with multiple imputations were used to evaluate the associations with acute renal failure and new-onset stage IV chronic kidney disease (CKD). RESULTS The median WIT was 21 minutes (range 4-55), the median percentage of kidney preserved was 80% (range 25%-98%), and the median preoperative glomerular filtration rate (GFR) was 61 mL/min/1.73 m2 (range 11-133). Postoperative acute renal failure occurred in 70 patients (19%). Of the 226 patients with a preoperative GFR>30 mL/min/1.73 m2, 38 (17%) developed new-onset stage IV CKD during follow-up. On multivariate analysis, the WIT (P=.021), percentage of kidney preserved (P=.009), and preoperative GFR (P<.001) were significantly associated with acute renal failure, and only the percentage of kidney preserved (P<.001) and preoperative GFR (P<.001) were significantly associated with new-onset stage IV CKD during follow-up. Using our previously published cutpoint of 25 minutes, a WIT of >25 minutes remained significantly associated with new-onset stage IV CKD in a multivariate analysis adjusting for the quantity and quality factors (hazard ratio 2.27, P=.049). CONCLUSION Our results have validated that the quality and quantity of kidney are the most important determinants of renal function after PN. In addition, we have also demonstrated that the WIT remains an important modifiable feature associated with short- and long-term renal function. The precision of surgery, maximizing the amount of preserved, vascularized parenchyma, should be a focus of study for optimizing the PN procedure.

Nomenclature of Natural Orifice Translumenal Endoscopic Surgery (NOTES™) and Laparoendoscopic Single-Site Surgery (LESS) Procedures in Urology

INTRODUCTION The twenty first century has witnessed some amazing advancements in surgery. In urology minimally invasive surgery has become the standard treatment for many disease processes and procedures. One of the newest innovations into this field has been the development of Natural Orifice Translumenal Endoscopic Surgery (NOTES) and Laparoendoscopic Single-site Surgery (LESS). While the practice and application of these new techniques are in their infancy, there has been a great deal of confusion regarding the nomenclature and terminology associated with these procedures. The aim of this publication is to attempt to define the many issues associated with the standardization of terminology for these procedures in order to promote effective scientific progress and communication. MATERIALS AND METHODS A literature search using Medline and pubmed focusing on all terminology to describe NOTES and LESS from 1990 to 2008 was done. In addition, various acronyms were searched using four separate online acronym databases. The information was recorded by number of citations and by the number of citations specific to the urologic literature. Based on common usage, definitions and criteria were developed to describe these procedures for current scientific publication. These terms were then collectively reviewed and agreed upon by the Urologic NOTES Working Group as a platform for consensus to begin the arduous process of standardization. RESULTS There is wide variation in the terminology and use of acronyms for natural orifice translumenal endoscopic surgery and laparo-endoscopic single-site surgery. The keyword literature search uncovered 8710 citations from MEDLINE and pubmed, with 363 citations specific to urology. There was significant overlap in the search of different terms. The search of established abbreviation and acronym databases revealed many citations, but relatively few specific to urology. CONCLUSION Standardization of the nomenclature applied to natural orifice transluminal endoscopic surgery (NOTES) and laparo-endoscopic single-site surgery (LESS) is essential as the body of literature continues to grow in order to allow clear and precise scientific communication. As the techniques continue to evolve, we propose that NOTES and LESS be designated as the common terms to define these new procedures in urology.

Histologic coagulative tumor necrosis as a prognostic indicator of renal cell carcinoma aggressiveness

Prognostic markers for renal cell carcinoma (RCC), such as patient symptoms, tumor stage, tumor size, and tumor grade, are useful for determining appropriate follow‐up and selecting patients for adjuvant therapy. Histologic coagulative tumor necrosis, also reported to be a prognostic marker for RCC, has not previously been extensively described or investigated. Hence, the objective of the current study was to characterize tumor necrosis as a prognostic feature of RCC.

Consensus statement on natural orifice transluminal endoscopic surgery and single-incision laparoscopic surgery: heralding a new era in urology?

Matthew T. Gettman *, Geoffrey Box , Timothy Averch , Jeffrey A. Cadeddu , Edward Cherullo , Ralph V. Clayman , Mihr Desai , Igor Frank , Indebir Gill , Mantu Gupta , Georges-Pascal Haber , Mitchell Humphreys , Jihad Kaouk , Jaime Landman , Estevao Lima , Lee Ponsky e Mayo Clinic, Department of Urology, Rochester, MN, United States University of California Irvine, CA, United States University of Pittsburgh Medical Center, PA, United States University of Texas Southwestern Medical Center, Dallas, TX, United States Case Western Reserve University, Cleveland, OH, United States Cleveland Clinic, Cleveland, OH, United States Columbia University Medical Center, New York, NY, United States University of Minho, School of Health Science, Braga, Portugal

T-Cell Coregulatory Molecule Expression in Urothelial Cell Carcinoma: Clinicopathologic Correlations and Association with Survival

Purpose: Aberrant expression of T-cell coregulatory molecules has been investigated as a mechanism by which certain cancers may evade host immune surveillance. We evaluated expression of the T-cell coregulators B7-H1, B7-H3, and PD-1 in urothelial cell carcinoma (UCC) of the bladder. Experimental Design: Immunohistochemistry for B7-H1, B7-H3, and PD-1 was done on paraffin-embedded sections from 318 consecutive patients with UCC who underwent radical cystectomy. Expression was correlated with clinicopathologic outcomes and postoperative survival. Results: B7-H3 was widely expressed in UCC, as 222 of 314 (70.7%) tumors showed positive staining. Expression of B7-H3 in UCC was significantly increased compared with adjacent, nontumor urothelium, as a median of 70% of tumor cells expressed B7-H3, compared with 20% of cells in nontumor specimens (P < 0.001). The increase in B7-H3 expression was independent of tumor stage (P = 0.13). Expression of B7-H1 by UCC tumors (P < 0.001) and PD-1 by tumor-infiltrating lymphocytes (P = 0.012) were significantly associated with increased pathologic stage. Patients who had received intravesical bacillus Calmette-Guerin before cystectomy tended to show increased expression of B7-H3 (P = 0.023) and PD-1 (P = 0.071) but were less likely to express B7-H1 (P = 0.027). Moreover, for the subset of patients with organ-confined disease (n = 167), B7-H1 expression independently predicted all-cause mortality after cystectomy (hazard ratio, 3.18; 95% confidence interval, 1.74-5.79; P < 0.001). Conclusions: B7-H3 is highly expressed in UCC across tumor stages, whereas B7-H1 and PD-1 expression are associated with advanced disease. B7-H1 expression predicts mortality after cystectomy for patients with organ-confined tumors. These molecules may represent novel diagnostic or prognostic markers, as well as therapeutic targets, for patients with UCC.