Miki Haifler

Renal Mass Biopsy: Always, Sometimes, or Never?

Renal mass biopsy is a useful clinical tool; nevertheless, in a majority of patients, renal mass biopsy in its current form does not alter clinical management. Its routine use in all-comers is not indicated outside of clinical protocols.

Current Role of Renal Biopsy in Urologic Practice

Most small renal masses (SRMs) are indolent. In fact, only approximately 80% of SRMs are malignant. Furthermore, SRMs are commonly detected in elderly and comorbid patients. Therefore, opportunities for better care intensity calibration exist. Renal mass biopsy (RMB), when appropriately used, is a valuable clinical tool to help with critical clinical decision-making in patients with SRM. This article summarizes the role of modern RMB in helping gauge care for patients with SRM.

External Validation of Contact Surface Area as a Predictor of Postoperative Renal Function in Patients Undergoing Partial Nephrectomy

Purpose We sought to externally validate a mathematical formula for tumor contact surface area as a predictor of postoperative renal function in patients undergoing partial nephrectomy for renal cell carcinoma. Materials and Methods We queried a prospectively maintained kidney cancer database for patients who underwent partial nephrectomy between 2014 and 2016. Contact surface area was calculated using data obtained from preoperative cross‐sectional imaging. The correlation between contact surface area and perioperative variables was examined. The correlation between postoperative renal functional outcomes, contact surface area and the R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines and tumor touches main renal artery or vein) nephrometry score was also assessed. Results A total of 257 patients who underwent partial nephrectomy had sufficient data to enter the study. Median contact surface area was 14.5 cm2 (IQR 6.2–36) and the median nephrometry score was 9 (IQR 7–10). Spearman correlation analysis showed that contact surface area correlated with estimated blood loss (rs = 0.42, p <0.001), length of stay (rs = 0.18, p = 0.005), and percent and absolute change in the estimated glomerular filtration rate (rs = –0.77 and –0.78, respectively, each p <0.001). On multivariable analysis contact surface area and nephrometry score were independent predictors of the absolute change in the estimated glomerular filtration rate (each p <0.001). ROC curve analysis revealed that contact surface area was a better predictor of a greater than 20% postoperative decline in the estimated glomerular filtration rate compared with the nephrometry score (AUC 0.94 vs 0.80). Conclusions Contact surface area correlated with the change in postoperative renal function after partial nephrectomy. It can be used in conjunction with the nephrometry score to counsel patients about the risk of renal functional decline after partial nephrectomy.

Update on Renal Mass Biopsy

Renal masses are diagnosed with an increasing frequency. However, a significant proportion of these masses are benign, and the majority of malignant tumors are biologically indolent. Furthermore, renal tumors are often harbored by the elderly and comorbid patients. As such, matching of renal tumor biology to appropriate treatment intensity is an urgent clinical need. Renal mass biopsy is currently a very useful clinical tool that can assist with critical clinical decision-making in patients with renal mass. Yet, renal mass biopsy is associated with limitations and, as such, may not be appropriate for all patients.

The convergent roles of NF-κB and ER stress in sunitinib-mediated expression of pro-tumorigenic cytokines and refractory phenotype in renal cell carcinoma

Renal cell carcinoma (RCC) is the most common form of kidney cancer. While cure remains exceptionally infrequent in RCC patients with systemic or recurrent disease, current targeted molecular strategies, including multi-targeted tyrosine kinase inhibitors (TKIs), notably changed the treatment paradigm of advanced renal cancer. Yet, complete and durable responses have been noted in only a few cases. Our studies reveal that sunitinib triggers two resistance-promoting signaling pathways in RCC cells, which emanate from the endoplasmic reticulum (ER) stress response: a PERK-driven ER stress response that induces expression of the pro-tumorigenic cytokines IL-6, IL-8, and TNF-α, and a TRAF2-mediated NF-κB survival program that protects tumor cells against cell death. PERK blockade completely prevents sunitinib-induced expression of IL-6, IL-8 and TNF-α, whereas NF-κB inhibition reinstates sensitivity of RCC cells to sunitinib both in vitro and in vivo. Taken together, our findings indicate that ER stress response may contribute to sunitinib resistance in RCC patients.

SWIR dispersive Raman spectroscopy for discrimination of normal and malignant kidney tissue (Conference Presentation)

Kidney cancer affects 65,000 new patients every. As computerized tomography became ubiquitous, the number of small, incidentally detected renal masses increased. About 6,000 benign cases are misclassified radiographically as malignant and removed surgically. Raman spectroscopy (RS) has been widely demonstrated for disease discrimination, however intense near-infrared auto-fluorescence of certain tissues (e.g kidney) can present serious challenges to bulk tissue diagnosis. A 1064nm excitation dispersive detection RS system demonstrated the ability to collect spectra with superior quality in tissues with strong auto-fluorescence. Our objective is to develop a 1064 nm dispersive detection RS system capable of differentiating normal and malignant renal tissue. We will report on the design and development of a clinical system for use in nephron sparing surgeries. We will present pilot data that has been collected from normal and malignant ex vivo kidney specimens using a benchtop RS system. A total of 93 measurements were collected from 12 specimens (6 Renal Cell Carcinoma, 6 Normal ). Spectral classification was performed using sparse multinomial logistic regression (SMLR). Correct classification by SMLR was obtained in 78% of the trials with sensitivity and specificity of 82% and 75% respectively. We will present the association of spectral features with biological indicators of healthy and diseased kidney tissue. Our findings indicate that 1064nm RS is a promising technique for differentiation of normal and malignant renal tissue. This indicates the potential for accurately separating healthy and cancerous tissues and suggests implications for utilizing RS for optical biopsy and surgical guidance in nephron sparing surgery.

Contemporary utilization trends of systemic chemotherapy for upper tract urothelial carcinoma (UTUC).

441 Background: There is currently no consensus regarding the use of systemic therapy (ST) for surgically-treated patients with invasive UTUC. Using a large national cancer registry, our objective was to assess temporal trends in utilization of ST for stage II-IV UTUC undergoing definitive resection. Methods: The National Cancer Database (NCDB) was queried for all patients surgically treated (nephroureterectomy, segmental resection) for stage II-IV UTUC from 1998-2012. Temporal trends in receipt of ST [neoadjuvant (NAT), adjuvant (AT), or unknown timing (UKT)] were assessed using chi square analyses. After exclusion of patients receiving NAT or UKT, adjusting for patient and clinicopathologic characteristics, multivariable logistic models were used to examine the association between clinicopathologic characteristics and receipt of ST within 9 months of resection. Kaplan Meier analyses and stratified log-rank tests were performed comparing overall survival (OS) between patients receiving ST < 9 months and ...

Harnessing Proteinuria as a Predictor of Postsurgical Outcomes in Kidney Cancer Patients

Care of patients with kidney cancer pivots on a nuanced balance of risk [1]. When faced with a patient with a renal mass, the urologist must carefully weigh the risks of forgoing intervention against the risks of treatment. When treatment is selected, numerous factors that are rooted in inherent trade-offs of each intervention and shaped by each patient’s age and comorbidity profile should guide each clinical decision [2]. One of the most important, and recently hotly debated, factors that direct kidney cancer management is the effect of posttreatment renal function on patients’ long-term outcomes. Chronic kidney disease (CKD) is known to be strongly associated with cardiovascular morbidity and allcause mortality [3]. As such, the urology community has embraced nephron-sparing surgery (NSS) as the reference standard treatment for patients with a renal mass, and retrospective assessments of institutional and administrative data sets support the use of NSS whenever possible [2]. Nevertheless, issues with selection bias [4] and the prospective trial conducted by the European Organization for Research and Treatment of Cancer that revealed an unanticipated improved survival for patients undergoing radical nephrectomy (RN) on an intention-to-treat analysis [5] has given the urologic community pause about recommending partial nephrectomy in all patients where additional risks of NSS may outweigh its theoretical benefits [2]. NSS for large and anatomically complex renal masses harbors potential risks not associated with RN [2]. Thus it is increasingly important to better risk-stratify patients prior to treatment for small renal masses to understand who may stand to benefit most from nephron preservation. In this context, the study by Zhang and colleagues [6] is noteworthy because it harnesses the latest progress from the field of nephrology and takes the first steps toward