Alexander Kutikov

The R.E.N.A.L. Nephrometry Score: A Comprehensive Standardized System for Quantitating Renal Tumor Size, Location and Depth

PURPOSEnTreatment decisions for renal malignancies depend largely on qualitative data, including a description of tumor anatomy and the experience of the treating surgeon. Currently characterization of renal tumor anatomical elements is descriptive and lacks standardization. Surgical decision making and data set comparisons would be significantly enhanced by a consistent, reproducible system that quantitates the pertinent characteristics of localized renal lesions. We have developed and propose a standardized nephrometry scoring system (R.E.N.A.L. Nephrometry Score) to quantify the anatomical characteristics of renal masses on computerized tomography/magnetic resonance imaging.nnnMATERIALS AND METHODSnThe nephrometry score is based on 5 critical and reproducible anatomical features of solid renal masses. Of the 5 components 4 are scored on a 1, 2 or 3-point scale with the 5th indicating the anterior or posterior location of the mass relative to the coronal plane of the kidney. We applied the R.E.N.A.L. Nephrometry Score to 50 consecutive masses resected at Fox Chase Cancer Center.nnnRESULTSnThe R.E.N.A.L. Nephrometry Score consists of (R)adius (tumor size as maximal diameter), (E)xophytic/endophytic properties of the tumor, (N)earness of tumor deepest portion to the collecting system or sinus, (A)nterior (a)/posterior (p) descriptor and the (L)ocation relative to the polar line. The suffix h (hilar) is assigned to tumors that abut the main renal artery or vein. The nephrometry scoring system accurately classified the complexity of 50 consecutive tumors undergoing excision at our institution.nnnCONCLUSIONSnStandardized reporting of renal tumor size, location and depth is essential for decision making and effective comparisons. The R.E.N.A.L. Nephrometry Score is a reproducible standardized classification system that quantitates the salient anatomy of renal masses. This novel approach for the systematic characterization of renal tumors provides a tool for meaningful comparisons of renal masses in clinical practice and in the urological literature.

Objective Measures of Renal Mass Anatomic Complexity Predict Rates of Major Complications Following Partial Nephrectomy

BACKGROUNDnThe association between tumor complexity and postoperative complications after partial nephrectomy (PN) has not been well characterized.nnnOBJECTIVEnWe evaluated whether increasing renal tumor complexity, quantitated by nephrometry score (NS), is associated with increased complication rates following PN using the Clavien-Dindo classification system (CCS).nnnDESIGN, SETTING, AND PARTICIPANTSnWe queried our prospectively maintained kidney cancer database for patients undergoing PN from 2007 to 2010 for whom NS was available.nnnINTERVENTIONSnAll patients underwent PN.nnnMEASUREMENTSnTumors were categorized into low- (NS: 4-6), moderate- (NS: 7-9), and high-complexity (NS: 10-12) lesions. Complication rates within 30 d were graded (CCS: I-5), stratified as minor (CCS: I or 2) or major (CCS: 3-5), and compared between groups.nnnRESULTS AND LIMITATIONSnA total of 390 patients (mean age: 58.0 ± 11.9 yr; 66.9% male) undergoing PN (44.6% open, 55.4% robotic) for low- (28%), moderate- (55.6%), and high-complexity (16.4%) tumors (mean tumor size: 3.74 ± 2.4 cm; median: 3.2 cm) from 2007 to 2010 were identified. Tumor size, estimated blood loss, and ischemia time all significantly differed (p<0.0001) between groups; patient age, body mass index (BMI), and operative time were comparable. When stratified by CCS, minor and major complication rates for all patients were 26.7% and 11.5%, respectively. Minor complication rates were comparable (26.6 vs. 24.9 vs 32.8%; p=0.45), whereas major complication rates differed (6.4 vs. 11.1 vs. 21.9%; p=0.009) among tumor complexity groups. Controlling for age, gender, BMI, type of surgical approach, operative duration, and tumor complexity, prolonged operative time (odds ratio [OR]: 1.01; confidence interval [CI], 1.0-1.02) and high tumor complexity (OR: 5.4; CI, 1.2-24.2) were associated with the postoperative development of a major complication. Lack of external validation is a limitation of this study.nnnCONCLUSIONSnIncreasing tumor complexity is associated with the development of major complications after PN. This association should be validated externally and integrated into the decision-making process when counseling patients with complex renal tumors.

Laparoscopic Pyeloplasty in the Infant Younger Than 6 Months—Is it Technically Possible?

PURPOSEnLaparoscopic dismembered pyeloplasty is an acceptable option for UPJ obstruction in the pediatric population. We report our initial experience with this approach in infants.nnnMATERIALS AND METHODSnEight infants 3 to 5 months old (mean 4.5) underwent transperitoneal laparoscopic pyeloplasty for ureteropelvic junction obstruction. All patients underwent dismembered pyeloplasty with renal pelvis tapering. Two patients underwent concomitant pyelolithotomy and 1 underwent contralateral nephrectomy. Outcome measures included operative time, length of hospital stay, and resolution of obstruction by ultrasonography and DRI.nnnRESULTSnMean operative time was 1.8 hours for the pyeloplasty portion. Mean hospital stay was 1.2 days. The stent was removed 6 weeks postoperatively in all patients except 1. This patient, 1 of the 2 patients who underwent concomitant pyelolithotomy, had development of a new stone while the stent was still indwelling. Laparoscopic pyeloplasty resulted in 100% resolution of UPJ obstruction in this series.nnnCONCLUSIONSnWe believe that laparoscopic dismembered pyeloplasty is technically possible in infants younger than 6 months.

A Literature Review of Renal Surgical Anatomy and Surgical Strategies for Partial Nephrectomy

CONTEXTnA detailed understanding of renal surgical anatomy is necessary to optimize preoperative planning and operative technique and provide a basis for improved outcomes.nnnOBJECTIVEnTo evaluate the literature regarding pertinent surgical anatomy of the kidney and related structures, nephrometry scoring systems, and current surgical strategies for partial nephrectomy (PN).nnnEVIDENCE ACQUISITIONnA literature review was conducted.nnnEVIDENCE SYNTHESISnSurgical renal anatomy fundamentally impacts PN surgery. The renal artery divides into anterior and posterior divisions, from which approximately five segmental terminal arteries originate. The renal veins are not terminal. Variations in the vascular and lymphatic channels are common; thus, concurrent lymphadenectomy is not routinely indicated during PN for cT1 renal masses in the setting of clinically negative lymph nodes. Renal-protocol contrast-enhanced computed tomography or magnetic resonance imaging is used for standard imaging. Anatomy-based nephrometry scoring systems allow standardized academic reporting of tumor characteristics and predict PN outcomes (complications, remnant function, possibly histology). Anatomy-based novel surgical approaches may reduce ischemic time during PN; these include early unclamping, segmental clamping, tumor-specific clamping (zero ischemia), and unclamped PN. Cancer cure after PN relies on complete resection, which can be achieved by thin margins. Post-PN renal function is impacted by kidney quality, remnant quantity, and ischemia type and duration.nnnCONCLUSIONSnSurgical renal anatomy underpins imaging, nephrometry scoring systems, and vascular control techniques that reduce global renal ischemia and may impact post-PN function. A contemporary ideal PN excises the tumor with a thin negative margin, delicately secures the tumor bed to maximize vascularized remnant parenchyma, and minimizes global ischemia to the renal remnant with minimal complications.nnnPATIENT SUMMARYnIn this report we review renal surgical anatomy. Renal mass imaging allows detailed delineation of the anatomy and vasculature and permits nephrometry scoring, and thus precise, patient-specific surgical planning. Novel off-clamp techniques have been developed that may lead to improved outcomes.

Perioperative Outcomes of Robotic and Open Partial Nephrectomy for Moderately and Highly Complex Renal Lesions

PURPOSEnWe compared outcomes in patients undergoing robotic vs open partial nephrectomy stratified by moderately and highly complex tumor nephrometry scores.nnnMATERIALS AND METHODSnPatients treated with partial nephrectomy from 2007 to 2010 were grouped by tumor characteristics into low-nephrotomy score 4 to 6, moderate-7 to 9 and high-10 to 12 anatomical complexity cohorts. Lesions with low complexity were excluded from study. Demographic, surgical and pathological outcomes were compared between patients undergoing robotic vs open partial nephrectomy in the moderately and highly complex cohorts.nnnRESULTSnA total of 281 patients, of whom 63.3% were male, with a mean±SD age of 58.1±11.7 years and a mean followup of 21.3±16.3 months underwent partial nephrectomy. Moderately complex lesions were noted in 81 robotic and 136 open partial nephrectomy cases with a mean tumor size of 3.8±2.2 cm. Highly complex lesions were noted in 10 robotic and 54 open partial nephrectomy cases with a mean tumor size of 4.8±3.0 cm. There were no differences between the groups in patient age, race, gender, body mass index or American Society of Anesthesiologists classification. Cases treated with open partial nephrectomy for moderately or highly complex lesions were of higher pathological stage (p=0.02 and 0.01, respectively). The percent change in creatinine and the glomerular filtration rate were similar for robotic and open partial nephrectomy in the moderately and highly complex tumor groups. In patients undergoing robotic vs open partial nephrectomy for moderately complex lesions we noted differences in pathological tumor size (mean 3.2±1.8 vs 4.1±2.3 cm, p<0.0001) and operative time (205.9±52.5 vs 189.5±52.0 minutes, p<0.01) while decreased estimated blood loss (131.3±127.8 vs 256.5±291.3 ml) and hospital length of stay (3.7±1.6 vs 5.6±3.9 days, each p<0.001) were observed in the robotic group. Comparison of highly complex lesions revealed decreased hospital length of stay (2.9±1.4 vs 6.1±4.1 days, p<0.0001) in the robotic partial nephrectomy group.nnnCONCLUSIONSnIn our large institutional series of patients with moderate and highly complex solid renal tumors classified by the nephrometry score robotic partial nephrectomy offered comparable perioperative and functional outcomes with the added benefit of decreased hospital length of stay.

Competing Risks of Death in Patients with Localized Renal Cell Carcinoma: A Comorbidity Based Model

PURPOSEnMultiple risks compete with cancer as the primary cause of death. These factors must be considered against the benefits of treatment. We constructed a model of competing causes of death to help contextualize treatment trade-off analyses in patients with localized renal cell carcinoma.nnnMATERIALS AND METHODSnWe identified 6,655 individuals 66 years old or older with localized renal cell carcinoma in the linked SEER (Surveillance, Epidemiology and End Results)-Medicare data set for 1995 to 2005. We used Fine and Gray competing risks proportional hazards regression to predict probabilities of competing mortality outcomes. Prognostic markers included race, gender, tumor size, age and the Charlson comorbidity index score.nnnRESULTSnAt a median followup of 43 months, age and comorbidity score strongly correlated with patient mortality and were most predictive of nonkidney cancer death, as measured by concordance statistics. Patients with localized, node negative kidney cancer had a low 3 (4.7%), 5 (7.5%) and 10-year (11.9%) probability of cancer specific death but a significantly higher overall risk of death from competing causes within 3 (10.9%), 5 (20.1%) and 10 years (44.4%) of renal cell carcinoma diagnosis, depending on comorbidity score.nnnCONCLUSIONSnInformed treatment decisions regarding patients with solid tumors must integrate not only cancer related variables but also factors that predict noncancer death. We established a comorbidity based predictive model that may assist in patient counseling by allowing quantification and comparison of competing risks of death in patients 66 years old or older with localized renal cell carcinoma who elect to proceed with surgery.

Assessing the burden of complications after surgery for clinically localized kidney cancer by age and comorbidity status.

OBJECTIVEnTo examine the association between high-risk patient status (age >75 years or Charlson comorbidity index count >2) and postoperative complications in patients undergoing surgical management for clinically localized renal tumors.nnnMATERIALS AND METHODSnPatients undergoing radical nephrectomy (RN) or partial nephrectomy (PN) (2005-2012) for localized renal cell carcinoma were analyzed. Multivariate logistic regressions were used to test the association between high-risk status and postoperative complications adjusting for patient, tumor, and operative characteristics.nnnRESULTSnOf 1092 patients undergoing PN (71.9%) or RN (28.1%) for clinically localized renal tumors, 255 (23.4%) were classified as high risk, and 175 patients (16%) developed at least 1 complication (mean 1.6 ± 1.0). Of note, 22.4% and 14.1% of high- and low-risk patients developed a complication, respectively (P = .002). Comparing high- and low-risk patients, significant differences in Clavien I-II (20.4% vs 11.1%; P <.001) and medical (16.1% vs 8.1%, P <.001) complications were observed, whereas no differences were seen in Clavien III-V or surgical complications. No differences in complications were observed comparing patients treated with RN and PN, albeit high-risk patients were more likely to undergo RN (35.3% vs 25.9%, P = .04). After adjustment, the odds of incurring any complication were 1.9 times higher in high- compared with low-risk patients (odds ratio 1.9 [confidence interval 1.3-2.8]).nnnCONCLUSIONnRegardless of surgical type, patients deemed high risk by age and comorbidity criteria were more likely to incur a postoperative complication after renal mass resection. Improved understanding of surgical risks in the elderly and infirmed will help better inform patients deciding between active surveillance and resection of renal tumors.

Piperlongumine promotes autophagy via inhibition of Akt/mTOR signalling and mediates cancer cell death

Background:The Akt/mammalian target of rapamycin (mTOR) signalling pathway serves as a critical regulator of cellular growth, proliferation and survival. Akt aberrant activation has been implicated in carcinogenesis and anticancer therapy resistance. Piperlongumine (PL), a natural alkaloid present in the fruit of the Long pepper, is known to exhibit notable anticancer effects. Here we investigate the impact of PL on Akt/mTOR signalling.Methods:We examined Akt/mTOR signalling in cancer cells of various origins including prostate, kidney and breast after PL treatment. Furthermore, cell viability after concomitant treatment with PL and the autophagy inhibitor, Chloroquine (CQ) was assessed. We then examined the efficacy of in vivo combination treatment using a mouse xenograft tumour model.Results:We demonstrate for the first time that PL effectively inhibits phosphorylation of Akt target proteins in all tested cells. Furthermore, the downregulation of Akt downstream signalling resulted in decrease of mTORC1 activity and autophagy stimulation. Using the autophagy inhibitor, CQ, the level of PL-induced cellular death was significantly increased. Moreover, concomitant treatment with PL and CQ demonstrated notable antitumour effect in a xenograft mouse model.Conclusions:Our data provide novel therapeutic opportunities to mediate cancer cellular death using PL. As such, PL may afford a novel paradigm for both prevention and treatment of malignancy.

Enucleation of renal cell carcinoma with ablation of the tumour base

To retrospectively assess the effectiveness of cancer control with enucleation of renal cell carcinoma (RCC), which is surgically expedient, allows preservation of maximal renal parenchyma, and makes intraoperative renal ischaemia unnecessary, by two surgeons routinely enucleating renal tumours and ablating the tumour bed with argon beam and the Nd‐YAG laser.

Percutaneous vs surgical cryoablation of the small renal mass: is efficacy compromised?

Study Type – Therapy (systematic review) u2028Level of Evidenceu20031b