Louis S Krane

Near-infrared fluorescence imaging to facilitate super-selective arterial clamping during zero-ischaemia robotic partial nephrectomy

There is concern that warm ischaemia time during partial nephrectomy may have an adverse impact on postoperative renal function. As a result, there is increased interest in developing a safe and effective method for performing non‐ischaemic partial nephrectomy. Several novel approaches have recently been described. We present our initial experience performing zero‐ischaemia partial nephrectomy using near‐infrared fluorescence imaging to facilitate super‐selective arterial clamping. We report the operative and early postoperative outcomes from such cases as compared with a matched cohort of patients undergoing traditional partial nephrectomy with clamping of the main renal artery. We show that this technique is both safe and effective and may lead to improved renal preservation at short‐term follow‐up.

Cell Therapy with Human Renal Cell Cultures Containing Erythropoietin-Positive Cells Improves Chronic Kidney Injury

New therapeutic strategies for chronic kidney disease (CKD) are necessary to offset the rising incidence of CKD and donor shortage. Erythropoietin (EPO), a cytokine produced by fibroblast‐like cells in the kidney, has recently emerged as a renoprotective factor with anti‐inflammatory, antioxidant properties. This study (a) determined whether human renal cultures (human primary kidney cells [hPKC]) can be enriched in EPO‐positive cells (hPKC(F+)) by using magnetic‐bead sorting; (b) characterized hPKC(F+) following cell separation; and (c) established that intrarenal delivery of enriched hPKC(F+) cells would be more beneficial in treatment of renal injury, inflammation, and oxidative stress than unsorted hPKC cultures in a chronic kidney injury model. Fluorescence‐activated cell sorting analysis revealed higher expression of EPO (36%) and CD73 (27%) in hPKC(F+) as compared with hPKC. After induction of renal injury, intrarenal delivery of hPKC(F+) or hPKC significantly reduced serum creatinine, interstitial fibrosis in the medulla, and abundance of CD68‐positive cells in the cortex and medulla (p < .05). However, only hPKC(F+) attenuated interstitial fibrosis in the renal cortex and decreased urinary albumin (3.5‐fold) and urinary tubular injury marker kidney injury molecule 1 (16‐fold). hPKC(F+) also significantly reduced levels of renal cortical monocyte chemotactic protein 1 (1.8‐fold) and oxidative DNA marker 8‐hydroxy‐deoxyguanosine (8‐OHdG) (2.4‐fold). After 12 weeks, we detected few injected cells, which were localized mostly to the cortical interstitium. Although cell therapy with either hPKC(F+) or hPKC improved renal function, the hPKC(F+) subpopulation provides greater renoprotection, perhaps through attenuation of inflammation and oxidative stress. We conclude that hPKC(F+) may be used as components of cell‐based therapies for degenerative kidney diseases.

Oncologic Outcomes Following Robot-Assisted Laparoscopic Nephroureterectomy with Bladder Cuff Excision for Upper Tract Urothelial Carcinoma

PURPOSE Robot-assisted laparoscopic nephroureterectomy with bladder cuff excision is a minimally invasive alternative to open surgery for managing upper tract urothelial carcinoma. We report oncologic outcomes following robot-assisted laparoscopic nephroureterectomy with bladder cuff excision. MATERIALS AND METHODS The records of the initial 65 patients who underwent robot-assisted laparoscopic nephroureterectomy with bladder cuff excision for upper tract urothelial carcinoma between 2008 and 2014 were reviewed from our institutional review board approved, prospectively maintained database. All patients underwent surgery with the single docking technique. Baseline demographic features, pathological variables and perioperative data were analyzed. Kaplan-Meier methodology was used for survival analysis. Cox proportional hazards regression was applied to determine the prognostic effect of different variables on survival. RESULTS Mean patient age was 69.1 years. Final pathological evaluation revealed pT2 stage or lower in 65% of patients, pT3 in 28.3% and pT4 in 6.7%. High grade pathological findings were present in 85% of patients, including 13.3% with concomitant carcinoma in situ and 30% with lymphovascular invasion. Median followup was 25.1 months (range 6 to 68.9). At 2 and 5 years overall survival was 86.9% and 62.6%, cancer specific survival was 92.9% and 69.5%, and recurrence-free survival was 65.3% and 57.1%, respectively. A total of 23 patients experienced disease recurrence. Bladder recurrence developed in 15 patients, 12 had isolated bladder recurrence and 8 had metastatic disease. On univariate analysis age greater than 70 years, preoperative hydronephrosis, nodal disease and concomitant carcinoma in situ were significantly associated with decreased recurrence-free survival (p=0.002, 0.04, 0.006 and 0.001, respectively). However, none was statistically significant on multivariate analysis. On univariate analysis impaired preoperative renal function (creatinine greater than 2 mg/dl) and lymphovascular invasion were associated with reduced cancer specific survival (p=0.03 and 0.01, respectively). However, only lymphovascular invasion was associated with decreased cancer specific survival on multivariate analysis (p=0.048). CONCLUSIONS Our reported data on oncologic outcomes following robot-assisted laparoscopic nephroureterectomy with bladder cuff excision for upper tract urothelial carcinoma demonstrate satisfactory oncologic control at intermediate term followup. Long-term outcomes are required to assess true efficacy.

Halofuginone-Coated Urethral Catheters Prevent Periurethral Spongiofibrosis in a Rat Model of Urethral Injury

BACKGROUND AND PURPOSE Urethral strictures are from periurethral spongiofibrosis that develops as a result of urethral trauma, disease, or iatrogenic injury. The spongy tissue that surrounds the strictured urethra has an altered ratio of collagen, with increased collagen type I relative to type III. We evaluated the ability of a urethral catheter that was coated with halofuginone (HF), a potent type I collagen inhibitor, to prevent spongiofibrosis formation in a rat model. MATERIALS AND METHODS HF was coated on silicone catheters and release kinetics were measured. Success of impregnation was evaluated with scanning electron microscopy, serial weights, and drug elution data. Urethral strictures were induced in rats using electrocautery. Half the animals had placement of an HF-coated catheter while the others had uncoated silicone controls. Animals were sacrificed at predetermined time points, and urethral tissue was either processed for staining with Masson trichrome and anti-alpha-1 collagen or digested to determine HF concentration. Serum drug levels were also determined in treated animals. Slides were graded by a pathologist who was blinded to treatment to determine collagen deposition. RESULTS HF was coated successfully on silicone catheters. Local urethral concentration of HF was tenfold higher than serum concentration in treated rats. Animals with HF-coated catheters had no new type I collagen deposition after urethral injury. Control animals had increased periurethral collagen type I deposition, typical of urethral stricture formation. CONCLUSIONS HF can be coated successfully on silicone catheters. HF successfully inhibits periurethral type I collagen deposition after urethral injury. This may become an important therapy to prevent urethral stricture formation or recurrence after endoscopic therapy.

Does Sarcopenia Impact Complications and Overall Survival in Patients Undergoing Radical Nephrectomy for Stage III and IV Kidney Cancer

PURPOSE To investigate the association of sarcopenia (muscle mass wasting) with complications and survival in patients undergoing radical nephrectomy for advanced kidney cancer. PATIENTS AND METHODS We identified 137 patients with stage III and IV kidney cancer who underwent radical nephrectomy between 2008 and 2012. Preoperative cross-sectional imaging was used to measure total psoas area (TPA) at the level of L3 and controlled for height (m(2)). Sarcopenia was identified as TPA in the lowest gender-specific quartile. Patient characteristics and postoperative complications were compared between sarcopenic and nonsarcopenic patients. Kaplan-Meier survival curve estimates were generated for overall and gender-specific survival. RESULTS Preoperative cross-sectional imaging was available for 128 patients (93%, 85 men and 43 women). Mean TPA for men was 5.49 cm(2)/m(2) versus 4.27 cm(2)/m(2) for women (P < 0.05). Sarcopenia was associated with risk of Clavien grade III or higher complication (P = 0.03) and node-positive disease (P = 0.01). Median follow-up was 48.3 months. Kaplan-Meier estimates of overall and gender-specific survival were similar between sarcopenic and nonsarcopenic patients. CONCLUSION Sarcopenia appears to be associated with risk of major complication after radical nephrectomy for advanced kidney cancer. It was not related to overall survival, however. This preoperative imaging tool may be helpful in preoperative counseling and preparation.

Selective arterial clamping does not improve outcomes in robot-assisted partial nephrectomy: a propensity-score analysis of patients without impaired renal function.

To assess the benefit of selective arterial clamping (SAC) as an alternative to main renal artery clamping (MAC) during robot‐assisted partial nephrectomy (RAPN) in patients without underlying chronic kidney disease (CKD).

Surgeon-controlled robotic ureteral surgery.

Purpose of review Surgeon-controlled, robotic-assisted, ureteral reconstructive and ablative surgery is being performed routinely for both benign and malignant pathology at centers possessing this technology in their armamentarium. The aim of this review is to detail the options for surgeon-controlled robotic management of ureteral pathology and evaluate the developments in the last 2 years. Recent findings Surgeon-controlled robotic management of ureteric pathology involving all parts of the ureter with varying cause has been reported. Proximally, ureteral strictures and symptomatic retrocaval ureters have been repaired with long-term follow-up demonstrating resolution of obstruction. Ureterolysis and other mid-ureteral pathology have been treated with durable function results. Transitional cell carcinoma of the renal pelvis or distal ureter has been extirpated with successful oncologic outcomes. Reimplantation of refluxing ureters in children has been demonstrated to provide similar results of open surgery. Summary Surgeon-controlled, robotic-assisted ureteral surgery is well tolerated, feasible, and effective for ablative and reconstructive indications with minimal complications. Knowledge of anatomy, pathology, experience of surgical team, and appropriate preoperative patient selection augmented with proper port placement to provide excellent exposure is critical to provide optimal outcomes.

Association of Urine Dipstick Proteinuria and Postoperative Renal Function Following Robotic Partial Nephrectomy

INTRODUCTION In patients with normal estimated renal function before robot-assisted partial nephrectomy (RPN), there is still a risk for de Novo chronic kidney disease (CKD). We assessed the role of dipstick spot proteinuria in risk stratifying patients for CKD progression. MATERIALS AND METHODS From our prospectively maintained, institutional review board-approved database of patients undergoing RPN, we queried those with estimated glomerular filtration rate (eGFR) >60 and bilateral functional units. We assessed proteinuria through dipstick (trace or above) on voided urine in preoperative urologic appointment <3 weeks before RPN. Proteinuric patients were compared with the remainder of the cohort with parametric comparisons for continuous and chi-squared analysis for categoric variables. Multivariate logistic regression analyses were performed assessing the risk of de Novo CKD stage III development, estimated by the CKD-EPI equation. RESULTS We found 269 patients with eGFR >60 preoperatively, of whom 57 (21%) had proteinuria preoperatively. In univariate analysis, these patients were more likely to be diabetic (p = 0.023) and to be on an angiotensin converting enzyme inhibitor or angiotensin receptor blocker (p = 0.001) but had similar age (p = 0.13), body mass index (p = 0.09), and tumor size (p = 0.56) with similar rates of hypertension (p = 0.07). At a median 16 months, controlling for confounding variables, preoperative proteinuria on urinary dipstick was associated with a 2.3× (95% confidence interval 1.03-4.95) increased risk of de Novo CKD stage III progression. CONCLUSIONS Patients with proteinuria preoperatively, despite a normal eGFR, likely have intrinsic medicorenal disease. These patients should be counseled preoperatively that they have a higher risk of CKD progression following RPN.

Pheochromocytoma diagnosed pathologically with previous negative serum markers.

Patients presenting with adrenal masses require workup with catecholamine or metabolite measurements to rule out pheochromocytoma. There is a select portion of patients with marker negative pheochromocytoma. The aim of this study is to compare patient characteristics and presentations between marker positive and marker negative tumors.

A Nonrandomized Prospective Comparison of Robotic-assisted Partial Nephrectomy in the Elderly to a Younger Cohort: An Analysis of 339 Patients With Intermediate-term Follow-up

OBJECTIVE To assess the role of robotic-assisted partial nephrectomy (RAPN) in elderly patients focusing on perioperative, functional, and oncologic outcomes in comparison with a younger cohort. MATERIALS AND METHODS From a prospectively maintained institutional review board-approved database, 339 patients were divided into 2 groups defined by age ≥ 70 (n = 71) or <70 years (n = 268) at the time of RAPN. They were compared for perioperative outcomes and complications, including risk of chronic kidney disease (CKD) stage progression. The standard t test and chi square test were used for continuous and categorical variables, respectively. Logistic regression identified risk factors for progression of renal dysfunction. Kaplan-Meier estimates modeled tumor recurrence at 368 and 462 days in the elderly and young, respectively. RESULTS Elderly patients were more likely to have hypertension (86% vs 60%; P < .001) or coronary artery disease (27% vs 9%; P < .001), and rates of chronic obstructive pulmonary disorder and diabetes were also higher. Preoperative estimated glomerular filtration rate was significantly lower in the elderly (70 vs 82 mL/min/1.73 m2; P < .001). Twenty-four percent of elderly patients progressed in CKD stage as compared to 14% in the younger cohort (P = .08). Elderly age was not a statistically significant risk factor for CKD progression (relative risk, 2.34; 95% confidence interval, 0.81-6.05; P = .11). Surgical and medical complication rates were similar between the cohorts (P = .75 and .80, respectively) as were Kaplan-Meier estimates of risk of tumor recurrence (P = .47). Limitations include nonrandomized, single-center study, and intermediate-term follow-up for oncologic outcomes. CONCLUSION Elderly patients undergoing RAPN had no increased risk of perioperative complications. CKD progression and risk of oncologic recurrence were similar to younger patients at intermediate-term follow-up.