Mark Wille

Preoperative Hydronephrosis, Ureteroscopic Biopsy Grade and Urinary Cytology Can Improve Prediction of Advanced Upper Tract Urothelial Carcinoma

PURPOSE We evaluated the value of hydronephrosis, ureteroscopic biopsy grade and urinary cytology to predict advanced upper tract urothelial carcinoma. MATERIALS AND METHODS We reviewed the charts of 469 patients with upper tract urothelial carcinoma treated with radical nephroureterectomy or distal ureterectomy. Complete data on hydronephrosis (present vs absent), ureteroscopic grade (high vs low) and urinary cytology (positive vs negative) were available in 172 patients. The outcome was muscle invasive (pT2-pT4) or nonorgan confined (pT3 or greater, or lymph node metastasis) upper tract urothelial carcinoma. RESULTS Of the patients 92 (54%) had hydronephrosis, 74 (43%) had high grade disease on ureteroscopic biopsy and 137 (80%) had positive cytology. On univariate analysis hydronephrosis (p <0.001), high ureteroscopic grade (p <0.001) and positive cytology (p = 0.03) were associated with muscle invasive and nonorgan confined disease. On multivariate analysis adjusting for tumor site, gender and age hydronephrosis and high ureteroscopic grade were associated with muscle invasive carcinoma (HR 12.0 and 4.5, respectively, each p <0.001) but cytology was not (HR 2.3, p = 0.17). However, all 3 variables were independently associated with nonorgan confined disease (HR 5.1, p <0.001; HR 3.9, p <0.001; and HR 3.1, p = 0.035, respectively). Combining these 3 tests incrementally improved the prediction of upper tract urothelial carcinoma stage. Abnormality of all 3 tests had 89% and 73% positive predictive value for muscle invasive and nonorgan confined upper tract urothelial carcinoma, respectively, but when all tests were normal, the negative predictive value was 100%. CONCLUSIONS Preoperative evaluation for hydronephrosis, ureteroscopic grade and cytology can identify patients at risk for advanced upper tract urothelial carcinoma. Such knowledge may impact surgery choice and extent as well as the need for perioperative chemotherapy regimens.

Urinary cytology has a poor performance for predicting invasive or high‐grade upper‐tract urothelial carcinoma

Study Type – Therapy (case series)

Knotless closure of the collecting system and renal parenchyma with a novel barbed suture during laparoscopic porcine partial nephrectomy

INTRODUCTION Closure of the urinary collecting system and renal parenchyma is a technically challenging aspect of laparoscopic nephron-sparing surgery and an obstacle to its more widespread use. A novel barbed polydioxanone suture material Quill self-retaining suture (SRS) (Angiotech Pharmaceuticals) has been introduced for knot-free tissue approximation. We compared the outcomes of Quill SRS versus a conventional technique for kidney and collecting system closure during laparoscopic porcine partial nephrectomy. METHODS After approval of the Institutional Animal Care and Use Committee, 10 female pigs underwent bilateral transperitoneal laparoscopic lower pole heminephrectomy. Closure of the collecting system and approximation of the renal parenchyma was performed in two layers using continuous knotless barbed suture for one kidney (Quill SRS) and polyglactin (Vicryl) with absorbable polydioxanone clips (LapraTy; Ethicon) on the contralateral kidney. For both techniques, the collecting system was closed with 2-0 suture and renal parenchyma with #1 suture. Warm ischemia and suturing time were recorded, and resected tissue was weighed. All animals were sacrificed 1 week after surgery. Serum hemoglobin and visual inspection at necropsy were used to assess for bleeding; visual inspection of the peritoneum and bilateral retrograde pyelography were used to assess for urinary fistula. RESULTS Mean (+/-standard deviation [SD]) weight of resected tissue (barbed, 34 +/- 13 g; clips, 34 +/- 11 g; p = 0.6), mean (+/-SD) ischemia time (barbed, 34 +/- 8 minutes; clips, 34 +/- 10 minutes; p = 0.7), and mean (+/-SD) suturing time (barbed, 21 +/- 4 minutes; clips, 22 +/- 7 minutes; p = 0.7) were similar between groups. No animal had a visible hematoma or urinoma at necropsy. On retrograde pyelography, a small urinary leak was found in two kidneys in each group (p = 0.6). CONCLUSIONS In a porcine laparoscopic partial nephrectomy model, it appears that knotless barbed suture is as effective, efficient, and safe as a conventional technique. Further evaluation in humans is warranted and required.

Multi-institutional validation of the ability of preoperative hydronephrosis to predict advanced pathologic tumor stage in upper-tract urothelial carcinoma

OBJECTIVE The presence of hydronephrosis (HN) has been implicated as a predictor of poor outcomes for patients diagnosed with bladder cancer. Small, single institution preliminary reports suggest a similar negative relationship may exist for upper-tract urothelial carcinoma (UTUC). Herein, we attempt to validate the prognostic value of preoperative HN in a large, multi-institutional cohort of UTUC patients. MATERIALS AND METHODS Data on 469 patients with localized UTUC from 5 tertiary referral centers who underwent a radical nephroureterectomy (91%) or distal ureterectomy (9%) without neoadjuvant chemotherapy were integrated into a relational database. Preoperative HN data, including presence vs. absence and high vs. low grade, were available in 408 patients. The association of HN with pathologic features was evaluated. RESULTS A total of 254 men and 154 women with a median age of 69 years (IQR 15) were analyzed. Overall, 192 patients (47%) had ≥pT2 disease, 145 (36%) had non-organ-confined (NOC) cancers (≥pT3 and/or positive lymph nodes), and 298 (73%) had high grade UTUC on final pathology. Forty-six percent of patients had tumors in the renal pelvis, 27% in the ureter, and 27% in both locations. Preoperatively, 223 patients (55%) were noted to have ipsilateral HN (39% low grade and 61% high grade). Hydronephrosis was associated with ≥pT2 stage (P < 0.001), NOC disease (P < 0.001), and high grade cancers (P = 0.04). On multivariate analysis adjusting for gender, age, and tumor location, HN was an independent predictor of muscle invasive (HR 7.4, P < 0.001), NOC (HR 5.5, P < 0.001), and high pathologic grade (HR 1.6, P = 0.03) UTUC disease. CONCLUSION The presence of preoperative HN was associated with advanced stage UTUC. This readily available imaging modality may improve preoperative risk stratification for UTUC patients thereby guiding use of endoscopic versus extirpative surgery as well as the need for neoadjuvant chemotherapy regimens.

High-Grade Ureteroscopic Biopsy Is Associated with Advanced Pathology of Upper-Tract Urothelial Carcinoma Tumors at Definitive Surgical Resection

BACKGROUND AND PURPOSE Accurate assessment of upper-tract urothelial carcinoma (UTUC) pathology may guide use of endoscopic vs extirpative therapy. We present a multi-institutional cohort of patients with UTUC who underwent surgical resection to characterize the association of ureteroscopic (URS) biopsy features with final pathology results. PATIENTS AND METHODS URS biopsy data were available in 238 patients who underwent surgical resection of UTUC. Biopsies were performed using a brush biopsy kit, mechanical biopsy device, or basket. Stage was classified as a positive brush, nonmuscle-invasive (<pT(2)), or muscle invasive (MI; ≥pT(2)). Grade was classified as low or high. RESULTS On URS biopsy, 88/238 (37%) patients had a positive brush, 140 (59%) had a diagnosis of non-MI, and 10 (4%) had MI disease. Biopsy results showed low-grade cancer in 140 (59%) and high-grade cancer in 98 (41%). Pathologic evaluation at surgical resection demonstrated non-MI tumors in 140 (59%) patients, MI in 98 (41%), and high-grade disease in 150 (63%). On univariate analysis, high URS biopsy grade was associated with high-grade (positive predictive value [PPV] 92%, P<0.0001) and MI (PPV 60%, P<0.0001) UTUC at surgery. URS biopsy stage, however, was associated with surgical pathology grade (P=0.005), but not MI (P=0.16) disease. On multivariate analysis, high URS grade, but not biopsy stage, was associated with high final pathology grade (hazard ratio [HR] 16.6, 95% confidence interval [CI] 7.0-39.5, P<0.0001) and MI UTUC (HR 3.6, 95% CI 2.1-6.8, P<0.0001). CONCLUSION High URS biopsy grade, but not stage, is associated with adverse tumor pathology. This information may play a valuable role for risk stratification and in the appropriate selection of endoscopic management vs surgical extirpation for UTUC.

Continence Outcomes in Patients Undergoing Robotic Assisted Laparoscopic Mitrofanoff Appendicovesicostomy

PURPOSE Continent catheterizable channels for emptying the bladder are typically performed via an open surgical approach. We present our surgical approach and initial outcomes with specific attention to continence for robotic assisted laparoscopic Mitrofanoff appendicovesicostomy formation. MATERIALS AND METHODS Between February 2008 and April 2010, 13 patients were considered for robotic assisted laparoscopic Mitrofanoff appendicovesicostomy and 11 underwent the procedure (2 open conversions). Five patients underwent enterocystoplasty with appendicovesicostomy and 6 underwent isolated appendicovesicostomy. The appendicovesicostomy anastomosis was performed on the anterior (without augmentation) or posterior (with augmentation) bladder wall and the stoma was brought to the umbilical site or right lower quadrant. Detrusor backing (4 cm) was ensured except in 1 patient (number 5). RESULTS Mean patient age at surgery was 10.4 years (range 5 to 14). Mean estimated blood loss was 61.8 cc. Mean operative time for isolated appendicovesicostomy was 347 minutes and there were no intraoperative complications. Incontinence through the stoma developed in 1 patient with inadequate detrusor backing (less than 4 cm), which resolved with dextranomer/hyaluronic acid injection into the appendicovesicostomy anastomosis. This patient had resolution of incontinence with an increase in bladder capacity to 300 cc. Three patients required skin flap revision for cutaneous scarring. To date all patients are catheterizing without difficulty and are continent. Median followup was 20 months (range 3 to 29). CONCLUSIONS We are encouraged by our preliminary experience with the robotic assisted laparoscopic Mitrofanoff appendicovesicostomy continent urinary diversion with or without ileocystoplasty. Early in the experience we emphasize the importance of 4 cm of detrusor backing to maintain stomal continence.

High rates of advanced disease, complications, and decline of renal function after radical nephroureterectomy

OBJECTIVES Recurrences remain common following radical nephroureterectomy (RNU) for locally advanced upper-tract urothelial carcinoma (UTUC). We review a cohort of RNU patients to identify the incidence of locally advanced disease, decline in renal function, complications, and utilization of adjuvant chemotherapy (AC). METHODS Institutional databases from 7 academic medical centers identified 414 RNU patients treated between 2003 and 2012 who had not received neoadjuvant chemotherapy. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease equation. Complications were classified according to the modified Clavien system. Cox proportional hazard modeling and Kaplan-Meier analysis determined factors associated with cancer-specific survival. RESULTS Of 414 patients, 177 (43%) had locally advanced disease, including 118 pT3N0/Nx, 13 pT4N0/Nx, and 46 pTanyN+. Estimated 3- and 5-year cancer-specific survival was 47% and 34%, respectively. Only 31% of patients with locally advanced UTUC received AC. Mean estimated glomerular filtration rate declined from 59 to 51 ml/min/1.73 m(2) following RNU, including a new-onset decline below 60 and 45 ml/min/1.73 m(2) in 25% and 15% of patients, respectively (P<0.001 for both). Complications occurred in 46 of 177 (26%) patients, of which one-quarter were grade III or IV. Increasing age (Hazard Ratio (HR) 1.4, P = 0.03), positive surgical margins (HR 2.1, P = 0.01), and positive lymph nodes (HR 4.3, P<0.001) were associated with an increased risk of death from UTUC, whereas receipt of AC (HR 0.85, P = 0.05) was associated with a decrease in UTUC mortality. CONCLUSIONS Under one-third of RNU patients with locally advanced UTUC cancers received AC. Perioperative complications and decline in renal function may have contributed to this low rate. Such data further underscore the need for continued discussion regarding the use of chemotherapy in a neoadjuvant setting for appropriately selected patients with UTUC.

Microparticulate ICE slurry for renal hypothermia: laparoscopic partial nephrectomy in a porcine model.

OBJECTIVES Previously, we described the feasibility of renal hypothermia using microparticulate ice slurry during laparoscopy. In the present study, we compared surface cooling with the ice slurry versus near-frozen saline or warm ischemia (WI) during laparoscopic partial nephrectomy (LPN) in a porcine model. METHODS We used a single-kidney porcine model. Animals in 5 equal groups (n = 6 each) underwent right laparoscopic complete nephrectomy. In Phase I, left LPN was performed under 90 minutes of ischemia and 90-minute renal cooling with either slurry (Slurry group 1) or saline (Saline group 1). No cooling was applied in the WI group. In Phase II, to simulate more extreme condition, ischemia time was extended to 120 minutes and cooling shortened to 10 minutes (Slurry group 2 and Saline group 2). The study endpoints were renal and core temperature during the surgery and serum creatinine at baseline and days 1, 3, 7, and 14 after the procedure. RESULTS The ice slurry was easily produced and delivered. Nadir renal temperature (mean ± SD) was 8 ± 4 °C in Slurry group 1 vs. 22.5 ± 3 °C in Saline group 1 (P < .0001). Renal rewarming to 30 °C occurred after 61 ± 7 minutes in Slurry group 2 vs. 24 ± 6 minutes in Saline group 2 (P < .0001). Core temperature decreased on average to 35 °C in the Saline groups compared with 37 °C in the Slurry groups (P < .0001). Serum creatinine did not differ between the Saline and Slurry groups in Phases I and II at any time point. CONCLUSIONS Ice slurry provides superior renal cooling compared with near-frozen saline during LPN without associated core hypothermia.

Feasibility and early outcomes of robotic-assisted laparoscopic Mitrofanoff appendicovesicostomy in patients with prune belly syndrome.

Study Type – Therapy (case series) Level of Evidence 4

Forgotten ureteral stents: who's at risk?

The sequelae from forgotten stents carry significant morbidity and costs. In this study, we attempt to identify potential risk factors that may make patients less likely to follow up for stent removal so that more effective prevention efforts may be directed at these persons. A single-institution retrospective analysis of 187 consecutive patients who had stents placed between January 2010 and December 2010 was performed. Chart review was conducted to see if patients had undergone stent removal beyond the intended maximal stent life (MSL). Patients who were lost to follow-up were contacted to determine if stents were overdue. Logistic regression was performed to determine risk factors. Of the 187 patients who had stents placed, 147 had the stent removed before MSL and 28 had stents removed after the MSL. Twelve patients could not be contacted and were excluded from the analysis. Within our cohort of 175 patients, 48% were males, 73% were minorities (33% Latino, 30% Black, 8% Asian, and 2% Native American), 39% did not speak English, 79% were unemployed, 73% were uninsured, and 35% were married. Among the patients with forgotten stents, 68% were male, 64% were minorities (32% Latino, 29% Black, 4% Native American, and 0% Asian), 82% were unemployed, 39% did not speak English, 93% were uninsured, and 43% were married. Multivariate regression analysis demonstrated that uninsured patients (odds ratio [OR], 6.3; 95% confidence interval [CI], 1.4-28.2; P value 0.01) and males (OR, 2.8; CI, 1.2-6.8; P=0.02) had statistically significant associations with forgotten stents. Men were 2.8 times more likely to have forgotten stents than females. Patients without health insurance were six times more likely to have forgotten stents than patients with insurance. As efforts are made to prevent forgotten stents, increased attention should be given to these higher-risk patient populations.