Clinical Upstaging After Neoadjuvant Chemotherapy Impacting Eligibility for Vaginal-sparing Cystectomy: Identifying Bladder Cancer Patients Who May Benefit From Interim Imaging.

OBJECTIVE: Limited data exist on the frequency with which clinical progression during neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) impacts eligibility for a vaginal-sparing surgical approach or on the utility of interim imaging assessment. We sought to evaluate the incidence of clinical upstaging following NAC that would render a patient ineligible for a vaginal-sparing cystectomy. METHODS: Eighty-nine female patients with non-metastatic MIBC treated with NAC and radical cystectomy (RC) (2012-2023) were retrospectively reviewed. Tumor location(s) was determined from transurethral resection of bladder tumor operative reports. Pre- and post-NAC clinical staging was determined from imaging. Outcomes of interest included clinical upstaging and upstaging to vaginal invasion after NAC. RESULTS: 75/89 patients had pre- and post-NAC imaging. Fifty-five had no change in clinical staging, 6 patients were upstaged (4 cT2→cT3, 2 cT3→cT4), and 14 patients were downstaged (13 cT3→cT2, 1 cT4→cT2). Of the 75 patients with pre- and post-NAC imaging, 39 had trigone tumors. Of these, 28 had no change in clinical staging, 2 were upstaged (1 cT2→cT3, 1 cT3→cT4) and 9 were downstaged (8 cT3→cT2, 1 cT4→cT2). Overall, 6/75 (8%) of patients demonstrated clinical upstaging after NAC. 2/39 (5%) of patients with trigone tumors clinically progressed after NAC and both had vaginal invasion (pT4) on final pathology. CONCLUSION: Although clinical upstaging after NAC was infrequent, 5% of patients with trigonal MIBC were rendered ineligible for vaginal-sparing cystectomy following NAC due to progression. Interim imaging assessment may identify non-responders and preserve eligibility for vaginal-sparing RC.

Impact of pathologic re-review on grade, clinical stage, and risk stratification for patients with nonmuscle invasive bladder cancer.

OBJECTIVES: Pathologic re-review of transurethral resection of bladder tumor (TURBT) specimen is a common practice at our tertiary care center, but its impact on disease risk stratification remains unknown. We sought to determine how pathologic re-review of specimen initially read at an outside institution changed grade, clinical T (cT) stage, and AUA non-muscle-invasive bladder cancer (NMIBC) risk stratification. METHODS AND MATERIALS: The laboratory information system was searched for patients who underwent TURBT from 2021 to 2022, yielding 561 records. 173 patients met inclusion criteria: 113 with

Body morphometry may predict parastomal hernia following radical cystectomy with ileal conduit.

OBJECTIVE: To investigate whether preoperative body morphometry analysis can identify patients at risk of parastomal hernia (PH), which is a common complication after radical cystectomy (RC). PATIENTS AND METHODS: All patients who underwent RC between 2010 and 2020 with available cross-sectional imaging preoperatively and at 1 and 2 years postoperatively were included. Skeletal muscle mass and total fat mass (FM) were determined from preoperative axial computed tomography images obtained at the level of the L3 vertebral body using Aquarius Intuition software. Sarcopenia and obesity were assigned based on consensus definitions of skeletal muscle index (SMI) and FM index (FMI). PH were graded using both the Moreno-Matias and European Hernia Society criteria. Binary logistic regression and recursive partitioning were used to identify patients at risk of PH. The Kaplan-Meier method with log-rank and Cox proportional hazards models included clinical and image-based parameters to identify predictors of PH-free survival. RESULTS: A total of 367 patients were included in the final analysis, with 159 (43%) developing a PH. When utilising binary logistic regression, high FMI (odds ratio [OR] 1.63, P < 0.001) and low SMI (OR 0.96, P = 0.039) were primary drivers of risk of PH. A simplified model that only relied upon FMI, SMI, and preoperative albumin improved the classification of patients at risk of PH. On Kaplan-Meier analysis, patients who were obese or obese and sarcopenic had significantly worse PH-free survival (P < 0.001). CONCLUSION: Body morphometry analysis identified FMI and SMI to be the most consistent predictors of PH after RC.

Parenchymal obliteration by renal masses: Functional and oncologic implications.

OBJECTIVES: Most renal tumors merely displace nephrons while others can obliterate parenchyma in an invasive manner. Substantial parenchymal volume replacement (PVR) by renal cell carcinoma (RCC) may have oncologic implications; however, studies regarding PVR remain limited. Our objective was to evaluate the oncologic implications associated with PVR using improved methodology including more accurate and objective tools. PATIENTS/METHODS: A total of 1,222 patients with non-metastatic renal tumors managed with partial nephrectomy (PN) or radical nephrectomy (RN) at Cleveland Clinic (2011-2014) with necessary studies were retrospectively evaluated. Parenchymal volume analysis via semiautomated software was used to estimate split renal function and preoperative parenchymal volumes. Using the contralateral kidney as a control, %PVR was defined: (parenchymal volumecontralateral-parenchymal volumeipsilateral) normalized by parenchymal volumecontralateral x100%. PVR was determined preoperatively and not altered by management. Patients were grouped by degree of PVR: minimal (<5%, N = 566), modest (5%-25%, N = 414), and prominent (≥25%, N = 142). Kaplan-Meier was used to evaluate survival outcomes relative to degree of PVR. Multivariable Cox-regression models evaluated predictors of recurrence-free survival (RFS). RESULTS: Of 1,122 patients, 801 (71%) were selected for PN and 321 (29%) for RN. Overall, median tumor size was 3.1 cm and 6.8 cm for PN and RN, respectively, and median follow-up was 8.6 years. Median %PVR was 15% (IQR = 6%-29%) for patients selected for RN and negligible for those selected for PN. %PVR correlated inversely with preoperative ipsilateral GFR (r = -0.49, P < 0.01) and directly with advanced pathologic stage, high tumor grade, clear cell histology, and sarcomatoid features (all P < 0.01). PVR≥25% associated with shortened recurrence-free, cancer-specific, and overall survival (all P < 0.01). Male sex, ≥pT3a, tumor grade 4, positive surgical margins, and PVR≥25% independently associated with reduced RFS (all P < 0.02). CONCLUSIONS: Obliteration of normal parenchyma by RCC substantially impacts preoperative renal function and patient selection. Our data suggests that increased PVR is primarily driven by aggressive tumor characteristics and independently associates with reduced RFS, although further studies will be needed to substantiate our findings.

An exploratory study investigating the impact of the bladder tumor microbiome on Bacillus Calmette Guerin (BCG) response in non-muscle invasive bladder cancer.

PURPOSE: Intravesical Bacillus Calmette-Guerin (BCG) is standard of care for intermediate- and high-risk non-muscle invasive bladder cancer (NMIBC). The effect of the bladder microbiome on response to BCG is unclear. We sought to characterize the microbiome of bladder tumors in BCG-responders and non-responders and identify potential mechanisms that drive treatment response. MATERIALS AND METHODS: Patients with archival pre-treatment biopsy samples (2012-2018) were identified retrospectively. Prospectively, urine and fresh tumor samples were collected from individuals with high-risk NMIBC (2020-2023). BCG response was defined as tumor-free 2 years from induction therapy. Extracted DNA was sequenced for 16S rRNA and shotgun metagenomics. Primary outcomes were species richness (α-diversity) and microbial composition (ß-diversity). Paired t-tests were performed for α-diversity (Observed species/Margalef). Statistical analysis for ß-diversity (weighted and unweighted UniFrac distances, weighted Bray-Curtis dissimilarity) were conducted through Permanova, with 999 permutations. RESULTS: Microbial species richness (P < 0.001) and composition (P = 0.001) differed between BCG responders and non-responders. Lactobacillus spp. were significantly enriched in BCG-responders. Shotgun metagenomics identified possible mechanistic pathways such as assimilatory sulfate reduction. CONCLUSION: A compositional difference exists in the tumor microbiome of BCG responders and non-responders with Lactobacillus having increased abundance in BCG responders.

Parenchymal volume preservation during partial nephrectomy: improved methodology to assess impact and predictive factors.

OBJECTIVE: To rigorously evaluate the impact of the percentage of parenchymal volume preserved (PPVP) and how well the preserved parenchyma recovers from ischaemia (Recischaemia ) on functional outcomes after partial nephrectomy (PN) using an accurate and objective software-based methodology for estimating parenchymal volumes and split renal function (SRF). A secondary objective was to assess potential predictors of the PPVP. PATIENTS AND METHODS: A total of 894 PN patients with available studies (2011-2014) were evaluated. The PPVP was measured from cross-sectional imaging at ≤3 months before and 3-12 months after PN using semi-automated software. Pearson correlation evaluated relationships between continuous variables. Multivariable linear regression evaluated predictors of ipsilateral glomerular filtration rate (GFR) preserved and the PPVP. Relative-importance analysis was used to evaluate the impact of the PPVP on ipsilateral GFR preserved. Recischaemia was defined as the percentage of ipsilateral GFR preserved normalised by the PPVP. RESULTS: The median tumour size and R.E.N.A.L. nephrometry score were 3.4 cm and 7, respectively. In all, 49 patients (5.5%) had a solitary kidney. In all, 538 (60%)/251 (28%)/104 (12%) patients were managed with warm/cold/zero ischaemia, respectively. The median pre/post ipsilateral GFRs were 40/31 mL/min/1.73 m2 , and the median (interquartile range [IQR]) percentage of ipsilateral GFR preserved was 80% (71-88%). The median pre/post ipsilateral parenchymal volumes were 181/149 mL, and the median (IQR) PPVP was 84% (76-92%). In all, 330 patients (37%) had a PPVP of <80%, while only 34 (4%) had a Recischaemia of <80%. The percentage of ipsilateral GFR preserved correlated strongly with the PPVP (r = 0.83, P < 0.01) and loss of parenchymal volume accounted for 80% of the loss of ipsilateral GFR. Multivariable analysis confirmed that the PPVP was the strongest predictor of ipsilateral GFR preserved. Greater tumour size and endophytic and nearness properties of the R.E.N.A.L. nephrometry score were associated with a reduced PPVP (all P ≤ 0.01). Solitary kidney and cold ischaemia were associated with an increased PPVP (all P < 0.05). CONCLUSIONS: A reduced PPVP predominates regarding functional decline after PN, although a low Recischaemia can also contribute. Tumour-related factors strongly influence the PPVP, while surgical efforts can improve the PPVP as observed for patients with solitary kidneys.

Thermal Ablation Versus Partial Nephrectomy for cT1 Renal Mass in a Solitary Kidney: A Matched Cohort Comparative Analysis.

BACKGROUND: Nephron-sparing approaches are preferred for renal mass in a solitary kidney (RMSK), with partial nephrectomy (PN) generally prioritized. Thermal ablation (TA) also is an option for small renal masses in this setting; however, comparative functional/survival outcomes are not well-defined. METHODS: A retrospective study of 504 patients (1975-2022) with cT1 RMSK managed with PN (n = 409)/TA (n = 95) with necessary data for analysis was performed. Propensity score was used for matching patients, including age, preoperative glomerular filtration rate (GFR), tumor diameter, R.E.N.A.L. ((R)adius (tumor size as maximal diameter), (E)xophytic/endophytic properties of tumor, (N)earness of tumor deepest portion to collecting system or sinus, (A)nterior (a)/posterior (p) descriptor, and (L)ocation relative to polar lines), and comorbidities. Functional outcomes were compared, and Kaplan-Meier was used to analyze survival. RESULTS: The matched cohort included 132 patients (TA = 66/PN = 66), with median tumor diameter of 2.4 cm, R.E.N.A.L. of 6, and preoperative GFR of 52 ml/min/1.73 m2. Acute kidney injury occurred in 11%/61% in the TA/PN cohorts, respectively (p < 0.01). After recovery, median GFR preserved was 89%/83% for TA/PN, respectively (p = 0.02), and 5-year dialysis-free survival was 96% in both cohorts. Median follow-up was 53 months. Five-year recurrence-free survival (RFS) was 62%/86% in the TA/PN cohorts, respectively (p < 0.01). Five-year local recurrence (LR)-free survival was 74%/95% in the TA/PN cohorts, respectively (p < 0.01). Five-year cancer-specific survival (CSS) was 96%/98% in the TA/PN cohorts, respectively (p = 0.7). Local recurrence was observed in nine of 36 (25%) and five of 30 (17%) patients managed with laparoscopic versus percutaneous TA, respectively. For TA with LR (n = 14), nine patients presented with multifocality and/or cT1b tumors. Twelve LR were managed with salvage TA, and seven remained cancer-free, while five developed systemic recurrence, three with concomitant LR. CONCLUSIONS: Functional outcomes for TA for RMSK were improved compared with PN. Local recurrence was more common after TA and often was associated with the laparoscopic approach, multifocality, and large tumor size. Improved patient selection and greater experience with TA should improve outcomes. Salvage of LR was not always possible. Partial nephrectomy remains the reference standard for RMSK.

Impact of Neoadjuvant Chemotherapy on Pathologic Downstaging in Patients With Variant Histology Undergoing Radical Cystectomy.

INTRODUCTION: Variant histology (VH) bladder cancer is often associated with poor outcomes and the role of neoadjuvant chemotherapy (NAC) remains incompletely defined. Our objective was to determine comparative pathologic downstaging at radical cystectomy (RC) following NAC for patients with and without VH. PATIENTS AND METHODS: Patients who underwent RC at 2 tertiary referral centers (1996-2018) were included. Patients with VH (sarcomatoid, nested, micropapillary, plasmacytoid) were matched 1:2 to patients with pure urothelial carcinoma by age, sex, clinical T (cT)stage, clinical N (cN)stage, cystectomy year and receipt of NAC. The primary outcome was pathologic downstaging (pT-stage < cT-stage). The differential impact of NAC on pathologic downstaging between VH and non-VH was assessed using multivariable logistic regression with interaction analysis. RESULTS: 225 VH and 437 non-VH patients were included. One hundred twenty-eight of six hundred sixty-two (19.3%) patients experienced downstaging, including 54/121 (44.6%) patients who received NAC and 74/542 (13.2%) patients who did not (P < .01). Rates of downstaging after NAC for subgroups were: 45/78 (57.7%) urothelial, 3/8 (37.5%) sarcomatoid, 2/12 (16.7%) nested, 3/14 (21.4%) micropapillary, and 1/8 (12.5%) plasmacytoid. Collectively, 9/42 (21.4%) of VH patients who received NAC were downstaged. On multivariable analyses, NAC was associated with increased likelihood of downstaging in the overall cohort (OR 5.25, 95% CI, 3.29-8.36, P < .0001) and this effect was not modified by VH versus non-VH histology (P = .13 for interaction). VH patients had worse survival outcomes compared to non-VH (P < 0.01 for all). CONCLUSION: When comparing patients with VH to matched pure urothelial carcinoma controls, VH did not have an adverse effect on downstaging following NAC. VH patients should not be excluded from NAC if otherwise eligible.

Oncologic outcomes of intravesical therapy in the management of nonmuscle invasive bladder cancer with variant histology.

PURPOSE: There is limited data on oncologic outcomes in nonmuscle invasive bladder cancer (NMIBC) with variant histology (VH) managed with intravesical therapy. We sought to evaluate oncologic outcomes for this cohort at a high-volume center. MATERIALS AND METHODS: A retrospective review of an IRB-approved bladder cancer database was performed. Patients with a history of NMIBC with VH present on transurethral resection of bladder tumor (TURBT) treated with intravesical therapy (BCG or chemotherapy) were identified. Outcomes of interest included recurrence within the bladder, progression to muscle-invasive bladder cancer (MIBC), metastatic progression, cancer-specific, and overall survival. Survival time was computed from the date of initiation of intravesical therapy to the date of event or censoring. For patients who underwent radical cystectomy, recurrence-free, cancer-specific, and overall survival were also computed. The Kaplan-Meier method with log rank was utilized to compare survival time between VH sub-groups. RESULTS: Ninety patients were included in the final cohort with a median follow-up of 38 months. The majority of patients had T1 disease (72%) and received intravesical BCG (83%) as their only form of intravesical therapy. The most commonly represented VH in this series were glandular and squamous differentiation (26%). Forty-eight patients (53%) experienced recurrence within the bladder with a median recurrence-free survival of 24 months (95% Confidence Interval [CI]: 2-46 months). Five-year rates of progression to MIBC and distant metastasis were both 14% respectively. Twenty-six patients (28%) eventually required cystectomy. When stratifying by VH, patients with sarcomatoid, plasmacytoid, and micropapillary had significantly worse oncologic outcomes. CONCLUSION: In this series of highly-selected patients with NMIBC and VH, bladder-sparing treatment with intravesical therapy demonstrated acceptable oncologic outcomes for most VHs. This may be an acceptable treatment option for patients without plasmacytoid, sarcomatoid, or micropapillary features who are not suitable cystectomy candidates or who prioritize bladder-sparing treatment.

Functional recovery after partial nephrectomy in a solitary kidney.

OBJECTIVES: Partial nephrectomy (PN) is the reference standard for renal mass in a solitary kidney (RMSK), although factors determining functional recovery in this setting remain poorly defined. PATIENTS/METHODS: Single center, retrospective analysis of 841 RMSK patients (1975-2022) managed with PN with functional data, including 361/435/45 with cold/warm/zero ischemia, respectively. A total of 155 of these patients also had necessary studies for detailed analysis of parenchymal volume preserved. Acute kidney injury (AKI) was classified by RIFLE (Risk/Injury/Failure/Loss/Endstage). Recovery-from-ischemia (Rec-Ischemia) was defined as glomerular filtration rate (GFR) saved normalized by parenchymal volume saved. Logistic regression identified predictive factors for AKI and predictors of Rec-Ischemia were analyzed by multivariable linear regression. RESULTS: Overall, median preoperative GFR was 56.7 ml/min/1.73m2 and new-baseline and 5-year GFRs were 43.1 and 44.5 ml/min/1.73m2, respectively. Median follow-up was 55 months; 5-year dialysis-free survival was 97%. In the detailed analysis cohort, a primary focus of this study, median warm (n = 70)/cold (n = 85) ischemia times were 25/34 minutes, respectively; and median preoperative, new-baseline and 5-year GFRs were 57.8, 45.0, and 41.7 ml/min/1.73m2, respectively. Functional recovery correlated strongly with parenchymal volume preserved (r = 0.84, p < 0.001). Parenchymal volume loss accounted for 69% of the total median GFR decline associated with PN, leaving only 3 to 4 ml/min/1.73m2 attributed to ischemia and other factors. AKI occurred in 52% of patients and the only independent predictor of AKI was ischemia time. Independent predictors of reduced Rec-Ischemia were increased age, warm ischemia, and AKI. CONCLUSION: The main determinant of functional recovery after PN in RMSK is parenchymal volume preservation. Type/duration of ischemia, AKI, and age also correlated, although altogether their contributions were less impactful. Our findings suggest multiple opportunities for optimizing functional outcomes although preservation of parenchymal volume remains predominant. Long-term function generally remains stable with dialysis only occasionally required.

Neocapsular reconstruction for challenging partial nephrectomy: A feasibility study in a porcine model and recent clinical experience.

OBJECTIVES: Multifocal renal masses and large central-endophytic tumors can be challenging for partial nephrectomy (PN) due to the paucity of capsule remaining after tumor removal. Our objective was to develop a neocapsule to provide tamponade and test its feasibility/safety in a porcine model. METHODS: Eight live pigs (50-70 kg) underwent unclamped open right flank PN. Renal defects were 1 cm deep and had moderate ongoing venous bleeding. A 6 × 9 inch sheet of Nu-knit® was used for neocapsular reconstruction with Fibrillar™ packing to provide modest tamponade and preclude ongoing bleeding. Blood chemistry and hemoglobin (Hb) levels were drawn preoperatively and postoperative Days 3/5/8. On postoperative Day 8, euthanasia was performed, and both kidneys were inspected and analyzed for histologic changes. RESULTS: PN defects ranged from 1 × 1 × 1 cm to 4 × 2 × 1 cm; four pigs had PN performed in both poles and four in one pole. Neocapsular reconstruction was successful (n = 8), with no perioperative complications. Median baseline Hb was 10.4 g/dL, and median Hb postoperative Days 3/5/8 were 10.0/10.8/10.6 g/dL, respectively. Median baseline serum creatinine (SCr) was 1.9 mg/dL, and median SCr postoperative Days 3/5/8 were 1.5/1.4/1.5 mg/dL, respectively. At sacrifice, no significant hematomas were observed. Other than adjacent to the PN site, there were no significant histologic changes in the parenchyma for operative kidneys versus controls. Based on our experience, we recently performed neocapsular reconstruction safely/effectively after extensive PN for multifocal tumors and for an allograft with difficult-to-manage subcapsular hematoma. CONCLUSIONS: Neocapsular reconstruction after PN or capsular trauma appears feasible and safe and may be considered to reduce the risk of perioperative bleeding. However, further study will be needed to confirm the utility/efficacy of this approach.

Selective Use of Neoadjuvant Targeted Therapy Is Associated with Greater Achievement of Partial Nephrectomy for High-complexity Renal Masses in a Solitary Kidney.

Background: Partial nephrectomy (PN) is preferred for a renal mass in a solitary kidney (RMSK), although tumors with high complexity can be challenging. Objective: To evaluate the evolution of RMSK management with a focus on achievement of PN. Design setting and participants: Patients with nonmetastatic RMSK (n = 499) were retrospectively reviewed; 133 had high tumor complexity, including 80 in the pre-tyrosine kinase inhibitor (TKI) era (1999-2008) and 53 in the TKI era (2009-2022). After 2009, 23/53 patients received neoadjuvant TKI and 30/53 had immediate-surgery. Outcome measurements and statistical analysis: Functional outcomes, adverse events and complications, dialysis-free survival, and recurrence-free survival (RFS) were the measures evaluated. Mann-Whitney and χ2 tests were used to compare cohorts, and the log-rank test was applied for survival analyses. Results and limitations: Overall, the median RENAL score was 10 and the median tumor diameter was 5.2 cm. Demographic characteristics, tumor diameter, and RENAL scores were similar between the pre-TKI-era and TKI-era groups. In the TKI era, 23/53 patients (43%) with clear-cell histology were selected for neoadjuvant TKI. These 23 patients had a greater median tumor diameter (7.1 vs 4.4 cm; p = 0.02) and RENAL score (11 vs 10; p = 0.07). After TKI treatment, the median tumor diameter decreased to 5.6 cm and the RENAL score to 9, and tumor volume was reduced by 59% (all p < 0.05). PN was accomplished in 21/23 (91%) the TKI-treated cases and in 27/30 (90%) of the immediate-surgery cases (2009-2022). PN was only accomplished in 52/80 (65%) of the patients from the pre-TKI era (p < 0.01). The 5-yr dialysis-free survival rate was 59% in the pre-TKI-era group and 91% in the TKI-era group. The 5-yr RFS rate was lower in the TKI-era group (59% vs 74%; p = 0.21), which was mostly related to more aggressive tumor biology, as reflected by a predominance of systemic rather than local recurrences. Conclusions: Management of RMSK with high tumor complexity is challenging. Selective use of TKI therapy was associated with greater use of PN, although a randomized study is needed. RFS mostly reflected aggressive tumor biology rather than failure of local management. Patient summary: For complex kidney tumors in patients with a single kidney, management is challenging. Use of drugs called tyrosine kinase inhibitors before surgery was associated with reductions in tumor size and greater ability to achieve partial kidney removal for cancer control. Most recurrences were metastatic, which reflects aggressive tumor biology rather than failure of surgery.

Parenchymal volume analysis to assess longitudinal functional decline following partial nephrectomy.

OBJECTIVE: To identify factors associated with longitudinal ipsilateral functional decline after partial nephrectomy (PN). PATIENTS AND METHODS: Of 1140 patients managed with PN (2012-2014), 349 (31%) had imaging/serum creatinine levels pre-PN, 1-12 months post-PN (new baseline), and >3 years later necessary for inclusion. Parenchymal-volume analysis was used to determine split renal function. Patients were grouped as having significant renal comorbidity (CohortSRC : diabetes mellitus with insulin-dependence or end-organ damage, refractory hypertension, or severe pre-existing chronic kidney disease) vs not having significant renal comorbidity (CohortNoSRC ) preoperatively. Multivariable regression was used to identify predictors of annual ipsilateral parenchymal atrophy and functional decline relative to new baseline values post-PN, after the kidney had healed. RESULTS: The median follow-up was 6.3 years with 87/226/36 patients having cold/warm/zero ischaemia. The median cold/warm ischaemia times were 32/22 min. Overall, the median tumour size was 3.0 cm. The preoperative glomerular filtration rate (GFR) and new baseline GFR (NBGFR) were 81 and 71 mL/min/1.73 m2 , respectively. After establishment of the NBGFR, the median loss of global and ipsilateral function was 0.7 and 0.4 mL/min/1.73 m2 /year, respectively, consistent with the natural ageing process. Overall, the median ipsilateral parenchymal atrophy was 1.2 cm3 /year and accounted for a median of 53% of the annual functional decline. Significant renal comorbidity, age, and warm ischaemia were independently associated with ipsilateral parenchymal atrophy (all P < 0.01). Significant renal comorbidity and ipsilateral parenchymal atrophy were independently associated with annual ipsilateral functional decline (both P < 0.01). Annual median ipsilateral parenchymal atrophy and functional decline were both significantly increased for CohortSRC compared to CohortNoSRC (2.8 vs 0.9 cm3 , P < 0.01 and 0.90 vs 0.30 mL/min/1.73 m2 /year, P < 0.01, respectively). CONCLUSIONS: Longitudinal renal function following PN generally follows the normal ageing process. Significant renal comorbidities, age, warm ischaemia, and ipsilateral parenchymal atrophy were the most important predictors of ipsilateral functional decline following establishment of NBGFR.

Functional recovery after partial nephrectomy: next generation analysis.

OBJECTIVES: To provide a more rigorous assessment of factors affecting functional recovery after partial nephrectomy (PN) using novel tools that allow for analysis of more patients and improved accuracy for assessment of parenchymal volume loss, thereby revealing the potential impact of secondary factors such as ischaemia. PATIENTS AND METHODS: Of 1140 patients managed with PN (2012-2014), 670 (59%) had imaging and serum creatinine levels measured before and after PN necessary for inclusion. Recovery from ischaemia was defined as the ipsilateral glomerular filtration rate (GFR) saved normalised by parenchymal volume saved. Acute kidney injury was assessed through Spectrum Score, which quantifies the degree of acute ipsilateral renal dysfunction due to exposure to ischaemia that would otherwise be masked by the contralateral kidney. Multivariable regression was used to identify predictors of Spectrum Score and Recovery from Ischaemia. RESULTS: In all, 409/189/72 patients had warm/cold/zero ischaemia, respectively, with median (interquartile range [IQR]) ischaemia times for cold and warm ischaemia of 30 (25-42) and 22 (18-28) min, respectively. The median (IQR) global preoperative GFR and new baseline GFR (NBGFR) were 78 (63-92) and 69 (54-81) mL/min/1.73 m2 , respectively. The median (IQR) ipsilateral preoperative GFR and NBGFR were 40 (33-47) and 31 (24-38) mL/min/1.73 m2 , respectively. Functional recovery correlated strongly with parenchymal volume preserved (r = 0.83, P < 0.01). The median (IQR) decline in ipsilateral GFR associated with PN was 7.8 (4.5-12) mL/min/1.73 m2 with loss of parenchyma accounting for 81% of this loss. The median (IQR) recovery from ischaemia was similar across the cold/warm/zero ischaemia groups at 96% (90%-102%), 95% (89%-101%), and 97% (91%-102%), respectively. Independent predictors of Spectrum Score were ischaemia time, tumour complexity, and preoperative global GFR. Independent predictors of recovery from ischaemia were insulin-dependent diabetes mellitus, refractory hypertension, warm ischaemia, and Spectrum Score. CONCLUSIONS: The main determinant of functional recovery after PN is parenchymal volume preservation. A more robust and rigorous evaluation allowed us to identify secondary factors including comorbidities, increased tumour complexity, and ischaemia-related factors that are also independently associated with impaired recovery, although altogether these were much less impactful.

Long-Term Renal Function Following Renal Cancer Surgery: Historical Perspectives, Current Status, and Future Considerations.

Knowledge of functional recovery after partial (PN) and radical nephrectomy for renal cancer has advanced considerably, with PN now established as the reference standard for most localized renal masses. However, it is still unclear whether PN provides an overall survival benefit in patients with a normal contralateral kidney. While early studies seemingly demonstrated the importance of minimizing warm-ischemia time during PN, multiple new investigations over the last 10 years have proven that parenchymal mass lost is the most important predictor of new baseline renal function. Minimizing loss of parenchymal mass during resection and reconstruction is the most important controllable aspect of long-term post-operative renal function preservation.

Comprehensive Management of Renal Masses in Solitary Kidneys.

BACKGROUND: A renal mass in a solitary kidney (RMSK) has traditionally been managed with partial nephrectomy (PN), although radical nephrectomy (RN) is occasionally required. Most RMSK studies have focused on patients for whom PN was achieved. OBJECTIVE: To provide a comprehensive analysis of the management strategies/outcomes for an RMSK and address knowledge deficits regarding this challenging disorder. DESIGN, SETTING, AND PARTICIPANTS: A total of 1024 patients diagnosed with an RMSK (1975-2022) were retrospectively evaluated. Baseline characteristics and pathologic/functional/survival outcomes were analyzed. INTERVENTION: PN/RN/cryoablation (CA)/active surveillance (AS). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Functional outcomes, perioperative morbidity/mortality, and 5-yr recurrence-free survival (RFS) were evaluated. Kruskal-Wallis and chi-square tests were used to compare cohorts, and log-rank test and Cox proportional hazard model were used for survival analysis. RESULTS AND LIMITATIONS: Of 1024 patients, 842 underwent PN (82%), 102 CA (10%), 54 RN (5%), and 26 AS (3%). The median tumor size and RENAL([R]adius [tumor size as maximal diameter], [E]xophytic/endophytic properties of tumor, [N]earness of tumor deepest portion to collecting system or sinus, [A]nterior [a]/posterior [p] descriptor, and [L]ocation relative to polar lines) score were 3.7 cm and 8, respectively. The median follow-up was 53 mo. For PN, 95% were clamped, and the median warm and cold ischemia times were 22 and 45 min, respectively. For PN, the median preoperative glomerular filtration rate (GFR) was 57 ml/min/1.73 m2, and the median new baseline and 5-yr GFRs were 47 and 48 ml/min/1.73 m2, respectively. Dialysis-free survival for PN was 97% at 5 yr. Twenty-two (2.1%) patients with clear-cell renal cell carcinoma and RENAL score ≥10 (median = 11) received tyrosine kinase inhibitors (TKIs) to facilitate PN, leading to 57% median decrease of tumor volume; PN was accomplished in 20 (91%). Forty-one patients had planned RN (4.0%), most often due to severe pre-existing chronic kidney disease (CKD), and 13 were converted from PN to RN (1.5%). Clavien III-V perioperative complications were observed in 80 (8%) patients and 90-d mortality was 0.6%. Five-year RFS for PN, CA, and RN were 83%, 80%, and 72%, respectively (p = 0.03 for PN vs RN). CONCLUSIONS: Nephron-sparing approaches are feasible and successful in most RMSK patients. PN for an RMSK is often challenging but can be facilitated by selective use of TKIs. RN is occasionally required due to severe CKD, over-riding oncologic concerns, or conversion from PN. This is the first large RMSK study to provide a comprehensive analysis of all management strategies/outcomes. PATIENT SUMMARY: Kidney cancer in a solitary kidney is a major challenge for achieving cancer-free status and avoiding dialysis. Although partial nephrectomy is the principal treatment for a renal mass in a solitary kidney, other options are occasionally required to optimize outcomes.

The role of enhanced recovery after surgery protocols in the development of acute kidney injury following radical cystectomy.

PURPOSE: Recent reports have suggested that fluid restriction as part of Enhanced Recovery after Surgery (ERAS) pathways may increase the risk of AKI in radical cystectomy (RC) patients. We sought to evaluate the impact of ERAS initiation on AKI incidence at a high-volume tertiary care center. MATERIALS AND METHODS: We performed a retrospective review of our IRB approved database to identify patients receiving RC from 2010 to 2019. ERAS was initiated at our institution in October 2016. Acute kidney injuries were graded according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria and must have occurred within 7 days of indexed RC. Estimated glomerular filtration rate (eGFR) was captured at baseline, 1, 3, 6, and 12 months respectively. Categorical variables were compared with the Pearson-Chi square test. Quantitative variables were analyzed with the Wilcoxon-Rank sum test. Multivariable binary logistic regression and interaction analysis was used to identify predictors of AKI. RESULTS: Twelve hundred patients were included. Twenty-two percent of patients experienced an AKI within 7 days. Patients in the ERAS cohort experienced less AKIs after RC (18% vs. 25%, P = 0.003). When adjusting for year of surgery, ERAS was not a significant predictor for AKI on multivariable analysis (OR: 0.87, P = 0.73). On interaction analysis, during the ERAS era, intracorporeal robot-assisted radical cystectomy (iRARC) was associated with decreased odds of AKI (OR: 0.39, P = 0.034). There were no significant differences in eGFR at 12 months postoperatively (P = 0.16). CONCLUSION: Unlike previous reports, ERAS initiation was not associated with increased risk of AKI at a tertiary care high-volume center.

Partial Versus Radical Nephrectomy: Complexity of Decision-Making and Utility of AUA Guidelines.

INTRODUCTION: The American-Urological-Association(AUA) Guidelines for renal cancer(2017) recommend consideration for radical-nephrectomy(RN) over partial(PN) whenever there is increased oncologic-risk; and RN should be prioritized if three other criteria are all also met: 1) increased tumor-complexity; 2) no preexisting chronic-kidney-disease/ proteinuria, and 3) normal contralateral kidney that will likely provide estimated glomerular-filtration-rate (eGFR) >45ml/min/1.73m2 even if RN is performed. Our objective was to assess the complexity of decision-making about RN/PN and utility of AUA Guidelines statements regarding this issue. PATIENTS AND METHODS: Retrospective review of 267 consecutive RN/PN from 2019(100-RN/167-PN). High tumor-complexity was defined as R.E.N.A.L.≥9. Increased oncologic-risk was defined as tumor >7cm, locally-advanced or infiltrative-features on imaging, or high-risk pathology on biopsy, if obtained. New-baseline GFR after RN was estimated using global-GFR, split-renal-functioncontralateral, and presuming 25% renal-functional-compensation. RESULTS: 163 patients(61%) fit scenarios that are well-defined in the Guidelines. Of these, 34 had strong indications for RN, and all had RN. Twelve of 129 patients(9.3%) underwent RN despite Guidelines generally favoring PN. The remaining 104 patients(39%) did not fit within situations where the Guidelines provide specific recommendations. In these patients, RN was often performed despite functional-considerations favoring PN due to overriding concerns about oncologic-risk and/or tumor-complexity. CONCLUSION: Our data demonstrate complexity of decision-making about PN/RN as almost 40% of patients did not fit well-described AUA Guidelines descriptors. Compliance was generally strong although occasional overutilization of RN remains a concern in our series, and will be addressed with additional education. Further studies will be required to assess the generalizability of our findings in other institutions/settings.