Joseph Zabell

Acute Kidney Injury after Partial Nephrectomy: Role of Parenchymal Mass Reduction and Ischemia and Impact on Subsequent Functional Recovery

BACKGROUND Acute increase of serum creatinine (SCr) after partial nephrectomy (PN) is primarily due to parenchymal mass reduction or ischemia; however, only ischemia can impact subsequent functional recovery. OBJECTIVE We evaluate etiologies of acute kidney injury (AKI) after PN and their prognostic significance. DESIGN, SETTING, AND PARTICIPANTS From 2007-2014, 83 solitary kidneys managed with PN had necessary studies for detailed analysis of function and parenchymal mass before/after surgery. AKI was classified by Risk/Injury/Failure/Loss/Endstage classification and defined by either standard criteria (comparison to preoperative SCr) or proposed criteria (comparison to projected postoperative SCr based on parenchymal mass reduction). Subsequent recovery was defined as percent function preserved/percent mass saved. INTERVENTION PN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Predictive factors for AKI were evaluated by logistic regression. Relationship between AKI grade and subsequent functional recovery was assessed by linear regression. RESULTS AND LIMITATIONS Median duration warm ischemia (n=39) was 20 min and hypothermia (n=44) was 29 min. Median parenchymal mass reduction was 11%. AKI occurred in 45 patients based on standard criteria and 38 based on proposed criteria, and reflected injury/failure (grade = 2/3) in 23 and 16 patients, respectively. On multivariable analysis, only ischemia time associated with AKI occurrence (p=0.016). Based on the proposed criteria, median recovery from ischemia was 99% in patients without AKI and 95%/90%/88% for patients with grades 1/2/3 AKI, respectively. The coefficient for association between AKI grade based on proposed criteria and subsequent functional recovery was -4.168 (p=0.018). Main limitation is limited patient cohort. CONCLUSIONS Parenchymal mass reduction and ischemia both contribute to acute changes in SCr after PN. Classification of AKI by proposed criteria significantly associates with subsequent functional recovery. However, more robust numbers will be needed to further assess the merits of the proposed criteria. While AKI is associated with suboptimal recovery, even patients with grade 2/3 AKI reached 88-90% of recovery expected. PATIENT SUMMARY Acute decline in function after partial nephrectomy associates with more prolonged ischemia time, and appears to impact subsequent functional recovery. However, most kidneys eventually recover strongly, even if their function is sluggish in the first few days after surgery.

Intermediate-Term Outcomes for Men with Very Low/Low and Intermediate/High Risk Prostate Cancer Managed by Active Surveillance

Purpose: We compare intermediate term clinical outcomes among men with favorable risk and intermediate/high risk prostate cancer managed by active surveillance. Materials and Methods: A total of 635 men with localized prostate cancer have been on active surveillance since 2002 at a high volume academic hospital in the United States. Median followup is 50.5 months (IQR 31.1–80.3). Time to event analysis was performed for our clinical end points. Results: Of the cohort 117 men (18.4%) had intermediate/high risk disease. Overall 5 and 10‐year all cause survival was 98% and 94%, respectively. Cumulative metastasis‐free survival at 5 and 10 years was 99% and 98%, respectively. To date no cancer specific deaths had been observed. Overall freedom from intervention was 61% and 49% at 5 and 10 years, respectively. Overall cumulative freedom from failure of active surveillance, defined as metastasis or biochemical failure after local therapy with curative intent, was 97% and 91% at 5 and 10 years, respectively. Of the men 21 (9.9%) experienced biochemical failure after deferred treatment and the 5‐year progression‐free probability was 92%. Compared to men with favorable risk disease those with intermediate/high risk cancer experienced no difference in metastases, surveillance failure or curative intervention. However, patients at higher risk were at significantly increased risk for all cause mortality, likely reflecting patient selection factors. These conclusions may be limited by the small number of events and the duration of our study. Conclusions: Patients with localized prostate cancer who are on active surveillance demonstrated a low rate of active surveillance failure, prostate cancer specific mortality and metastases regardless of baseline risk.

Autopsy after traumatic death--a shifting paradigm.

OBJECTIVE The role of autopsy in evaluating missed injury after traumatic death is well established and discussed in the literature. The frequency of incidental findings in trauma patients has not been reported. We believe that incidental findings are under recognized and reported by trauma surgeons. PATIENTS AND METHODS This prospective, descriptive, cohort study was conducted at a Level 1 trauma center in a rural state. Four hundred ninety-six deaths over a 4-y period were identified from the trauma registry. Two hundred four complete autopsies were available for review. One thousand eighteen traumatic diagnoses were identified from 204 autopsies and corresponding medical records by trauma surgeons blinded to patient identity. The surgeons recorded missed diagnoses, incidental diagnoses identified at autopsy, and diagnoses known at the time of death confirmed by autopsy. RESULTS The surgeons had a κ-score of 0.82-0.84. Forty-two patients (21% of patients) had 68 severe missed injuries; 67 patients (33% of patients) had 94 minor missed injuries. Twenty-eight patients (14%) had significant incidental findings including premature atherosclerosis, multiple endocrine neoplasia, tuberculosis, and others. CONCLUSIONS The autopsy after traumatic death is more than a mechanism of quality control and teaching. A high proportion of patients will have incidental findings important to family members, and have public health importance. Systems need to be developed to review autopsy results with attention to identifying and communicating incidental findings. Given the incidence of significant missed injuries and incidental findings, the autopsy continues to have an important role in health care.

Devascularized Parenchymal Mass Associated with Partial Nephrectomy: Predictive Factors and Impact on Functional Recovery

Purpose: Parenchymal mass loss is the predominant factor associated with functional outcomes after partial nephrectomy. It is primarily due to excised and/or devascularized parenchymal mass. We evaluated the importance of excised and devascularized parenchymal mass relative to functional recovery after partial nephrectomy. Materials and Methods: In 168 patients who underwent partial nephrectomy the necessary studies were done to determine excised and devascularized parenchymal mass, and evaluate parenchymal mass changes and functional loss of the operated kidney. Parenchymal mass loss in the ipsilateral kidney was measured on contrast enhanced computerized tomography less than 2 months before and 3 to 12 months after partial nephrectomy. Excised parenchymal mass was estimated by subtracting tumor volume from specimen volume. Devascularized parenchymal mass was defined as total parenchymal mass loss minus excised parenchymal mass. We used the Pearson correlation to evaluate relationships between glomerular filtration rate preservation and parenchymal mass loss. Multivariable analysis was done to assess factors associated with devascularized parenchymal mass. Results: Median tumor size was 3.4 cm and median R.E.N.A.L. (radius, exophytic/endophytic tumor properties, nearness of tumor to collecting system or sinus, anterior/posterior and location relative to polar lines) score was 7. Warm and cold ischemia was used in 100 and 68 patients, respectively. Median excised parenchymal and devascularized parenchymal mass was 9 and 16 cm3, respectively (p <0.001). Total parenchymal mass loss and devascularized parenchymal mass were associated strongly with glomerular filtration rate preservation in the operated kidney (each r ≥0.55, p <0.001). However, excised parenchymal mass was only weakly associated with functional outcomes (r = 0.23). The preoperative glomerular filtration rate and endophytic status were associated with devascularized parenchymal mass on multivariable analysis. Conclusions: To our knowledge we report the first study to specifically evaluate the relative contributions of devascularized and excised parenchymal mass to functional recovery after partial nephrectomy. Our study suggests that devascularized parenchymal mass has more impact, which may have implications regarding surgical technique. Prospective study is required to further evaluate the relative contributions of excised and devascularized parenchymal mass in various settings.

Acute Ipsilateral Renal Dysfunction after Partial Nephrectomy in Patients with a Contralateral Kidney: Spectrum Score to Unmask Ischemic Injury

BACKGROUND Acute ischemic injury in the operated kidney after partial nephrectomy (PN) is often masked by a functional contralateral kidney; however, there is no practical method to assess this and its prognostic significance has not been defined. OBJECTIVE We propose a spectrum score to reflect the degree of ischemic insult in the ipsilateral kidney and study its relationship to subsequent functional recovery. DESIGN, SETTING, AND PARTICIPANTS From 2007 to 2014, 243 patients with a functional contralateral kidney underwent PN with necessary studies for detailed analysis of function and parenchymal mass before and after surgery in the ipsilateral kidney. Based on split function and percent parenchymal mass preserved in the ipsilateral kidney, we determined: serum creatinine (SCr)ideal-peak: expected peak SCr presuming no ischemic injury; and SCrworstcase-peak: expected peak SCr presuming temporary complete nonfunction of the ipsilateral kidney. The acute ipsilateral renal dysfunction spectrum score was defined: (observed peak SCr - SCrideal-peak)/(SCrworstcase-peak - SCrideal-peak). Subsequent functional recovery was defined: (percent function preserved)/(percent mass saved). INTERVENTION PN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Factors associated with spectrum score and relationship between spectrum score and subsequent functional recovery were evaluated by linear regression. RESULTS AND LIMITATIONS Median duration of warm ischemia (n=152) was 21min (interquartile range [IQR] = 15-27) and hypothermia (n=91) 26min (IQR=23-30). Median parenchymal mass preservation was 83% (IQR=74-91%). Warm ischemia and longer ischemia duration associated with higher spectrum score (both p<0.05). Increased spectrum score (<25%, 25-50%, 50-75%, and >75% quartiles) had decreased functional recovery (98%, 94%, 90%, and 89%, respectively, p<0.001). However, this trend was not observed in the hypothermia cohort. On multivariable analysis spectrum score and ischemia type significantly associated with functional recovery (both p<0.01), while age and comorbidities failed to associate (p=0.3-0.7). CONCLUSIONS Acute ipsilateral renal dysfunction spectrum score unmasks the degree of ischemic insult in the operated kidney after PN and associates with functional recovery. While increased spectrum score associates with suboptimal recovery, even patients with a high spectrum score reached 89-90% recovery. PATIENT SUMMARY Acute functional decline after partial nephrectomy is difficult to evaluate in patients with two kidneys, but a proposed spectrum score can be used to evaluate this. Increased spectrum score reflects increased ischemia and may impact the functional recovery of the kidney.

Excised Parenchymal Mass During Partial Nephrectomy: Functional Implications

OBJECTIVE To evaluate whether excised parenchymal mass (EPM) during partial nephrectomy (PN) correlates with functional decline and can serve as a surrogate for functional outcomes. MATERIALS AND METHODS All 215 patients managed with PN for unifocal renal mass with necessary studies to determine EPM and percent glomerular filtration rate (GFR) and parenchymal mass preserved (both global and specific to the operated kidney) were analyzed. EPM was estimated from the pathologic specimen by subtracting the tumor mass from the specimen mass, with both calculated using the elliptical formula. Vascularized parenchymal mass preserved was measured from computed tomography scans obtained <2 months prior and 3-12 months after surgery. All functional analyses were required to be within the same time frames, and patients with a contralateral kidney were also required to have nuclear renal scans. RESULTS The median tumor size was 3.5 cm and the median R.E.N.A.L. was 7. Warm and cold ischemia were utilized in 123 and 92 patients, respectively (median ischemia time = 23 minutes). The median global GFR preserved was 89%, the median total parenchymal mass preserved was 93%, and the median estimated EPM was 16 cm3. Whereas percent parenchymal mass preserved correlated strongly with global and ipsilateral GFR preserved (both P < .001), EPM failed to correlate with functional outcomes on both univariable and multivariable analyses. CONCLUSION Our data suggest that parenchymal mass preserved with standard PN by experienced surgeons associates strongly with function preserved, whereas EPM fails to correlate with functional outcomes. Further study of the functional impact of EPM in other circumstances will be required, such as enucleation or PN performed by less-experienced surgeons.

Ischemia and Functional Recovery from Partial Nephrectomy: Refined Perspectives

BACKGROUND Nephron mass preservation is a key determinant of functional outcomes after partial nephrectomy (PN), while ischemia plays a secondary role. Analyses focused specifically on recovery of the operated kidney appear to be most informative, yet have only included limited numbers of patients. OBJECTIVE To evaluate the relative impact of parenchymal preservation and ischemia on functional recovery after PN using a more robust cohort allowing for more refined perspectives about ischemia. DESIGN, SETTING, AND PARTICIPANTS A total of 401 patients managed with PN with necessary studies were analyzed for function and nephron mass preserved specifically within the kidney exposed to ischemia. INTERVENTION PN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The nephron mass preserved was measured from computed tomography scans <2 mo before and 3-12 mo after PN. Patients with two kidneys were required to have nuclear renal scans within the same timeframes. Recovery from ischemia was defined as the percent function preserved normalized by the percent nephron mass preserved. Pearson correlation was used to evaluate relationships between functional recovery and nephron mass preservation or ischemia time. Multivariable linear regression assessed predictors for recovery from ischemia. RESULTS AND LIMITATIONS The median tumor size was 3.5cm and the median RENAL score was 8. Cold and warm ischemia were utilized in 151 and 250 patients, and the median ischemia time was 27 and 21min, respectively. The function preserved was strongly correlated with nephron mass preserved(r=0.63; p<0.001). Median recovery from ischemia was significantly higher for hypothermia (99% vs 92%; p<0.001) and remained consistently strong even with longer duration. Multivariable analysis demonstrated that recovery from ischemia, which normalizes for nephron mass preservation, was significantly associated with ischemia type and duration (both p<0.05). However, each additional 10min of warm ischemia was associated with only a 2.5% decline in recovery from ischemia. Limitations include the retrospective design. CONCLUSIONS Our data suggest that functional recovery from clamped PN is most reliable with hypothermia. Longer intervals of warm ischemia are associates with reduced recovery; however, incremental changes are modest and may not be clinically significant in patients with a normal contralateral kidney. PATIENT SUMMARY Functional recovery after clamped partial nephrectomy is primarily dependent on preservation of nephron mass. Recovery is most reliable when hypothermia is applied. Longer intervals of warm ischemia are associated with reduced recovery; however, the incremental changes are modest.

Preoperative Prediction and Postoperative Surgeon Assessment of Volume Preservation Associated with Partial Nephrectomy: Comparison with Measured Volume Preservation

OBJECTIVE To evaluate whether surgeons can predict the percent parenchymal mass that will be preserved by partial nephrectomy (PN) based on preoperative imaging, which could have potential utility for preoperative surgical planning and patient counseling. The proportion of preserved viable parenchyma following PN is the primary determinant of functional recovery. However, direct measurement of parenchymal volume preservation (VP) can be complex and time consuming. MATERIALS AND METHODS For patients managed with PN at our institution (2007-2014), we randomly selected 45 with a third in each of low, intermediate, or high R.E.N.A.L. complexity groups. All patients had recorded postoperative surgeon assessment of volume preservation (SAVP) and measured VP based on preoperative or postoperative computed tomography. Nine clinical providers predicted VP based solely on review of preoperative imaging while blinded to SAVP and measured VP. Clinical experience of the providers ranged from medical students to experienced urologic surgeons. RESULTS Median age was 66 years, median tumor size was 4.0 cm, and median R.E.N.A.L. was 8. Median measured VP was 81% (interquartile range of 74-89%). Preoperative prediction of VP correlated poorly with measured VP among the different surgeons (mean correlation coefficient, R = 0.34, range = 0.24-0.40). Surgeon experience provided minimal incremental improvement. Correlation between R.E.N.A.L. and measured VP was also marginal (R = 0.43). In contrast, correlation between postoperative SAVP and measured VP was much more robust (R = 0.75, P <.001). CONCLUSION Preoperative prediction of VP and R.E.N.A.L. score correlated poorly with measured VP for patients managed with PN. In contrast, postoperative SAVP provided a relatively reliable estimate of VP, and should be considered an acceptable substitute in most clinical circumstances.

Impact of Comorbidities on Functional Recovery from Partial Nephrectomy

Purpose: Parenchymal mass preservation, and ischemia type and/or duration can influence functional recovery after partial nephrectomy. Some groups have hypothesized that relevant comorbidities may also impact nephron stability and functional recovery but this has not been adequately investigated. Materials and Methods: At our center 405 patients treated with partial nephrectomy from 2007 to 2015 had the necessary data to determine the function and parenchymal mass preserved in the ipsilateral kidney. Comorbidities potentially associated with renal functional status were reviewed, including various degrees of hypertension, diabetes, cardiovascular disease, obesity, smoking status and related medications. Multivariable linear regression was done to assess factors associated with functional recovery, defined as the percent of preserved ipsilateral glomerular filtration rate. Results: Median tumor size was 3.5 cm and the median 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 touching main renal artery or vein) score was 8. Warm and cold ischemia were done in 264 (65%) and 141 patients for a median duration of 21 and 27 minutes, respectively. The median preserved ipsilateral glomerular filtration rate was 79%. Patient age, comorbidity index, hypertension and proteinuria were each associated with the preoperative glomerular filtration rate (all p <0.01). On univariable and multivariable analyses the preserved parenchymal mass, and ischemia type and duration were significantly associated with functional recovery (all p <0.001). On univariable analysis of comorbidities only hypertension was significantly associated with functional recovery. However, on multivariable analysis none of the analyzed comorbidities were associated with functional recovery. Conclusions: Recovery of function after partial nephrectomy depends primarily on parenchymal mass preservation and ischemia characteristics. Comorbidities failed to be associated with functional outcomes. Comorbidities can impact function, leading to surgery, and may influence long‐term functional stability. However, our data suggest that they do not influence short‐term recovery after partial nephrectomy.

Functional Comparison of Renal Tumor Enucleation Versus Standard Partial Nephrectomy

BACKGROUND Tumor enucleation (TE) optimizes parenchymal preservation and could yield better function than standard partial nephrectomy (SPN), although data on this are conflicting. OBJECTIVE To compare functional outcomes for TE and SPN strategies. DESIGN, SETTING, AND PARTICIPANTS Patients managed with partial nephrectomy (PN) with necessary data for analysis of preservation of ipsilateral parenchymal mass (IPM) and global glomerular filtration rate (GFR) from two centers were included. All studies were required <2 mo before and 3-12 mo after surgery. Patients with a solitary kidney or multifocal tumors were excluded. INTERVENTION Partial nephrectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Vascularized IPM was estimated from contrast-enhanced CT scans preoperatively and postoperatively. Serum creatinine-based estimates of global GFR were also obtained in the same timeframes. Univariable and multivariable linear regression evaluated factors associated with new-baseline global GFR. RESULTS/LIMITATIONS Analysis included 71 TE and 373 SPN cases. The median preoperative global GFR was comparable for TE and SPN (75 vs 78ml/min/1.73m2; p=0.6). The median tumor size was 3.0cm for TE and 3.3cm for SPN (p=0.03). The median RENAL score was 7 in both cohorts. For TE, warm ischemia and zero ischemia were used in 51% and 49% of cases, respectively. For SPN, warm ischemia and cold ischemia were used in 72% and 28% of patients, respectively. Capsular closure was performed in 46% of TE and 100% of SPN cases (p<0.001). Positive margins were found in 8.5% of TE and 4.8% of SPN patients (p=0.2). The median vascularized IPM preserved was 95% (interquartile range [IQR] 91-100%) for TE and 84% (IQR 76-92%) for SPN (p<0.001). The median global GFR preserved was 101%(IQR 93-111%) and 89% (IQR 81-96%) for TE and SPN, respectively (p<0.001). On multivariable analysis, resection strategy, preoperative GFR, and vascularized IPM preserved were all significantly associated (p<0.001) with new-baseline global GFR. Limitations include the retrospective design and the lack of resection outcome data. CONCLUSIONS Our analysis suggests that TE has potential for maximum IPM preservation compared to SPN and may provide optimized functional recovery. Further investigation will be required to evaluate the clinical significance of these findings. PATIENT SUMMARY Tumor enucleation for kidney cancer involves dissection along the tumor capsule and optimally preserves normal kidney tissue, which may lead to better functional recovery. The importance of this approach in various clinical settings will require further investigation.