Publications by authors named "Erik Castle"

157 Publications

Outcomes of post-chemotherapy robot-assisted retroperitoneal lymph node dissection in testicular cancer: multi-institutional study.

World J Urol 2021 May 7. Epub 2021 May 7.

Department of Urology, Naval Medical Center San Diego, San Diego, CA, USA.

Objective: To evaluate the perioperative and oncological outcomes after post-chemotherapy robot-assisted retroperitoneal lymph node dissection (PC-RARPLND).

Materials And Methods: We retrospectively reported the perioperative and oncological outcomes of all the patients with testicular cancer who underwent PC-RARPLND at three tertiary teaching centers. Descriptive statistical measures were used to report demographic, clinical, intraoperative, postoperative and oncological outcomes.

Results: There were 43 consecutive patients who underwent PC-RARPLND at the participating institutions. Mean patient age was 29.2 years (± 8.2), BMI was 26.6 kg/m (± 6.2). The mean size of retroperitoneal mass was 4.1 cm (± 3.5). Full bilateral template dissection was performed in 38 (88.3%) patients. Nerve sparing was attempted in 19 (44.1%) patients. Mean operative time was 374 min (± 132) and estimated blood loss was 292 ml (± 445.6). The mean postoperative LOS was 2.8 days (± 5.9). There was a total of 12 complications in 10 patients (Clavien grade I = 5, II = 3, III = 3 and IV = 1). Postoperative pathology demonstrated 24 patients (55%) with necrosis/fibrosis, 16 (37%) with teratoma and 3 (7%) with viable tumor. Mean lymph node (LN) yield was 26.5 LNs (SD ± 16.1). Patients were followed for a mean of 30.7 months (± 24.7). No deaths were documented during follow-up and 2 pulmonary recurrences were identified. Antegrade ejaculation was preserved in 70.6% of patient who underwent nerve sparing. Limitations included retrospective nature and limited follow up.

Conclusion: PC-RAPLND is safe and technically reproducible. It provides improved morbidity and less convalescence.
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http://dx.doi.org/10.1007/s00345-021-03712-7DOI Listing
May 2021

Learning Curve for Robotic-Assisted Laparoscopic Retroperitoneal Lymph Node Dissection.

J Endourol 2021 Apr 6. Epub 2021 Apr 6.

Urology Department, Naval Medical Center San Diego, San Diego, California, USA.

Robotic retroperitoneal lymph node dissection (R-RPLND) is a challenging procedure. We hypothesized that surgical times and operative complications would decrease as surgeons became more facile with R-RPLND. We retrospectively reviewed 121 consecutive R-RPLNDs performed at Naval Medical Center San Diego and Mayo Clinic Arizona by 4 fellowship trained robotic surgeons between 2008 and 2018. Linear regression was used to analyze independent predictors of setup time, operative time, and lymph node counts. Logistic regression was used to analyze open conversions, overall complications, and high-grade complications. Variables included as independent predictors were: sequential case number, surgeon, clinical stage, chemotherapy status, RPLND template, and body mass index. Univariate and multivariate analyses were conducted. Statistical significance was established at α = 0.05. There was no change in setup time with case number ( = 0.317), but differences were noted between surgeons. Operative times decreased with increasing case number ( < 0.001) but were negatively affected by clinical stage III testis cancer ( = 0.029) and history of chemotherapy exposure ( = 0.050). Surgical times are predicted to decrease by 1 hour after 44 cases. Lymph node counts were dependent only on the surgeon. No factors were predictive of open conversions. Fewer overall complications occurred as experience was gained ( = 0.001), but high-grade complications could not be predicted. Consistent with the learning curves shown for other technologically advanced surgical techniques, experience appears to improve surgical times and lower complication rates for R-RPLND.
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http://dx.doi.org/10.1089/end.2020.0549DOI Listing
April 2021

Identification of DNA methylation signatures associated with poor outcome in lower-risk Stage, Size, Grade and Necrosis (SSIGN) score clear cell renal cell cancer.

Clin Epigenetics 2021 Jan 18;13(1):12. Epub 2021 Jan 18.

Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.

Background: Despite using prognostic algorithms and standard surveillance guidelines, 17% of patients initially diagnosed with low risk clear cell renal cell carcinoma (ccRCC) ultimately relapse and die of recurrent disease, indicating additional molecular parameters are needed for improved prognosis.

Results: To address the gap in ccRCC prognostication in the lower risk population, we performed a genome-wide analysis for methylation signatures capable of distinguishing recurrent and non-recurrent ccRCCs within the subgroup classified as 'low risk' by the Mayo Clinic Stage, Size, Grade, and Necrosis score (SSIGN 0-3). This approach revealed that recurrent patients have globally hypermethylated tumors and differ in methylation significantly at 5929 CpGs. Differentially methylated CpGs (DMCpGs) were enriched in regulatory regions and genes modulating cell growth and invasion. A subset of DMCpGs stratified low SSIGN groups into high and low risk of recurrence in independent data sets, indicating that DNA methylation enhances the prognostic power of the SSIGN score.

Conclusions: This study reports a global DNA hypermethylation in tumors of recurrent ccRCC patients. Furthermore, DMCpGs were capable of discriminating between aggressive and less aggressive tumors, in addition to SSIGN score. Therefore, DNA methylation presents itself as a potentially strong biomarker to further improve prognostic power in patients with low risk SSIGN score (0-3).
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http://dx.doi.org/10.1186/s13148-020-00998-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814746PMC
January 2021

Use of treatment pathway improves neoadjuvant chemotherapy use in muscle-invasive bladder cancer.

Int Urol Nephrol 2021 Jan 3. Epub 2021 Jan 3.

Department of Urology, Mayo Clinic Hospital, 5777 E Mayo Blvd, Phoenix, AZ, 85054, USA.

Purpose: To assess the trends of neoadjuvant chemotherapy (NAC) use since its introduction in our practice pathway in patients with cT2 + bladder cancer over a 20-year period.

Methods: This is a retrospective review of patients with cT2 + bladder cancer who underwent RC between 01/01/1998 and 01/01/2018 that aimed to evaluate the trends of NAC use and associated after implementation of a multidisciplinary treatment pathway. Cohorts were stratified into eras: pre-NAC (1998-2007) to NAC eras (2008-2018). Univariate analysis was conducted using Chi-squared test and Kaplan-Meier estimates were used to evaluate survival.

Results: In 904 total patients who underwent RC, there were 493 with cT2 + UCC disease. The rate of NAC peaked at 84.2% in the most recent year of analysis in all patients and was 100% in cT2 + patients eligible for NAC. There was an increased rate of complete response (downstage to pT0) from 8.7% to 15.8% (p = 0.018) between the two eras. Unadjusted survival analysis revealed improved overall survival (OS) between eras with 5-year OS 53.2% vs. 42.7% and 10-year OS 42.7% vs. 26.4% in the NAC vs. pre-NAC cohorts, respectively (p = 0.016).

Conclusions: In this review of 20 years of experience, we report a dramatic rise in the use of NAC after adoption of a multidisciplinary pathway that is associated with expected survival benefits.
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http://dx.doi.org/10.1007/s11255-020-02752-zDOI Listing
January 2021

Robot Assisted Renal Allograft Nephrectomy: Initial Case Series and Description of Technique.

Urology 2020 Dec 20;146:118-124. Epub 2020 Oct 20.

Mayo Clinic Arizona, Department of Urology, Phoenix, AZ.

Objective: To evaluate the outcomes and perioperative complication rates following robot- assisted transplant nephrectomy ((RATN).

Methods: All patients who underwent RATN at our institution were included. No exclusion criteria were applied. Clinical records were retrospectively reviewed and reported. This included preoperative, intraoperative, and postoperative outcomes. Complications were reported utilizing the Clavien-Dindo classification system. Descriptive statistics were reported using frequencies and percentages for categorical variables, means and standard deviation for continuous variables.

Results: Between July 2014 and April 2018, 15 patients underwent RATN. Most patients had the transplant in the right iliac fossa (13/15). Ten patients underwent a concomitant procedure. The total operative time for the entire cohort was 336 (±102) minutes (including cases who had concomitant procedures) and 259 (±46 minutes) when cases with concomitant procedures were excluded. Mean estimated blood loss was 383 (±444) mL. Postoperatively, 3 patients required blood transfusion. Average hospital stay was 4 (±2.7) days. Most patients had finding consistent with graft rejection on final pathology. There were 5 complications; 3 of which were minor (grade 2 = 2 and grade 3 = 1); one patient had a wound infection requiring dressing (3A) and one patient died due to pulmonary embolism following discharge. Limitations include small series and retrospective nature of the study.

Conclusion: This case series demonstrate that RATN is technically feasible. With continued experience and larger case series, the robotic approach may provide a minimally invasive alternative to open allograft nephrectomy.
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http://dx.doi.org/10.1016/j.urology.2020.10.008DOI Listing
December 2020

Outcome prediction following radical nephroureterectomy for upper tract urothelial carcinoma.

Urol Oncol 2021 02 15;39(2):133.e9-133.e16. Epub 2020 Oct 15.

Mayo Clinic in Arizona, Department of Urology, Phoenix, AZ.

Objective: To predict overall survival, cancer, and metastasis specific survival in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU).

Materials And Methods: All nonmetastatic UTUC patients who underwent RNU with a curative intent at 1 institution between December 1998 and January 2017 were included.  Detailed data were collected. End points for this study included OS, CCS, and MFS. Univariate and multivariate analysis were conducted. Log Rank tests and Kaplan-Meier curves were generated. Backward elimination and boot strapping was used to identify the most parsimonious model with the smallest number of variables in order to predict the outcomes of interest. A separate second institution data base was used for external validation.

Results: There were 218 patients in the development cohort. Mean follow-up was 42 months (±39.6). There was 99 (45.4%) deaths, 28 (12.8%) cancer related deaths, 72 (33%) recurrences, and 54 (24.8%) metastases. The c-index for our model was 0.71 for OS, 0.72 for MFS and 0.74 for CSS. The nomograms did not show significant deviation from actual observations using our calibration plots. We divided the patient into 3 different groups (low, intermediate and high risk) based on their final total score for each outcome and compared them. On external validation our accuracy was 78.4%, 71.4%, and 75.3% for OS, CSS, and MFS survival respectively.

Conclusion: We designed a predictive model for survival outcomes following RNU in UTUC. This model uses simple, readily available data for patients without the need for expensive or additional testing.
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http://dx.doi.org/10.1016/j.urolonc.2020.08.021DOI Listing
February 2021

The effect of urinary diversion on long-term kidney function after cystectomy.

Urol Oncol 2020 10 30;38(10):796.e15-796.e21. Epub 2020 May 30.

Department of Urology (Drs Faraj, Swanson, Andrews, Ferrigni, Humphreys, Castle, and Tyson), Mayo Clinic Hospital, Phoenix, Arizona. Electronic address:

Objectives: Cystectomy with urinary diversion is associated with decreased long-term kidney function due to several factors. One factor that has been debated is the type of urinary diversion used: ileal conduit (IC) vs. neobladder (NB). We tested the hypothesis that long-term kidney function will not vary by type of urinary diversion.

Methods And Materials: We retrospectively identified all patients who underwent cystectomy with urinary diversion at our institution from January 1, 2007, to January 1, 2018. Data were collected on patient demographics, comorbid conditions, perioperative radiotherapy, and complications. Creatinine values were measured at several time points up to 120 months after surgery. Glomerular filtration rate (GFR) (ml/min per 1.73 m) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. A linear mixed model with inverse probability of treatment weighting (IPTW) was used to compare GFR between the IC and NB cohorts over time. Multiple sensitivity analyses were performed based on 2 different calculations of GFR (Chronic Kidney Disease Epidemiology Collaboration equation vs. Modification of Diet in Renal Disease), with and without excluding patients with preoperative GFR less than 40 ml/min per 1.73 m.

Results: Among 563 patients who underwent cystectomy with urinary diversion, a NB was used for 72 (12.8%) individuals. Patients who had a NB were significantly younger, had a lower American Society of Anesthesiologists score, greater baseline GFR, better Eastern Cooperative Oncology Group performance status, lower median Charlson comorbidity index, and were less likely to have received preoperative abdominal radiation (all P < 0.05). Both NB and IC patients had decreased kidney function over time, with mean GFR losses at 5 years of 17% and 14% of baseline values, respectively. The IPTW-adjusted linear mixed model revealed that IC patients had slightly more deterioration in kidney function over time, but this was not statistically significant (estimate, 0.12; P = 0.06). The sensitivity analyses yielded a similar trend, in that GFR decrease appeared to be greater in the IC cohort. This trend was statistically significant when using Modification of Diet in Renal Disease (P = 0.04).

Conclusions: Among highly selected patients with an NB, deterioration of kidney function may potentially be lower over time than among IC patients. However, the statistical significance varied between analyses and we cautiously attribute these observed differences to patient selection.
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http://dx.doi.org/10.1016/j.urolonc.2020.05.003DOI Listing
October 2020

Health Related Quality of Life of Patients with Bladder Cancer in the RAZOR Trial: A Multi-Institutional Randomized Trial Comparing Robot versus Open Radical Cystectomy.

J Urol 2020 Sep 9;204(3):450-459. Epub 2020 Apr 9.

Department of Urology, University of Miami Miller School of Medicine, Miami, Florida.

Purpose: We evaluated health related quality of life following robotic and open radical cystectomy as a treatment for bladder cancer.

Materials And Methods: Using the Randomized Open versus Robotic Cystectomy (RAZOR) trial population we assessed health related quality of life by using the Functional Assessment of Cancer Therapy (FACT)-Vanderbilt Cystectomy Index and the Short Form 8 Health Survey (SF-8) at baseline, 3 and 6 months postoperatively. The primary objective was to assess the impact of surgical approach on health related quality of life. As an exploratory analysis we assessed the impact of urinary diversion type on health related quality of life.

Results: Analyses were performed in subsets of the per-protocol population of 302 patients. There was no statistically significant difference between the mean scores by surgical approach at any time point for any FACT-Vanderbilt Cystectomy Index subscale or composite score (p >0.05). The emotional well-being score increased over time in both surgical arms. Patients in the open arm showed significantly better SF-8 sores in the physical and mental summary scores at 6 months compared to baseline (p <0.05). Continent diversion (versus noncontinent) was associated with worse FACT-bladder-cystectomy score at 3 (p <0.01) but not at 6 months, and the SF-8 physical component was better in continent-diversion patients at 6 months (p=0.019).

Conclusions: Our data suggests lack of significant differences in the health related quality of life in robotic and open cystectomies. As robotic procedures become more widespread it is important to discuss this finding during counseling.
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http://dx.doi.org/10.1097/JU.0000000000001029DOI Listing
September 2020

How the Beneficial Effects of Alvimopan Differ With Surgical Approach for Radical Cystectomy.

Urology 2020 Jun 27;140:107-114. Epub 2020 Feb 27.

Department of Urology, Mayo Clinic Hospital, Phoenix, AZ. Electronic address:

Objective: To assess whether the beneficial perioperative effects of alvimopan differ with surgical approach for patients who undergo open radical cystectomy (ORC) vs robot-assisted radical cystectomy (RARC).

Methods: This retrospective study reviewed all patients who underwent cystectomy with urinary diversion at our institution between January 1, 2007, and January 1, 2018. Data were collected on demographic characteristics, comorbidities, surgical approach, alvimopan therapy, hospital length of stay (LOS), days until return of bowel function (ROBF), and complications. Outcomes and interactions were evaluated through regression analysis.

Results: Among 573 patients, 236 (41.2%) underwent RARC, 337 (58.8%) underwent ORC, and 205 (35.8%) received alvimopan. Comparison of 4 cohorts (ORC with alvimopan, ORC without alvimopan, RARC with alvimopan, and RARC without alvimopan) showed that patients who underwent ORC without alvimopan had the highest rate of postoperative ileus (25.6%, P = .02), longest median hospital LOS (7 days, P < .001), and longest time until ROBF (4 days, P < .001). On multivariable analysis, the interaction between surgical approach and alvimopan use was significant for the outcome of ROBF (estimate, 1.109; 95% confidence interval, 0.418-1.800; P = .002). In the RARC cohort, multivariable analysis showed no benefit of alvimopan with respect to ileus (P = .27), LOS (P = .09), or ROBF (P = .36). Regarding joint effects of robotic approach and alvimopan, RARC had no effect on gastrointestinal tract outcomes.

Conclusion: We observed a diminished beneficial effect of alvimopan among patients undergoing RARC and a statistically significant benefit of alvimopan among patients undergoing ORC. The implications of these findings may permit more selective medication use for patients who would benefit the most from this drug.
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http://dx.doi.org/10.1016/j.urology.2019.12.058DOI Listing
June 2020

Comparison of Open and Robot Assisted Radical Nephrectomy With Level I and II Inferior Vena Cava Tumor Thrombus: The Mayo Clinic Experience.

Urology 2020 Feb 14;136:152-157. Epub 2019 Nov 14.

Department of Urology, Mayo Clinic Arizona, Phoenix, AZ.

Objective: To compare the perioperative and oncologic outcomes associated with open radical nephrectomy with tumor thrombus (O-RNTT) vs robot assisted radical nephrectomy with tumor thrombus (RA-RNTT). Renal cell carcinoma with venous tumor thrombus has traditionally been managed through an open surgical approach. The robot assisted approach may offers improved perioperative outcomes compared to open, but there are few studies comparing these 2.

Methods: We analyzed patients with renal cell carcinoma and inferior vena cava tumor thrombus between 1998 and 2018, comparing perioperative and oncologic outcomes of these patients with Level I and Level II thrombus. Cohorts were stratified by surgical approach: O-RNTT vs RA-RNTT. Univariate analysis was conducted using chi-squared test and t tests when appropriate. Kaplan-Meier estimates were used to evaluate survival.

Results And Limitation: Twenty-seven patients were in the O-RNTT group, and 24 in the RA-RNTT group. Patients in the RA-RNTT group, compared to the O-RNTT group, demonstrated shorter length of stay (3 vs 7 nights, P = .03), lower estimate blood loss (450 vs 1800 mL, P <.01), and lower transfusion rate (21% vs 82%, P <.01). The RA-RNTT group had 26% fever complications compared to the open (17% vs 43%, P <.01). There was no significant difference in estimated overall survival or recurrence-free survival between the O-RNTT and RA-RNTT groups.

Conclusion: RA-RNTT produced a shorter length of stay, less transfusions, and a lower rate of complications with no significant difference in overall survival.
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http://dx.doi.org/10.1016/j.urology.2019.11.002DOI Listing
February 2020

Single-dose perioperative mitomycin-C versus thiotepa for low-grade noninvasive bladder cancer.

Can J Urol 2019 10;26(5):9922-9930

Department of Urology, Mayo Clinic Hospital, Phoenix, Arizona, USA.

Introduction: Mitomycin-C (MMC) and thiotepa are intravesical agents effective in reducing the recurrence of low-grade noninvasive bladder cancer when instilled perioperatively. No studies have compared these agents as a single-dose perioperative instillation. This study tests whether there is a difference in recurrence-free survival in patients with low-grade noninvasive bladder cancer who received intravesical MMC versus thiotepa.

Materials And Methods: A retrospective review was performed of patients who underwent cystoscopic excision of a bladder mass identified as a small, low-grade, treatment-naïve, noninvasive, wild-type urothelial carcinoma of the bladder and who received either intravesical thiotepa (30 mg/15 cc) or MMC (40 mg/20 cc) between January 1, 2002, and January 1, 2016. Data were collected for demographic characteristics, comorbid conditions, operative information, surveillance, and recurrence. The primary outcome was disease-free survival. Cohorts were compared via the doubly robust estimation approach, which used logistic regression to model the probability of recurrence.

Results: Of 154 total patients, 84 received intravesical MMC; 70, thiotepa. No statistical differences were shown between groups for age, sex, race, body mass index, smoking status, or baseline comorbid conditions; mass size, tumor multifocality, or tumor grade; and unadjusted recurrence rates (MMC, 36.0%; thiotepa, 46.0%; p = .33) at similar median follow up (MMC, 20.4; thiotepa, 22.8 months; p = .46). The robust logistic regression analysis yielded no differences in recurrence rates between MMC and thiotepa (OR, 0.65 [95% CI, 0.33-1.31]; p = .23). No episodes of myelosuppression or frozen pelvis were identified.

Conclusions: As single-dose perioperative agents, both thiotepa and MMC were associated with similar recurrence-free survival rates.
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October 2019

Robot Assisted Surgery of the Vena Cava: Perioperative Outcomes, Technique, and Lessons Learned at The Mayo Clinic.

J Endourol 2019 12;33(12):1009-1016

Department of Urology, Mayo Clinic Arizona, Phoenix, Arizona.

This study aims to describe robot assisted surgery of the inferior vena cava (IVC) by assessing techniques utilized, perioperative outcomes, complications, and long-term patency of the IVC. A retrospective review was performed on all robotic surgeries involving dissection and repair of the IVC at our institution. Patient characteristics, operative reports, and follow-up visits were analyzed. Preoperative and postoperative imaging was independently reviewed by a single radiologist to determine changes in IVC diameter. Complications were analyzed according to early (<30 days) late (>30 days). Thirty-four patients underwent robot assisted surgery of the vena cava from 2008 to 2018. Twenty-six cases were performed for urologic malignancy, four were performed for IVC filter explantation, and four renal vein transpositions were performed for nutcracker syndrome. Twenty-four of the 26 patients with urologic malignancy underwent radical nephrectomy with IVC tumor thrombectomy. Three cases were converted to open. Median length of stay was two nights, and mean estimated blood loss (EBL) was 375 mL. There were five complications, ranging from Clavien-Dindo grade II-IIIa, four of which were early complications. No patients required return to the operating room, and there were no perioperative mortalities. IVC diameter was reduced by 41% on axial diameter, with no patients experiencing compromised venous return. Robot assisted surgery offers the advantage of minimally invasive surgery with the ability to apply open surgical principles. In our series, an experienced multidisciplinary team approach yielded low EBL, short length of stay, and low complication rates.
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http://dx.doi.org/10.1089/end.2019.0429DOI Listing
December 2019

Molecular Inhibitor of QSOX1 Suppresses Tumor Growth .

Mol Cancer Ther 2020 01 1;19(1):112-122. Epub 2019 Oct 1.

School of Life Sciences, Arizona State University, Tempe, Arizona.

Quiescin sulfhydryl oxidase 1 (QSOX1) is an enzyme overexpressed by many different tumor types. QSOX1 catalyzes the formation of disulfide bonds in proteins. Because short hairpin knockdowns (KD) of QSOX1 have been shown to suppress tumor growth and invasion and , we hypothesized that chemical compounds inhibiting QSOX1 enzymatic activity would also suppress tumor growth, invasion, and metastasis. High throughput screening using a QSOX1-based enzymatic assay revealed multiple potential QSOX1 inhibitors. One of the inhibitors, known as "SBI-183," suppresses tumor cell growth in a Matrigel-based spheroid assay and inhibits invasion in a modified Boyden chamber, but does not affect viability of nonmalignant cells. Oral administration of SBI-183 inhibits tumor growth in 2 independent human xenograft mouse models of renal cell carcinoma. We conclude that SBI-183 warrants further exploration as a useful tool for understanding QSOX1 biology and as a potential novel anticancer agent in tumors that overexpress QSOX1.
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http://dx.doi.org/10.1158/1535-7163.MCT-19-0233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946859PMC
January 2020

Predictors of Recurrence, and Progression-Free and Overall Survival following Open versus Robotic Radical Cystectomy: Analysis from the RAZOR Trial with a 3-Year Followup.

J Urol 2020 03 24;203(3):522-529. Epub 2019 Sep 24.

Division of Urologic Oncology, Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas.

Purpose: The RAZOR (Randomized Open versus Robotic Cystectomy) trial revealed noninferior 2-year progression-free survival for robotic radical cystectomy. This update was performed with extended followup for 3 years to determine potential differences between the approaches. We also report 3-year overall survival and sought to identify factors predicting recurrence, and progression-free and overall survival.

Materials And Methods: We analyzed the per protocol population of 302 patients from the RAZOR study. Cumulative recurrence was estimated using nonbladder cancer death as the competing risk event and the Gray test was applied to assess significance in differences. Progression-free survival and overall survival were estimated by the Kaplan-Meier method and compared with the log rank test. Predictors of outcomes were determined by Cox proportional hazard analysis.

Results: Estimated progression-free survival at 36 months was 68.4% (95% CI 60.1-75.3) and 65.4% (95% CI 56.8-72.7) in the robotic and open groups, respectively (p=0.600). At 36 months overall survival was 73.9% (95% CI 65.5-80.5) and 68.5% (95% CI 59.8-75.7) in the robotic and open groups, respectively (p=0.334). There was no significant difference in the cumulative incidence rates of recurrence (p=0.802). Patient age greater than 70 years, poor performance status and major complications were significant predictors of 36-month progression-free survival. Stage and positive margins were significant predictors of recurrence, and progression-free and overall survival. Surgical approach was not a significant predictor of any outcome.

Conclusions: This analysis showed no difference in recurrence, 3-year progression-free survival or 3-year overall survival for robotic vs open radical cystectomy. It provides important prospective data on the oncologic efficacy of robotic radical cystectomy and high level data for patient counseling.
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http://dx.doi.org/10.1097/JU.0000000000000565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487279PMC
March 2020

Recurrence After Robotic Retroperitoneal Lymph Node Dissection Raises More Questions than Answers.

Eur Urol 2019 11 19;76(5):610-611. Epub 2019 Sep 19.

Brady Department of Urology, Johns Hopkins Medical Center, USA.

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http://dx.doi.org/10.1016/j.eururo.2019.08.013DOI Listing
November 2019

Robot Assisted Cystectomy With Holmium Laser Debridement for Osteomyelitis of the Pubic Symphysis With Urinary Fistula.

Urology 2019 12 19;134:124-134. Epub 2019 Sep 19.

Mayo Clinic in Arizona, Department of Urology, Phoenix, AZ.

Objective: To assess the success of robot-assisted holmium laser debridement of the pubic symphysis for osteomyelitis of the pubic symphysis with associated urosymphyseal fistula. Traditionally, excision of the fistulous tract and concomitant cystectomy with urinary diversion and pubic symphyseal debridement has been done using an open approach. This paper presents patients who were successfully managed with this approach.

Methods And Materials: Between January 2007 and January 2018, all patients who underwent pubic symphyseal debridement with or without cystectomy were identified. We reviewed patients who underwent planned robot-assisted cystectomy with holmium laser debridement for osteomyelitis of the pubic symphysis as a result of urinary fistula. Data on clinical presentation, perioperative outcomes, and recurrence of urinary tract fistula and symptoms were collected.

Results: Twelve patients underwent holmium laser debridement of the pubic symphysis during robot-assisted cystectomy for urinary fistula. Eleven patients had prior radiation treatments for prostate cancer with all having failed prior conservative management. Median operative time was 270 minutes with median length of stay of 5 days. At last follow-up, 11 (91.7%) of patients had complete resolution of their urinary fistula at median follow-up of 29 months. No patients developed osteonecrosis of the bone or complications from their urinary diversion at last follow-up.

Conclusion: Definitive surgical treatment with holmium laser debridement of the pubic symphysis with concomitant robot-assisted cystectomy and urinary diversion is a safe and durable approach to the complex problem of urinary fistula with pubic symphysis osteomyelitis.
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http://dx.doi.org/10.1016/j.urology.2019.08.049DOI Listing
December 2019

Robot Assisted Radical Cystectomy vs Open Radical Cystectomy: Over 10 years of the Mayo Clinic Experience.

Urol Oncol 2019 12 13;37(12):862-869. Epub 2019 Sep 13.

Department of Urology, Mayo Clinic Hospital, Phoenix, AZ.

Objectives: There is scant information about intermediate / long-term comparative outcomes between robot assisted radical cystectomy (RARC) and open radical cystectomy (ORC). The purpose of this study is to present survival and oncological outcomes between bladder cancer patients who undergo RARC vs. ORC with an overall median follow-up of over 5 years.

Materials And Methods: A query of all patients who underwent radical cystectomy between January, 2007 and January, 2018 at Mayo Clinic Arizona yielded 595 patients. After excluding cystectomy performed for nonmalignant indication, cancer secondary to nonbladder primary, and cancers with grossly metastatic disease at the time of surgery, 481 patients remained. Data was collected on patient demographics, preoperative information, operative details, complications, and follow-up. Statistical analyses were generated using SPSS 22.0.

Results: In 481 total patients, 203 (42.2%) underwent RARC and 278 (57.8%) underwent ORC. The median follow-up for the entire cohort was 66 months. The 5-year recurrence-free survival (RFS) was 70.8% vs. 64.7% and the 10-year RFS was 69.6% vs. 62.7% for the RARC vs. ORC, respectively (P = 0.135). The 5-year overall survival (OS) was 58.9% vs. 57.7% and the 10-year OS was 39.9% vs. 45.6% for RARC vs. ORC patients, respectively (P = 0.466). There were no differences in any recurrence patterns, including the incidence of atypical recurrences (1.5% vs. 1.8% [P = 0.786], respectively). A Cox-proportional hazards model was fitted that included independent predictors of RFS and OS. The results revealed no difference in RFS (HR 1.235, 95% CI: 0.832-1.833, P = 0.295) or OS (HR 0.790, 95% CI: 0.550-1.135, P = 0.202) between the respectively.

Conclusions: Recurrence free survival, OS, and recurrence patterns are similar in bladder cancer patients who undergo either RARC or ORC.
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http://dx.doi.org/10.1016/j.urolonc.2019.07.019DOI Listing
December 2019

Primary robotic RLPND for nonseminomatous germ cell testicular cancer: a two-center analysis of intermediate oncologic and safety outcomes.

World J Urol 2020 Apr 9;38(4):859-867. Epub 2019 Sep 9.

Department of Urology, Mayo Clinic, Phoenix, AZ, USA.

Objective: To evaluate the intermediate-term oncologic outcomes and safety profile of the largest case series of primary robotic retroperitoneal lymphadenectomy for low-clinical-stage non-seminomatous germ cell testicular cancer.

Methods: This was a two-center retrospective analysis of robotic RPLND cases for low-clinical-stage (stage I-IIB) non-seminomatous germ cell testicular cancer in the primary setting. Demographic, perioperative, operative and oncologic variables were collected between March 2008 and May 2019. Descriptive analyses were performed and presented as medians with interquartile ranges for continuous variables and frequency and proportions for categorical variables. A survival analysis of time to recurrence was performed using Cox proportional hazards model. Using logistic regression, risk factors for complications were analyzed. Both univariate and multivariate analyses were performed.

Results: A total of 58 patients (CS 1 = 56, CS IIA = 2, CS IIB = 0) were identified. The median follow-up was 47 months and the 2-year recurrence-free survival rate was 91%. The five recurrences were all out of the performed dissection template (pelvis = 1 and lung = 4). Only five patients (29%) with occult metastasis underwent adjuvant chemotherapy. The median operative time was 319 min [interquartile range (IQR) 276-355 min], estimated blood loss was 100 ml (IQR 75-200 ml), node count was 26 (IQR 20-31), and length of stay 2 d (IQR 1-3 days). There were 2 (3.3%) intraoperative complications, 19 (32.7%) 30-day postoperative complications to include 14 (24.1%) Clavien grade I, 4 (6.9%) Clavien grade II, 1 (1.7%) Clavien grade III and 0 Clavien grade IV complications. No statistical significance was found on multivariate or univariate analysis for survival analysis of time to recurrence and risk factors for complications.

Conclusions: This study represents the largest case series of primary R-RPLND for the treatment of low-stage non-seminomatous germ cell tumors (NSGCT). With 47 months of follow-up and a low rate of adjuvant chemotherapy, intermediate oncologic efficacy appears to be comparable to the gold standard open approach.
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http://dx.doi.org/10.1007/s00345-019-02900-wDOI Listing
April 2020

Role of robot-assisted retroperitoneal lymph node dissection in malignant mesothelioma of the tunica vaginalis: case series and review of the literature.

Can J Urol 2019 06;26(3):9752-9757

Department of Urology, Mayo Clinic Hospital, Phoenix, Arizona, USA.

Introduction: The management of malignant mesothelioma of the tunica vaginalis (MMTVT) is not clearly defined. Retroperitoneal lymph node dissection has been reported as a potential management option. Herein we present our experience with robot-assisted retroperitoneal lymph node dissection (RARPLND) in our series of patients with MMTVT.

Materials And Methods: The Mayo Clinic cancer registry was queried from 1972-present for all patients who had a diagnosis of MMTVT. Six patients were identified, five of whom were treated with RPLND, where four underwent RARPLND.

Results: In five patients who underwent RPLND, the median age was 50 years (IQR 34-51). Four patients originally presented with right sided symptomatic hydroceles, while one presented with right sided chronic epididymitis. Orchiectomy (one simple, two inguinal radical) was performed in three patients prior to presentation. Preoperative cross-sectional imaging, including PET-CT scan in three patients, was negative for lymphadenopathy or metastasis. RARPLND was performed in 4/5 (80%) cases and concomitant hemiscrotectomy in 4/5 (80%) cases. Full bilateral template was performed in three patients and right modified template was performed in the remaining two. Median lymph node yield was 29 (IQR 22-32) and median blood loss was 275 cc (IQR 200-300). Positive retroperitoneal lymph nodes were found in 3/5 (60%) cases. All patients who underwent RARPLND were discharged home on postoperative day one. Mean follow up was 27 months (range 3-47). No patients recurred.

Conclusions: Regardless of the approach, RPLND may provide a diagnostic benefit in patients who present with MMTVT, with the robotic approach affording a potentially expedited recovery.
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June 2019

Intracorporeal orthotopic neobladder formation: Why not to do it?

Arch Esp Urol 2019 04;72(3):318-325

Department of Urology. Mayo Clinic Arizona. Phoenix. Arizona. USA.

Objectives: There has been growing  interest in intracorporeal techniques to urinary diversion during cystectomy in the modern area. There is little high-quality evidence that this technique is superior to  extracorporeal diversion in patients who are obtaining  an orthotopic intracorporeal neobladder urinary diversion. This study describes the proposed advantages and  disadvantages of intracorporeal orthotopic neobladder urinary diversion and expert opinion on preference.  METHODS: We reviewed the literature for all studies  discussing the outcomes and advantages of intracorporeal orthotopic neobladder urinary diversion, including those comparing the intracorporeal and extracorporeal approach. The studies were reviewed and these findings were summarized based on categories of the proposed advantages and disadvantages of the intracorporeal approach. We provided an assessment of the claims made in favor of the intracorporeal approach and discussed advantages of the extracorporeal approach that may persuade even the most experienced robotic surgeons to lean away from the former.  RESULTS AND CONCLUSIONS: Herein we review the studies that propose advantages of the intracorporeal diversion, as well as the studies that do not demonstrate any advantage to this approach. Some of the proposedadvantages addressed include decreased stricture rate, lower complications and shorter hospitalization. Furthermore, we address the issues of the steep learningcurve and the impact on resident education. We conclude that the proposed benefits of an intracorporeal approach to urinary diversion are not substantiated and it is the preference of the authors to primarily perform extracorporeal urinary diversions.
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April 2019

Robotic vs. open cystectomy: How length-of-stay differences relate conditionally to age.

Urol Oncol 2019 06 13;37(6):354.e1-354.e8. Epub 2019 Feb 13.

Department of Urology, Mayo Clinic Hospital, Phoenix, AZ. Electronic address:

Objectives: The length-of-stay (LOS) benefit of minimally invasive cystectomy varies in the published literature, potentially because of subgroup effects. Here, we investigated the effect of minimally invasive cystectomy on LOS among different age groups.

Methods And Materials: Adult patients who underwent cystectomy (open or minimally invasive) from January 1, 2012, to December 31, 2016, were identified from the National Surgical Quality Improvement Program database. Multivariable linear regression was used to evaluate the adjusted association between the surgical approach and LOS after stratifying patients by age (40-64, 65-79, and ≥80 years). A sensitivity analysis was performed after multiple imputation by using age as a continuous variable with a third-order polynomial term.

Results: Of the 5,561 patients identified, 640 underwent minimally invasive cystectomy and 4,921 had open cystectomy. The unadjusted analysis showed that minimally invasive cystectomy was associated with a shorter mean LOS compared with the open approach (8.0 vs. 9.7 days; P < 0.001). The predicted difference in LOS between the 2 approaches was 0.72 days (95% confidence interval (CI), -0.28 to 1.72; P = 0.16) for patients aged 40 to 64 years, 1.48 days (95% CI, 0.73-2.23; P < 0.001) for 65 to 79 years, and 2.56 days (95% CI, 0.84-4.29; P = 0.01) for ≥80 years favoring the minimally invasive approach. The sensitivity analysis did not materially change the results.

Conclusions: Older patients may derive more LOS benefit from minimally invasive approaches than younger patients. Given the greater expense associated with the minimally invasive approach, an age-adapted strategy to using this technology may be reasonable.
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http://dx.doi.org/10.1016/j.urolonc.2019.01.028DOI Listing
June 2019

Loss of SETD2 Induces a Metabolic Switch in Renal Cell Carcinoma Cell Lines toward Enhanced Oxidative Phosphorylation.

J Proteome Res 2019 01 27;18(1):331-340. Epub 2018 Nov 27.

Division of Hematology/Oncology , Mayo Clinic Arizona , Phoenix , Arizona 85054 , United States.

SETD2, a histone H3 lysine trimethyltransferase, is frequently inactivated and associated with recurrence of clear cell renal cell carcinoma (ccRCC). However, the impact of SETD2 loss on metabolic alterations in ccRCC is still unclear. In this study, SETD2 null isogenic 38E/38F clones derived from 786-O cells were generated by zinc finger nucleases, and subsequent metabolic, genomic, and cellular phenotypic changes were analyzed by targeted metabolomics, RNA sequencing, and biological methods, respectively. Our results showed that compared with parental 786-O cells, 38E/38F cells had elevated levels of MTT/Alamar blue levels, ATP, glycolytic/mitochondrial respiratory capacity, citrate synthase (CS) activity, and TCA metabolites such as aspartate, malate, succinate, fumarate, and α-ketoglutarate. The 38E/38F cells also utilized alternative sources beyond pyruvate to generate acetyl-CoA for the TCA cycle. Moreover, 38E/38F cells showed disturbed gene networks mainly related to mitochondrial metabolism and the oxidation of fatty acids and glucose, which was associated with increased PGC1α, mitochondrial mass, and cellular size/complexity. Our results indicate that SETD2 deficiency induces a metabolic switch toward enhanced oxidative phosphorylation in ccRCC, which can be related to PGC1α-mediated metabolic networks. Therefore, this current study lays the foundation for the further development of a global metabolic analysis of cancer cells in individual patients, which ultimately will have significant potential for the discovery of novel therapeutics and precision medicine in SETD2-inactivated ccRCC.
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http://dx.doi.org/10.1021/acs.jproteome.8b00628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465098PMC
January 2019

Behavior of blood plasma glycan features in bladder cancer.

PLoS One 2018 24;13(7):e0201208. Epub 2018 Jul 24.

School of Molecular Sciences, Arizona State University, Tempe, AZ, United States of America.

Despite systemic therapy and cystectomy, bladder cancer is characterized by a high recurrence rate. Serum glycomics represents a promising source of prognostic markers for monitoring patients. Our approach, which we refer to as "glycan node analysis", constitutes the first example of molecularly "bottom-up" glycomics. It is based on a global glycan methylation analysis procedure that is applied to whole blood plasma/serum. The approach detects and quantifies partially methylated alditol acetates arising from unique glycan features such as α2-6 sialylation, β1-4 branching, and core fucosylation that have been pooled together from across all intact glycans within a sample into a single GC-MS chromatographic peak. We applied this method to 122 plasma samples from former and current bladder cancer patients (n = 72 former cancer patients with currently no evidence of disease (NED); n = 38 non-muscle invasive bladder cancer (NMIBC) patients; and n = 12 muscle invasive bladder cancer (MIBC) patients) along with plasma from 30 certifiably healthy living kidney donors. Markers for α2-6 sialylation, β1-4 branching, β1-6 branching, and outer-arm fucosylation were able to separate current and former (NED) cases from certifiably healthy controls (ROC curve c-statistics ~ 0.80); but NED, NMIBC, and MIBC were not distinguished from one another. Based on the unexpectedly high levels of these glycan nodes in the NED patients, we hypothesized that recurrence of this disease could be predicted by some of the elevated glycan features. Indeed, α2-6 sialylation and β1-6 branching were able to predict recurrence from the NED state using a Cox proportional hazards regression model adjusted for age, gender, and time from cancer. The levels of these two glycan features were correlated to C-reactive protein concentration, an inflammation marker and known prognostic indicator for bladder cancer, further strengthening the link between inflammation and abnormal plasma protein glycosylation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0201208PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057681PMC
January 2019

Surgical excision of an acutely symptomatic subpubic cartilaginous cyst in a 70 year old male.

Urol Case Rep 2018 Sep 5;20:62-64. Epub 2018 Jul 5.

Mayo Clinic Hospital, Department of Urology, 5777 E Mayo Blvd, Phoenix, AZ, 85054, USA.

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http://dx.doi.org/10.1016/j.eucr.2018.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039317PMC
September 2018

Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): an open-label, randomised, phase 3, non-inferiority trial.

Lancet 2018 06;391(10139):2525-2536

Department of Urology, Division of Urologic Oncology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Background: Radical cystectomy is the surgical standard for invasive bladder cancer. Robot-assisted cystectomy has been proposed to provide similar oncological outcomes with lower morbidity. We aimed to compare progression-free survival in patients with bladder cancer treated with open cystectomy and robot-assisted cystectomy.

Methods: The RAZOR study is a randomised, open-label, non-inferiority, phase 3 trial done in 15 medical centres in the USA. Eligible participants (aged ≥18 years) had biopsy-proven clinical stage T1-T4, N0-N1, M0 bladder cancer or refractory carcinoma in situ. Individuals who had previously had open abdominal or pelvic surgery, or who had any pre-existing health conditions that would preclude safe initiation or maintenance of pneumoperitoneum were excluded. Patients were centrally assigned (1:1) via a web-based system, with block randomisation by institution, stratified by type of urinary diversion, clinical T stage, and Eastern Cooperative Oncology Group performance status, to receive robot-assisted radical cystectomy or open radical cystectomy with extracorporeal urinary diversion. Treatment allocation was only masked from pathologists. The primary endpoint was 2-year progression-free survival, with non-inferiority established if the lower bound of the one-sided 97·5% CI for the treatment difference (robotic cystectomy minus open cystectomy) was greater than -15 percentage points. The primary analysis was done in the per-protocol population. Safety was assessed in the same population. This trial is registered with ClinicalTrials.gov, number NCT01157676.

Findings: Between July 1, 2011, and Nov 18, 2014, 350 participants were randomly assigned to treatment. The intended treatment was robotic cystectomy in 176 patients and open cystectomy in 174 patients. 17 (10%) of 176 patients in the robotic cystectomy group did not have surgery and nine (5%) patients had a different surgery to that they were assigned. 21 (12%) of 174 patients in the open cystectomy group did not have surgery and one (1%) patient had robotic cystectomy instead of open cystectomy. Thus, 302 patients (150 in the robotic cystectomy group and 152 in the open cystectomy group) were included in the per-protocol analysis set. 2-year progression-free survival was 72·3% (95% CI 64·3 to 78·8) in the robotic cystectomy group and 71·6% (95% CI 63·6 to 78·2) in the open cystectomy group (difference 0·7%, 95% CI -9·6% to 10·9%; p=0·001), indicating non-inferiority of robotic cystectomy. Adverse events occurred in 101 (67%) of 150 patients in the robotic cystectomy group and 105 (69%) of 152 patients in the open cystectomy group. The most common adverse events were urinary tract infection (53 [35%] in the robotic cystectomy group vs 39 [26%] in the open cystectomy group) and postoperative ileus (33 [22%] in the robotic cystectomy group vs 31 [20%] in the open cystectomy group).

Interpretation: In patients with bladder cancer, robotic cystectomy was non-inferior to open cystectomy for 2-year progression-free survival. Increased adoption of robotic surgery in clinical practice should lead to future randomised trials to assess the true value of this surgical approach in patients with other cancer types.

Funding: National Institutes of Health National Cancer Institute.
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http://dx.doi.org/10.1016/S0140-6736(18)30996-6DOI Listing
June 2018

Robotic-assisted left renal vein transposition as a novel surgical technique for the treatment of renal nutcracker syndrome.

J Vasc Surg Cases Innov Tech 2018 Mar 13;4(1):31-34. Epub 2018 Feb 13.

Department of Vascular Surgery, Mayo Clinic Arizona, Phoenix, Ariz.

Renal nutcracker syndrome is an anatomic anomaly characterized by the compression of the left renal vein between the superior mesenteric artery and the aorta or between the aorta and the vertebral body. Diagnosis is often challenging. Common presenting symptoms include hematuria, abdominal pain, and pelvic congestion. Several open and endovascular techniques have been described to treat this syndrome. We report a novel surgical technique with robotic-assisted left renal vein transposition to treat a 19-year-old woman with renal nutcracker syndrome. Robotic vascular surgery can be a safe and effective therapy for this condition.
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http://dx.doi.org/10.1016/j.jvscit.2017.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849791PMC
March 2018

Stage Dependence, Cell-Origin Independence, and Prognostic Capacity of Serum Glycan Fucosylation, β1-4 Branching, β1-6 Branching, and α2-6 Sialylation in Cancer.

J Proteome Res 2018 01 21;17(1):543-558. Epub 2017 Nov 21.

School of Molecular Sciences, Arizona State University , Tempe, Arizona 85287, United States.

Glycans represent a promising but only marginally accessed source of cancer markers. We previously reported the development of a molecularly bottom-up approach to plasma and serum (P/S) glycomics based on glycan linkage analysis that captures features such as α2-6 sialylation, β1-6 branching, and core fucosylation as single analytical signals. Based on the behavior of P/S glycans established to date, we hypothesized that the alteration of P/S glycans observed in cancer would be independent of the tissue in which the tumor originated yet exhibit stage dependence that varied little between cancers classified on the basis of tumor origin. Herein, the diagnostic utility of this bottom-up approach as applied to lung cancer patients (n = 127 stage I; n = 20 stage II; n = 81 stage III; and n = 90 stage IV) as well as prostate (n = 40 stage II), serous ovarian (n = 59 stage III), and pancreatic cancer patients (n = 15 rapid autopsy) compared to certifiably healthy individuals (n = 30), nominally healthy individuals (n = 166), and risk-matched controls (n = 300) is reported. Diagnostic performance in lung cancer was stage-dependent, with markers for terminal (total) fucosylation, α2-6 sialylation, β1-4 branching, β1-6 branching, and outer-arm fucosylation most able to differentiate cases from controls. These markers behaved in a similar stage-dependent manner in other types of cancer as well. Notable differences between certifiably healthy individuals and case-matched controls were observed. These markers were not significantly elevated in liver fibrosis. Using a Cox proportional hazards regression model, the marker for α2-6 sialylation was found to predict both progression and survival in lung cancer patients after adjusting for age, gender, smoking status, and stage. The potential mechanistic role of aberrant P/S glycans in cancer progression is discussed.
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http://dx.doi.org/10.1021/acs.jproteome.7b00672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978412PMC
January 2018

Validation of Gene Expression Signatures to Identify Low-risk Clear-cell Renal Cell Carcinoma Patients at Higher Risk for Disease-related Death.

Eur Urol Focus 2016 Dec 2;2(6):608-615. Epub 2016 Apr 2.

Division of Hematology and Oncology and Cancer Center and Breast Clinic, Mayo Clinic, Jacksonville, FL, USA. Electronic address:

Background: Approximately 5-10% of patients with "low-risk" clear cell renal cell carcinoma (ccRCC), as stratified by externally validated clinicopathologic prognostic algorithms, eventually have disease relapse and die. Improving prognostic algorithms for these low-risk patients could help to provide improved individualized surveillance recommendations.

Objective: To identify genes that are differentially expressed in patients with low-risk ccRCC who did and did not die of their disease.

Design, Setting, And Participants: Using the Mayo Clinic Renal Registry, we identified formalin-fixed paraffin-embedded samples from patients with low-risk ccRCC, as defined by Mayo Clinic stage, size, grade, and necrosis score of 0-3. We conducted a nested case-control study between patients who did (cases) and did not (controls) have ccRCC relapse and death, using two independent sets (discovery and validation). We performed RNA sequencing of all samples in the discovery set to identify differentially expressed genes. In the independent validation set, we assessed the top 50 expressed genes using the nCounter Analysis System (NanoString Technologies, Seattle, WA, USA).

Results And Limitations: In the discovery set of 24 cases and 24 controls, 92 genes were differentially expressed with p<0.001. The top 50 genes were validated in an independent set of 22 cases and 22 controls using linear mixed models. In the validation set, 10 genes remained differentially expressed between the groups.

Conclusions: RNA signatures from formalin-fixed paraffin-embedded blocks can identify patients with low-risk ccRCC who die of their disease. This finding provides an opportunity to help guide improved surveillance in patients with low-risk ccRCC.

Patient Summary: In the current study we identified RNA signatures from low-risk clear cell renal cell carcinoma patients who died from this disease. Improving prognostic algorithms for these low-risk patients could help to provide improved individualized surveillance recommendations.
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http://dx.doi.org/10.1016/j.euf.2016.03.008DOI Listing
December 2016

Natural Orifice Transluminal Endoscopic Partial Prostatectomy: A Real-time Image-guided Focal Extirpative Feasibility Study.

Urology 2017 Sep 24;107:262-266. Epub 2017 May 24.

Department of Urology, Mayo Clinic Hospital, Phoenix, AZ. Electronic address:

Objective: To assess the feasibility of focal endoscopic excision of prostate cancer (PCa) under guidance of real-time magnetic resonance imaging (MRI) or magnetic ultrasound fusion (MUF).

Materials And Methods: Using a cadaveric model, multifocal PCa was simulated using 2 MRI-compatible fiducial markers. These were inserted transrectally and used to generate regions of interests (ROIs) on a 1.5-T surface-coil MRI. The first marker was placed in the right mid-peripheral zone (ROI 1), and the second marker was placed in the left seminal vesicle as a referent lesion for subsequent imaging. MRI of the specimen was then obtained. The radiologist created ROIs using fusion biopsy system at each marker. Two additional incidental ROIs were identified in the left transitional zone (ROI 2-suspicious for benign prostatic hyperplasia nodule) and in the right anterior peripheral zone (ROI 3-suspicious for PCa). Holmium laser enucleation of the transitional zone of the prostate was performed to gain access to the peripheral zone lesions. MUF was used during endoscopic laser excision to convey targeting accuracy. The cadaver was then reimaged to determine the adequacy of resection and examined for histopathologic correlation.

Results: Real-time MUF imaging identified the target lesions consistently at the locations designated as ROIs. Complete endoscopic resection of ROIs was possible. Repeated MUF imaging and the postprocedure MRI confirmed the completeness of resection. Pathologic examination demonstrated complete excision, intact neurovascular bundles, and posterior prostatic capsule.

Conclusion: This approach may represent a new minimally invasive frontier for focal surgical resection of PCa, making histopathologic margin status determination possible.
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http://dx.doi.org/10.1016/j.urology.2017.05.024DOI Listing
September 2017

Robot-assisted Transplanted Ureteral Stricture Management.

Urology 2017 Jul 11;105:197-201. Epub 2017 Apr 11.

Department of Urology, Mayo Clinic Arizona, Phoenix, AZ.

Objective: To assess the feasibility of robot-assisted transplanted ureteral reimplantation as a minimally invasive alternative to open surgery.

Material And Methods: Between August 2015 and March 2016, 5 patients presented with transplanted ureteral strictures after failure of a previous endoscopic management. All patients underwent robot-assisted ureteral reimplantation. Patients' demographics, perioperative outcomes, and complications are reported.

Results: All patients presented with deterioration of kidney function with or without recurrent urinary tract infection. Two patients had short strictures (<1 cm) and 2 had long strictures (>1 cm), whereas 1 patient had a nitinol ureteral stent in situ. The location of the stricture varied among these patients with 3 distal and 1 proximal. Intraoperatively, 3 patients had a modified Lich-Gregoir reimplantation and 2 patients had a pyelovesicostomy. The mean operative time was 164 (±52) minutes. There were no intraoperative complications, conversion to open surgery, or significant blood loss necessitating blood transfusion. There were no urine leaks in the immediate or late postoperative period. One patient developed a Clavien grade IVa complication (sepsis). The median length of stay, the duration of catheterization, and the duration of stenting were 1 day (range 1-5 days), 7 days (range 6-14 days), and 39 days (range 25-51 days), respectively. After a median follow-up of 79 days (range 40-139 days), no strictures or delayed leakages were identified.

Conclusion: Robot-assisted transplanted ureteral reimplantation is technically feasible. With a larger number of cases and a longer follow-up, robot-assisted transplanted ureteral reimplantation may provide a new and effective, minimally invasive alternative for the treatment of this complex surgical problem.
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http://dx.doi.org/10.1016/j.urology.2017.04.005DOI Listing
July 2017