Transvesical robotic excision of a Müllerian duct remnant.

Müllerian duct remnants are rare and found in patients with disorders of sexual development. Presenting symptoms vary and many parents opt for surgical management. Literature on robotic repair is limited to small series, single case reports and all were approached extravesically. We present our case of a unique transvesical approach. Perioperative parameters were favorable with no complications, suggesting robotic repair is a safe and effective treatment strategy for these unique patients.

How I Do It: The pudendal nerve block for pediatric ambulatory urologic surgery.

Regional analgesia is an important adjunct for perioperative pain management in the setting of pediatric penile surgeries. Caudal epidural analgesia (CEA) is the most common analgesic technique performed, but it has limitations and associated morbidity. The pudendal nerve block (PNB) is an effective alternative to CEA with a lower risk profile; in prior examination of the approach, PNB has been demonstrated to have similar postoperative pain control outcomes. We describe our technique and highlight observations made as we have transitioned from CEA to PNB for many patients.

Discharge Opioid Prescription Patterns After Kidney Cancer Surgery.

OBJECTIVE: To describe opioid prescribing patterns for patients undergoing kidney cancer surgery and evaluate associations with medical resource utilization in the postoperative setting. METHODS: Linked Surveillance, Epidemiology, and End Results - Medicare data were used to identify patients with kidney cancer who underwent partial or radical nephrectomy (open vs. minimally invasive) from 2007 to 2015. Total dose of discharge opioid prescriptions was quantified into 3 exposure groups based on observed tertiles: 1-199 (low), 200-300 (moderate), and >300 (high) oral morphine milligram equivalents. Associations between exposure groups and patient demographics, clinical factors, and hospital volumes were measured using multivariate logistic regression. Additionally, we identified associations with prior opioid exposure and postoperative medical resource utilization. RESULTS: Of 4538 patients meeting inclusion criteria, exposure group distributions were 35% (low), 43.5% (moderate) and 21.6% (high). Over one-third of patients (39.5%) received an opioid prescription within 6 months preceding surgery. High opioid prescriptions were associated with prior exposure, younger age, rural residence and open surgery (P < .001). High opioid prescriptions had increased risk of 90-day readmissions (OR 1.21; CI 1.01-1.45) and long-term opioid exposure (OR 1.34; CI 1.17-1.53). CONCLUSION: Prescribing patterns after kidney cancer surgery vary widely. Higher prescribed dose of post-surgical opioids is associated with 90-day hospital readmissions and long-term exposure. Prior opioid exposure conveys a higher risk of medical resource utilization. More judicious opioid prescribing may limit medical resource utilization and help combat the opioid epidemic.

The pudendal nerve block for ambulatory urology: What's old is new again. A quality improvement project.

INTRODUCTION: Caudal epidural analgesia (CEA) is a common analgesic technique performed for pediatric penile surgeries; however, it has associated morbidity. The pudendal nerve block (PNB) has been described as an effective analgesic alternative to CEA. OBJECTIVE: In this quality improvement study, we aim to assess the efficacy of PNB as compared to CEA within our ambulatory surgery center (ASC). We demonstrate our initial experience employing PNB for ambulatory pediatric urology procedures. STUDY DESIGN: Using retrospective, non-randomized, time-series, observational data, a comparative effectiveness study of CEA and PNB was performed. Patients less than three years old, who underwent circumcision, hypospadias repair, congenital chordee repair, correction of penile angulation/torsion, and buried penis repair with or without scrotoplasty, between January 1, 2015-September 9, 2019 with either CEA or PNB in an ASC at a single institution were included. Standard protocols for local and postoperative analgesia were used. Outcome measures were post anesthesia care unit (PACU) pain scores, morphine rescue rates, and PACU length of stay (LOS). These were analyzed using statistical process control (SPC) charts; standard SPC rules were used to detect special cause variation. RESULTS: A total of 999 patients were identified; 746 (74.7%), 172 (17.2%) and 81 (8.1%) received CEA, ultrasound guided PNB (US-PNB) and landmark directed PNB (LD-PNB), respectively. Demographic data was comparable between the three cohorts. There was no special cause variation in the outcome measures between the CEA, US-PNB and LD-PNB cohorts for maximum pain score, morphine rescue rates and PACU LOS. DISCUSSION: Pain outcomes and PACU LOS were similar between the CEA, US-PNB and LD-PNB cohorts, suggesting equivalent postoperative pain control between these techniques within our cohort. Previous published data has reported lower postoperative pain scores with PNB as compared to CEA for patients undergoing circumcision and hypospadias repair. CONCLUSION: PNB is non-inferior to CEA for analgesia for pediatric penile surgery, with LD-PNB being as effective as US-PNB. Given the simplicity and documented lower risk profile, PNB may be preferred to CEA for ambulatory pediatric urology procedures.

Inpatient Opioid Use Poorly Predicts Discharge Opioid Prescriptions Following Nephrectomy.

INTRODUCTION: The overprescribing of opioids after urological surgery places patients at risk for opioid overuse and dependency. However, few guidelines exist to help urologists consistently prescribe appropriate quantities of pain medications. We sought to characterize the variation in opioid prescribing habits at time of discharge following nephrectomy. METHODS: We performed a retrospective review of patients who underwent partial or radical nephrectomy between November 2016 and May 2018 at an academic medical center. We reviewed patient, procedure and provider level variables potentially associated with high opioid use. Daily inpatient opioid use and discharge opioid prescriptions were tabulated in oral morphine equivalents. RESULTS: We identified 173 eligible patients who used a daily average of 36 oral morphine equivalents during their hospitalization weaning to 27 oral morphine equivalents on the day of discharge. All but 2 patients were prescribed opioids at discharge with an average of 367 oral morphine equivalents per prescription (SD 284). On multiple linear regression preoperative opioid use, open vs minimally invasive approach, length of stay and last day opioid use were associated with discharge oral morphine equivalents (R2=0.51, p <0.05). CONCLUSIONS: Patients were discharged with excessive opioids with an average discharge prescription equivalent to 13.6 times the last inpatient day's use. When combined with other potential predictors of discharge opioid prescriptions inpatient use accounts for less than 50% of the variance between prescriptions. Systems are needed to help minimize variability in opioid prescribing practices and reduce the overall quantity prescribed.

Seeded Biopsy Tract Recurrence After Extirpative Surgery for Renal Cell Carcinoma.

Background: Renal mass biopsy (RMB) is an increasingly utilized modality in the work-up of patients with suspicious renal masses. Recurrence of renal cell carcinoma (RCC) from biopsy tract seeding is exceedingly rare in the literature. We report a case of such a phenomenon. Case Presentation: Our patient is a 75-year-old Caucasian man and former smoker with a functionally solitary left kidney, initially worked up for gross hematuria and left flank pain. Imaging revealed hydronephrosis and a left renal mass, which was biopsied. Pathology analysis demonstrated clear cell RCC, and a left robotic radical nephrectomy was performed with negative surgical margins. Sixteen months postoperatively, imaging revealed multiple small masses along the biopsy tract, suspicious for recurrence. These were biopsied and pathology analysis confirmed recurrent clear cell RCC. Conclusion: Despite its rarity, biopsy tract seeding is a serious complication of RMB. This warrants thorough counseling and shared decision making between providers and all patients with renal masses planning to undergo a RMB.

Magnetic Resonance Imaging/Transrectal Ultrasonography Fusion Prostate Biopsy Significantly Outperforms Systematic 12-Core Biopsy for Prediction of Total Magnetic Resonance Imaging Tumor Volume in Active Surveillance Patients.

OBJECTIVE: To correlate the highest percentage core involvement (HPCI) and corresponding tumor length (CTL) on systematic 12-core biopsy (SBx) and targeted magnetic resonance imaging/transrectal ultrasonography (MRI/TRUS) fusion biopsy (TBx), with total MRI prostate cancer (PCa) tumor volume (TV). PATIENTS AND METHODS: Fifty patients meeting criteria for active surveillance (AS) based on outside SBx, who underwent 3.0T multiparametric prostate MRI (MP-MRI), followed by SBx and TBx during the same session at our institution were examined. PCa TVs were calculated using MP-MRI and then correlated using bivariate analysis with the HPCI and CTL for SBx and TBx. RESULTS: For TBx, HPCI and CTL showed a positive correlation (R(2)=0.31, P<0.0001 and R(2)=0.37, P<0.0001, respectively) with total MRI PCa TV, whereas for SBx, these parameters showed a poor correlation (R(2)=0.00006, P=0.96 and R(2)=0.0004, P=0.89, respectively). For detection of patients with clinically significant MRI derived tumor burden greater than 500 mm(3), SBx was 25% sensitive, 90.9% specific (falsely elevated because of missed tumors and extremely low sensitivity), and 54% accurate in comparison with TBx, which was 53.6% sensitive, 86.4% specific, and 68% accurate. CONCLUSIONS: HPCI and CTL on TBx positively correlates with total MRI PCa TV, whereas there was no correlation seen with SBx. TBx is superior to SBx for detecting tumor burden greater than 500 mm(3). When using biopsy positive MRI derived TVs, TBx better reflects overall disease burden, improving risk stratification among candidates for active surveillance.

Use of serial multiparametric magnetic resonance imaging in the management of patients with prostate cancer on active surveillance.

INTRODUCTION: We evaluated the performance of multiparametric prostate magnetic resonance imaging (mp-MRI) and MRI/transrectal ultrasound (TRUS) fusion-guided biopsy (FB) for monitoring patients with prostate cancer on active surveillance (AS). MATERIALS AND METHODS: Patients undergoing mp-MRI and FB of target lesions identified on mp-MRI between August 2007 and August 2014 were reviewed. Patients meeting AS criteria (Clinical stage T1c, Gleason grade ≤ 6, prostate-specific antigen density ≤ 0.15, tumor involving ≤ 2 cores, and ≤ 50% involvement of any single core) based on extended sextant 12-core TRUS biopsy (systematic biopsy [SB]) were included. They were followed with subsequent 12-core biopsy as well as mp-MRI and MRI/TRUS fusion biopsy at follow-up visits until Gleason score progression (Gleason ≥ 7 in either 12-core or MRI/TRUS fusion biopsy). We evaluated whether progression seen on mp-MRI (defined as an increase in suspicion level, largest lesion diameter, or number of lesions) was predictive of Gleason score progression. RESULTS: Of 152 patients meeting AS criteria on initial SB (mean age of 61.4 years and mean prostate-specific antigen level of 5.26 ng/ml), 34 (22.4%) had Gleason score ≥ 7 on confirmatory SB/FB. Of the 118 remaining patients, 58 chose AS and had at least 1 subsequent mp-MRI with SB/FB (median follow-up = 16.1 months). Gleason progression was subsequently documented in 17 (29%) of these men, in all cases to Gleason 3+4. The positive predictive value and negative predictive value of mp-MRI for Gleason progression was 53% (95% CI: 28%-77%) and 80% (95% CI: 65%-91%), respectively. The sensitivity and specificity of mp-MRI for increase in Gleason were also 53% and 80%, respectively. The number needed to biopsy to detect 1 Gleason progression was 8.74 for SB vs. 2.9 for FB. CONCLUSIONS: Stable findings on mp-MRI are associated with Gleason score stability. mp-MRI appears promising as a useful aid for reducing the number of biopsies in the management of patients on AS. A prospective evaluation of mp-MRI as a screen to reduce biopsies in the follow-up of men on AS appears warranted.

The Role of Magnetic Resonance Image Guided Prostate Biopsy in Stratifying Men for Risk of Extracapsular Extension at Radical Prostatectomy.

PURPOSE: Magnetic resonance imaging detects extracapsular extension by prostate cancer with excellent specificity but low sensitivity. This limits surgical planning, which could be modified to account for focal extracapsular extension with image directed guidance for wider excision. In this study we evaluate the performance of multiparametric magnetic resonance imaging in extracapsular extension detection and determine which preoperative variables predict extracapsular extension on final pathology when multiparametric magnetic resonance imaging predicts organ confined disease. MATERIALS AND METHODS: From May 2007 to March 2014, 169 patients underwent pre-biopsy multiparametric magnetic resonance imaging, magnetic resonance imaging/transrectal ultrasound fusion guided biopsy, extended sextant 12-core biopsy and radical prostatectomy at our institution. A subset of 116 men had multiparametric magnetic resonance imaging negative for extracapsular extension and were included in the final analysis. RESULTS: The 116 men with multiparametric magnetic resonance imaging negative for extracapsular extension had a median age of 61 years (IQR 57-66) and a median prostate specific antigen of 5.51 ng/ml (IQR 3.91-9.07). The prevalence of extracapsular extension was 23.1% in the overall population. Sensitivity, specificity, and positive and negative predictive values of multiparametric magnetic resonance imaging for extracapsular extension were 48.7%, 73.9%, 35.9% and 82.8%, respectively. On multivariate regression analysis only patient age (p=0.002) and magnetic resonance imaging/transrectal ultrasound fusion guided biopsy Gleason score (p=0.032) were independent predictors of extracapsular extension on final radical prostatectomy pathology. CONCLUSIONS: Because of the low sensitivity of multiparametric magnetic resonance imaging for extracapsular extension, further tools are necessary to stratify men at risk for occult extracapsular extension that would otherwise only become apparent on final pathology. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy Gleason score can help identify which men with prostate cancer have extracapsular extension that may not be detectable by imaging.

Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer.

IMPORTANCE: Targeted magnetic resonance (MR)/ultrasound fusion prostate biopsy has been shown to detect prostate cancer. The implications of targeted biopsy alone vs standard extended-sextant biopsy or the 2 modalities combined are not well understood. OBJECTIVE: To assess targeted vs standard biopsy and the 2 approaches combined for the diagnosis of intermediate- to high-risk prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 1003 men undergoing both targeted and standard biopsy concurrently from 2007 through 2014 at the National Cancer Institute in the United States. Patients were referred for elevated level of prostate-specific antigen (PSA) or abnormal digital rectal examination results, often with prior negative biopsy results. Risk categorization was compared among targeted and standard biopsy and, when available, whole-gland pathology after prostatectomy as the "gold standard." INTERVENTIONS: Patients underwent multiparametric prostate magnetic resonance imaging to identify regions of prostate cancer suspicion followed by targeted MR/ultrasound fusion biopsy and concurrent standard biopsy. MAIN OUTCOMES AND MEASURES: The primary objective was to compare targeted and standard biopsy approaches for detection of high-risk prostate cancer (Gleason score ≥ 4 + 3); secondary end points focused on detection of low-risk prostate cancer (Gleason score 3 + 3 or low-volume 3 + 4) and the biopsy ability to predict whole-gland pathology at prostatectomy. RESULTS: Targeted MR/ultrasound fusion biopsy diagnosed 461 prostate cancer cases, and standard biopsy diagnosed 469 cases. There was exact agreement between targeted and standard biopsy in 690 men (69%) undergoing biopsy. Targeted biopsy diagnosed 30% more high-risk cancers vs standard biopsy (173 vs 122 cases, P < .001) and 17% fewer low-risk cancers (213 vs 258 cases, P < .001). When standard biopsy cores were combined with the targeted approach, an additional 103 cases (22%) of mostly low-risk prostate cancer were diagnosed (83% low risk, 12% intermediate risk, and 5% high risk). The predictive ability of targeted biopsy for differentiating low-risk from intermediate- and high-risk disease in 170 men with whole-gland pathology after prostatectomy was greater than that of standard biopsy or the 2 approaches combined (area under the curve, 0.73, 0.59, and 0.67, respectively; P < .05 for all comparisons). CONCLUSIONS AND RELEVANCE: Among men undergoing biopsy for suspected prostate cancer, targeted MR/ultrasound fusion biopsy, compared with standard extended-sextant ultrasound-guided biopsy, was associated with increased detection of high-risk prostate cancer and decreased detection of low-risk prostate cancer. Future studies will be needed to assess the ultimate clinical implications of targeted biopsy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00102544.

The role of image guided biopsy targeting in patients with atypical small acinar proliferation.

PURPOSE: Men diagnosed with atypical small acinar proliferation are counseled to undergo early rebiopsy because the risk of prostate cancer is high. However, random rebiopsies may not resample areas of concern. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy offers an opportunity to accurately target and later retarget specific areas in the prostate. We describe the ability of magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy to detect prostate cancer in areas with an initial diagnosis of atypical small acinar proliferation. MATERIALS AND METHODS: Multiparametric magnetic resonance imaging of the prostate and magnetic resonance imaging/transrectal ultrasound fusion guided biopsy were performed in 1,028 patients from March 2007 to February 2014. Of the men 20 met the stringent study inclusion criteria, which were no prostate cancer history, index biopsy showing at least 1 core of atypical small acinar proliferation with benign glands in all remaining cores and fusion targeted rebiopsy with at least 1 targeted core directly resampling an area of the prostate that previously contained atypical small acinar proliferation. RESULTS: At index biopsy median age of the 20 patients was 60 years (IQR 57-64) and median prostate specific antigen was 5.92 ng/ml (IQR 3.34-7.48). At fusion targeted rebiopsy at a median of 11.6 months 5 of 20 patients (25%, 95% CI 6.02-43.98) were diagnosed with primary Gleason grade 3, low volume prostate cancer. On fusion rebiopsy cores that directly retargeted areas of previous atypical small acinar proliferation detected the highest tumor burden. CONCLUSIONS: When magnetic resonance imaging/transrectal ultrasound fusion guided biopsy detects isolated atypical small acinar proliferation on index biopsy, early rebiopsy is unlikely to detect clinically significant prostate cancer. Cores that retarget areas of previous atypical small acinar proliferation are more effective than random rebiopsy cores.

Identification of threshold prostate specific antigen levels to optimize the detection of clinically significant prostate cancer by magnetic resonance imaging/ultrasound fusion guided biopsy.

PURPOSE: Prostate specific antigen sensitivity increases with lower threshold values but with a corresponding decrease in specificity. Magnetic resonance imaging/ultrasound targeted biopsy detects prostate cancer more efficiently and of higher grade than standard 12-core transrectal ultrasound biopsy but the optimal population for its use is not well defined. We evaluated the performance of magnetic resonance imaging/ultrasound targeted biopsy vs 12-core biopsy across a prostate specific antigen continuum. MATERIALS AND METHODS: We reviewed the records of all patients enrolled in a prospective trial who underwent 12-core transrectal ultrasound and magnetic resonance imaging/ultrasound targeted biopsies from August 2007 through February 2014. Patients were stratified by each of 4 prostate specific antigen cutoffs. The greatest Gleason score using either biopsy method was compared in and across groups as well as across the population prostate specific antigen range. Clinically significant prostate cancer was defined as Gleason 7 (4 + 3) or greater. Univariate and multivariate analyses were performed. RESULTS: A total of 1,003 targeted and 12-core transrectal ultrasound biopsies were performed, of which 564 diagnosed prostate cancer for a 56.2% detection rate. Targeted biopsy led to significantly more upgrading to clinically significant disease compared to 12-core biopsy. This trend increased more with increasing prostate specific antigen, specifically in patients with prostate specific antigen 4 to 10 and greater than 10 ng/ml. Prostate specific antigen 5.2 ng/ml or greater captured 90% of upgrading by targeted biopsy, corresponding to 64% of patients who underwent multiparametric magnetic resonance imaging and subsequent fusion biopsy. Conversely a greater proportion of clinically insignificant disease was detected by 12-core vs targeted biopsy overall. These differences persisted when controlling for potential confounders on multivariate analysis. CONCLUSIONS: Prostate cancer upgrading with targeted biopsy increases with an increasing prostate specific antigen cutoff. Above a prostate specific antigen threshold of 5.2 ng/ml most upgrading to clinically significant disease was achieved by targeted biopsy. In our population this corresponded to potentially sparing biopsy in 36% of patients who underwent multiparametric magnetic resonance imaging. Below this value 12-core biopsy detected more clinically insignificant cancer. Thus, the diagnostic usefulness of targeted biopsy is optimized in patients with prostate specific antigen 5.2 ng/ml or greater.

Multiparametric magnetic resonance imaging and image-guided biopsy to detect seminal vesicle invasion by prostate cancer.

OBJECTIVES: To evaluate the correlation between multiparametric prostate MRI (MP-MRI) suspicion for seminal vesicle invasion (SVI) by prostate cancer (PCa) and pathology on MRI/ultrasound (US) fusion-guided biopsy. PATIENTS AND METHODS: From March 2007 to June 2013, 822 patients underwent MP-MRI at 3 Tesla and MRI/US fusion-guided biopsy. Of these, 25 patients underwent targeted biopsy of the seminal vesicles (SVs). In six patients, bilateral SVI was suspected, resulting in 31 samples. MP-MRI findings that triggered these SV biopsies were scored as low, moderate, or high suspicion for SVI based on the degree of involvement on MRI. Correlative prostate biopsy and radical prostatectomy (RP) pathology were reviewed by a single genitourinary pathologist. RESULTS: At the time of MP-MRI, the median age was 64 years with a median prostate-specific antigen of 10.74 ng/mL. Of the 31 SV lesions identified, MP-MRI suspicion scores of low, moderate, and high were assigned to 3, 19, and 9 lesions, respectively. MRI/US fusion-guided biopsy detected SVI in 20/31 (65%) of cases. For the four patients who underwent RP after a preoperative assessment of SVI, biopsy pathology and RP pathology were concordant in all cases. CONCLUSIONS: As this technology becomes more available, MP-MRI and MRI/US fusion-guided biopsy may play a role in the preoperative staging for PCa. Future work will determine if improved preoperative staging leads to better surgical outcomes.

Can selective arterial clamping with fluorescence imaging preserve kidney function during robotic partial nephrectomy?

OBJECTIVE: To compare renal functional outcomes in robotic partial nephrectomy (RPN) with selective arterial clamping guided by near-infrared fluorescence (NIRF) imaging to a matched cohort of patients who underwent RPN without selective arterial clamping and NIRF imaging. METHODS: From April 2011 to December 2012, NIRF imaging-enhanced RPN with selective clamping was used in 42 cases. Functional outcomes of successful cases were compared with a cohort of patients, matched by tumor size, preoperative estimated glomerular filtration rate (eGFR), functional kidney status, age, sex, body mass index, and American Society of Anesthesiologists score, who underwent RPN without selective clamping and NIRF imaging. RESULTS: In matched-pair analysis, selective clamping with NIRF was associated with superior kidney function at discharge, as demonstrated by postoperative eGFR (78.2 vs 68.5 mL/min/1.73 m(2); P = .04), absolute reduction of eGFR (-2.5 vs -14.0 mL/min/1.73 m(2); P <.01), and percent change in eGFR (-1.9% vs -16.8%; P <.01). Similar trends were noted at 3 month follow-up, but these differences became nonsignificant (P[eGFR] = .07; P[absolute reduction of eGFR] = .10; and P[percent change in eGFR] = .07). In the selective clamping group, a total of 4 perioperative complications occurred in 3 patients, all of which were Clavien grade I-III. CONCLUSION: Use of NIRF imaging was associated with improved short-term renal functional outcomes when compared with RPN without selective arterial clamping and NIRF imaging. With this effect attenuated at later follow-up, randomized prospective studies and long-term assessment of kidney-specific functional outcomes are needed to further assess the benefits of this technology.

Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells.

Chronic inflammation is a complex process that promotes carcinogenesis and tumor progression; however, the mechanisms by which specific inflammatory mediators contribute to tumor growth remain unclear. We and others recently demonstrated that the inflammatory mediators IL-1beta, IL-6, and PGE(2) induce accumulation of myeloid-derived suppressor cells (MDSC) in tumor-bearing individuals. MDSC impair tumor immunity and thereby facilitate carcinogenesis and tumor progression by inhibiting T and NK cell activation, and by polarizing immunity toward a tumor-promoting type 2 phenotype. We now show that this population of immature myeloid cells induced by a given tumor share a common phenotype regardless of their in vivo location (bone marrow, spleen, blood, or tumor site), and that Gr1(high)CD11b(high)F4/80(-)CD80(+)IL4Ralpha(+/-)Arginase(+) MDSC are induced by the proinflammatory proteins S100A8/A9. S100A8/A9 proteins bind to carboxylated N-glycans expressed on the receptor for advanced glycation end-products and other cell surface glycoprotein receptors on MDSC, signal through the NF-kappaB pathway, and promote MDSC migration. MDSC also synthesize and secrete S100A8/A9 proteins that accumulate in the serum of tumor-bearing mice, and in vivo blocking of S100A8/A9 binding to MDSC using an anti-carboxylated glycan Ab reduces MDSC levels in blood and secondary lymphoid organs in mice with metastatic disease. Therefore, the S100 family of inflammatory mediators serves as an autocrine feedback loop that sustains accumulation of MDSC. Since S100A8/A9 activation of MDSC is through the NF-kappaB signaling pathway, drugs that target this pathway may reduce MDSC levels and be useful therapeutic agents in conjunction with active immunotherapy in cancer patients.