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PDF file - 76K, Summary statistics for Fig. 1C and Fig.2A

PDF file - 410K, Calcium influx in myeloid cells induced by CCL1 and SDF1

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PDF file - 70K, CCR8+ myeloid cells induce FoxP3 expression in T cells

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PDF file - 51K, CCL1-induced IL6 production

PDF file - 169K, CCR8 expression in myeloid cells isolated from blood of cancer patients

Purpose: Chemokines are involved in cancer-related inflammation and malignant progression. In this study, we evaluated expression of CCR8 and its natural cognate ligand CCL1 in patients with urothelial carcinomas of bladder and renal cell carcinomas.Experimental Design: We examined CCR8 expression in peripheral blood and tumor tissues from patients with bladder and renal carcinomas. CCR8-positive myeloid cells were isolated from cancer tissues with magnetic beads and tested in vitro for cytokine production and ability to modulate T-cell function.Results: We show that monocytic and granulocytic myeloid cell subsets in peripheral blood of patients with cancer with urothelial and renal carcinomas display increased expression of chemokine receptor CCR8. Upregulated expression of CCR8 is also detected within human cancer tissues and primarily limited to tumor-associated macrophages. When isolated, CD11b+CCR8+ cell subset produces the highest levels of proinflammatory and proangiogenic factors among intratumoral CD11b myeloid cells. Tumor-infiltrating CD11b+CCR8+ cells selectively display activated Stat3 and are capable of inducing FoxP3 expression in autologous T lymphocytes. Primary human tumors produce substantial amounts of the natural CCR8 ligand CCL1.Conclusions: This study provides the first evidence that CCR8+ myeloid cell subset is expanded in patients with cancer. Elevated secretion of CCL1 by tumors and increased presence of CCR8+ myeloid cells in peripheral blood and cancer tissues indicate that CCL1/CCR8 axis is a component of cancer-related inflammation and may contribute to immune evasion. Obtained results also implicate that blockade of CCR8 signals may provide an attractive strategy for therapeutic intervention in human urothelial and renal cancers. Clin Cancer Res; 19(7); 1670–80. ©2013 AACR.

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Several features noted on renal mass biopsy (RMB) can influence treatment selection including tumor histology and nuclear grade. However, there is poor concordance between renal cell carcinoma (RCC) nuclear grade on RMB compared to nephrectomy specimens. Here, we evaluate the association of nuclear grade with aorta-lesion-attenuation-difference (ALAD) values determined on preoperative CT scan. A retrospective review of preoperative CT scans and surgical pathology was performed on patients undergoing nephrectomy for solid renal masses. ALAD was calculated by measuring the difference in Hounsfield units (HU) between the aorta and the lesion of interest on the same image slice on preoperative CT scan. The discriminative ability of ALAD to differentiate low-grade (nuclear grade 1 and 2) and high-grade (nuclear grade 3 and 4) tumors was evaluated by sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve (AUC) using ROC analysis. Sub-group analysis by histologic sub-type was also performed. A total of 368 preoperative CT scans in patients with RCC on nephrectomy specimen were reviewed. Median patient age was 61 years (IQR 52–68). The majority of patients were male, 66% (243/368). Tumor histology was chromophobe RCC in 7.6%, papillary RCC in 15.5%, and clear cell RCC in 76.9%. The majority, 69.3% (253/365) of tumors, were stage T1a. Nuclear grade was grade 1 in 5.46% (19/348), grade 2 in 64.7% (225/348), grade 3 in 26.2% (91/348), and grade 4 in 3.2% (11/348). Nephrographic ALAD values for grade 1, 2, 3, and 4 were 73.7, 46.5, 36.4, and 43.1, respectively (p = 0.0043). Nephrographic ALAD was able to differentiate low-grade from high-grade RCC with a sensitivity of 32%, specificity of 89%, PPV of 86%, and NPV of 36%. ROC analysis demonstrated the predictive utility of nephrographic ALAD to predict high- versus low-grade RCC with an AUC of 0.60 (95% CI 0.51–0.69). ALAD was significantly associated with nuclear grade in our nephrectomy series. Strong specificity and PPV for the nephrographic phrase demonstrate a potential role for ALAD in the pre-operative setting that may augment RMB findings in assessing nuclear grade of RCC. Although this association was statistically significant, the clinical utility is limited at this time given the results of the statistical analysis (relatively poor ROC analysis). Sub-group analysis by histologic subtype yielded very similar diagnostic performance and limitations of ALAD. Further studies are necessary to evaluate this relationship further.

Following radical nephroureterectomy for upper tract urothelial carcinoma, bladder tumor recurrence is a common event occurring in up to 22-47% of cases within the first post-operative year. In this review, we summarize the current knowledge on predictors of bladder tumor recurrence after radical nephroureterectomy and methods for reducing the risk of bladder tumor recurrence. Risk factors can be classified as modifiable and non-modifiable. Of these, the treating urologist has the greatest potential to decrease bladder tumor recurrence by focusing on treatment specific risk factors. Procedures which may decrease the risk of bladder tumor recurrence include limiting diagnostic ureteroscopy with biopsy to cases with equivocal diagnosis, use of perioperative intravesical chemotherapy, and complete distal ureterectomy with bladder cuff excision. Ongoing studies evaluating the timing and choice of intravesical chemotherapy during/after radical nephroureterectomy may help to further reduce bladder tumor recurrence in the future.

PURPOSE Daily aspirin use following cardiovascular intervention is commonplace and creates concern regarding bleeding risk in patients undergoing surgery. Despite its cardio-protective role, aspirin is often discontinued 5-7 days prior to major surgery due to bleeding concerns. Single institution studies have investigated perioperative outcomes of aspirin use in robotic partial nephrectomy (RPN). We sought to evaluate the outcomes of perioperative aspirin (pASA) use during RPN in a multicenter setting. MATERIALS AND METHODS We performed a retrospective evaluation of patients undergoing RPN at 5 high volume RPN institutions. We compared perioperative outcomes of patients taking pASA (81 mg) to those not on aspirin. We analyzed the association between pASA use and perioperative transfusion. RESULTS Of 1,565 patients undergoing RPN, 228 (14.5%) patients continued pASA and were older (62.8 vs 56.8 years, p

Objective To evaluate the ability of Aorta-Lesion-Attenuation Difference (ALAD) to differentiate malignant renal tumors from renal oncocytomas. Methods A retrospective review of preoperative computed tomography (CT) scans and surgical pathology was performed on patients undergoing partial nephrectomy for small, solid renal masses. ALAD was calculated by measuring the difference in Hounsfield units (HU) between the aorta and the lesion of interest on the same image slice on preoperative CT scan. The discriminative ability of ALAD to differentiate malignant pathology from oncocytoma was evaluated by sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve (AUC) using receiver operating characteristic analysis. Results A total of 227 preoperative CT scans and corresponding pathology reports were reviewed. ALAD values were calculated during the excretory and nephrographic phases. Nephrographic ALAD was able to differentiate malignant pathology from oncocytoma using a HU threshold of 24 with a sensitivity of 84%, specificity of 86%, PPV of 98%, and NPV of 33%. The AUC for malignant pathology vs oncocytoma was 0.86 (95% confidence intervals 0.77-0.96). Nephrographic ALAD was able to differentiate chromophobe renal cell carcinoma (RCC) from oncocytoma using a HU threshold of 24 with a sensitivity of 100%, specificity of 86%, PPV of 75%, and NPV of 100%. The AUC for chromophobe RCC vs oncocytoma was 0.98 (95% confidence intervals 0.91-1.00). Conclusion ALAD discriminates well between chromophobe RCC and oncocytoma, which may aid in the management of patients with indeterminate diagnoses of oncocytic neoplasm on diagnostic needle biopsy. Further validation of ALAD will be necessary prior to routine use in clinical practice.

In order to determine the distribution characteristics of Se in soil-crop systems, we carried out a study on the Se-rich soil threshold by collecting 8789 surface soils and 155 deep soils in the Qianjiang District of Chongqing City, China, and 141 corn seeds and 159 rice seeds (simultaneously collecting 141 and 159 corresponding root soil samples, respectively). We then analyzed the Se content, organic matter, S, Mn, TFe

Introduction: A 17-year-old male with Zinner syndrome, a right seminal vesicle cyst, and a solitary left kidney presented with chronic pelvic pain. Previous surgeons had attempted robot-assisted laparoscopic seminal vesicle cyst aspiration and transurethral resection of the ejaculatory duct. Neither surgery provided sustained symptom relief. Abdominal and pelvic MRI showed a cystic structure lodged between the prostate and bladder. The right seminal vesicle, kidney, and ureter were not observed. Materials and Methods: A robot-assisted laparoscopic seminal vesiculectomy was planned. Dissection distal to the right vas deferens and between the bladder neck and prostate revealed a cystic seminal vesicle-like structure. Attached to this was a tubular structure coursing deep to the vas deferens from the right renal fossa. This was presumed to be a dysplastic ureter. The dysplastic ureter was transected from the seminal vesicle and the seminal vesicle was marsupialized to the deep pelvis. Proximally, the dysplastic ureter was transected and left open. Results: Histologic assessment of the specimen revealed an ∼12.1 cm tubular mesonephric remnant. The postoperative course was uncomplicated. At 6 months follow-up, the patient remains free of symptoms with preserved ejaculatory volume. Conclusions: Mesonephric duct abnormalities and symptoms present on a spectrum. We present a safe and effective resection of a mesonephric duct remnant from a 17-year-old male with Zinner syndrome. A robotic approach localized to the right allowed for excellent observation without compromising left-sided genitourinary anatomy. In males presenting with renal agenesis and pelvic symptoms, clinicians should be suspicious of Zinner syndrome and other mesonephric abnormalities.

We previously noted that the aorta-lesion-attenuation difference (ALAD) determined on CT scan discriminated well between chromophobe RCC and oncocytoma. The current evaluation seeks to validate these initial findings in a second cohort of nephrectomy patients.A retrospective review of preoperative CT scans and surgical pathology was performed on patients undergoing nephrectomy for small, solid renal masses. ALAD was calculated by measuring the difference in Hounsfield units (HU) between the aorta and the lesion of interest on the same image slice on preoperative CT scan. The discriminative ability of ALAD to differentiate malignant pathology from oncocytoma was evaluated by sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve (AUC) using ROC analysis.Twenty-one preoperative CT scans and corresponding pathology reports were reviewed and included in the validation cohort. ALAD values were calculated during the excretory and nephrographic phases. Compared to the training cohort, patients in the validation cohort were significantly older (62 versus 59 years old), had larger tumors (3.7 versus 2.7 cm), and higher stage disease (59% versus 79% T1a disease). Nephrographic ALAD was able to differentiate malignant pathology from oncocytoma in the training and validation cohorts with a sensitivity of 84% versus 73%, specificity of 86% and 67%, PPV of 98% versus 91%, and NPV of 33% versus 35%. The AUC for malignant pathology versus oncocytoma in the validation cohort was 0.72 (95% CI 0.63-0.82). Nephrographic ALAD was able to differentiate chromophobe RCC from oncocytoma in the training and validation cohorts with a sensitivity of 100% versus 67%, specificity of 86% versus 67%, PPV of 75% versus 43%, and NPV of 100% versus 84%. The AUC for chromophobe RCC versus oncocytoma in the validation cohort was 0.72 (95% CI 0.48-0.96).The ability of ALAD to discriminate between chromophobe RCC and oncocytoma was diminished in the validation cohort compared to the training cohort, but remained significant. The current findings support further investigation in the role of ALAD in the management of patients with indeterminate diagnoses of oncocytic neoplasm.

INTRODUCTION AND OBJECTIVE:Recommended aspirin use following cardiovascular intervention is commonplace and creates challenges for patients undergoing surgery. Despite its cardio-protective role, a...

Chyluria is a rare complication following renal intervention including partial nephrectomy and percutaneous ablation. To date, there are no reported cases of chyluria following renal cryoablation. An 82-year-old female patient at our institution underwent CT-guided percutaneous cryoablation for a renal cell carcinoma and presented with macroscopic fat in the urine 5 months after cryoablation. Presenting symptoms were polyuria, dysuria, and cloudy white urine. CT showed a fat-urine level in the ureter and bladder most consistent with chyluria. The patient experienced several episodes of presumptive lower urinary tract infection following diagnosis for which she was treated medically. Follow-up CT imaging 5 months post-diagnosis revealed persistent fat-fluid level in the collecting system and bladder. Operators performing renal cryoablation should be aware of the clinical and imaging manifestations of this complication.

First proposed by Kimball and Ferris in 1933 for the treatment of papillary tumors in the upper urinary tract, radical nephroureterectomy (RNU) with bladder cuff excision remains the gold standard for management of high-risk upper tract urothelial carcinoma involving the proximal ureter and/or pelvicaliceal system. Over three decades since the first description of laparoscopic RNU, minimally invasive approaches to RNU have continued to evolve and become increasingly utilized. More recently, robot-assisted RNU (RARNU) has increasingly become a viable approach. Specifically, RARNU affords a reduction in perioperative morbidity and improved convalescence as a minimally invasive approach, all while adhering to traditional open surgical principles and providing surgeons with improved technical ergonomics and streamlined operating room logistics, particularly with the advent of the da Vinci Xi platform. In this study, we describe our approach to transperitoneal RARNU, including indications, operating room setup, step-by-step surgical technique, and perioperative care.

The incidental detection of small renal masses (SRMs) is on the rise. However, not all require aggressive treatments as up to 20% are identified as benign, and the majority of malignant tumors harbor indolent features. Improved preoperative diagnostics are needed to differentiate tumors requiring aggressive treatment from those more suitable for surveillance. This chapter introduces the novel concept of confocal laser endomicroscopy (CLE) as a real-time, diagnostic optical biopsy tool for SRMs. Pertinent CLE studies in urology as well as other medical specialties are discussed, including a detailed review of a recent study specifically addressing CLE in ex vivo human SRMs. Future directions in CLE applications and research are explored for a comprehensive look at one of the leading optical imaging technologies currently under development.

We sought to describe a methodology of crowdsourcing for obtaining quantitative performance ratings of surgeons performing renal artery and vein dissection of robotic partial nephrectomy (RPN). We sought to compare assessment of technical performance obtained from the crowdsourcers with that of surgical content experts (CE). Our hypothesis is that the crowd can score performances of renal hilar dissection comparably to surgical CE using the Global Evaluative Assessment of Robotic Skills (GEARS).A group of resident and attending robotic surgeons submitted a total of 14 video clips of RPN during hilar dissection. These videos were rated by both crowd and CE for technical skills performance using GEARS. A minimum of 3 CE and 30 Amazon Mechanical Turk crowdworkers evaluated each video with the GEARS scale.Within 13 days, we received ratings of all videos from all CE, and within 11.5 hours, we received 548 GEARS ratings from crowdworkers. Even though CE were exposed to a training module, internal consistency across videos of CE GEARS ratings remained low (ICC = 0.38). Despite this, we found that crowdworker GEARS ratings of videos were highly correlated with CE ratings at both the video level (R = 0.82, p 0.001) and surgeon level (R = 0.84, p 0.001). Similarly, crowdworker ratings of the renal artery dissection were highly correlated with expert assessments (R = 0.83, p 0.001) for the unique surgery-specific assessment question.We conclude that crowdsourced assessment of qualitative performance ratings may be an alternative and/or adjunct to surgical experts' ratings and would provide a rapid scalable solution to triage technical skills.

Background Results of randomized trials support a single dose of intravesical chemotherapy following radical nephroureterectomy (RNU) for urothelial carcinoma. Objective To evaluate the impact of the timing of intravesical mitomycin C (MMC) administration on the rate of bladder tumor recurrence (BTR) following RNU. Methods We performed a retrospective review of patients who underwent RNU for upper tract urothelial carcinoma (UTUC) and received intravesical MMC between 2008 and 2016. Patients were categorized into two separate groups based on the timing of MMC administration: patients who received MMC intraoperatively (IO) and patients who received MMC on post-operative day 1 or later (PO). Our primary endpoint was BTR rate within the first year after surgery. Results Fifty-one patients met our inclusion criteria: (IO: n = 30; PO: n = 21). There were no statistically significant differences in baseline characteristics of age, gender, race, surgical approach, tumor grade, tumor stage, surgical margins, nodal status, concomitant CIS, or history of bladder cancer. The median length of follow-up for each group was 22 months for IO and 12 months for PO (P = 0.10). The estimated probability of 1-year BTR rates for the IO and PO groups were 16% and 33%, respectively (p = 0.09). Cox analysis noted that the IO patients had a significantly lower rate of BTR in the first year postoperatively (HR = 0.113, 95% CI = 0.28-0.63, p = 0.01). Conclusions The use of intraoperative MMC at the time of RNU was associated with a decrease in the risk of 1-year recurrence within the bladder.

We evaluate the contemporary incidence and consequences of postoperative rhabdomyolysis after extirpative renal surgery.We conducted a population based, retrospective cohort study of patients who underwent extirpative renal surgery with a diagnosis of a renal mass or renal cell carcinoma in the United States between 2004 and 2013. Regression analysis was performed to evaluate 90-day mortality (Clavien grade V), nonfatal major complications (Clavien grade III-IV), hospital readmission rates, direct costs and length of stay.The final weighted cohort included 310,880 open, 174,283 laparoscopic and 69,880 robotic extirpative renal surgery cases during the 10-year study period, with 745 (0.001%) experiencing postoperative rhabdomyolysis. The presence of postoperative rhabdomyolysis led to a significantly higher incidence of 90-day nonfatal major complications (34.7% vs 7.3%, p0.05) and higher 90-day mortality (4.4% vs 1.02%, p0.05). Length of stay was twice as long for patients with postoperative rhabdomyolysis (incidence risk ratio 1.83, 95% CI 1.56-2.15, p0.001). The robotic approach was associated with a higher likelihood of postoperative rhabdomyolysis (vs laparoscopic approach, OR 2.43, p 0.05). Adjusted 90-day median direct hospital costs were USD 7,515 higher for patients with postoperative rhabdomyolysis (p0.001). Our model revealed that the combination of obesity and prolonged surgery (more than 5 hours) was associated with a higher likelihood of postoperative rhabdomyolysis developing.Our study confirms that postoperative rhabdomyolysis is an uncommon complication among patients undergoing extirpative renal surgery, but has a potentially detrimental impact on surgical morbidity, mortality and costs. Male gender, comorbidities, obesity, prolonged surgery (more than 5 hours) and a robotic approach appear to place patients at higher risk for postoperative rhabdomyolysis.

The incidental detection of small renal masses is increasing. However, not all require aggressive treatments as up to 20% are benign and the majority of malignant tumors harbor indolent features. Improved preoperative diagnostics are needed to differentiate tumors requiring aggressive treatment from those more suitable for surveillance. We evaluated and compared confocal laser endomicroscopy with standard histopathology in ex vivo human kidney tumors as proof of principle towards diagnostic optical biopsy.Patients with a solitary small renal mass scheduled for partial or radical nephrectomy were enrolled in study. Two kidneys were infused with fluorescein via intraoperative intravenous injection and 18 tumors were bathed ex vivo in dilute fluorescein prior to confocal imaging. A 2.6 mm confocal laser endomicroscopy probe was used to image tumors and surrounding parenchyma from external and en face surfaces after specimen bisection. Confocal laser endomicroscopy images were compared to standard hematoxylin and eosin analysis of corresponding areas.Ex vivo confocal laser endomicroscopy imaging revealed normal renal structures that correlated well with histology findings. Tumor tissue was readily distinguishable from normal parenchyma, demonstrating features unique to benign and malignant tumor subtypes. Topical fluorescein administration provided more consistent confocal laser endomicroscopy imaging than the intravenous route. Additionally, en face tumor imaging was superior to external imaging.We report what is to our knowledge the first feasibility study using confocal laser endomicroscopy to evaluate small renal masses ex vivo and provide a preliminary atlas of images from various renal neoplasms with corresponding histology. These findings serve as an initial and promising step toward real-time diagnostic optical biopsy of small renal masses.

This study aimed at reviewing a contemporary series of patients who underwent robotic renal and adrenal surgery by a single surgeon at a tertiary referral academic medical center over a 6-year period, specifically focusing on the unique and serious complication of post-operative rhabdomyolysis of the dependent lower extremity. The cases of 315 consecutive patients who underwent robotic upper tract surgery over a 6-year period from August 2008 to June 2014 using a standardized patient positioning were reviewed and analyzed for patient characteristics and surgical variables that may be associated with the development of post-operative rhabdomyolysis. The incidence of post-operative rhabdomyolysis in our series was 3/315 (0.95%). All three affected patients had undergone robotic nephroureterectomy. Those patients who developed rhabdomyolysis had significantly higher mean Body Mass Index, Charlson Comorbidity Index, and median length of stay than those who did not. The mean OR time in the rhabdomyolysis group was noted to be 52 min longer than the non-rhabdomyolysis group, though this value did not reach statistical significance. Given the trends of increasing obesity in the United States and abroad as well as the continued rise in robotic upper tract urologic surgeries, urologists need to be increasingly vigilant for recognizing the risk factors and early treatment of the unique complication of post-operative rhabdomyolysis.

Robotic surgery represents a shift in the surgical paradigm and is consequently associated with a unique set of challenges and complications in comparison to open or conventional laparoscopic surgery. For the first time, the surgeon is not directly at the bedside but is rather directing an intermediary machine and a separate bedside team to perform the operation. This, in addition to the lack of tactile feedback, the greater reliance on visual anatomic clues when performing robotic surgery, and the inherent risk of malfunction or mechanical failure of robotic components may all contribute to complications noted during robot-assisted radical prostatectomy (RARP). In this chapter, we outline the risks and incidence of the more common complications associated with RARP and present methods to manage them.