Transcriptional profiling of tumor associated macrophages in human renal cell carcinoma reveals significant heterogeneity and opportunity for immunomodulation.

Among the more notable immunotherapies are checkpoint inhibitors, which prevent suppressive signaling on T cells, thereby (re)activating them to kill tumor cells. Despite remarkable treatment responses to immune checkpoint blockade, with a subset of patients achieving complete responses, a large population have little-to-no response, dictating the necessity of further research in this field. Myeloid derived cells heavily infiltrate the tumor microenvironment (TME) of many cancers and are believed to have a number of potent anti-inflammatory effects. Here we use primary non-metastatic renal cell carcinoma to interrogate the gene expression profiles of M2-tumor associated macrophages (M2-TAMs). We performed Fluorescent Activated Cell (FACS) sorting on monocytes from the peripheral blood and tumors of fresh clear cell renal cell carcinoma (ccRCC) samples obtained after patients underwent a partial (7 patients-87.5%) or radical (1 patient-12.5%) nephrectomy. We then utilized NanoString gene expression profiling to show that TAMs express a heterogeneous transcriptional profile that does not cleanly fit into the traditional M1-M2 TAM paradigm. We identified expression of M1 associated costimulatory molecules, a multitude of diverse chemokines, canonical M2 associated molecules, as well as factors involved in the Complement system and checkpoint receptors. Our data are in agreement with other published literature investigating TAMs in various non-ccRCC TMEs, and support the growing literature concerning expression of Complement factors and checkpoint receptors on TAMs.

Diagnosis of hemophilia in newborn circumcision: A case presentation.

Circumcision is often the earliest surgery performed in a young male's life. Though complications in this procedure are rare, prolong postoperative bleeding may be the first sign of undiagnosed hemophilia. Hemophilia is a rare X-linked bleeding disorder and if not treated prophylactically or promptly during surgical intervention can be fatal. In this case presentation we describe the diagnosis of hemophilia in a child presenting with postoperative bleeding from circumcision. We review the literature regarding the history of this disease with early surgery and highlight the current treatments.

Individual renal unit urine sampling to identify unilateral metabolic defects
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AIMS: Preventing kidney stone recurrence relies on detecting and modifying urine chemistry abnormalities. The assumption is that an abnormality is due to a global metabolic defect present in both kidneys. However, we hypothesize that clinically significant unilateral defects may exist. We aimed to identify these patients by sampling urine from each renal unit. MATERIALS AND METHODS: Adults undergoing retrograde upper urinary tract surgery were eligible for inclusion. Excluded were patients with a solitary kidney, suspected urothelial malignancy, or urinary tract infection. Following informed consent, all patients proceeded to the operating room. After induction of anesthesia, cystoscopy with ureteral catheterization was performed with urine collected via gravity drainage for 10 minutes. Urine samples with adequate volume were analyzed for chemistry concentrations. A difference greater than the 75th percentile between matched pairs was considered significant. For urine pH, a difference of 0.5 was considered significant. RESULTS: A total of 47 patients were screened for eligibility with only 13 (28%) electing to enroll in the study (26 renal units). All subjects underwent successful bilateral ureteral catheterization with no adverse events observed or later reported. The mean (± SD) urine volume captured from the right and left renal units was 5.0 ± 7.4 cm3 and 6.6 ± 6.4 cm3, respectively. Urine was only captured from paired renal units in 8 participants (8/13; 62%). Of these 8 participants, 5 (5/8; 63%) had at least 1 unilateral metabolic defect. CONCLUSION: Unilateral renal unit urine sampling is safe and feasible. However, captured urine volumes are small and variable, but chemical analysis can still be performed. Unilateral defects in renal electrolyte handling are relatively common, but the clinical implications of these differences are still yet to be determined.
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A User-Friendly Application to Automate CT Renal Stone Measurement.

INTRODUCTION: CT is the gold standard for visualizing renal and ureteral calculi. CT three-dimensional reformatting allows for automatic, accurate, and reliable measurement of stone size, volume, density, and location. In this study, we aimed to develop and test a software platform capable of calculating a battery of clinically important urinary stone parameters at the point-of-care (POC). METHODS: The syngo Calcium Scoring (Siemens Corporation) algorithm was modified to identify calcium-based stones using an attenuation threshold (250 HU) within a region of interest. Information automatically obtained after reconstruction included voxel sum and calculated volume, maximum diameter, largest diameter in the x, y, and z planes, cumulative diameter, distribution of attenuation in HU, and position relative to the skin for calculation of the skin-to-stone distance (SSD). This algorithm was packaged into a stand-alone application (MATLAB 9.1). From April 2017 to May 2017, all patients undergoing a noncontrast CT of the abdomen or the abdomen and pelvis at the Johns Hopkins Hospital were eligible for inclusion in this validation cohort. RESULTS: A total of 55 index renal stones were included. The mean volume calculated by voxel sum was 216.53 mm3 (standard deviation [SD] ±616.19, range 1.50-4060.13). The mean volume calculated using the Ackermann's formula and for a sphere was 232.96 mm3 (SD ± 702.65, range 1.24-4074.04) and 1214.63 mm3 (SD ± 4233.41, range 1.77-25,246.40), respectively. The mean largest diameter in any one direction was 6.95 mm (SD ± 7.31, range 1.50-36.40). The maximum density of the stones ranged from 164 to 1725 HU. The mean SSD at the shortest possible point was 14.19 cm (SD ± 6.13, range 6.67-31.28). CONCLUSIONS: We developed a stand-alone platform with a simple easy-to-use interface, which will allow any user the ability to calculate a battery of clinically important urinary stone parameters from CT imaging at the POC. This program is now freely available online.

Urinary Stone Disease: Diagnosis, Medical Therapy, and Surgical Management.

Clinical suspicion of urolithiasis should be evaluated with low-dose computed tomography as the first-line imaging modality for nonpregnant, adult patients. A period of observation may be appropriate for ureteral stones less than 10 mm, and medical expulsive therapy may be beneficial for facilitating passage of distal ureteral stones. Regardless of stone type, patients should adhere to a low-sodium diet and attempt to achieve a urine volume of more than 2.5 L daily. Individuals with calcium stones should maintain a normal calcium diet, and if stones persist, citrate therapy or thiazide diuretics in the setting of hypercalciuria may be indicated.

Prostate Specific Antigen Testing after Radical Prostatectomy-Can We Stop at 20 Years?

PURPOSE: We examined the clinical features and outcomes associated with delayed biochemical recurrence after radical prostatectomy, specifically among men with more than 20 years of followup. MATERIALS AND METHODS: A total of 16,720 men underwent radical prostatectomy and 2,699 experienced biochemical recurrence. We determined predictors of delayed biochemical recurrence as well as metastasis-free and cancer specific survival rates for recurrence at various time points after radical prostatectomy. We performed subset analysis of the 732 men with 20 or more years of recurrence-free followup. Cumulative incidence curves for metastasis and prostate cancer death were calculated and stratified by biochemical recurrence time points. RESULTS: Predictors of delayed biochemical recurrence included elevated prostate specific antigen at radical prostatectomy, higher clinical and pathological stage, and positive surgical margins. Delayed biochemical recurrence was associated with favorable cumulative incidence curves for metastasis and prostate cancer death compared to early biochemical recurrence. Among the 732 men with undetectable prostate specific antigen at 20 years biochemical recurrence developed in 17 (2.3%), metastatic disease developed in a single patient and none died of prostate cancer. The actuarial probability of biochemical recurrence among men with undetectable prostate specific antigen at 20 years increased with adverse pathological features. CONCLUSIONS: Men with delayed biochemical recurrence have favorable clinical features and improved survival. Men with undetectable prostate specific antigen 20 years after radical prostatectomy had a low rate of recurrence and no deaths from prostate cancer. This suggests that 20 years is a reasonable time to discontinue prostate specific antigen testing.

Margin Assessment in Renal Surgery Using a Handheld Optical Coherence Tomography Probe.

OBJECTIVE: To assess the use of a handheld optical coherence tomography (OCT) probe for the evaluation of intraoperative surgical margins during partial nephrectomy (PN). METHODS: In an initial feasibility study, a radical nephrectomy specimen with a 9-cm tumor was cut into 19 sections, exposing 0 mm (n = 8), 1 mm (n = 6), and 2 mm (n = 5) gross margins. OCT was used to determine the margin width in each specimen. Second, a prospective ex vivo assessment of 15 PN tumor specimens was performed with OCT to determine margin status and to measure the attenuation coefficient of tumor and renal parenchyma. RESULTS: Median OCT margin width measurements for sectioned samples were 0 mm, 0.9 mm (range 0.7-2.9 mm), and 2.7 (range 1.65-2.8 mm) for grossly 0 mm (positive), 1 mm, and 2 mm margins, respectively. The difference between measurements from all margin groups was statistically significant (P <.04). The sensitivity and specificity for identifying positive margins were both 100%. In the PN specimens, OCT correctly found that all specimens had negative margins (within <.0001). CONCLUSION: We have demonstrated the feasibility of using a handheld OCT probe to assess margins ex vivo during PN. OCT may reduce the need for intraoperative frozen section and aid in minimizing parenchymal excision.

Endoscopic Stone Measurement During Ureteroscopy.

INTRODUCTION: Currently, stone size cannot be accurately measured while performing flexible ureteroscopy (URS). We developed novel software for ureteroscopic, stone size measurement, and then evaluated its performance. METHODS: A novel application capable of measuring stone fragment size, based on the known distance of the basket tip in the ureteroscope's visual field, was designed and calibrated in a laboratory setting. Complete URS procedures were recorded and 30 stone fragments were extracted and measured using digital calipers. The novel software program was applied to the recorded URS footage to obtain ureteroscope-derived stone size measurements. These ureteroscope-derived measurements were then compared with the actual-measured fragment size. RESULTS: The median longitudinal and transversal errors were 0.14 mm (95% confidence interval [CI] 0.1, 0.18) and 0.09 mm (95% CI 0.02, 0.15), respectively. The overall software accuracy and precision were 0.17 and 0.15 mm, respectively. The longitudinal and transversal measurements obtained by the software and digital calipers were highly correlated (r = 0.97 and 0.93). Neither stone size nor stone type was correlated with error measurements. CONCLUSIONS: This novel method and software reliably measured stone fragment size during URS. The software ultimately has the potential to make URS safer and more efficient.

Frontiers in robot-assisted retroperitoneal oncological surgery.

Robot assistance has been rapidly adopted by urological surgeons and has become particularly popular for oncological procedures involving the retroperitoneal space. The wide dissemination of robot assistance probably reflects the limited amount of operating space available within the retroperitoneum and the advantages provided by robot-assisted approaches, including 3D imaging, wristed instrumentation and the shorter learning curve compared with that associated with the equivalent laparoscopic techniques. Surgical procedures that have traditionally been performed using an open or laparoscopic approach, such as partial nephrectomy, radical nephrectomy, retroperitoneal lymph node dissection, nephroureterectomy and adrenalectomy, are now often being performed using robot assistance. The frontiers of robot-assisted retroperitoneal oncological surgery are constantly expanding, with an emphasis on maintaining oncological and functional outcomes, while minimizing the level of surgical invasiveness.

Evaluating the Ergonomics of Flexible Ureteroscopy.

INTRODUCTION: To date, the ergonomics of flexible ureteroscopy (URS) have not been well described. We performed a study to assess the biomechanical stresses on urologists performing URS and to investigate the effect of ureteroscope type on these parameters. METHODS: Electromyography (EMG) was used to quantify the activation level of muscle groups involved in URS. Surface EMG electrodes (Delsys, Boston, MA) were placed on the right and left thenar, flexor carpi ulnaris (FCU), extensor carpi ulnaris (ECU), biceps, triceps, and deltoid. Three endoscopes were studied: single-use digital (Boston Scientific LithoVue), reusable digital (Karl Storz Flex-Xc), and reusable fiber-optic (Karl Storz Flex-X2). Each ureteroscope was used to perform a set sequence of navigation and procedural tasks in a training model. EMG data were processed and normalized to compare the maximum voluntary contractions between muscle groups. Cumulative muscular workload (CMW) and average muscular work per second (AWS) were used for comparative analysis. RESULTS: For navigational tasks, CMW and AWS were greatest for the ECU, followed in descending order by right and left thenar, FCU, biceps, deltoid, and triceps. For procedural tasks, CMW and AWS were greatest for the right thenar, followed in descending order by the left thenar, ECU, FCU, triceps, biceps, and deltoid. During navigational tasks, both LithoVue and Flex-Xc had lower CMWs for every muscle group than Flex-X2 (p < 0.05). LithoVue and Flex-Xc had similar AWS and both were lower than Flex-X2 for the right thenar, ECU, biceps, and deltoid activation (p < 0.05). During procedural tasks, both LithoVue and Flex-Xc had lower CMWs and AWS for right and left thenar, ECU, and biceps than Flex-X2 (p < 0.05). CONCLUSIONS: This study provides the first description of EMG-measured ergonomics of URS. Both the single-use and reusable digital ureteroscopes have similar profiles, and both have significantly better ergonomic metrics than the reusable fiber-optic ureteroscope.

Prostate MRI prior to radical prostatectomy: effects on nerve sparing and pathological margin status.

OBJECTIVES: The aim of this study was to assess the positive surgical margin (PSM) and nerve sparing (NS) rates in patients who underwent prostate MRI (pMRI) prior to radical prostatectomy (RP) and compare them with matched, nonimaged control RP patients. METHODS: We identified 204 men who underwent preoperative pelvic MRI (pelMRI), of whom 176 (86.3%) underwent pMRIs, within 60 days of RP, and compared them (1:1) with a nonim-aged control group matched by surgeon, age, race, body mass index (BMI), prostate-specific antigen (PSA), pathological Gleason score, prostate specimen weight, and RP year. RESULTS: The rates of nonfocal extracapsular extension (nfECE) on RP pathology in the MRI and control groups were similar. PSM rates were lower in the MRI group (13.7% vs 19.3%; P=0.14), but the difference did not meet statistical significance; this was also the case in patients with nfECE on RP pathology (27.7% vs 39.5%; P=0.3). NS rates were similar between groups. In the MRI group, 54 (26.5%) patients had an MRI suspicious for nfECE; their PSM rate (20.4%) was higher than that of patients with an MRI not suspicious for nfECE (11.3%; P=0.11), but the difference lacked statistical significance; the former group had significantly lower rates of NS. Limitations of the study include sample power and nonuniform heeding of MRI results by each surgeon. CONCLUSION: MRI did not significantly decrease the rates of PSM, including in the subset of patients with nfECE on final pathology. Even wider resection may be necessary in patients with MRIs suggesting locally-advanced disease. Studies with greater power are needed.

Preventing the Forgotten Ureteral Stent by Using a Mobile Point-of-Care Application.

INTRODUCTION: The forgotten ureteral stent (FUS) can lead to patient morbidity. To date, tracking ureteral stents is a cumbersome task, given their high frequency of insertion and variable indwelling times. To simplify this process, an application was developed to track patients with indwelling ureteral stents. We report our initial user experience and clinical outcomes with this application. METHODS: Ureteral Stent Tracker™ (UST) is a secure, Health Insurance Portability and Accountability Act (HIPPA)-compliant, cloud-based point-of-care application. It is designed for logging stent insertion, scheduling the date of anticipated stent extraction, and confirming stent removal. It is accessible via a mobile phone application or web browser interface. We consecutively enrolled all patients who underwent ureteral stent insertion for any indication by two urologists from January 10, 2015, to October 10, 2016. A retrospective chart review was performed of all patients included in the UST database. Data extracted included patient demographics, diagnosis, procedure, and stent characteristics. RESULTS: A total of 115 patients were included with a mean age of 52.4 years; 54% (62/115) were male and 58% (67/115) were Caucasian. This cohort represented 146 ureteral stent care plans with 23 patients (23/115; 20%) having more than one care plan during the study period. The most common procedure performed was ureteroscopy (70/146; 48%) for a diagnosis of nephrolithiasis (108/146; 74%). The median indwelling ureteral stent time was 14 days (interquartile range: 7-45 days). A total of three patients (3/115; 3%) did not return for their scheduled extraction, but were identified only through the application. Each patient was contacted, resulting in effective removal of all three stents in the office. CONCLUSIONS: Tracking of ureteral stents is critical to prevent the patient safety issue of the FUS. The UST is a secure, HIPPA-compliant, cloud-based application, which once incorporated into the workflow of a urologic practice can prevent the FUS.

Inguinal Hernia Repair During Extraperitoneal Robot-Assisted Laparoscopic Radical Prostatectomy.

INTRODUCTION: One third of men undergoing radical prostatectomy have a comorbid inguinal hernia (IH). Previous studies have shown that adding total extraperitoneal (TEP) IH repair to extraperitoneal laparoscopic radical prostatectomy (LRP) lacks adverse effects. However, outcomes of extraperitoneal robot-assisted laparoscopic radical prostatectomy (RALP) and TEP are unknown. We compared RALP+TEP with LRP+TEP and also with RALP alone. METHODS: Eleven RALP+TEP cases were retrospectively compared with 26 LRP+TEP cases and 22 control RALP without TEP. Outcomes compared between groups included operative time, estimated blood loss (EBL), discharge hematocrit (hct), time to diet advancement, length of hospital stay (LOS), postoperative complications, and hernia recurrence. RESULTS: Unilateral TEP added 32 minutes to RALP and 31 minutes to LRP, whereas bilateral TEP added 80 minutes to RALP and 36 minutes to LRP. There were no differences between RALP+TEP and LRP+TEP or RALP without TEP controls in regard to EBL, discharge hct, time to diet advancement, LOS, or postoperative complications. One patient developed an anterior mesh seroma, which resolved without intervention. No IH recurrences were noted on the mean follow-up of 33 months in the RALP group and 50 months in the LRP cohort. CONCLUSIONS: Unilateral and bilateral TEP added operative time to RALP but had equivalent outcomes to both LRP+TEP and RALP alone. This is likely due to the similar surgical space used for RALP and TEP, which obviates the need for substantial further dissection. For men with prostate cancer and comorbid IH, combined RALP+TEP appears to be an appropriate surgical combination.

Instrument Life for Robot-assisted Laparoscopic Radical Prostatectomy and Partial Nephrectomy: Are Ten Lives for Most Instruments Justified?

OBJECTIVE: To investigate the rate of premature instrument exchange during robot-assisted laparoscopic radical prostatectomy (RALRP) and robot-assisted partial nephrectomy (RAPN). The majority of robotic instruments have a predetermined lifespan of 10 uses; however, it is unknown if instruments are routinely exchanged before 10 uses in clinical practice. METHODS: We retrospectively reviewed instrument use in consecutive RALRP and RAPN cases performed by high-volume robotic surgeons at 1 tertiary care center between January 2011 and October 2014. The number of instruments used per case was evaluated and instances of additional instrument utilization were noted. Exchange number was compared between the first and second half of cases performed. Operative times were compared between cases with and without exchange. Student's t-test and Pearson's χ(2)-test were used to determine statistical significance. RESULTS: Three surgeons performed 1579 RALRP procedures and 2 surgeons performed 313 RAPN procedures. During RALRP, monopolar curved scissors required exchange in 12.4% cases. Other instruments were exchanged in less than 2% of cases. Exchange rates were similar to those for RAPN. Only exchange of Prograsp forceps decreased with increasing surgeon experience (P = .02) and instrument exchange did not lengthen operative times (P >.05 for all instruments). CONCLUSION: During RALRP and RAPN, monopolar curved scissors required exchange in approximately 10% of cases whereas other instruments were rarely exchanged. Robotic instrument lifetime may not uniformly be 10 uses. The preset lifetime of robotic instruments and/or pricing should be reevaluated.

Heterogeneity and hypothesis testing in neuropsychiatric illness.

The confounding effects of heterogeneity in biological psychiatry and psychiatric genetics have been widely discussed in the literature. We suggest an approach in which heterogeneity may be put to use in hypothesis testing and may find application in evaluation of the Crespi and Badcock (C&B) imprinting hypothesis. Here we consider three potential sources of etiologic subtypes for analysis.