Extended Opioid Exposure Modulates the Molecular Metabolism of Clear Cell Renal Cell Carcinoma.

Opioids are commonly prescribed for extended periods of time to patients with advanced clear cell renal cell carcinoma to assist with pain management. Because extended opioid exposure has been shown to affect the vasculature and to be immunosuppressive, we investigated how it may affect the metabolism and physiology of clear cell renal cell carcinoma. RNA sequencing of a limited number of archived patients' specimens with extended opioid exposure or non-opioid exposure was performed. Immune infiltration and changes in the microenvironment were evaluated using CIBERSORT. A significant decrease in M1 macrophages and T cells CD4 memory resting immune subsets was observed in opioid-exposed tumors, whereas the changes observed in other immune cells were not statistically significant. Further RNA sequencing data analysis showed that differential expression of KEGG signaling pathways was significant between non-opioid-exposed specimens and opioid-exposed specimens, with a shift from a gene signature consistent with aerobic glycolysis to a gene signature consistent with the TCA cycle, nicotinate metabolism, and the cAMP signaling pathway. Together, these data suggest that extended opioid exposure changes the cellular metabolism and immune homeostasis of ccRCC, which might impact the response to therapy of these patients, especially if the therapy is targeting the microenvironment or metabolism of ccRCC tumors.

Rapid On-Site Microscopy and Mapping of Diagnostic Biopsies for See-And-Treat Guidance of Localized Prostate Cancer Therapy.

Prostate cancer continues to be the most diagnosed non-skin malignancy in men. While up to one in eight men will be diagnosed in their lifetimes, most diagnoses are not fatal. Better lesion location accuracy combined with emerging localized treatment methods are increasingly being utilized as a treatment option to preserve healthy function in eligible patients. In locating lesions which are generally <2cc within a prostate (average size 45cc), small variance in MRI-determined boundaries, tumoral heterogeneity, patient characteristics including location of lesion and prostatic calcifications, and patient motion during the procedure can inhibit accurate sampling for diagnosis. The locations of biopsies are recorded and are then fully processed by histology and diagnosed via pathology, often days to weeks later. Utilization of real-time feedback could improve accuracy, potentially prevent repeat procedures, and allow patients to undergo treatment of clinically localized disease at earlier stages. Unfortunately, there is currently no reliable real-time feedback process for confirming diagnosis of biopsy samples. We examined the feasibility of implementing structured illumination microscopy (SIM) as a method for on-site diagnostic biopsy imaging to potentially combine the diagnostic and treatment appointments for prostate cancer patients, or to confirm tumoral margins for localized ablation procedures. We imaged biopsies from 39 patients undergoing image-guided diagnostic biopsy using a customized SIM system and a dual-color fluorescent hematoxylin & eosin (H&E) analog. The biopsy images had an average size of 342 megapixels (minimum 78.1, maximum 842) and an average imaging duration of 145 s (minimum 56, maximum 322). Comparison of urologist's suspicion of malignancy based on MRI, to pathologist diagnosis of biopsy images obtained in real time, reveals that real-time biopsy imaging could significantly improve confirmation of malignancy or tumoral margins over medical imaging alone.

Oncologic Outcomes Following Robot-Assisted Laparoscopic Nephroureterectomy with Bladder Cuff Excision for Upper Tract Urothelial Carcinoma.

PURPOSE: Robot-assisted laparoscopic nephroureterectomy with bladder cuff excision is a minimally invasive alternative to open surgery for managing upper tract urothelial carcinoma. We report oncologic outcomes following robot-assisted laparoscopic nephroureterectomy with bladder cuff excision. MATERIALS AND METHODS: The records of the initial 65 patients who underwent robot-assisted laparoscopic nephroureterectomy with bladder cuff excision for upper tract urothelial carcinoma between 2008 and 2014 were reviewed from our institutional review board approved, prospectively maintained database. All patients underwent surgery with the single docking technique. Baseline demographic features, pathological variables and perioperative data were analyzed. Kaplan-Meier methodology was used for survival analysis. Cox proportional hazards regression was applied to determine the prognostic effect of different variables on survival. RESULTS: Mean patient age was 69.1 years. Final pathological evaluation revealed pT2 stage or lower in 65% of patients, pT3 in 28.3% and pT4 in 6.7%. High grade pathological findings were present in 85% of patients, including 13.3% with concomitant carcinoma in situ and 30% with lymphovascular invasion. Median followup was 25.1 months (range 6 to 68.9). At 2 and 5 years overall survival was 86.9% and 62.6%, cancer specific survival was 92.9% and 69.5%, and recurrence-free survival was 65.3% and 57.1%, respectively. A total of 23 patients experienced disease recurrence. Bladder recurrence developed in 15 patients, 12 had isolated bladder recurrence and 8 had metastatic disease. On univariate analysis age greater than 70 years, preoperative hydronephrosis, nodal disease and concomitant carcinoma in situ were significantly associated with decreased recurrence-free survival (p=0.002, 0.04, 0.006 and 0.001, respectively). However, none was statistically significant on multivariate analysis. On univariate analysis impaired preoperative renal function (creatinine greater than 2 mg/dl) and lymphovascular invasion were associated with reduced cancer specific survival (p=0.03 and 0.01, respectively). However, only lymphovascular invasion was associated with decreased cancer specific survival on multivariate analysis (p=0.048). CONCLUSIONS: Our reported data on oncologic outcomes following robot-assisted laparoscopic nephroureterectomy with bladder cuff excision for upper tract urothelial carcinoma demonstrate satisfactory oncologic control at intermediate term followup. Long-term outcomes are required to assess true efficacy.

A nonrandomized prospective comparison of robotic-assisted partial nephrectomy in the elderly to a younger cohort: an analysis of 339 patients with intermediate-term follow-up.

OBJECTIVE: To assess the role of robotic-assisted partial nephrectomy (RAPN) in elderly patients focusing on perioperative, functional, and oncologic outcomes in comparison with a younger cohort. MATERIALS AND METHODS: From a prospectively maintained institutional review board-approved database, 339 patients were divided into 2 groups defined by age ≥ 70 (n = 71) or <70 years (n = 268) at the time of RAPN. They were compared for perioperative outcomes and complications, including risk of chronic kidney disease (CKD) stage progression. The standard t test and chi square test were used for continuous and categorical variables, respectively. Logistic regression identified risk factors for progression of renal dysfunction. Kaplan-Meier estimates modeled tumor recurrence at 368 and 462 days in the elderly and young, respectively. RESULTS: Elderly patients were more likely to have hypertension (86% vs 60%; P < .001) or coronary artery disease (27% vs 9%; P < .001), and rates of chronic obstructive pulmonary disorder and diabetes were also higher. Preoperative estimated glomerular filtration rate was significantly lower in the elderly (70 vs 82 mL/min/1.73 m2; P < .001). Twenty-four percent of elderly patients progressed in CKD stage as compared to 14% in the younger cohort (P = .08). Elderly age was not a statistically significant risk factor for CKD progression (relative risk, 2.34; 95% confidence interval, 0.81-6.05; P = .11). Surgical and medical complication rates were similar between the cohorts (P = .75 and .80, respectively) as were Kaplan-Meier estimates of risk of tumor recurrence (P = .47). Limitations include nonrandomized, single-center study, and intermediate-term follow-up for oncologic outcomes. CONCLUSION: Elderly patients undergoing RAPN had no increased risk of perioperative complications. CKD progression and risk of oncologic recurrence were similar to younger patients at intermediate-term follow-up.

Robotic and laparoscopic partial nephrectomy for T1b tumors.

PURPOSE OF REVIEW: Laparoscopic and robotic-assisted partial nephrectomy have been widely adopted for the management of small renal masses; however, usage in T1b (greater than 4 cm) lesions is less established. Herein, we report a review on the published series of minimally invasive partial nephrectomies for such renal masses. RECENT FINDINGS: Several institutions have described laparoscopic and robotic-assisted partial nephrectomy as a safe management option for pathologic T1b lesions. The oncologic results are promising, with low positive margin rates and few cases of progressive disease. Longer-term renal dysfunction does not appear at an increasing rate in this cohort of patients. The safety profile appears acceptable; however, there is a slightly increased rate of complications in these cohorts of patients. SUMMARY: Laparoscopic and robotic-assisted partial nephrectomy is a well tolerated and viable option for performing minimally invasive surgical extirpation of cT1b renal masses. The oncologic and functional results are excellent with acceptable safety profiles. In patients with such masses minimally invasive partial nephrectomy should be considered for elective and absolute indications. In order to achieve excellent functional and oncologic outcomes with minimal perioperative complications an experienced surgeon with assistant and assessment of tumor with patient comorbidities are important.

Impact of percutaneous suprapubic tube drainage on patient discomfort after radical prostatectomy.

BACKGROUND: Patients undergoing radical prostatectomy (RP) traditionally require urethral catheterization for adequate bladder drainage in the postoperative period. However, many patients have significant discomfort from the urethral catheter. OBJECTIVE: To describe a technique of percutaneous suprapubic tube (PST) bladder drainage after robotic-assisted laparoscopic radical prostatectomy (RALP) and to evaluate patient discomfort, complications, continence, and stricture rate after this procedure. DESIGN, SETTING, AND PARTICIPANTS: Two hundred two patients undergoing RALP were drained with a 14F PST instead of a urethral catheter. The PST was placed robotically at the conclusion of the urethrovesical anastomosis and secured to the skin over a plastic button. Beginning on postoperative day 5, patients clamped the PST, urinated per urethra, and measured the postvoid residual (PVR) drained by PST. The PST was removed when residuals were <30 cm(3) per void. The control group consisted of 50 consecutive patients undergoing RALP with urethral catheter drainage. MEASUREMENTS: The primary end point was catheter-associated discomfort as measured with the Faces Pain Score-Revised (FPS-R). Secondary end points included use of anticholinergics, complications related to the PST, urinary continence, and urethral stricture. RESULTS AND LIMITATIONS: When compared with urethral catheter patients, PST patients had significantly decreased catheter-related discomfort on postoperative days 2 and 6 (p<0.001). Anticholinergic medication was required by one PST and four urethral catheter patients (p<0.001). Ten patients required urethral catheterization for PST dislodgement (n=5) or urinary retention (n=5). No patient has developed a urethral stricture at a mean follow-up of 7 mo. CONCLUSIONS: PST provides adequate urinary drainage following RALP with less patient discomfort and no increased risk of urethral stricture.

Maximizing console surgeon independence during robot-assisted renal surgery by using the Fourth Arm and TilePro.

PURPOSE: We describe multiple uses of the fourth robotic arm and TilePro on the da Vinci S surgical system to maximize console surgeon independence from the assistant during robot-assisted renal surgery. MATERIALS AND METHODS: We prospectively evaluated the use of the fourth robotic arm and TilePro on the da Vinci S during robot-assisted radical nephrectomy (RRN) and robot-assisted partial nephrectomy (RPN). The fourth robotic arm was used to provide kidney retraction, place the renal hilum on stretch, control vascular structures, apply and remove bulldog clamps during partial nephrectomy, and secure renal capsular stitches. TilePro was used to project intraoperative ultrasonography and preoperative CT images onto the console screen. RESULTS: From January 2006 to June 2008, 90 robot-assisted kidney procedures were performed, of which the fourth robotic arm was used in 46 cases (RRN, 18; RPN, 24; nephroureterectomy, 4). The fourth robotic arm facilitated consistent kidney retraction for dissection of the renal hilum and mobilization of the kidney. The robotic Hem-o-Lok clip applier effectively controlled renal hilar vessels during eight RPN cases and secured renal capsular stitches during two RPN cases. Bulldog clamps were successfully applied to the renal artery during RPN using the fourth arm in two cases. TilePro was used during 22 RPN cases to project intraoperative ultrasonographic images and preoperative CT images onto the console screen as a picture-on-picture image to guide tumor resection. CONCLUSIONS: Robotic instruments used with the fourth robotic arm may give the console surgeon greater independence from the assistant during robot-assisted kidney surgery by facilitating steps such as kidney retraction, hilar dissection, and vascular control. The TilePro feature of the da Vinci S can be used to project intraoperative ultrasonography and preoperative imaging onto the console screen, potentially guiding tumor localization and resection during RPN without the need to leave the console to view external images.

Robotic nephrectomy for the treatment of benign and malignant disease.

OBJECTIVES: To report our experience and describe our technique of robotic nephrectomy. PATIENTS AND METHODS: We retrospectively evaluated 42 patients who underwent robotic nephrectomy at our institution from January 2004 to March 2008. Variables assessed included patient age, body mass index, operative duration, estimated blood loss (EBL), complications, hospital stay, analgesia requirements and specimen pathology. Radical nephrectomy (RN) was performed for suspected malignant disease and simple nephrectomy (SN) was performed for benign disease. RESULTS: In all, 42 patients with a mean (range) age of 59.4 (17-38) years, underwent robotic nephrectomy (RN 35, SN seven) using a transperitoneal (39) or retroperitoneal (three) approach. The mean operative console time was 158 min, mean EBL was 223 mL, mean tumour size was 5.1 cm, and the mean hospital stay was 2.4 days. Renal hilar vessels were controlled using robotic suture ligation (25), robotic haemolock clips (12), or laparoscopic staplers (five). No patients required open conversion. One morbidly obese patient developed a wound dehiscience (complication rate 2.6%). On final tumour pathology, the RN specimens included 34 renal cell carcinomas (clear cell 23, papillary nine, chromophobe two) and an oncocytoma. The SN specimens showed chronic xanthogranulomatous pyelonephritis (four) and atrophic kidneys (three). All surgical margins were negative for malignancy with no evidence of tumour recurrence at a mean (range) follow-up of 15.7 (1-51) months. CONCLUSIONS: Robotic nephrectomy is a safe and feasible option for minimally invasive surgical removal of the kidney for benign and malignant conditions and can be performed through a transperitoneal or retroperitoneal approach.