Parth Modi

Safety of Robot-Assisted Radical Prostatectomy with Pneumoperitoneum of 20 mm Hg: A Study of 751 Patients

BACKGROUND AND PURPOSE Early studies describing robot-assisted radical prostatectomy (RARP) reported the use of pneumoperitoneum at a pressure of 15 mm Hg. While higher insufflation pressures (20 mm Hg) may reduce venous oozing and improve visualization, the safety of this method has not been confirmed. This study evaluates the short-term perioperative outcomes of patients undergoing RARP with insufflation pressures of 20 mm Hg. PATIENTS AND METHODS A single-surgeon, prospectively maintained database of patients undergoing RARP was retrospectively analyzed. Patients who underwent RARP with a pneumoperitoneum pressure of 15 and 20 mm Hg for the entire procedure were analyzed. Preoperative and postoperative hemoglobin levels and estimated glomerular filtration rate (eGFR) were compared. Complications, operative time, and estimated blood loss were also examined. RESULTS The number of patients in the experimental (20 mm Hg) and control (15 mm Hg) groups were 550 and 201, respectively. The groups were well matched with respect to age and operative time. The experimental group had a significantly smaller decrease in mean hemoglobin levels after surgery (-1.18 vs-2.13 mg/dL, P<0.0001). There was no significant difference in the eGFR on the first day after surgery (postoperative day [POD]1) (88.4 vs 85.0 mL/min/1.73m(2), P=0.11) or in the change in eGFR from preoperative to POD1 levels (-0.49 vs 1.54 mL/min/1.73m(2), P=0.18). The complication rate in the experimental group was 8.55% vs 8.46% in the control group. CONCLUSION Pneumoperitoneum using a pressure of 20 mm Hg for RARP is safe and has no significant short-term effects on renal function and hemoglobin. Increased insufflation pressure was not associated with a higher complication rate.

Secondary infections of thoracic and abdominal aortic endografts.

PURPOSE To review several cases of stent-graft infection with respective outcomes to identify clinical presentations and responses to treatment options. MATERIALS AND METHODS The authors performed a single-center retrospective review of all secondary endograft infections from January 2000 to June 2007. Infections were identified from an institutional database containing all abdominal and thoracic endovascular aneurysm repairs (EVAR and TEVAR) performed at the treating hospital. RESULTS From January 2000 to June 2007, 389 EVAR and 105 TEVAR were performed at the treating hospital. Ten endograft infections were identified (five EVAR and five TEVAR). Four infections occurred in grafts placed at outside institutions and six in grafts placed in-house. The in-house prevalence of EVAR and TEVAR infection is 0.26% and 4.77%, respectively. None were placed for a presumed pre-existing mycotic aneurysm. The mean time from the index procedure to the diagnosis of infection was 243.6 days +/- 74.5. Two patients who underwent EVAR presented with a contained rupture, and the remaining eight patients presented with constitutional symptoms and/or abscess formation on imaging studies. Microbiology cultures revealed Propionibacterium species (n = 3), Staphylcoccus species (n = 3), Streptococcus species (n = 2), and Enterobacter cloacae (n = 1). All EVAR patients underwent removal of the infected endograft and reconstruction with extraanatomic bypass (n = 3) or in situ homograft placement (n = 2). During a mean follow-up of more than 1 year, there were no recognized complications or recurrence of infection. Only one of the five TEVAR patients underwent removal and interposition grafting with an antibiotic-impregnated Dacron graft. The remaining four patients were medically managed--one patient survived and was placed in hospice care, two died of mycotic aneurysm rupture, and one died from multiorgan system failure secondary to sepsis. CONCLUSIONS Graft-related septic complications following EVAR or TEVAR are rare but associated with significant mortality. Several surgical treatment options are available, each potentially equally successful. The effect of prophylactic antibiotic use during subsequent invasive procedures must be solidified.

Prostate cancer risk alleles significantly improve disease detection and are associated with aggressive features in patients with a “normal” prostate specific antigen and digital rectal examination

Several reports suggest that a combination of risk alleles may be associated with prostate cancer (CaP) risk and tumor features. However, their ability to detect CaP and tumor characteristics in patients with a “normal” PSA (<4 ng/ml) and non‐suspicious digital rectal examination (DRE) remains to be determined.

Ureteral Stent-Associated Pain: A Review

PURPOSE Ureteral stent-related pain is a well-known side effect of stent placement. To date, there is a paucity of resources that address this topic. Herein, we present theories on stent pain pathophysiology, summarize available pain outcome data for different stent designs, and provide an overview of the management of stent pain, including preplacement modifiers, medical management, and other considerations. MATERIALS AND METHODS This narrative review focused primarily on articles indexed in the PubMed(®), Google Scholar™, and EMBASE databases. No formal search strategy was used and no meta-analysis of data was performed. RESULTS Stent pain pathophysiology is multifactorial and likely a result of mucosal irritation along with retrograde reflux of urine. While there is a consensus on the lack of association between stent length, diameter, and stent-related flank pain, stents should be properly sized so as to prevent dislodgement. Insufficient data exist comparing stent materials and durometry. Multiple drug-eluting stents are in development and have demonstrated promising early results. Alpha-blockers have shown efficacious results and should be considered along with or in combination with anticholinergics and nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of ureteral stent-related symptoms, with judicious consideration of their side effect profiles. Periureteral botulinum toxin A injections are a promising, novel treatment modality. CONCLUSIONS Ureteral stent pain is common and multiple modalities have been studied and are in clinical use for its treatment. Care should be taken to avoid placement of stents if possible, with continual reassessment of indications to maintain stents in patients. Relative heterogeneity among studies and small sample sizes make creating specific evidence-based pain management recommendations challenging. Alpha-blockers, antimuscarinics, and NSAIDs are all generally well tolerated and effectively reduce symptoms, but patient-specific factors must be the paramount consideration when choosing monotherapy or combination therapy. Future studies are needed to better define ideal material characteristics and pharmacologic treatments.

Reconstruction of late-onset transplant ureteral stricture disease

Study Type – Therapy (case series) Level of Evidence 4

Improving our understanding of papillary renal cell carcinoma with integrative genomic analysis

Papillary renal cell carcinoma (pRCC) is a heterogeneous and incompletely understood histologic subtype of kidney cancer. Recently, authors from The Cancer Genome Atlas Research Network performed a comprehensive molecular characterization of pRCC. Using multiple analytic methods, they identified 4 subgroups of pRCC with varied genotypic anomalies and probabilities of overall survival. This analysis elucidated the differences between type 1 and type 2 pRCC. Furthermore, type 2 pRCC was found to be heterogeneous itself, with at least 3 subtypes with distinct molecular features. This improved characterization and insight about potential driver mutations and altered pathways may lead to the development of more targeted agents and better patient stratification in clinical trials for pRCC.

Medications and Surgical Interventions for Benign Prostatic Hyperplasia Are Potential Confounders of Prostate-Specific Antigen

Prostate-specific antigen (PSA) is the most widely used marker for prostate cancer (CaP) screening and monitoring benign prostatic hyperplasia (BPH) progression. However, lack of an established abnormal threshold and the presence of other benign processes confound the interpretation of PSA levels. Many factors besides inflammation, trauma, and instrumentation can influence PSA levels; specifically, BPH and its associated medical and surgical therapies frequently complicate the interpretation of this serum blood test. For example, the commonly used 5 alpha reductase inhibitor (5ARI) medications directly affect PSA levels by decreasing prostate volume. The amount of time and potentially even the 5ARI formulary a patient is administered has been implicated to directly impact the degree of reduction in PSA (a proxy for prostate volume). In addition, each of the currently available surgical procedures for BPH appears to remove varying amounts of prostatic adenoma. This directly confounds CaP screening because each procedure is associated with a relatively specific postoperative nadir PSA level, and PSA kinetics are not well described in the literature. Taken together, it is important for clinicians to comprehend that BPH and its associated medical and surgical interventions should directly influence their interpretation of PSA and PSA velocity when screening for CaP or following BPH progression.

Intracrine androgen biosynthesis in renal cell carcinoma

Background:Renal cell carcinoma (RCC) is one of the most lethal genitourinary cancers. The presence of androgen receptor (AR) in RCC has recently been shown to be associated with higher tumour stage irrespective of gender. Because the clinical context of androgens in female RCC patients is similar to that of prostate cancer patients undergoing androgen-deprivation therapy, mechanisms underlying the emergence of castration-resistant prostate cancer (CRPC) may be at play in AR-positive RCC cells. Therefore, we hypothesized that AR-positive RCC has intratumoral steroidogenesis and that anti-androgen therapy may result in tumour suppression.Methods:Mice were injected with an AR-positive RCC cell line. When tumours became palpable, surgical castration was performed and tumour volume was measured. Using ELISA, the levels of intracellular testosterone and dihydrotesterone were measured in AR-positive human RCC cell lines. Lastly, male mice containing xenografts were treated with enzalutamide or abiraterone acetate (AA) for 3 weeks to measure tumour volume.Results:We first observed in vivo that castration retards the growth of AR-positive RCC tumour xenograft in mice. Next, AR-positive human RCC cell lines and tissues were found to have elevated levels of testosterone and dihydrotestosterone and express key enzymes required for intracellular androgen biosynthesis. A mouse xenograft study with AR-positive RCC cell line using the commonly used anti-androgen therapies showed significant tumour suppression (P<0.01).Conclusions:Intracrine androgen biosynthesis is a potential source of androgen in AR-positive RCC and that the androgen signaling axis is a potential target of intervention in RCC.

Long-Term Outcomes of Using Hyaluronic Acid-Carboxymethylcellulose Adhesion Barrier Film on the Neurovascular Bundle

INTRODUCTION/OBJECTIVE We hypothesize that the use of hyaluronic acid-carboxymethylcellulose (HACM) adhesion barrier at the neurovascular bundle may hasten the return of erectile function after robot-assisted laparoscopic prostatectomy. MATERIALS AND METHODS A retrospective review identified 462 consecutive patients who underwent a nerve-sparing prostatectomy between 2009 and 2012. The first 246 patients were administered the barrier film, while the next 216 patients, the control group, did not receive HACM. Postoperative erectile function and oncologic outcomes were compared. Independent t-test and Kaplan-Meier analysis were conducted, p < 0.05 was considered significant. RESULTS The two groups were well matched, without significant differences in age, weight, operative time, prostate size, preoperative prostate-specific antigen, sexual health inventory for men (SHIM), or AUA symptom scores. The mean SHIM was significantly higher for the experimental group at 6 months (6.39 vs 4.75, p = 0.008), 9 months (7.32 vs 5.44, p = 0.006), 1 year (8.52 vs 6.90, p = 0.049), and 18 months (10.01 vs 7.60, p = 0.018). This effect was not noted beyond 18 months. A subgroup analysis of patients with initial SHIM scores 22 or greater demonstrated a higher rate of return to the preoperative SHIM score for the barrier film group, 23% vs 12% (p = 0.046). There was no significant difference in biochemical recurrence between groups, with a median follow-up duration of 18 months. CONCLUSIONS HACM application at the neurovascular bundle during prostatectomy may decrease the time to return of erectile function, with improved SHIM at 6 to 18 months after surgery. This effect is more pronounced in patients with better baseline erectile function. There is no significant effect on biochemical recurrence.

MP60-08 INTRACRINE ANDROGEN BIOSYNTHESIS IN RENAL CELL CARCINOMA

INTRODUCTION AND OBJECTIVES: We previously reported that high MET and matriptase expression in RCC cells in bone metastasis indicates their importance in bone metastasis (Mukai et al. Hum Cell, 2015). MET is a high-affinity receptor tyrosine kinase of hepatocyte growth factor (HGF). HGF is secreted as an inactive singlechain precursor, which requires proteolytic activation for conversion to an active form. Matriptase is the most efficient known cellular activator of pro-HGF. Furthermore, activation of matriptase is regulated by HGF activator inhibitor (HAI). In this study, we employed a previously reported mouse model of bone metastasis (Strube et al. Clin Exp Metastasis, 2010) to clarify the significance of the matriptase-induced HGF/MET signaling axis in RCC bone metastasis. METHODS: Luciferase-transfected 786-O cells were injected into the left cardiac ventricle of female nude mice (5 weeks old). After 6 weeks, we confirmed the formation of bone metastasis by whole-body bioluminescent imaging, and extracted specimens. Expression of matriptase, MET and HAI was analyzed by PCR, immunohistochemistry (IHC) and immunoblots. Phosphorylation of MET was also investigated. Based on the result, we produced HAI-2 (specific inhibitor of matriptase) stable knock down (KD) 786-O cells, and analyzed the difference of expression in each molecule, cell-migration assay and invasion assay. RESULTS: Expression of matriptase was increased significantly in bone metastasis compared with parent cell line, and we confirmed increased phosphorylation of MET in bone metastasis. On the other hand, decreased expression of HAI-2 was observed in bone metastasis. Interestingly, increased matriptase expression was observed by HAI-2 KD in 786-O cells. In addition, invasive activity was increased significantly by knock down of HAI-2. CONCLUSIONS: These results have suggested that matriptase contributes to the HGF-dependent MET activation in the pericellular microenvironment of bone metastasis in RCC. In addition, upregulation of matriptase and downregulation of HAI-2 may have important roles in their progression.