Patient reported functional outcomes following robotic-assisted (RARP), laparoscopic (LRP), and open radical prostatectomies (ORP).

BACKGROUND: Radical prostatectomy for prostate cancer is associated with significant complications, such as urinary incontinence and erectile dysfunction. Debate remains regarding the influence of surgical technique on these important functional outcomes. AIM: The aim of this study was to compare the early functional outcomes following robotic-assisted (RARP), laparoscopic (LRP), and open radical prostatectomy (ORP) in a rapid access cohort. METHODS: A retrospective review of a prospectively maintained database was performed between 2011 and 2014. Functional status was objectively assessed using the International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5), and a self-reported continence score. RESULTS: Two hundred and ninety-two patients underwent RP (85 RARP, 100 LRP, 107 ORP). The mean age was 61.3 years with a mean initial PSA was 6.2 ng/ml. There was no difference noted in urinary function between ORP, LRP, and RARP at 3 months (p = 0.894), 6 months (p = 0.244), 9 months (p = 0.068) or 12 months (p = 0.154). All men noted a deterioration in erectile function; however, there was no difference at 3 months (p = 0.922), 6 months (p = 0.723), 9 months (p = 0.101) or 12 months (p = 0.395), CONCLUSION: Equivalent good early functional outcomes are being achieved in patients undergoing RP irrespective of surgical approach. Longer follow-up in a prospective randomized fashion is required to fully assess the most appropriate surgical technique.

Efficacy of vacuum erectile devices (VEDs) after radical prostatectomy: the initial Irish experience of a dedicated VED clinic.

Controversy exists regarding optimal penile rehabilitation program following radical prostatectomy (RP). Vacuum erectile devices (VEDs) have become an important component of penile rehabilitation protocols. The aim of this study was to assess the efficacy and patient satisfaction of a dedicated VED clinic. A voluntary telephone questionnaire was performed of all patients who attended a VED clinic to date in two university teaching hospitals. Patient demographics, histopathological characteristics and functional status (International Index of Erectile Function (IIEF) scores) were obtained from a retrospective review of a prospectively maintained database. Sixty-five men attended the dedicated VED clinic in the two university teaching hospitals. Forty-men (76.3%) men purchased a VED following the dedicated clinic. There was significant differences noted between the mean preoperative and the 3-month postoperative IIEF scores (22.08±3.16 vs 11.3±3.08, P=0.0001) and between the 3-month postoperative IIEF score and the post-VED use IIEF score (11.3±3.08 vs 16.74±2.62, P=0.0001). Despite VED use, there was a significant reduction in erectile function from presurgery status (22.08±3.16 vs 16.74±2.62, P=0.0001). All patients reported that the dedicated VED was helpful and would recommend it to other patients. Our study demonstrates that, despite a reduction in erectile function after RP, successful erections are attainable with a VED. There is potential and need for the development of a standard penile rehabilitation program and treatment of ED after RP internationally.

Single centre experience of hypothermic machine perfusion of kidneys from extended criteria deceased heart-beating donors: a comparative study.

INTRODUCTION: Kidneys from extended criteria donors are associated with higher rates of delayed graft function (DGF). Hypothermic machine perfusion (MP) for storage is associated with more favourable outcomes. METHODS: A retrospective analysis was performed in 93 patients where the kidney was stored using hypothermic MP (LifePort(®)) and compared to an age-matched control group where the kidney was stored in cold static storage (CSS) using University of Wisconsin solution. RESULTS: Median age was similar in both groups (59.2 years in MP vs 59.9 years in CSS, p = 0.5598). Mean cold storage time was 15.6 h in MP vs 17.9 h in CSS. Post transplant mean serum creatinine was as follows; MP group-144.7 µmol/L at 1 month; 138.3 µmol/L at 3 months and 129.5 µmol/L at 12 months. In the CSS group-163 µmol/L at 1 month; 154.9 µmol/L at 3 months and 140.2 µmol/L at 12 months. There was a statistically significant difference at 1 month (p = 0.0096) and 3 months (p = 0.0236). DGF was defined as the need for haemodialysis within 7 days post transplant. In the MP group, DGF occurred in 17.2 % patients with mean of 6 days (range 1-18). In the CSS group, 25.8 % patients with mean of 8.1 days (range 3-25). One-year graft survival rate was better in the MP group (97.85 vs 96.77 %). CONCLUSION: Our experience to date recommends the use of hypothermic MP for storage of kidneys from extended criteria deceased heart-beating donors.

A single centre experience of active surveillance as management strategy for low-risk prostate cancer in Ireland.

INTRODUCTION: Active surveillance (AS) is a management strategy for addressing the widely acknowledged problem of over diagnosis and over treatment of clinically indolent prostate cancer. METHODS: A total of 80 patients were enrolled on the AS program in our institution between January 2008 and June 2012. All data were collected prospectively in a secure database. RESULTS: The mean age of patients enrolled was 62.7 years (range 50-72). Median PSA at enrolment was 5.6 ng/mL (range 1.2-13.4). The mean follow-up was 32 months (range 2-54). In total, 85 % of patients had a repeat biopsy after 1-year with 30 % having another biopsy after 3 years. Overall, 45 % of patients remain on AS. In the remainder; 42.5 % of patients have been removed from AS for definitive treatment, while 8.75 % of patients are now on watchful waiting, 2.5 % of patients self discharged from the program and one patient died of cardiovascular disease. The prostate cancer specific survival rate is 100 %. Reasons for removal from AS and referral for treatment were; 67.6 % of patients had upgrade of disease on repeat biopsy, 17.6 % of patients had PSA progression, 11.8 % patients had progression of disease on MRI, and one patient developed a palpable nodule. Regarding definitive treatment; 52.9 % of patients have been for referred for external beam radiotherapy, 14.7 % have been referred for brachytherapy, 29.4 % have been referred for surgery and one patient has refused definitive treatment. CONCLUSION: Our findings to date support active surveillance as a valid strategy for early, localised prostate cancer.

A review of inpatient urology consultations in an Irish tertiary referral centre.

INTRODUCTION: Our institution is a 680-bed tertiary referral centre with broad medical and surgical subspecialty services. We retrospectively audited the pattern of inpatient consultations from all specialities within our institution to the urology department over a 1-year period. METHODS: All consultations to the urology service were identified from our computerised inpatient consultation system from July 2010 to June 2011. Follow up data on investigations, interventions and subsequent outpatient appointments were also identified by review of individual patient discharge letters. RESULTS: Seven hundred and twenty five inpatient consultations were received over the period. The male to female ratio was 7:3. Mean age of patients was 66 (15-96) years. Seventy three percent of referrals were from medical sub-specialities, most commonly nephrology (17%), gastroenterology (11%) and respiratory medicine (9%). The remainder were from general surgery (16%) and other surgical sub specialities (11%). Interns (66%) and senior house officers (SHO) (28%) communicated the majority of consults. Male lower urinary tract/benign prostate related issues resulted in 25% of all consultations. Less than half of consults (47%) resulted in interventions initiated by urology, most commonly of which were catheter insertions (48%) and endoscopic procedures (35%). Only 43% of consultations were followed up in the outpatients setting. CONCLUSIONS: Inpatient consultations constitute a significant workload for urology services. The majority of these referrals did not require any urological intervention and could have been seen routinely in the outpatient setting. Providing structured referral guidelines and achieving better communication with referring teams may help to optimise this service.

Long-term outcome of cadaveric renal transplant after treatment of symptomatic lymphocele.

PURPOSE: Between January 1993 and December 2002 a total of 1,289 renal transplants were performed at our institution. Symptomatic post-transplant lymphocele presenting as increased creatinine and hydronephrosis of the allograft was recorded at 0.02%. Records of the 27 patients in whom symptomatic lymphocele developed and of those who underwent contralateral kidney transplant (control group) were compared to determine the long-term effects of lymphocele formation on allograft function. MATERIALS AND METHODS: A total of 37 procedures for the treatment of lymphocele were performed in 24 patients. Open marsupialization (12) and laparoscopic marsupialization (3) procedures were performed as primary treatments. Two patients underwent repeat open marsupialization. Aspiration and percutaneous catheter drainage were performed as a primary procedure in 7 and 1 cases, respectively. Percutaneous nephrostomy was required in 4 cases before definitive treatment. RESULTS: The mean time to development of a lymphocele was 121 days (range 35 to 631). Symptomatic lymphocele did not require treatment in 3 patients. Of 19 patients undergoing primary marsupialization, recurrence in 2 necessitated repeat surgery. However, aspiration and percutaneous drainage proved to be definitive in only 2 cases. In total 8 patients required more than 1 procedure. At a mean followup of 63 months (SD 30.3) 21 allografts continued to function with a mean serum creatinine of 152 mumol/l (SD 67.9). In the control group 3 patients experienced graft failure and mean serum creatinine was 154 mumol/l (SD 51.9). Five patients died in the lymphocele group, 2 with functioning grafts compared to 4 deaths in the control group. CONCLUSIONS: Surgical marsupialization is the preferred primary treatment for symptomatic lymphocele and is associated with excellent long-term allograft outcome.

Long-term outcome of cadaveric pediatric en bloc transplantation--a 15-year experience.

Pediatric en bloc transplantation of infant organs into adult recipients is a recognized technique to expand the number of kidneys available for transplantation. We reviewed our experience with this technique over a 15-year period to determine the long-term outcomes. Twelve patients underwent pediatric en bloc transplantation from donors aged <4 years. All transplants functioned immediately with no graft thrombosis. Two patients died 12 and 10 years posttransplant with functioning grafts. The remaining 10 recipients experienced excellent graft function with a mean follow-up time of 73.8 months (range, 10 to 169 months) with no evidence of hyperfiltration injury. We conclude that pediatric en bloc transplantations achieve excellent long-term allograft function in selected recipients.

Prostaglandin E2 receptors EP2 and EP4 are down-regulated in human mononuclear cells after injury.

BACKGROUND: Recent characterization of prostaglandin receptor subtypes shows that each is critical to cellular functions and operates through separate signaling pathways that may explain differing effects of prostanoids. This study aimed to determine whether prostaglandin receptors EP2 and EP4 are modulated after injury and to evaluate the effect of prostaglandin E(2) (PGE(2)) addition and blockade on EP receptor expression. METHODS: Peripheral blood mononuclear cells (PBMCs) isolated from 10 patients sustaining fracture or burn injury and 10 control subjects were stimulated with lipopolysaccharide +/- NS-398, an inhibitor of PGE(2) production. Samples were evaluated for production of PGE(2), tumor necrosis factor--alpha, and leukotriene B(4) as well as mRNA expression of EP receptors and COX-2. EP receptor expression was also evaluated after treating control PBMCs with PGE(2). RESULTS: PBMCs from injured patients exhibited significant increases in PGE(2) production and COX-2 mRNA compared with control subjects, and these increases were inhibited by NS-398. In contrast, EP2 and EP4 receptors were markedly down-regulated after injury and NS-398 restored expression to control levels. Decreased EP2 and EP4 receptor expression after injury was replicated by coincubation of PBMCs with PGE(2). CONCLUSIONS: Specific PGE(2) receptors are down-regulated after injury and NS-398 reverses this response. Furthermore, PGE(2) mediates EP2 and EP4 down-regulation. These data suggest that specific EP receptor subtypes may provide critical targets for augmenting the immune response after injury in humans.

Macrophage effector mechanisms in melanoma in an experimental study.

BACKGROUND: The tumor-bearing state is known to induce immune dysfunction that contributes to increased infectious complications and tumor progression. However, the mechanisms underlying this immunosuppression remain unclear. HYPOTHESIS: Macrophage (MO) dysfunction may play a role in tumor-induced immunosuppression. DESIGN AND MAIN OUTCOME MEASURES: Using a murine model, this study investigated the effects of melanoma growth on peritoneal macrophage effector molecule and prostaglandin production, MO-mediated cytotoxicity, and candidacidal mechanisms. Female C57BL/6 mice were inoculated with 106 B16 melanoma cells or a salt solution subcutaneously. Mice were euthanized 3 weeks later and peritoneal MOs were harvested and assayed for nitric oxide, superoxide anion, tumor necrosis factor alpha, and prostaglandin E(2)production. Macrophage-mediated cytotoxicity against B16 melanoma targets and MO candidacidal mechanisms were also measured. RESULTS: Macrophage production of nitric oxide, superoxide anion, and tumor necrosis factor alpha were significantly decreased, while prostaglandin E(2)production was increased in MOs from melanoma-bearing mice. Concomitantly, MO-mediated cytotoxicity and candidacidal mechanisms were significantly impaired. CONCLUSIONS: Melanoma growth leads to decreased MO effector molecule production, increased prostaglandin E(2)production, and impaired MO cytotoxic and candidacidal mechanisms. These results may help explain the observed increased infectious complications in the tumor-bearing host. Strategies aimed at restoring MO function may have therapeutic potential.

Overlapping CRE and E-box promoter elements can independently regulate COX-2 gene transcription in macrophages.

Macrophage cyclooxygenase-2 (COX-2) transcription is mediated through the collaboration of different promoter elements. Here, the role of an overlapping cyclic AMP responsive element (CRE)/E-box was investigated. Nuclear proteins bound both the CRE and E-box, which synergized with other promoter elements to induce COX-2 transcription. Endotoxin induced binding of nuclear proteins to the CRE and E-box and each element independently induced higher COX-2 transcription levels than the overlapping CRE/E-box. Transcription factors associated with the CRE binding complex included c-Jun and CRE binding protein and with the E-box binding complex USF-1; their overexpression significantly induced COX-2 transcription. Therefore, both CRE and E-box promoter elements regulate COX-2 transcription in macrophages.

NS-398 treatment after trauma modifies NF-kappaB activation and improves survival.

Prostaglandin E(2) (PGE(2)) production after trauma contributes to immune alterations that increase susceptibility to infections. We hypothesize that blocking PGE(2) with NS-398, a selective COX-2 inhibitor, will modulate this response and improve outcome. This study evaluated the effect of NS-398 given over 7 days on proinflammatory cytokines, intracellular signaling, and survival after a septic challenge. Balb/C mice (n = 8/group) were given 10 mg/kg NS-398 intraperitoneally over 7 days, starting after anesthesia or trauma (femur fracture + 40% hemorrhage). Four groups, anesthesia + vehicle (C), anesthesia + NS-398 (CN), trauma + vehicle (T), or trauma + NS-398 (TN), were studied. On Day 7 after trauma, mice were sacrificed, serum was collected, and splenic macrophages were evaluated for PGE(2), LTB(4), IL-6, TNF-alpha, and NO production. Additionally, macrophage COX-2 mRNA, IkappaB-alpha, and NF-kappaB were evaluated. In a separate study, mice (n = 10-11/group) were traumatized and given NS-398 over 7 days, and then cecal ligation and puncture (CLP) were performed. Mice were then followed for survival over 10 days (via log-rank test). NS-398 treatment of injured mice decreased PGE(2) production compared to T (3.9 +/- 0.3 vs 3.1 +/- 0.4 pg/microg protein), and significantly decreased IL-6, NO, and TNF-alpha production. NS-398 treatment also attenuated COX-2 mRNA levels and NF-kappaB activation. These cellular events correlate with a significant survival advantage in TN versus T mice after CLP. These data suggest that a specific COX-2 inhibitor not only suppresses PGE(2), but normalizes proinflammatory cytokines after trauma through changes that may partly be mediated via transcriptional events. This correlates with significantly increased survival in TN mice given a septic challenge and suggests that COX-2 inhibitors contribute to modulating the inflammatory response and improving survival after trauma.