Garrett C. Durkan

A Double-Blind Randomized Controlled Clinical Trial to Assess the Effect of Doppler Optimized Intraoperative Fluid Management on Outcome Following Radical Cystectomy

PURPOSE Cardiovascular optimization via esophageal Doppler can minimize gastrointestinal hypoperfusion, reducing the risk of multiple organ dysfunction and postoperative complications during major surgery. We assessed the effect of esophageal Doppler guided cardiovascular optimization in patients undergoing radical cystectomy. MATERIALS AND METHODS We conducted a prospective, randomized, double-blind controlled trial at a United Kingdom teaching hospital between 2006 and 2009. A total of 66 patients were randomized to a control arm (34) and an intervention arm (32). The control group received standard intraoperative fluids. The intervention group received (additional) Doppler guided fluid. Primary outcomes were markers of gastrointestinal morbidity such as ileus, flatus and bowel opening. Secondary outcomes were postoperative nausea and vomiting, wound infection and operative intravenous fluid volumes (total and hourly). RESULTS There were significant reductions in the control and intervention arms in the incidence of ileus (18 vs 7, p <0.001), flatus (5.36 vs 3.55 days, p <0.01) and bowel opening (9.79 vs 6.53 days, p = 0.02), respectively. Nausea and vomiting were significantly reduced in the study group at 24 and 48 hours postoperatively (11 vs 3, p <0.01 and 13 vs 1, p <0.0001). Wound infection rates were significantly reduced (8 vs 1 superficial, p <0.01 and 10 vs 2 combined, p <0.01). Study patients received significantly higher volumes (ml/kg per minute) of intravenous fluid (0.19 vs 0.23, p <0.01) related to a significantly higher volume (ml/kg) in the first hour of surgery (14.1 vs 21.0, p = 0.0001). CONCLUSIONS Cardiovascular optimization using esophageal Doppler significantly improved postoperative markers of gastrointestinal function.

Developing a Laparoscopic Radical Prostatectomy Service: Defining the Learning Curve

BACKGROUND AND PURPOSE Laparoscopic radical prostatectomy (LRP) is an established treatment for patients with prostate cancer in selected centers with appropriate expertise. We studied our single-center experience of developing a LRP service and subsequent training of two additional surgeons by the initial surgeon. We assessed the learning curve of the three surgeons with regard to perioperative outcomes and oncologic results. PATIENTS AND METHODS Three hundred consecutive patients underwent a LRP between January 2005 and April 2011. Patients were divided into three equal groups (1-100 group 1], 101-200 [group 2], and 201-300 [group 3]). Age, American Society of Anesthesiologists score, preoperative comorbidities, and indications for LRP were comparable for all three patient groups. Perioperative and oncologic outcomes were compared across all three groups to assess the impact of the learning curve for LRP. All surgical complications were classified using the Clavien-Dindo system (CDS). RESULTS The mean age was 61.9 years (range 46-74 y). There was a significant reduction in the mean operative time (P<0.05), mean blood loss (P<0.05), mean duration of hospital stay (P<0.05), and duration of catherization (P<0.05) between the three groups as the series progressed. The two most important factors predictive of positive surgical margins at LRP were the initial prostate-specific antigen level and tumor stage at diagnosis. The overall positive margin rate was 27.7%. For pT(2) tumors, the positive margin rate was 21%, while patients with pT(3) tumors had a positive margin of 44%. For pT(2) tumors, positive margin rates decreased with increasing experience (group 1, 27% vs group 2, 17% vs group 3, 19%). The incidence of major complications--ie, grade CDS score ≤ III--was 4.6% (14/300). CONCLUSION LRP is a safe procedure with low morbidity. As surgeons progress through the learning curve, perioperative parameters and oncologic outcomes improve. Using a carefully mentored approach, LRP can be safely introduced as a new procedure without compromising patient outcomes.

The Role of Early Re-Resection in pTaG3 Transitional Cell Carcinoma of the Urinary Bladder

Aim: The clinical outcome and optimal treatment methodology for pTaG3 transitional cell carcinoma (TCC) of the urinary bladder remains controversial. We retrospectively evaluate the clinical behaviour and final outcome of 64 patients diagnosed with primary pTaG3 TCC bladder and evaluate the role of early re-resection following initial diagnosis. Patients and methods: Between January 2000 and December 2008, 64 patients were diagnosed with primary pTaG3 TCC of the urinary bladder at our institution. Following a careful retrospective review of their medical records, clinical parameters including patient age, gender, tumour morphology, operating surgeons experience and adjuvant therapies were entered into a database. The outcome of re-resection, recurrence rate, progression and overall survival were recorded. All patients had their upper tracts screened with an ultrasound and intravenous urogram (IVU). Results: The mean age at time of diagnosis was 78 years (range 59–98). Seventy seven percent (49) of patients underwent an early re-resection (group 1). Residual tumour was identified in 49% (24) patients and the incidence of tumour upstaging was 10% (7). At re-resection 3% (2) of patients were found to have muscle-invasive disease. Twenty three percent (15) of patients did not have an early re-resection (group 2). There was a significant reduction in the incidence of recurrent TCC in group 1 in comparison to group 2 (5% vs. 62%) [p < 0.05]. At a mean follow up of 48.9 months (range 12–124), 48 patients (75%) were alive; 25% (16) of patients had died of causes unrelated to bladder cancer. Disease-specific survival in both groups was 100%. Conclusion: pTaG3 TCC of the urinary bladder shows a variable clinical course and early re-resection significantly reduces the risk of recurrence. We strongly recommend treatment with early re-resection and subsequent treatment as per histology at re-resection. All patients with primary pTaG3 TCC of the urinary bladder should be followed up with further close surveillance using a strict follow up as these patients have a potential for disease progression.

Feasibility study of a randomized controlled trial comparing docetaxel chemotherapy and androgen deprivation therapy with sequential prostatic biopsies from patients with advanced non-castration-resistant prostate cancer.

BACKGROUND AND OBJECTIVE Sequential tissue biopsies taken during clinical trials of novel systemic anticancer therapies for advanced prostate cancer (PCa) may aid pharmacodynamic evaluation and biomarker discovery. We conducted a single institution phase-II open-labeled randomized study to assess the safety, tolerability, and early efficacy of docetaxel chemotherapy plus androgen deprivation therapy (ADT) vs. ADT alone for patients with advanced non-castration-resistant PCa with sequential prostatic biopsies. PATIENTS AND METHODS We randomized 30 patients with newly diagnosed high-grade locally advanced or metastatic (cT3-4/N0-1/M0-1) PCa to receive ADT with (n = 15) or without (n = 15) docetaxel. Transrectal ultrasound-guided prostatic biopsies were taken at randomization and ~22 weeks after treatment initiation. Primary end point: biochemical response rate. Secondary end points: time to progression and tumor profiling. RESULTS Both treatments appear to be well tolerated, and there was no difference in mean nadir prostate-specific antigen and time to prostate-specific antigen relapse between treatment arms (P>0.05). No adverse effects of pre- and post-treatment prostatic biopsies were observed. The study was neither designed nor sufficiently powered to demonstrate statistically significant differences in oncological outcomes or safety profiles between the 2 treatment arms. CONCLUSIONS Despite the lack of statistical power, our study suggests that docetaxel and ADT in combination may be well tolerated with apparently similar short-term efficacy compared with ADT alone for high-grade locally advanced or metastatic non-castration-resistant PCa, Sequential prostatic biopsies may provide tissue for tumor profiling to yield mechanistic or prognostic insights relating to novel systemic anticancer therapies.

Urinary function and health-related quality of life of patients after laparoscopic radical prostatectomy: two methods of assessment for 112 patients with up to six years of follow-up

Background: Wide variation exists between methods of assessment of urinary function following laparoscopic radical prostatectomy (LRP). Objective: To assess post-operative urinary function and quality of life (QOL) after LRP using validated questionnaires and compare these results with subjective assessments obtained during outpatient consultations. Design, setting and participants: Between January 2004 and December 2009, 200 men with organ-confined prostate cancer underwent LRP at our centre. Post-operative urinary function and QOL were evaluated using validated questionnaires (ICIQ-MLUTS and FACT-P). Data regarding urinary function, which were collected at the outpatient clinic (OPC), were also available for these 112 patients. Outcome measurements and statistical analysis: Objective post-operative urinary function obtained from validated questionnaires using univariate and multivariate logistic regression models to evaluate the impact of urinary symptoms on QOL. Results and limitations: Based on the validated questionnaires, 75% (75/112) of patients had low incontinence scores (0 to 8/24) at a mean follow-up of 37 months. On subjective assessment at the OPC, 82% (92/112) of patients were considered dry (pad free). The majority of patients had a high QOL score (109–156), indicating good quality of life. Urinary symptoms’ severity was significantly correlated with QOL, where severe symptoms were associated with lower QOL. A literature search revealed wide discrepancies in the assessment of functional outcomes following LRP rendering comparison between studies extremely difficult. Conclusions: The functional outcomes of LRP vary depending on the assessment used. There continues to be a lack of congruity between the methodologies used in the literature and few studies published have used validated questionnaires.

The influence of high-grade and low-grade histological sub-classification of G2 pT1 transitional cell cancer of bladder on tumour recurrence and progression rates—5-Year retrospective analysis

Aim: We assess the impact of the histological sub-classification of newly diagnosed G2 pT1 TCC bladder into low-grade and high-grade groups on the pattern of disease recurrence and progression. Method: A retrospective case note analysis of all newly diagnosed G2 pT1 TCC bladder between January 2003 and December 2007 was performed. The pattern of disease recurrence and progression was recorded and correlated with the histological grade of the original tumour. In addition, the use of adjuvant intravesical chemotherapy or immunotherapy was recorded and the effect of these agents noted. Results: 101 patients were included in the study of which 75 had high-grade disease, 14 had focally high-grade disease and 11 had low-grade disease. The recurrence rate was 42% in the high-grade group and 25% in the low-grade group. The progression rate was 13% in the high-grade group and no progression was seen in the low-grade group. Those patients with high-grade disease receiving adjuvant intravesical BCG (Bacillus Calmette-Guerin) immunotherapy had a progression rate of 6%, whereas those not receiving BCG treatment had a 18% progression rate. Conclusions: This study supports the view that the presence of high-grade elements in G2 pT1 TCC bladder makes it more likely to progress and therefore this group of patients should be treated aggressively, perhaps in a similar fashion to G3 pT1 TCC bladder.

Diagnosis and management of prostate cancer in the older man

Prostate cancer is the most common malignancy and the second leading cause of cancer death, in men, in western countries. Prostate cancer is diagnosed in very few people aged younger than 50 years (

Is contralateral testicular biopsy warranted at the time of orchidectomy

Objective: Previous studies have suggested that biopsy of the contralateral testis at the time of radical inguinal orchidectomy for unilateral testicular cancer should be performed to exclude intra tubular germ cell neoplasia (ITGCN). This practice has become routine in many urology departments. We reviewed the histological outcome of contralateral testis biopsy in patients with testis cancer to determine if it was appropriate to routinely continue this practice. Methods: The medical records of all men presenting to our institution with testicular cancer between 1998 and 2006 were retrospectively reviewed. The histological diagnosis following inguinal orchidectomy and the outcome of contralateral testis biopsy (where this had been performed) were recorded. The median duration of follow-up was 56 months and the incidence of metachronous tumours during this period was noted. Results: There were 193 consecutive cases of testicular cancer (seminoma, n = 108; nonseminatous germ cell tumour [NSGCT], n =73; non-GCT, n =8; lymphoma, n = 4). Nine patients had a history of maldescent, 12 had microlithiasis and 9 had atrophic testes. One hundred and fifty-one men had contralateral testis biopsies, but there were no cases of ITGCN, regardless of original tumour type or stage. Four patients (all with initial seminomas) developed metachronous tumours, 3 were seminomas and 1 was a mixed GCT. In 3 of the 4 cases, the previous contralateral testis biopsy was normal while the fourth patient was not biopsied at the time of his initial surgery. There were 4 (3%) cases of haematoma following contralateral testis biopsy. Conclusion: Contralateral testis biopsy was unhelpful in predicting metachronous tumour occurrence, carries a small risk of morbidity and should not be routinely performed in men undergoing orchidectomy for testicular cancer.