Hitendra R.H. Patel

Guidelines for perioperative care after radical cystectomy for bladder cancer: Enhanced Recovery After Surgery (ERAS®) society recommendations

PURPOSE Enhanced recovery after surgery (ERAS) pathways have significantly reduced complications and length of hospital stay after colorectal procedures. This multimodal concept could probably be partially applied to major urological surgery. OBJECTIVES The primary objective was to systematically assess the evidence of ERAS single items and protocols applied to cystectomy patients. The secondary objective was to address a grade of recommendation to each item, based on the evidence and, if lacking, on consensus opinion from our ERAS Society working group. EVIDENCE ACQUISITION A systematic literature review was performed on ERAS for cystectomy by searching EMBASE and Medline. Relevant articles were selected and quality-assessed by two independent reviewers using the GRADE approach. If no study specific to cystectomy was available for any of the 22 given items, the authors evaluated whether colorectal guidelines could be extrapolated. EVIDENCE SYNTHESIS Overall, 804 articles were retrieved from electronic databases. Fifteen articles were included in the present systematic review and 7 of 22 ERAS items were studied. Bowel preparation did not improve outcomes. Early nasogastric tube removal reduced morbidity, bowel recovery time and length of hospital stay. Doppler-guided fluid administration allowed for reduced morbidity. A quicker bowel recovery was observed with a multimodal prevention of ileus, including gum chewing, prevention of PONV and minimally invasive surgery. CONCLUSIONS ERAS has not yet been widely implemented in urology and evidence for individual interventions is limited or unavailable. The experience in other surgical disciplines encourages the development of an ERAS protocol for cystectomy.

Effects of Tadalafil Treatment on Erectile Function Recovery Following Bilateral Nerve-sparing Radical Prostatectomy: A Randomised Placebo-controlled Study (REACTT)

BACKGROUND The potential rehabilitative and protective effect of phosphodiesterase type 5 inhibitors (PDE5-Is) on penile function after nerve-sparing radical prostatectomy (NSRP) remains unclear. OBJECTIVE The primary objective was to compare the efficacy of tadalafil 5mg once daily and tadalafil 20mg on demand versus placebo taken over 9 mo in improving unassisted erectile function (EF) following NSRP, as measured by the proportion of patients achieving an International Index of Erectile Function-Erectile Function domain (IIEF-EF) score ≥ 22 after 6-wk drug-free washout (DFW). Secondary measures included IIEF-EF, Sexual Encounter Profile question 3 (SEP-3), and penile length. DESIGN, SETTING, AND PARTICIPANTS Randomised, double-blind, double-dummy, placebo-controlled trial in men ≤ 68 yr of age with adenocarcinoma of the prostate (Gleason ≤ 7) and normal preoperative EF who underwent NSRP at 50 centres from nine European countries and Canada. INTERVENTIONS 1:1:1 randomisation to 9 mo of treatment with tadalafil 5mg once daily, tadalafil 20mg on demand, or placebo followed by a 6-wk DFW and 3-mo open-label tadalafil once daily (all patients). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Logistic regression, mixed-effects model for repeated measures, and analysis of covariance, adjusting for treatment, age, and country, were applied to IIEF-EF scores ≥ 22, SEP-3, and penile length. RESULTS AND LIMITATIONS Four hundred twenty-three patients were randomised to tadalafil once daily (n=139), on demand (n=143), and placebo (n=141). The mean age was 57.9 yr of age (standard deviation: 5.58 yr); 20.9%, 16.9%, and 19.1% of patients in the tadalafil once daily, on demand, and placebo groups, respectively, achieved IIEF EF scores ≥ 22 after DFW; odds ratios for tadalafil once daily and on demand versus placebo were 1.1 (95% confidence interval [CI], 0.6-2.1; p=0.675) and 0.9 (95% CI, 0.5-1.7; p=0.704). At the end of double-blind treatment (EDT), least squares (LS) mean IIEF-EF score improvement significantly exceeded the minimally clinically important difference (MCID: ΔIIEF-EF ≥ 4) in both tadalafil groups; for SEP-3 (MCID ≥ 23%), this was the case for tadalafil once daily only. Treatment effects versus placebo were significant for tadalafil once daily only (IIEF-EF: p=0.016; SEP-3: p=0.019). In all groups, IIEF-EF and SEP-3 decreased during DFW but continued to improve during open-label treatment. At month 9 (EDT), penile length loss was significantly reduced versus placebo in the tadalafil once daily group only (LS mean difference 4.1mm; 95% CI, 0.4-7.8; p=0.032). CONCLUSIONS Tadalafil once daily was most effective on drug-assisted EF in men with erectile dysfunction following NSRP, and data suggest a potential role for tadalafil once daily provided early after surgery in contributing to the recovery of EF after prostatectomy and possibly protecting from penile structural changes. Unassisted EF was not improved after cessation of active therapy for 9 mo. TRIAL REGISTRATION ClinicalTrials.gov identifier NCT01026818.

Enhanced Recovery After Surgery: Are We Ready, and Can We Afford Not to Implement These Pathways for Patients Undergoing Radical Cystectomy?

Enhanced recovery after surgery (ERAS) for radical cystectomy seems logical, but our study has shown a paucity in the level of clinical evidence. As part of the ERAS Society, we welcome global collaboration to collect evidence that will improve patient outcomes.

Complications associated with extraperitoneal robot-assisted radical prostatectomy using the standardized Martin classification.

OBJECTIVE To report and identify the predictors of early and long-term complications in a large series of extraperitoneal robot-assisted radical prostatectomy using the standardized Martin criteria. MATERIALS AND METHODS A total of 1503 patients underwent extraperitoneal robot-assisted radical prostatectomy for the treatment of clinically localized prostate cancer from July 2003 to August 2010 at a tertiary referral center. The median follow-up was 28.9 months. Fishers exact test was used to examine the association of multiple variables in a bivariate analysis with the incidence and types of complications. Independent predictors were also examined in a multivariate analysis using logistic regression models. RESULTS A total of 151 complications were recorded in 127 of 1503 patients (8.45%). Approximately one third (30.5%) were classified as major complications requiring intervention (Clavien grade III and IV). The most commonly encountered complications were lymphocele (1.46%), bladder neck contracture (1.33%), and anastomotic leak (1.20%). The operative time was a significant predictor of all complications and of major complications on multivariate analysis. Surgeon experience was also predictive of complications on multivariate analysis. CONCLUSION Extraperitoneal robot-assisted radical prostatectomy remains an underused alternative approach for the treatment of localized prostate cancer. Its safety profile is equivalent to that of other approaches in experienced hands.

An Evaluation Framework for Defining the Contributions of Telestration in Surgical Telementoring

Background An increasing quantity of research in the domain of telemedicine show a growing popularity and acceptance of care over distance systems among both clinicians and patients. We focus on telementoring solutions, developed for providing remote guidance to less experienced surgeons. Telestration is often regarded as an extra functionality of some telementoring systems. However, we advocate that telestration must be viewed as a core feature of telementoring due to its advantages. Objective To analyze and define concepts, parameters, and measurement procedures to evaluate the impact of using telestration while telementoring. Methods A systematic review of research dealing with telestration during remote guidance sessions was performed by querying three major online research databases (MEDLINE, Association of Computing Machinery, and Institute of Electrical and Electronics Engineers) using a predefined set of keywords (“laparoscopy”, “annotate”, “telestrate”, “telestration”, “annotation”, “minimally invasive”, and “MIS”). Results The keyword-based search identified 117 papers. Following the guidelines for performing a systematic review, only 8 publications were considered relevant for the final study. Moreover, a gap in research defining the impacts of telestration during telementoring was identified. To fill this niche, a framework for analyzing, reporting, and measuring the impacts of telestration was proposed. Conclusions The presented framework lays the basics for the structured analysis and reporting of telestration applied to telementoring systems. It is the first step toward building an evidence knowledge base documenting the advantages of live video content annotation and supporting the presented connections between the concepts.

New phosphodiesterase inhibitors in the treatment of erectile dysfunction

Sildenafil revolutionised the treatment of erectile dysfunction (ED) on its introduction in 1998. Not only is it effective, but is, perhaps even more importantly, an extremely acceptable manner in which to treat ED (i.e., oral pharmacotherapy), compared to the other treatments that were available at that time (e.g., intracavernosal injection). Whilst sildenafil remains the market leader for ED treatment, it does have some shortcomings: its clinical efficacy is diminished in ‘difficult to treat’ patient groups, such as diabetics, side effects, such as blue-tinged vision and headache, and the need to time the ingestion of sildenafil to 1 h prior to expected time of sexual intercourse. Recently, newer phosphodiesterase inhibitors (‘sons of viagra’) have become available, and potentially to improve upon, what has become regarded as the gold standard for ED treatment. This review article discusses the differences between vardenafil, tadalafil and sildenafil, in order to allow the clinician to make an informed decision as to which phosphodiesterase inhibitor to prescribe when dealing with the ever expanding number of patients seeking help for ED.

Allogeneic stem-cell transplantation for renalcellcancer

Summary Metastatic renal-cell carcinoma (RCC) is resistant to chemotherapy, and patients with this disease have a poor outlook. Immunotherapy by use of cytokines and vaccines against tumour antigens has shown encouraging results in a small group of patients. Advances in the understanding of the graft-versus-tumour effect in haematological malignant disorders have led to the use of stem-cell transplantation for treatment of solid-organ malignant diseases such as RCC. Techniques of bone-marrow ablation have been superseded by safer conditioning regimens, with occasional complete remission and partial remission in some patients. Graftversus- host disease, engraftment failure, and disease progression remain important obstacles to the widespread use of new techniques for metastatic RCC. Here, we summarise important issues surrounding immunotherapy for RCC, the problems encountered with use of immunotherapy, and the present use of non-myeloablative techniques for treatment of this disease.

High expression of PDGFR-β in prostate cancer stroma is independently associated with clinical and biochemical prostate cancer recurrence

Due to a lack of sufficient diagnostic tools to predict aggressive disease, there is a significant overtreatment of patients with prostate cancer. Platelet derived growth factors (PDGFs) and their receptors (PDGFRs) are key regulators of mesenchymal cells in the tumor microenvironment, and has been associated with unfavorable outcome in several other cancers. Herein, we aimed to investigate the prognostic impact of PDGFR-β and its ligands (PDGF-B and PDGF-D) in a multicenter prostatectomy cohort of 535 Norwegian patients. Using tissue microarrays and immunohistochemistry, the expression of ligands PDGF-B and PDGF-D and their corresponding receptor, PDGFR-β, was assessed in neoplastic tissue and tumor-associated stroma. PDGFR-β was expressed in benign and tumor associated stroma, but not in epithelium. High stromal expression of PDGFR-β was independently associated with clinical relapse (HR = 2.17, p = 0.010) and biochemical failure (HR = 1.58, p = 0.002). This large study highlights the prognostic importance of PDGFR-β expression, implicating its involvement in prostate cancer progression even in early stage disease. Hence, analyses of PDGFR-β may help distinguish which patients will benefit from radical treatment, and since PDGFR-β is associated with relapse and shorter survival, it mandates a focus as a therapeutic target.

Is robotic-assisted radical cystectomy (RARC) with intracorporeal diversion becoming the new gold standard of care?

BackgroundTotally intracorporeal robotic-assisted radical cystectomy (RARC) has perceived difficulties compared to open radical cystectomy (ORC). As the technique is increasingly adopted around the world, the benefits of RARC with intra- or extracorporeal urinary diversion or ORC for the patients are still unclear. In this article, we consider the current evidence for this issue.MethodsWe assessed two questions through using expert opinion and the medical literature: (A) Is RARC better than ORC for removing the cancer surgery and outcome? (B) Is RARC better than ORC for the urinary diversion?Outcomes(A) RARC is better than ORC for shorter length of stay, blood loss and complication rates. (B) Intracorporeal orthotopic neobladder may have a significant physiological and surgical benefit to the patient recovery.ConclusionsRARC with total intracorporeal reconstruction has potential benefits to the patient. We recommend that all surgeons document patient-related outcome measures, urodynamics and enhanced recovery protocols for cystectomy patients to help us understand the real improvements within bladder cancer surgery and reconstruction.

Targets of Wnt/ß-catenin transcription in penile carcinoma.

Penile squamous cell carcinoma (PeCa) is a rare malignancy and little is known regarding the molecular mechanisms involved in carcinogenesis of PeCa. The Wnt signaling pathway, with the transcription activator ß-catenin as a major transducer, is a key cellular pathway during development and in disease, particularly cancer. We have used PeCa tissue arrays and multi-fluorophore labelled, quantitative, immunohistochemistry to interrogate the expression of WNT4, a Wnt ligand, and three targets of Wnt-ß-catenin transcription activation, namely, MMP7, cyclinD1 (CD1) and c-MYC in 141 penile tissue cores from 101 unique samples. The expression of all Wnt signaling proteins tested was increased by 1.6 to 3 fold in PeCa samples compared to control tissue (normal or cancer adjacent) samples (p<0.01). Expression of all proteins, except CD1, showed a significant decrease in grade II compared to grade I tumors. High magnification, deconvolved confocal images were used to measure differences in co-localization between the four proteins. Significant (p<0.04-0.0001) differences were observed for various permutations of the combinations of proteins and state of the tissue (control, tumor grades I and II). Wnt signaling may play an important role in PeCa and proteins of the Wnt signaling network could be useful targets for diagnosis and prognostic stratification of disease.