Erik Veskimäe

Updated 2016 EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer

CONTEXT Invasive bladder cancer is a frequently occurring disease with a high mortality rate despite optimal treatment. The European Association of Urology (EAU) Muscle-invasive and Metastatic Bladder Cancer (MIBC) Guidelines are updated yearly and provides information to optimise diagnosis, treatment, and follow-up of this patient population. OBJECTIVE To provide a summary of the EAU guidelines for physicians and patients confronted with muscle-invasive and metastatic bladder cancer. EVIDENCE ACQUISITION An international multidisciplinary panel of bladder cancer experts reviewed and discussed the results of a comprehensive literature search of several databases covering all sections of the guidelines. The panel defined levels of evidence and grades of recommendation according to an established classification system. EVIDENCE SYNTHESIS Epidemiology and aetiology of bladder cancer are discussed. The proper diagnostic pathway, including demands for pathology and imaging, is outlined. Several treatment options, including bladder-sparing treatments and combinations of treatment modalities (different forms of surgery, radiation therapy, and chemotherapy) are described. Sequencing of these modalities is discussed. Potential indications and contraindications, such as comorbidity, are related to treatment choice. There is a new paragraph on organ-sparing approaches, both in men and in women, and on minimal invasive surgery. Recommendations for chemotherapy in fit and unfit patients are provided including second-line options. Finally, a follow-up schedule is provided. CONCLUSIONS The current summary of the EAU Muscle-invasive and Metastatic Bladder Cancer Guidelines provides an up-to-date overview of the available literature and evidence dealing with diagnosis, treatment, and follow-up of patients with metastatic and muscle-invasive bladder cancer. PATIENT SUMMARY Bladder cancer is an important disease with a high mortality rate. These updated guidelines help clinicians refine the diagnosis and select the appropriate therapy and follow-up for patients with metastatic and muscle-invasive bladder cancer.

The Impact of the Extent of Lymphadenectomy on Oncologic Outcomes in Patients Undergoing Radical Cystectomy for Bladder Cancer: A Systematic Review

CONTEXT Controversy exists regarding the therapeutic value of lymphadenectomy (LND) in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). OBJECTIVE To systematically review the relevant literature assessing the impact of LND on oncologic and perioperative outcomes in patients undergoing RC for MIBC. EVIDENCE ACQUISITION Medline, Medline In-Process, Embase, the Cochrane Central Register of Controlled Trials, and the Latin American and Caribbean Center on Health Sciences Information (LILACS) were searched up to December 2013. Comparative studies reporting on no LND, limited LND (L-LND), standard LND (S-LND), extended LND (E-LND), superextended LND (SE-LND), and oncologic and perioperative outcomes were included. Risk-of-bias and confounding assessments were performed. EVIDENCE SYNTHESIS Twenty-three studies reporting on 19,793 patients were included. All but one study were retrospective. Planned meta-analyses were not possible because of study heterogeneity; therefore, data were synthesized narratively. There were high risks of bias and confounding across most studies as well as extreme heterogeneity in the definition of the anatomic boundaries of LND templates. All seven studies comparing LND with no LND favored LND in terms of better oncologic outcomes. Seven of 14 studies comparing (super)extended LND with L-LND or S-LND reported a beneficial outcome for (super)extended LND in at least a subset of patients. No difference in outcome was reported in two studies comparing E-LND and S-LND. The comparative harms of different extents of LND remain unclear. CONCLUSIONS Although the quality of the data was poor, the available evidence indicates that any kind of LND is advantageous over no LND. Similarly, E-LND appears to be superior to lesser degrees of dissection, while SE-LND offered no additional benefits. It is hoped that data from ongoing randomized clinical trials will clarify remaining uncertainties. PATIENT SUMMARY The current literature suggests that removal of lymph nodes in bladder cancer surgery is beneficial and might result in better outcomes in terms of prolonging survival; however, the quality of the available studies is poor, and high-quality studies are needed.

Detection of prostate cancer by an electronic nose: a proof of principle study.

PURPOSE We evaluate the ability of an electronic nose to discriminate prostate cancer from benign prostatic hyperplasia using urine headspace, potentially offering a clinically applicable noninvasive and rapid diagnostic method. MATERIALS AND METHODS The ChemPro® 100-eNose was used to discriminate prostate cancer from benign prostatic hyperplasia using urine sample headspace. Its performance was tested with 50 patients with confirmed prostate cancer and 24 samples from 15 patients with benign prostatic hyperplasia (15 patients provided urine preoperatively and 9 patients provided samples 3 months postoperatively) scheduled to undergo robotic assisted laparoscopic radical prostatectomy or transurethral resection of prostate, respectively. The patients provided urine sample preoperatively and those with benign prostatic hyperplasia also provided samples 3 months postoperatively to be used as a pooled control sample population. A discrimination classifier was identified for eNose and subsequently, sensitivity and specificity values were determined. Leave-one-out cross-validation was performed. RESULTS Using leave-one-out cross-validation the eNose reached a sensitivity of 78%, a specificity of 67% and AUC 0.77. CONCLUSIONS The electronic nose is capable of rapidly and noninvasively discriminating prostate cancer and benign prostatic hyperplasia using urine headspace in patients undergoing surgery.

Analysis of free, mono- and diacetylated polyamines from human urine by LC-MS/MS.

Polyamines are promising biochemical markers of cancer and many other pathophysiological conditions, and thus their concentrations in biological fluids are a matter of interest. However, since the concentrations of these compounds are low, their quantitation is typically based on methods requiring laborious sample preparation. Here we developed and validated an LC-MS/MS method to analyze simultaneously free (DAP, PUT, CAD, SPD, SPM) monoacetylated (AcPUT, AcCAD, N(1)AcSPD, N(8)AcSPD, N(1)AcSPM) and diacetylated (DiAcPUT, DiAcCAD, DiAcSPD, DiAcSPM) polyamines from human urine without the need for derivatization. Deuterium labeled polyamines were the internal standards for each analyte. Diluted urine samples spiked with internal standards were filtered through a strong anion exchange resin prior to LC-MS/MS analysis. The chromatographic separation of 14 polyamines was achieved in 12min on C18 column with 0.1% HFBA (v/v) as the ion-pairing agent and a water-acetonitrile gradient. Ionization was performed with positive electrospray ionization (ESI) and detection was with a triple quadrupole mass spectrometer with selected reaction monitoring. Calibration curves ranged from up to 5 to 10,000nM. The accuracy and precision of the method were determined using urine based quality control samples, and matrix effects were examined by using standard addition methods. This novel method is suitable for elucidating differences in urinary polyamine excretion in cancer patients and healthy humans.

Detection of smell print differences between nonmalignant and malignant prostate cells with an electronic nose

AIM To determine whether an electronic nose can differentiate cultured nonmalignant and malignant prostatic cells from each other and whether the smell print is secreted to the surrounding medium. MATERIALS & METHODS Prostatic nonmalignant (EP-156T and controls) and malignant (LNCaP) cell lines, as well as conditioned and unconditioned media, were collected. The smell prints of the samples were analyzed by a ChemPro(®) 100 electronic nose device. The data were normalized and dimension reduction was conducted. The samples were classified and misclassification rates were calculated. RESULTS The electronic nose differentiated the nonmalignant and malignant cell lines from each other, achieving misclassification rates of 2.9-3.6%. Cells did not differ from the conditioned medium but differed from the unconditioned medium (misclassification rates: 0.0-25.6%). CONCLUSION Malignant and nonmalignant prostatic cell lines have distinct smell prints. Prostatic cancer cells seem to modify the smell print of their medium.

Systematic review of the oncological and functional outcomes of pelvic organ-preserving radical cystectomy (RC) compared with standard RC in women who undergo curative surgery and orthotopic neobladder substitution for bladder cancer

Pelvic organ‐preserving radical cystectomy (POPRC) for women may improve postoperative sexual and urinary functions without compromising the oncological outcome compared with standard radical cystectomy (RC).

Outcomes of Early Endoscopic Realignment Versus Suprapubic Cystostomy and Delayed Urethroplasty for Pelvic Fracture-related Posterior Urethral Injuries: A Systematic Review

CONTEXT The evidence base for optimal acute management of pelvic fracture-related posterior urethral injuries needs to be reviewed because of evolving endoscopic techniques. The current standard of care is suprapubic cystostomy followed by delayed urethroplasty. OBJECTIVE To systematically review the evidence base comparing early endoscopic realignment with cystostomy and delayed urethroplasty regarding stricture rate, the need for subsequent procedures, and functional outcomes. EVIDENCE ACQUISITION A systematic search in Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Review, and www.clinicaltrials.gov without time or language limitations. Both medical subject heading and free text terms as well as variations of root word were searched. Randomised controlled trials (RCTs), nonrandomised comparative studies and single-arm case series were included, as long as ≥10 patients were enrolled. Data were narratively synthesised in light of methodological and clinical heterogeneity. The risk of bias of each included study was assessed. EVIDENCE SYNTHESIS No RCTs were found. Six nonrandomised comparative studies and met inclusion criteria and were selected for data extraction. Noncomparative studies with more than 10 participants were included resulting in seven eligible studies. From the comparative papers the results of 219 patients were reported: 142 in the realignment group and 77 in the group undergoing cystostomy with delayed repair. The noncomparative studies reported on a further 150 cases. An overall stricture rate of 49% was evident in the endoscopic realignment group. Of these patients, 50% (28.1% overall) could be managed by endoscopic procedures and 40.3% (18.5% of intervention group) required anastomotic repair. CONCLUSIONS No RCTs were found and the included nonrandomised studies have heterogeneous populations and a high degree of bias. About half of the patients were free of stricture and thus did not undergo delayed urethroplasty in case early endoscopic realignment had been performed. PATIENT SUMMARY This systematic review of literature of urethral trauma revealed there are no well conducted comparative studies of newer endoscopic treatments versus standard treatments which include more extensive surgery. The results of the reports we selected based on specific characteristics are often influenced by variable factors. After careful analysis of these results we can conclude that the newer endoscopic techniques might resolve the risk of urethral injury due to pubic fractures in about half of the patients. Because of various confounders we cannot identify those patients who would benefit from this procedure or who might be possibly harmed.

11C-acetate PET/MRI in bladder cancer staging and treatment response evaluation to neoadjuvant chemotherapy: a prospective multicenter study (ACEBIB trial)

BackgroundTo evaluate the accuracy of 11C-acetate Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) in bladder cancer (BC) staging and monitoring response to neoadjuvant chemotherapy (NAC).MethodsEighteen patients were prospectively enrolled. Fifteen treatment naive patients underwent 11C-acetate PET/MRI before transurethral resection of bladder tumor (TUR-BT) for primary tumor evaluation. Five patients with muscle invasive BC were imaged after NAC and prior to radical cystectomy (RC) with extended pelvic lymph node dissection (ePLND) for NAC treatment response evaluation. Two patients were part of both cohorts. 11C-acetate PET/MRI findings were correlated with histopathology. Accuracy for lymph node detection was evaluated on patient and the ePLND template (10 regions) levels.ResultsThe sensitivity, specificity and accuracy of 11C-acetate PET/MRI for the detection of muscle invasive BC was 1.00, 0.69 and 0.73 while the area under the receiver operating characteristic curve (95% confidence interval) was 0.85 (0.55–1.0), respectively. All five NAC patients underwent chemotherapy as planned and 11C-acetate PET/MRI correctly staged three patients, overstaged one and understaged one patient compared with RC and ePLND findings. A total of 175 lymph node were removed, median of 35 (range, 27–43) per patient in five patients who had RC and ePLND while 12 (7%) harboured metastases. Sensitivity, specificity, accuracy and AUC for N-staging were 0.20, 0.96, 0.80 and 0.58 on the ePLND template (10 regions) level.Conclusions11C-acetate PET/MRI is feasible for staging of BC although sensitivity for the detection of nodal metastases is low. Monitoring response to NAC shows promise and warrants evaluation in larger studies.Trial registrationClinicalTrials.gov Identifier: NCT01918592, registered August 8 2013

Is Nonoperative Management the Best First-line Option for High-grade Renal trauma? A Systematic Review

CONTEXT The management of high-grade (Grade IV-V) renal injuries remains controversial. There has been an increase in the use of (NOM) but limited data exists comparing outcomes with open surgical exploration. OBJECTIVE To conduct a systematic review to determine if NOM is the best first-line option for high-grade renal trauma in terms of safety and effectiveness. EVIDENCE ACQUISITION Medline, Embase, and Cochrane Library were searched for all relevant publications, without time or language limitations. The primary harm outcome was overall mortality and the primary benefit outcome was renal preservation rate. Secondary outcomes included length of hospital stay and complication rate. Single-arm studies were included as there were few comparative studies. Only studies with more than 50 patients were included. Data were narratively synthesised in light of methodological and clinical heterogeneity. The risk of bias of each included study was assessed. EVIDENCE SYNTHESIS Seven nonrandomised comparative and four single-arm studies were selected for data extraction. Seven hundred and eighty-seven patients were included from the comparative studies with 535 patients in the NOM group and 252 in the open surgical exploration group. A further 825 patients were included from single-arm studies. Results from comparative studies: overall mortality: NOM (0-3%), open surgical exploration (0-29%); renal preservation rate: NOM (84-100%), open surgical exploration (0-82%); complication rate: NOM (5-32%), open surgical exploration (10-76%). Overall mortality and renal preservation rate were significantly better in the NOM group whereas there was no statistical difference with regard to complication rate. Length of hospital stay was found be significantly reduced in the NOM group. Patients in the open surgical exploration group were more likely to have Grade V injuries, have a lower systolic blood pressure, and higher injury severity score on admission. CONCLUSIONS No randomised controlled trials were identified and significant heterogeneity existed with regard to outcome reporting. However, NOM appeared to be safe and effective in a stable patient with a higher renal preservation rate, a shorter length of stay, and a comparable complication rate to open surgical exploration. Overall mortality was higher in the open surgical exploration group, though this was likely due to selection bias. PATIENT SUMMARY The data of this systematic review suggest nonoperative management continues to be favoured to surgical exploration in the management of high-grade renal trauma whenever possible. However, comparisons between both interventions are difficult as patients who have surgery are often more seriously injured than those managed nonoperatively, and existing studies do not report on outcomes consistently.