Hemopatch® is effective and safe to use: real-world data from a prospective European registry study.

Surgical procedures are often impeded by bleeding and/or leakage of body fluids. These complications cannot always be resolved by conventional surgical techniques. Hemopatch® is a hemostatic patch that also functions as a sealant. Here we document the effectiveness and safety of Hemopatch® for routine procedures of multiple surgical disciplines. To this end, we performed a prospective, multicenter, single-arm, observational registry study. Patients were eligible if they had received Hemopatch® during an open or minimally invasive procedure in one of these specialties: hepatobiliary, cardiovascular, urological, neurological/spinal, general, or lung surgery. Patients were excluded if they had a known hypersensitivity to bovine proteins or brilliant blue, intraoperative pulsatile or severe bleeding and/or infection at the target application site (TAS). The primary endpoint for intraoperative effectiveness was hemostasis assessed as the percentage of patients achieving hemostasis within 2 min and the percentage of patients achieving hemostasis without re-bleeding at the time of surgical closure. The registry enrolled 621 patients at 23 study sites in six European countries. Six hundred twenty patients had completed follow-up information. Hemostasis within 2 min was achieved at 463 (74.5%) of all 621 TASs. Hemostasis without re-bleeding was observed at 620 (99.8%) TASs. Adverse events were reported in 64 patients (10.3%). This Hemopatch® registry shows that Hemopatch® efficiently establishes hemostasis and sealing in a variety of surgical specialties, including minimally invasive procedures. Furthermore, we provide evidence for the safety of Hemopatch® across all the specialties included in the registry. This study is registered at clinicaltrials.gov: NCT03392662.

[The Onkonet database: taking stock of an Internet-based, multi-centre database on surgical prostate cancer treatment]. / Die Onkonet-Datenbank: Bilanz einer Internet-basierten, multizentrischen Dokumentationsplattform zur Erfassung der operativen Therapie des Prostatakarzinoms.

BACKGROUND: The Onkonet database has been developed and coordinated by the Berliner Tumorzentrum e. V. (http://www.prostata-ca.net) and contains data on pre-, peri- and postoperative parameters of radical prostatectomy documented since January 2005. With its user-friendly interface and its integrated benchmarking tool, the main goal of Onkonet was to outline and improve the surgical care of prostate cancer patients in Germany. This study aimed to analyse all Onkonet data documented from the beginning of the project until June 2018. We focused on the completeness and plausibility of data to investigate and define the possibilities and limits of further analyses. PATIENTS AND METHODS: All patients who underwent radical prostatectomy in one of the urological clinics participating in this project until June 2018 were included in this retrospective study. The completeness of all documented patient data was analysed using Excel 2013. The statistical analysis was descriptive. RESULTS: A total of 21 474 patients were documented in Onkonet. 58,6 % (12 591) of them had a complete dataset including date of birth, date of surgery, dates of hospitalisation and discharge, initial PSA value, Gleason score of the biopsy, clinical T stage, pathological T stage, pathological Gleason score, as well as information on the surgical technique. Mean completeness of pre-operative parameters was 26,8 %, of hospitalisation parameters 64,5 %, and of pathological parameters 58,1 %. Amongst these, the documentation of the pathological T stage was complete in 80,1 %, documentation of N stage in 78,8 %, of M stage in 74,8 %, of pathological Gleason Score in 78,7 %, and of R1 status in 78,7 %. Completeness of follow-up data was 8,1 %, with PSA data being available in 27,2 %, continence data in 23,0 %, and potency data in 13,9 %. CONCLUSIONS: Comprising 21 474 documented patients and over 200 parameters, Onkonet is one of the most comprehensive clinical registers for the documentation of prostate cancer patients in Germany. The data analysis showed that the limitations of such a database are mainly due to the high number of parameters and the high susceptibility to errors due to manual data submission.

A call for HoLEP: en-bloc vs. two-lobe vs. three-lobe.

PURPOSE: Holmium Laser Enucleation of the Prostate (HoLEP) is widely accepted as standard laser enucleation technique for patients with benign prostate obstruction (BPO). Initially developed as a three-lobe enucleation technique, several modifications have been published. Comparison of the enucleation techniques is lacking. Therefor we aimed to compare outcomes of three enucleation techniques (en-bloc vs. two-lobe vs. three-lobe). MATERIAL AND METHODS: We prospectively collected data of 600 patients treated between 01/2017 and 12/2017 with HoLEP for BPO. Patients were randomised to either enbloc, two-lobe, or three-lobe enucleation, respectively. Data collection consisted of parameters on operation time, perioperative parameters, and functional outcomes. Univariate and multivariate analyses (ANOVA-test for continuous variables; Chi2-test for categorical variables) were performed regarding differences between the three enucleation techniques. RESULTS: Patient characteristics were not significantly different (all p > 0.05). Significant differences were observed with respect to overall operation time (en-bloc vs. two-lobe vs. three-lobe: 40.5 vs. 40.7 vs. 47.9, respectively; p < 0.001), speed (g/min.) (en-bloc vs. two-lobe vs. three-lobe, 1.82 vs. 1.76 vs. 1.67, respectively; p 0.006), and enucleation time (en-bloc vs. two-lobe vs. three-lobe: 31.7 vs. 32 vs. 37.7, respectively; p < 0.001). When solely comparing en-bloc vs. two-lobe enucleation, differences in terms of enucleation time, operation time, and speed were not significantly different (p 0.8, 0.9, and 0.2, respectively). Postoperative outcomes were not significantly different. CONCLUSION: All three HoLEP enucleation techniques show similar postoperative outcomes. However, enbloc and two-lobe enucleation are significantly faster with respect to enucleation, overall operation time, and speed compared to the three-lobe technique.

Perioperative Safety in Patient Under Oral Anticoagulation During Holmium Laser Enucleation of the Prostate.

INTRODUCTION AND OBJECTIVES: To evaluate the safety of holmium laser enucleation of the prostate (HoLEP) in patients on oral anticoagulation (OA) with respect to intra- and postoperative bleeding complications. METHODS: Between January 2013 and October 2016, 2178 patients were included in this study, of whom 94 received direct oral anticoagulants (DOACs) and 151 received vitamin K antagonists (VKAs) before HoLEP. All patients either ceased OA (DOACs) or were bridged subtherapeutically (VKAs, international normalized ratio <2) during surgery. These patients were compared to a sample size of 1933 nonanticoagulated patients. RESULTS: A significant longer postoperative stay was noted for the patients on DOACs (5.2 [4-6] days) and VKAs (5.3 [4-5] days) compared to the control group (4.5 [4-4] days). The mean drop in hemoglobin was significantly higher in the VKA group compared to the DOAC and control group. There was a significantly higher rate of postoperative bladder tamponades/secondary coagulation in patients on OA with 6 (7.9%)/3 (3.9%) patients in the DOAC group, 10 (7.4%)/6 (4.4%) patients in the VKA group compared to 37 (2.2%)/21 (2.1%) patients in the control group, respectively (p < 0.001). Eight patients required blood transfusions with a distribution of 1 (1.3%), 3 (2.2%), and 4 (0.2%) patients in the DOAC, VKA, and control group, respectively (p < 0.001). CONCLUSIONS: Our findings indicate that bridged patients who's DOACs and VKAs were ceased before HoLEP are at higher risk of intra- and postoperative bleeding complications. Nonetheless, HoLEP appears to be a safe and effective procedure in those patients.

Assessing the clinical benefit of a nomogram to predict specimen-confined disease at radical prostatectomy in patients with high-risk prostate cancer: An external validation.

OBJECTIVE: The objective of the current study was to test generalizability and clinical value of a recently published nomogram to predict specimen-confined disease (SCD, pT2-pT3a+R0+pN0) at radical prostatectomy (RP) in patients with clinical high-risk prostate cancer (HRPCa). The nomogram allows improved decision making with curative intent within this heterogeneous patient cohort, which is important, as RP in patients with clinical HRPCa remains a topic of controversy. METHODS: We externally validated the nomogram in 1,669 men with clinical HRPCa who underwent RP and extended pelvic lymph node dissection between 1992 and 2011. A Kaplan-Meier analysis to estimate 5- and 10-year biochemical recurrence-free survival was performed. To investigate the SCD model׳s performance, the previously reported regression coefficients of the SCD nomogram were applied. Within loess calibration plots, the extent of overestimation or underestimation was graphically explored. Finally, decision curve analysis (DCA) to assess the clinical value of the SCD nomogram was performed. RESULTS: Overall, 49% of men showed SCD after RP. The 5- and 10-year biochemical recurrence rates for men with SCD were 66% and 56%, respectively, vs. 32% and 20%, respectively, for men without SCD (log-rank test P<0.001). External validation demonstrated comparable accuracy in relation to accuracy derived from internal validation (68.1% vs. 72.0%). Calibration was suboptimal, showing a tendency to underestimate SCD probability. In DCA, the nomogram׳s usage was associated with a clinical net benefit relative to both treating all and none. CONCLUSIONS: Within our cohort, the nomogram׳s use was associated with a clinical net benefit according to DCA. However, one-third of men were falsely classified as having SCD or non-SCD. Nevertheless, in the absence of superior tools, the SCD nomogram represents a useful clinical decision aid.

Quantum Critical Elasticity.

We discuss elastic instabilities of the atomic crystal lattice at zero temperature. Because of long-range shear forces of the solid, at such transitions the phonon velocities vanish, if at all, only along certain crystallographic directions, and, consequently, the critical phonon fluctuations are suppressed to a lower dimensional manifold and governed by a Gaussian fixed point. In the case of symmetry-breaking elastic transitions, a characteristic critical phonon thermodynamics arises that is found, e.g., to violate Debye's T(3) law for the specific heat. We point out that quantum critical elasticity is triggered whenever a critical soft mode couples linearly to the strain tensor. In particular, this is relevant for the electronic Ising-nematic quantum phase transition in a tetragonal crystal as discussed in the context of certain cuprates, ruthenates, and iron-based superconductors.

Laparoscopic versus open partial nephrectomy for clinical T1 renal masses: no impact of surgical approach on perioperative complications and long-term postoperative quality of life.

OBJECTIVES: Beyond oncological safety, consideration of 30-day complications according to Clavien-Dindo, as well as postoperative quality of life (QoL) after nephron-sparing surgery for clinical T1 renal masses, represents important factors for treatment decision counseling. The objective of this study was to compare the effect of laparoscopic versus open partial nephrectomy (LPN vs. OPN) on 30-day complications and long-term postoperative QoL for clinical T1 renal masses. METHODS: Retrospective, longitudinal analysis of 293 patients treated with either LPN versus OPN for T1 renal masses. The investigated endpoints were 30-day Clavien-Dindo complications and health-related QoL (EORTC QLQ-C30). Respectively, logistic and linear regression models analyzed the effect of surgical partial nephrectomy approach on endpoints. RESULTS: Overall complication rates were similar in patients undergoing OPN or LPN (16.1 vs. 14.6 %, p = 0.8). Significantly less major complications (2.4 vs. 10.4 %, p = 0.025) occurred after LPN. Despite a shorter convalescence period for LPN patients (p = 0.035), in uni- and multivariable analyses, surgical approach was not associated with 30-day complications nor long-term differences in QoL (all p > 0.05). CONCLUSIONS: Despite a faster recovery time after LPN, our findings suggest that LPN and OPN are equivalent with regard to 30-day Clavien-Dindo complication rates and long-term QoL.

EORTC progression score identifies patients at high risk of cancer-specific mortality after radical cystectomy for secondary muscle-invasive bladder cancer.

BACKGROUND: The aim of this study was to develop a risk stratification of patients with muscle-invasive bladder cancer (MIBC) after radical cystectomy (RC). For this purpose, we compared the cancer-specific mortality (CSM) of patients with primary MIBC and patients with secondary MIBC in different risk groups according to the European Organisation for Research and Treatment of Cancer (EORTC) progression score. PATIENTS AND METHODS: The records of 521 consecutive patients treated with RC for clinical MIBC according to transurethral resection of bladder cancer (TURBT) diagnosis were reviewed. Of the 521 patients, 399 (76.6%) had primary MIBC (study group 1 [SG1]) and 122 (23.4%) had secondary MIBC (study group 2 [SG2]). Patients in SG2 were stratified into risk groups according to the results of the first and last TURBT in non-MIBC using the EORTC progression score. RESULTS: CSM for patients with primary and secondary MIBC did not differ significantly. Patients in SG2 with the highest risk for tumor stage progression at time of the first and last TURBT in non-MIBC showed a significantly higher CSM after RC compared with patients with low-to-intermediate risk and compared with patients in SG1. In multivariable analyses, stage pT 3/4 (hazard ratio [HR], 2.12; P < .001), lymphovascular invasion (LVI) (HR, 3.47; P < .001), female sex (HR, 1.35; P = .048), and time from diagnosis of MIBC to RC > 90 days (HR, 2.07; P < .001) were significantly associated with higher CSM. CONCLUSION: Risk stratification by the EORTC progression score can help to identify those patients with the highest risk of CSM after progression to MIBC and thus enable us to offer these patients a multimodal treatment. Our results need to be verified in large prospective studies.

Gender-specific differences in cancer-specific survival after radical cystectomy for patients with urothelial carcinoma of the urinary bladder in pathologic tumor stage T4a.

BACKGROUND: Bladder cancer (UCB) staged pT4a show heterogeneous outcome after radical cystectomy (RC). No risk model has been established to date. Despite gender-specific differences, no comparative studies exist for this tumor stage. MATERIALS AND METHODS: Cancer-specific survival (CSS) of 245 UCB patients without neoadjuvant chemotherapy staged pT4a, pN0-2, M0 after RC were analyzed in a retrospective multi-center study. Seventeen patients were excluded from further analysis due to carcinoma in situ (CIS) of the prostatic urethra and/or positive surgical margins. Average follow-up period was 30 months (IQR: 14-45). The influence of different clinical and histopathologic variables on CSS was determined through uni- and multivariate Cox regression analyses. Two risk groups were generated using factors with independent effect in multivariate models. Internal validity of the prediction model was evaluated by bootstrapping. RESULTS: Eighty-four percent of the patients (n = 192) were male; 72% (n = 165) showed lymphovascular invasion (LVI). The 5-year CSS rate was 31%, and significantly different between male and female (35% vs. 15%, P = 0.003). Multivariate Cox regression modeling, female gender (HR = 1.83, P = 0.008), LVI (HR = 1.92, P = 0.005), and absence of adjuvant chemotherapy (HR = 0.61, P = 0.020) significantly worsened CSS. Two risk groups were generated using these 3 criteria, which differed significantly between each other in CSS (5-year-CSS: 46% vs. 12%, P < 0.001). The c-index value of the risk model was 0.61 (95% CI: 0.53-0.68, P < 0.001). CONCLUSIONS: Prognosis in UCB staged pT4a is heterogeneous. Female gender and LVI are adverse factors. Adjuvant chemotherapy seems to improve outcome. The present analysis establishes the first risk model for this demanding tumor stage.

Mott metal-insulator transition on compressible lattices.

The critical properties of the finite temperature Mott end point are drastically altered by a coupling to crystal elasticity, i.e., whenever it is amenable to pressure tuning. Similar as for critical piezoelectric ferroelectrics, the Ising criticality of the electronic system is preempted by an isostructural instability, and long-range shear forces suppress microscopic fluctuations. As a result, the end point is governed by Landau criticality. Its hallmark is, thus, a breakdown of Hooke's law of elasticity with a nonlinear strain-stress relation characterized by a mean-field exponent. Based on a quantitative estimate, we predict critical elasticity to dominate the temperature range ΔT*/T(c)≃8%, close to the Mott end point of κ-(BEDT-TTF)(2)X.

Analysis of sex differences in cancer-specific survival and perioperative mortality following radical cystectomy: results of a large German multicenter study of nearly 2500 patients with urothelial carcinoma of the bladder.

BACKGROUND: Outcome of patients with urothelial carcinoma of the bladder (UCB) varies between sexes. Although overall incidence is higher in men, cancer-specific survival (CSS) has been suggested to be lower in women. Although the former effect is attributed to greater exposure to carcinogens in men, the latter has not been elucidated. OBJECTIVES: The aim of the study was to identify sex-specific outcomes based on one of the largest databases of patients with UCB who underwent radical cystectomy (RC). METHODS: This retrospective multicenter series comprised 2483 patients in Stage M0 who underwent RC for UCB from 1989 to 2008; 20.4% of patients were women. The impact of sex on CSS in the entire study group and in specific subgroups was analyzed. The median follow-up time was 42 months (interquartile range, 21-79). RESULTS: Histopathologic criteria of pathologic tumor (pT), pathologic nodal (pN), grade, lymphovascular invasion (LVI), and associated carcinoma in situ (CIS) of the study did not differ between sexes. The percentage of female patients increased over time. Five-year CSS in female patients was significantly lower than in male patients (60% vs 66%; P = 0.005). In multivariate analysis adjusted to other covariates, tumor stage ≥pT3 (hazard ratio [HR] = 2.44; P < 0.001), positive pN status (HR = 1.91; P < 0.001), LVI (HR = 1.48; P < 0.001), lower count of lymph nodes removed (HR = 0.98; P = 0.002), older age (HR = 1.01; P < 0.001), and female gender (HR = 1.26; P = 0.011) had an independent impact on CSS. Deterioration of CSS in female patients was pronounced when LVI was present (HR = 1.57; P < 0.001) and when RC was performed in the earlier time period (HR = 2.44; P < 0.001). However, women showed significantly lower perioperative mortality (within 90 days after RC) compared with men. CONCLUSIONS: After RC for UCB, cancer-specific mortality was higher in female patients; this disadvantage was more pronounced in earlier time periods. In addition, worse outcome of women with verified LVI was shown to be comparable with men. These findings were suggestive of different tumor biology and potentially unequal access to timely RC in earlier time periods because of reduced awareness of UCB in women. Further studies are required to improve UCB outcome in both sexes, notably in female patients.

Transurethral holmium laser enucleation versus transurethral resection of the prostate and simple open prostatectomy--which procedure is faster?

PURPOSE: The longer operative time of holmium laser enucleation of the prostate compared to transurethral resection of the prostate or simple open prostatectomy reported in the literature might have been biased by the unavailability of a soft tissue morcellator, limited surgical experience with holmium laser prostate enucleation or the fact that significantly more tissue was removed by enucleation than by resection. We objectively compared the resection speed of contemporary holmium laser enucleation vs transurethral resection of the prostate and of holmium laser enucleation vs simple open prostatectomy. MATERIALS AND METHODS: The study cohort consisted of 100 cases of transurethral prostate resection and 60 of simple open prostatectomy from our previous randomized, controlled trials. These cases were subjected to matched pair analysis with greater than 1,000 from our prospective contemporary database on holmium laser prostate enucleation. Exact matches were made for the same amount of resected tissue. In all contemporary holmium laser enucleation cases a mechanical soft tissue morcellator was used. We calculated and compared the specific resection speed in gm per minute and operative time for the same amount of resected tissue. RESULTS: In groups 1 and 2 we matched 99 exact laser enucleation-transurethral resection pairs and 53 exact laser enucleation-simple open prostatectomy pairs, respectively. Resection speed and operative time for laser enucleation were statistically significantly faster than for resection (0.61 vs 0.51 gm per minute and 62 vs 73 minutes, p <0.01) and similar to those of simple open prostatectomy (0.92 vs 1.0 gm per minute and 101 vs 90 minutes, respectively, p ≥0.21). CONCLUSIONS: Resection speed seems to be an objective criterion for comparing the efficacy of prostatic tissue removal. Based on resection speed holmium laser enucleation of the prostate is faster than transurethral resection of the prostate and similar to simple open prostatectomy.

External validation of a risk model to predict recurrence-free survival after radical cystectomy in patients with pathological tumor stage T3N0 urothelial carcinoma of the bladder.

PURPOSE: Patients with stage pT3N0 urothelial bladder cancer vary in outcome after radical cystectomy. To improve prognosis estimation a model was recently developed that defines 3 risk groups for recurrence-free survival based on pT substaging, lymphovascular invasion and positive surgical margin. We present what is to our knowledge the first external validation of this risk model. MATERIALS AND METHODS: Analogous to the risk model derivation cohort our study group comprised 472 patients with stage pT3, pN0, cM0 disease without perioperative chemotherapy and with a median followup of 42 months (IQR 20-75). The primary end point was recurrence-free survival. The effect of variables was determined by univariate and multivariate Cox regression analysis, and predictive accuracy was determined by ROC analysis. RESULTS: Stage pT3aN0 and pT3bN0 cases showed significantly different recurrence-free survival after 5 years (51% vs 29%, p<0.001). In the multivariate Cox model pT3 substage (HR 1.86, p<0.001), lymphovascular invasion (HR 1.48, p=0.002), positive surgical margins (HR 1.90, p=0.030) and patient age with a dichotomy at 70 years (HR 1.51, p=0.001) had an independent effect on recurrence-free survival. In the low (221 patients or 47%), intermediate (184 or 39%) and high (67 or 14%) risk groups the 5-year recurrence-free survival rate was 55%, 45% and 13%, respectively (p<0.001). The concordance index of the risk model to predict recurrence-free survival was 0.64 (95% CI 0.59-0.69). CONCLUSIONS: This user friendly risk model can be recommended to estimate prognosis in patients with stage pT3N0 after radical cystectomy. Patients at high risk showed clearly compromised recurrence-free survival and should be included in adjuvant therapy studies.

Gender-dependent cancer-specific survival following radical cystectomy.

OBJECTIVE: To assess the impact of detailed clinical and histopathological criteria on gender-dependent cancer-specific survival (CSS) in a large consecutive series of patients following radical cystectomy (RCE) for muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: Between 1992 and 2007, 388 men and 133 women (25.5%) underwent RCE for MIBC. A prospectively maintained database was analysed retrospectively. Uni- and multivariable Cox-regression analyses calculated the impact of detailed clinical and histopathological criteria on CSS. Median follow-up was 59 months (2-162). RESULTS: Among clinical and histopathological parameters, only type of urinary diversion differed between men and women. In univariable analysis, CSS did not differ between genders. In multivariable Cox-regression analysis, advanced pT-stage (HR = 2.12; P < 0.001), lymphovascular invasion (LVI) (HR = 3.47; P < 0.001), time interval between diagnosis of MIBC and RCE exceeding 90 days (HR = 2.07; P < 0.001) and female gender (HR = 1.35; P = 0.048) were related to reduced CSS. In separate multivariable Cox-models for time period of surgery between 1992 an 1999 (HR = 1.52; P = 0.050), age ≤55 years (HR = 3.00; P = 0.022), presence of LVI (HR = 1.45; P = 0.031) and female gender were associated with independent reduced CSS. CONCLUSION: Established clinical and histopathological parameters do not differ significantly between both genders in the present series. Reduced CSS in women is present in historic cohorts possibly suggesting improvement in management over the last years. In particular, female gender has a significant negative impact on CSS in patients younger of age and with positive LVI status possibly suggesting different clinical phenotypes.

Multicenter evaluation of the prognostic value of pT0 stage after radical cystectomy due to urothelial carcinoma of the bladder.

OBJECTIVE: •To evaluate the characteristics and long-term outcome of patients with pT0 stage after radical cystectomy (RC) for urothelial carcinoma of the urinary bladder (UCB). PATIENTS AND METHODS: •Clinical and pathological records of 2403 patients treated with RC for UCB were collected in a multi-institutional database. •The patients met the following criteria: clinical tumour stage cTa-cT2, cN0, cM0, no neoadjuvant chemotherapy or radiotherapy. •Overall (OS) and cancer-specific survival rates (CSS) were calculated for the various clinical tumour stages in relation to their corresponding pathological tumour stage in the RC sample. •Further to this, a multivariable prediction model was developed based on the available clinical data to estimate the probability of tumour stage pT0. RESULTS: •The mean follow-up was 53 months and 132 patients (5.5%) were stage pT0. •Patients with stage cT2-pT0 had a 5-year CSS of 87% vs 69% for cT2-pT2 (P= 0.012) and 57% for cT2-pT+ (P < 0.001). •In a multivariable Cox-model, stage pT0 led to a significant reduction of cancer-specific mortality (hazard ratio0.27; 95% confidence interval 0.12-0.61). •A logistical regression model identified clinical tumour stage (advantage for non-invasive stages) and transurethral resection of the urinary bladder (TURB) time frame (advantage for more recent surgery) as independent predictors for stage pT0. CONCLUSIONS: •In muscle-invasive clinical tumour stages, patients with pathological tumour stage pT0 form a subgroup showing a significantly better CSS. •A radical TURB is, assumedly, not causative of this improved survival rate, but rather it is that individual tumour characteristics allow for complete tumour eradication through the TURB procedure. •A TURB with R0 resection is, as such, only a sign of a better tumour prognosis.

Pathological upstaging detected in radical cystectomy procedures is associated with a significantly worse tumour-specific survival rate for patients with clinical T1 urothelial carcinoma of the urinary bladder.

OBJECTIVE: Due to their variable oncological course, clinical stage T1 (cT1) urothelial carcinomas of the bladder (UCBs) are the subject of controversial discussion with regard to indication for radical cystectomy (RC).This study aimed to evaluate the frequency and prognosis of upstaging in patients undergoing RC due to UCB. MATERIAL AND METHODS: Clinical and pathological records of 607 patients, having undergone RC for treatment of UCB in cT1N0M0, were summarized in a multi-institutional database. Cancer-specific survival (CSS) and overall survival (OS) rates were calculated. A multivariable prognostic model predicting the possibility of an upstaging in RC specimens was developed based on clinical information. RESULTS: In 210patients (35%) an upstaging (> pT1 and/or pN+) was detected in the RC specimen. Five-year CSS was 86%, 78%, 60%and 34%, respectively, for tumour stages < pT2N0 (n = 397), pT2N0 (n = 78), > pT2N0 (n = 63)and pN+ (n = 69) (p < 0.001). In a multivariable Cox regression model, pN stage, pT stage and lymphovascular invasion (LVI) revealed an independent influence on CSS (OS: pN, pT, age). An upstaging of cT1 tumours was enhanced by the criteria of G3 tumour grading and absent Tis in the transurethral resection of the bladder (TURB)specimen. Detection of LVI in RC specimens was also independently associated with an upstaging and, therefore, is recommended as a relevant prognostic parameter for the histopathological evaluation of TURB specimens. CONCLUSIONS: More than one-third of patients with cT1 tumours had an upstaging that was associated with significant prognosis deterioration. Further valid markers are required for an early identification of these patients. LVI represents such a criterion and, therefore, should be evaluated in prospectively designed trials with accurate histopathological assessment of TURB specimens.

Lymph node density affects cancer-specific survival in patients with lymph node-positive urothelial bladder cancer following radical cystectomy.

BACKGROUND: The prognosis for patients with lymph node (LN)-positive bladder cancer (BCa) is likely affected by the extent of lymphadenectomy in radical cystectomy (RC) cases. Specifically, the prognostic significance of the LN density (ratio of positive LNs to the total number removed) has been demonstrated. OBJECTIVE: To evaluate the prognostic signature of lymphadenectomy variables, including the LN density, for a large, multicentre cohort of RC patients with LN-positive BCa. DESIGN, SETTING, AND PARTICIPANTS: The clinical and histopathologic data from 477 patients with LN-positive urothelial BCa (pN1-2) were analysed. The median follow-up period for all living patients was 28 mo. MEASUREMENTS: Multivariable Cox regression analysis was used to test the effect of various pelvic lymph node dissection (PLND) variables on cancer-specific survival (CSS) based on colinearity in various models. RESULTS AND LIMITATIONS: The median number of LNs removed was 12 (range: 1-66), and the median number of positive LNs was 2 (range: 1-25). Two hundred ninety (60.8%) of the patients presented with stage pN2 disease. The median and mean LN density was 17.6% and 29% (range: 2.3-100), respectively, where 268 (56.2%) and 209 (43.8%) patients exhibited am LN density of ≤20% and >20%, respectively. In separate multivariable Cox regression models adjusted for age, sex, pTN stage, grade, associated Tis, and adjuvant chemotherapy, the interval-scaled LN density (hazard ratio [HR]: 1.01; p=0.002) and the LN density, ordinal-scaled by 20% (HR: 1.65; p<0.001) exhibit independent effects on CSS. In addition, an independent contribution appears from the pT but not the pN stage. Limitations include surgeon selection bias when determining the extent of lymphadenectomy. CONCLUSIONS: Our results support the prognostic relevance of LN density in patients with LN-positive BCa, where a threshold value of 20% stratifies the population into two prognostically distinct groups. Before LN density is integrated into the clinical decision-making process, these results should be validated by prospective studies with defined LN templates and standardised histopathologic methods.

Association between the number of dissected lymph nodes during pelvic lymphadenectomy and cancer-specific survival in patients with lymph node-negative urothelial carcinoma of the bladder undergoing radical cystectomy.

BACKGROUND: A larger number of dissected lymph nodes (LN) during pelvic lymphadenectomy in patients with muscle-invasive transitional-cell carcinoma of the bladder treated by radical cystectomy (RC) is crucial for exact tumor staging and is associated with a positive oncological outcome. METHODS: Clinical and pathological records of 1291 patients undergoing RC due to LN-negative transitional-cell carcinoma of the bladder were summarized and evaluated in a multi-institutional database. The number of removed LNs and the presence or absence of lymphovascular invasion were assessed. On the basis of multivariate Cox regression analyses, a threshold number of removed LNs was defined that exerted an independent influence on cancer-specific survival (CSS). RESULTS: In multivariate Cox regression models for different numbers of removed LNs, a statistically significant enhancement of CSS could be demonstrated for a LN count of 16. Furthermore, the integration of the dichotomized LN count of 16 resulted in a statistically significantly enhanced predictive ability of the model for CSS. Patients with <16 and ≥16 removed LNs showed CSS rates after 5 years of 72% and 83%, respectively (P = 0.01). In addition, age, sex, pT stage, and lymphovascular invasion had independent influences on CSS in every Cox regression model. CONCLUSIONS: In patients undergoing RC, removal of a higher LN count is associated with an improved oncological outcome. The information resulting from an assessment of lymphovascular invasion and an extended lymphadenectomy is critical for stratification of risk groups and identification of patients who might benefit from adjuvant treatment.

Biochemical recurrence after radical prostatectomy: multiplicative interaction between surgical margin status and pathological stage.

PURPOSE: A positive surgical margin after radical prostatectomy is considered an adverse prognostic feature. However, few groups have explored the potential interaction between surgical margin status and other cancer characteristics, specifically pathological stage. We addressed the first degree of interaction between positive surgical margins and other established adverse predictors of biochemical recurrence after radical prostatectomy. MATERIALS AND METHODS: We used univariate and multivariate analysis to test the effect of surgical margin status on biochemical recurrence in 4,490 patients treated at a single institution between 1992 and 2008. We systematically tested all first-degree interactions between surgical margin status, and pretreatment prostate specific antigen, pT and pN stage, and radical prostatectomy Gleason sum. If interactions were significant, we quantified the effect on the biochemical recurrence rate. RESULTS: Overall 850 patients (18.9%) had positive surgical margins. In those with negative vs positive surgical margins the 5-year biochemical recurrence-free survival rate was 95% vs 83%, 74% vs 62% and 47% vs 29% for pT2, pT3a and pT3b disease, respectively. In multivariate models only the pT stage-surgical margin status interaction achieved independent predictor status (p = 0.003). Negative vs positive surgical margin multivariate HRs were 1 vs 2.9, 2.3 vs 4.3 and 4.1 vs 5.6 in pT2, pT3a and pT3b cases, respectively. CONCLUSIONS: Compared to negative surgical margins, positive surgical margins increase the absolute biochemical recurrence 5-year rate by 12% to 18%. More importantly, positive surgical margins may substantially worsen the prognosis beyond that of the original pathological disease stage.

Prognostic significance of a positive surgical margin in pathologically organ-confined prostate cancer.

OBJECTIVE: To identify risk factors of a positive surgical margin (PSM) and the significance of a PSM after radical prostatectomy (RP) on biochemical recurrence (BCR) in exclusively pathologically confirmed organ-confined (OC) prostate cancer, as despite an excellent prognosis after RP, some patients with pathologically confirmed OC disease have BCR, and the prognostic significance of a PSM in these men remains unclear. PATIENTS AND METHODS: We assessed 932 men with pathologically OC disease who were treated with RP by nine different surgeons between 1992 and 2004. The prognostic significance of clinical and pathological variables, including tumour volume (TV) and percentage of high-grade TV (%HGTV) were assessed. Logistic and Cox regression models were fitted to identify risk factors of a PSM and BCR. BCR was defined as a prostate-specific antigen (PSA) level of 0.1 ng/mL and increasing after an undetectable PSA level. RESULTS: The total PSM rate was 12.9% (120 men); the mean TV (P < 0.001), but not %HGTV (P= 0.2) was significantly higher in patients with PSM. TV, nerve-sparing RP technique and surgical volume were independent risk factors for a PSM (P= 0.03). After a median follow-up of 35 months the overall BCR rate was 8.8% (82 men). Patients with a PSM had significantly higher BCR rates (21.7% vs 6.9%; P < 0.001). In univariable analysis, a high %HGTV (70.4%) was the most informative risk factor of BCR, followed by RP Gleason score (65.8%) and PSM (65.7%). Removal of PSM from a multivariable Cox model decreased the accuracy by 12.1% (P < 0.001). CONCLUSIONS: Our findings show that in OC prostate cancer, the risk of a PSM depends on TV, surgical technique and surgical volume. PSM is a significant risk factor for BCR. However, only 20% men with OC disease and a PSM develop BCR; conversely, 80% of men are cured despite a PSM. Therefore, adjuvant therapy must be considered, with caution to avoid unnecessary overtreatment.