Comorbidity and performance indices as predictors of cancer-independent mortality but not of cancer-specific mortality after radical cystectomy for urothelial carcinoma of the bladder

Background

Comorbidity and performance indices allow assessment of preoperative health status. However, the optimal tool for use in patients with urothelial carcinoma of the bladder (UCB) who are undergoing radical cystectomy (RC) has not yet been established.

Objective

To evaluate correlation of Adult Comorbidity Evaluation-27 (ACE27), Charlson Comorbidity Index, Age-Adjusted Charlson Comorbidity Index, Eastern Cooperative Oncology Group performance status, and American Society of Anesthesiologists (ASA) score with survival.

Design, setting, and participants

A retrospective multicenter study was carried out on 555 unselected consecutive patients who underwent RC for UCB from 2000 to 2010.

Intervention

RC with pelvic lymph node dissection in patients with UCB without neoadjuvant chemotherapy.

Outcome measurements and statistical analysis

Cox regression models were calculated with established variables to assess predictive capacity for cancer-specific mortality (CSM) and cancer-independent mortality (CIM).

Results and limitations

All indices were independent predictors for CIM but not for CSM. The ASA score was the only index that significantly increased the predictive accuracy of the predefined CIM model (+2.3%; p = 0.045). To create a clinically valuable tool, we devised a weighted prognostic model including age and the best prognosticators within the performance and comorbidity scores (ASA/ACE27 0–1/2–3). A 3-yr CIM rate of 8%, 26%, and 47% was calculated for the low-, intermediate-, and high-risk groups, respectively. Patients >75 yr of age with ASA 3/4 and ACE27 >1 exhibited a CIM risk seven times greater than patients ≤75 yr with ASA 1/2 and ACE27 0/1. This study is limited by the short follow-up and its retrospective nature.

Conclusions

Comorbidity and performance assessment is mandatory in the preoperative prediction of CIM for patients undergoing RC for UCB. The present results indicate that the ASA score is the tool of choice. External and prospective validation is warranted.     

Cancer-specific and other-cause mortality after radical prostatectomy versus observation in patients with prostate cancer: competing-risks analysis of a large North American population-based cohort

Background

Initial treatment options for low-risk clinically localized prostate cancer (PCa) include radical prostatectomy (RP) or observation.

Objective

To examine cancer-specific mortality (CSM) after accounting for other-cause mortality (OCM) in PCa patients treated with either RP or observation.

Design, setting, and participants

Using the Surveillance Epidemiology and End Results Medicare-linked database, a total of 44 694 patients ≥65 yr with localized (T1/2) PCa were identified (1992-2005).

Intervention

RP and observation.

Measurements

Propensity-score matching was used to adjust for potential selection biases associated with treatment type. The matched cohort was randomly divided into the development and validation sets. Competing-risks regression models were fitted and a competing-risks nomogram was developed and externally validated.

Results and limitations

Overall, 22 244 (49.8%) patients were treated with RP versus 22450 (50.2%) with observation. Propensity score-matched analyses derived 11 669 matched pairs. In the development cohort, the 10-yr CSM rate was 2.8% (2.3-3.5%) for RP versus 5.8% (5.0-6.6%) for observation (absolute risk reduction: 3.0%; relative risk reduction: 0.5%; p < 0.001). In multivariable analyses, the CSM hazard ratio for RP was 0.48 (0.38-0.59) relative to observation (p < 0.001). The competing-risks nomogram discrimination was 73% and 69% for prediction of CSM and OCM, respectively, in external validation. The nature of observational data may have introduced a selection bias.

Conclusions

On average RP reduces the risk of CSM by half in patients aged ≥65 yr, relative to observation. The individualized protective effect of RP relative to observation may be quantified with our nomogram.     

Immunocytology is a strong predictor of bladder cancer presence in patients with painless hematuria: a multicentre study

Background

Although the performance of immunocytology has been established in the surveillance of patients with urothelial carcinoma of the bladder (UCB), its value in the initial detection of UCB in patients with painless hematuria remains unclear.

Objective

To determine whether immunocytology improves our ability to predict the likelihood of UCB in patients with painless hematuria. Further, to test the clinical benefit of immunocytology in this setting using decision curve analysis.

Design, setting, and participants

The subjects were 1182 consecutive patients without a history of UCB presenting with painless hematuria and were enrolled at three centres.

Intervention

All patients underwent upper-tract imaging, cystourethroscopy, voided urine cytology, and immunocytology analysis. Bladder tumors were biopsied and histologically confirmed as UCB.

Measurements

Multivariable regression models were developed. Area under the curve was measured and compared using the DeLong test. A nomogram was constructed from the full multivariable model. Decision curve analysis was performed to evaluate the clinical benefit associated with use of the multivariable models including immunocytology.

Results and limitations

Immunocytology had the largest contribution to a multivariable model for the prediction of UCB (odds ratio: 18.3; p < 0.0001), which achieved a 90.8% predictive accuracy. Decision curve analysis revealed that models incorporating immunocytology achieved the highest net benefit at all threshold probabilities.

Conclusions

Immunocytology is a strong predictor of the presence of UCB in patients who present with painless hematuria. Incorporation of immunocytology into predictive models improves diagnostic accuracy by a statistically and clinically significant margin. The use of immunocytology in the diagnostic workup of patients with hematuria appears promising and should be further evaluated.     

Prospective Evaluation of a Molecular Marker Panel for Prediction of Recurrence and Cancer-specific Survival After Radical Cystectomy

Background

Retrospective studies demonstrated that cell cycle–related and proliferation biomarkers add information to standard pathologic tumor features after radical cystectomy (RC). There are no prospective studies validating the clinical utility of markers in bladder cancer.

Objective

To prospectively determine whether a panel of biomarkers could identify patients with urothelial carcinoma of the bladder (UCB) who were likely to experience disease recurrence or mortality.

Design, setting, and participants

Between January 2007 and January 2012, every patient with high-grade bladder cancer, including 216 patients treated with RC and lymphadenectomy, underwent immunohistochemical staining for tumor protein p53 (Tp53); cyclin-dependent kinase inhibitor 1A (p21, Cip1) (CDKN1A); cyclin-dependent kinase inhibitor 1B (p27, Kip1); antigen identified by monoclonal antibody Ki-67 (MKI67); and cyclin E1.

Intervention

Every patient underwent RC and lymphadenectomy, and marker staining.

Outcome measurements and statistical analysis

Cox regression analyses tested the ability of the number of altered biomarkers to predict recurrence or cancer-specific mortality (CSM).

Results and limitations

Pathologic stage among the study population was pT0 (5%), pT1 (35%), pT2 (19%), pT3 (29%), and pT4 (13%); lymphovascular invasion (LVI) was seen in 34%. The median number of removed lymph nodes was 23, and 60 patients had lymph node involvement (LNI). Median follow-up was 20 mo. Expression of p53, p21, p27, cyclin E1, and Ki-67 were altered in 54%, 26%, 46%, 15%, and 75% patients, respectively. In univariable analyses, pT stage, LNI, LVI, perioperative chemotherapy (CTx), margin status, and number of altered biomarkers predicted disease recurrence. In a multivariable model adjusting for pathologic stage, margins, LNI, and adjuvant CTx, only LVI and number of altered biomarkers were independent predictors of recurrence and CSM. The concordance index of a baseline model predicting CSM (including pathologic stage, margins, LVI, LNI, and adjuvant CTx) was 80% and improved to 83% with addition of the number of altered markers.

Conclusions

Molecular markers improve the prediction of recurrence and CSM after RC. They may identify patients who might benefit from additional treatments and closer surveillance after cystectomy.     

Gender-specific Differences in Clinicopathologic Outcomes Following Radical Cystectomy: An International Multi-institutional Study of More Than 8000 Patients

Background

The impact of gender on the staging and prognosis of urothelial carcinoma of the bladder (UCB) is insufficiently understood.

Objective

To assess gender-specific differences in pathologic factors and survival of UCB patients treated with radical cystectomy (RC).

Design, setting, and participants

Data from 8102 patients treated with RC (6497 men [80%] and 1605 women [20%]) for UCB between 1971 and 2012 were analyzed.

Outcome measurements and statistical analysis

Multivariable competing-risk regression analyses were performed to evaluate the relationship of gender on disease recurrence (DR) and cancer-specific mortality (CSM). We also tested the interaction of gender and tumor stage, nodal status, and lymphovascular invasion (LVI).

Results and limitations

Female patients were older at the time of RC (p = 0.033) and had higher rates of pathologic stage T3/T4 disease (p < 0.001). In univariable, but not in multivariable analysis, female gender was associated with a higher risk of DR (p = 0.022 and p = 0.11, respectively). Female gender was an independent predictor for CSM (p = 0.004). We did not find a significant interaction between gender and stage, nodal metastasis, or LVI (all p values >0.05).

Conclusions

We found female gender to be associated with a higher risk of CSM following RC. However, these findings do not appear to be explained by gender differences in pathologic stage, nodal status, or LVI. This gender disparity may be due to differences in care and/or the biology of UCB.     

Urethroplasty for strictures after phallic reconstruction: a single-institution experience

Background

Treatment recommendations for strictures after phalloplasty are lacking.

Objective

Our aim was to evaluate the outcome of urethroplasty for strictures after phalloplasty and to provide treatment recommendations based on this experience.

Design, setting, and participants

One hundred and eighteen urethroplasties were performed in 79 patients. Mean patient age was 37.6 yr. Mean follow-up was 39 mo.

Intervention

Different types of urethroplasty were used: meatotomy, Heineke-Mikulicz principle (HMP), excision and primary anastomosis (EPA), free graft urethroplasty (FGU), pedicled flap urethroplasty (PFU), two-stage urethroplasty (TSU), and perineostomy followed by urethral reconstruction (PUR).

Measurements

Stricture recurrence was defined as the need for additional instrumentation or surgery.

Results and limitations

Mean stricture length was 3.6 cm. Stricture location was at the meatus, phallic urethra, anastomosis, fixed part, and different locations in 18, 28, 48, 15, and 9 urethroplasties, respectively. Stricture recurrence was observed in 44 urethroplasties (41.12%). Stricture recurrence rate for meatotomy, HMP, EPA, FGU, PFU, TSU, and PUR was 25%, 42.11%, 42.86%, 50%, 40%, 30.3%, and 61.9%, respectively.

Conclusions

The main stricture location after phalloplasty is the anastomosis between the phallic and the fixed part. Urethroplasty for strictures after phalloplasty is associated with a relatively high recurrence rate.

Trial registration

EC UZG 2007/434.     

Disease-free survival following salvage cryotherapy for biopsy-proven radio-recurrent prostate cancer

Background

The optimum treatment of prostate cancer recurrence following radiation therapy (RT) remains controversial due to the lack of long-term data.

Objective

Our aim was to review the survival of patients who underwent salvage cryotherapy to the prostate gland for biopsy-proven recurrent prostate cancer and establish prognostic indicators.

Design, setting, and participants

A retrospective analysis was performed on all patients undergoing salvage cryotherapy at an academic urology unit for biopsy-proven locally recurrent prostate cancer after RT from 1995 to 2004. Patients’ preoperative, perioperative, and postoperative data were reviewed and recorded.

Intervention

Two freeze-thaw cycles of transperineal cryotherapy were performed under transrectal ultrasound guidance by a single surgeon.

Measurements

The primary outcome was survival. Secondary outcomes were disease-free survival (DFS), metastasis-free survival, and progression to androgen-deprivation therapy.

Results and limitations

Of 187 patients, 176 had records available for follow-up (follow-up rate: 94%). Mean follow-up was 7.46 yr (range: 1-14 yr). Fifty-two patients were followed for >10 yr. DFS at 10 yr was 39%. Risk factors for recurrence were presalvage prostate-specific antigen (PSA), preradiation, and presalvage Gleason score. A PSA nadir >1.0 ng/dl was highly predictive of early recurrence.

Conclusions

Salvage cryotherapy led to an acceptable 10-yr DFS. Presalvage PSA and Gleason score were the best predictors of disease recurrence. A PSA nadir >1 ng/dl following cryotherapy indicated a poor prognosis, and recurrence of disease was universal in these patients.     

Does the extent of lymphadenectomy in radical cystectomy for bladder cancer influence disease-free survival? A prospective single-center study

Background

Controversy exists regarding the optimal extent of lymphadenectomy and the number of lymph nodes to be retrieved at radical cystectomy (RC).

Objective

To compare the disease-free survival of patients with standard lymphadenectomy (endopelvic region composed of the internal, external iliac, and obturator groups of lymph nodes) versus extended lymphadenectomy (up to the level of origin of the inferior mesenteric artery) at RC in a prospective cohort of patients at a single, high-volume center.

Design, setting, and participants

Prospective data were collected from 400 consecutive patients treated with RC for bladder cancer by two high-volume surgeons at Mansoura Urology and Nephrology Center. Of the 400 patients, 200 (50%) received extended lymphadenectomy and the other 200 (50%) underwent standard lymphadenectomy at RC. The patients did not receive any neoadjuvant or adjuvant therapy.

Measurements

Patient characteristics and outcomes are evaluated.

Results and limitations

Median patient age for the entire group was 53.0 yr. Ninety-six patients (24.0%) had lymph node metastases. Median follow-up was 50.2 mo. Estimates of 5-yr disease-free survival in the extended lymphadenectomy group were 66.6% compared with 54.7% for patients with standard lymphadenectomy (p = 0.043). Extended lymphadenectomy was associated with better disease-free survival after adjusting for the effects of standard pathologic features (p = 0.02). When restricting the analyses to lymph node-positive patients, patients with extended lymphadenectomy had much better 5-yr disease-free survival compared with patients with standard lymphadenectomy (48.0% vs 28.2%; p = 0.029). The study was nonrandomized.

Conclusions

Extended lymphadenectomy is associated with better disease-free survival for bladder cancer patients with endopelvic lymph node involvement and should be considered in these patients.     

Characteristics and Outcomes of Patients with Clinical T1 Grade 3 Urothelial Carcinoma Treated with Radical Cystectomy: Results from an International Cohort

Background

Management of T1 grade 3 (T1G3) urothelial carcinoma of the bladder (UCB), with its variable behaviour, represents one of the most difficult challenges for urologists and patients alike.

Objective

To evaluate the characteristics and long-term outcome of patients with clinical T1G3 UCB treated with radical cystectomy (RC).

Design, setting, and participants

Data from 1136 patients treated with RC for clinical T1G3 UCB without neoadjuvant chemotherapy were collected at 12 centres located in Europe, the United States, and Canada. Median age was 67 yr (range: 29–94), with a male-to-female ratio of 4:1.

Measurements

Patients’ characteristics and outcome are evaluated.

Results and limitations

Of the 1136 patients, 33.4% had non–organ-confined stage at cystectomy, and 16.2% had lymph node (LN) metastasis; 49.7% were upstaged after RC to muscle-invasive disease, while 21.4% were downstaged to lower than T1G3. Within a median follow-up of 48 mo, 35.5% of patients died of metastatic UCB.

Conclusions

Approximately half of the patients treated with RC without neoadjuvant chemotherapy for clinical T1G3 UCB are upstaged to muscle-invasive UCB. These rates support the inadequacy of clinical decision making based on current treatment paradigms and staging tools. Therefore, identification of patients with clinical T1G3 disease at high risk of disease progression is of the utmost importance, as these patients are likely to benefit from early RC.     

Should follow-up cystoscopy in bacillus Calmette-Guérin-treated patients continue after five tumour-free years?

Background

It is not known how long follow-up cystoscopy in tumour-free bacillus Calmette-Guérin (BCG)-treated patients should continue.

Objective

Determine the incidence of late recurrences and progression after a tumour-free period of >5 yr after BCG treatment.

Design, setting, and participants

Data on 542 patients with non-muscle-invasive bladder cancer treated with BCG between 1986 and 2003 were analysed. Of 542 patients, 204 patients (37.6%) were tumour-free for ≥5 yr. The median tumour-free period was 105.5 mo (range: 60-252 mo).

Measurements

To compare the tumour-free group with patients who were not tumour-free for 5 yr, traditional variables (tumour grade, tumour stage, age, gender, tumour number and size, primary or recurrent tumour, BCG strain, previous chemotherapy, previous upper tract tumour, number of earlier resections, and European Organisation for Research and Treatment of Cancer recurrence and progression risk groups) were analysed using the Fisher exact test for dichotomous variables, the Mantel-Haenszel chi-square test for ordered categorical variables, and the Mann-Whitney U-test for continuous variables. Kaplan-Meier curves for time to recurrence were constructed using Statistica software (StatSoft, Tulsa, Oklahoma, USA). Differences between groups were tested with the log-rank test. For continuous variables, Cox proportional hazard regression was performed to find significant effect on the time to recurrence.

Results and limitations

Twenty-two of 204 patients (10.8%) had a recurrence after being tumour-free for ≥5 yr. The Kaplan-Meier estimated risk for recurrence was 12.5% at 10 yr and 20.5% at 15 yr. Among patients with TaG1-TaG2 before BCG, 11 of 79 patients (13.9%) had recurrences, including three patients with invasive extravesical tumours. Among the bladder recurrences were seven TaG1 s and one carcinoma in situ (CIS). Among the 125 patients with TaG3/CIS/T1 before BCG, 11 patients (8.8%) had recurrences, including 2 patients with invasive ureter tumours. The bladder recurrences were one T2, four CIS, and four TaG1. Late recurrences were 8.5 times more common among patients with recurrent tumours before BCG compared with patients treated after their first tumour episode. The study was retrospective and nonrandomised but unselected and population-based.

Conclusions

A tumour-free period of 5 yr after BCG treatment is a good prognostic sign, but recurrences after >10 yr are not unusual. Literature data and the present report support cystoscopy follow-up for ≥10-15 tumour-free years, at least among patients with recurrent tumours and/or high-grade lesions before BCG treatment.     

Hepatoprotective effect of prolactin and cysteine contained in perfusion and preservation solutions on porcine liver stored in simple hypothermia

Introduction

The aim of our study was to determine the results of histidine-tryptophan-ketoglutarate (HTK) solutions modified by the addition of the antioxidant cysteine (Cys), and of prolactin (PRL) on storage of isolated porcine livers.

Methods

We measured in the media of isolated livers stored for 24 hours in HTK (control group) or modified HTK + Cys (0.3 mmol/L) + PRL (3 IU/L study group) the amounts of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), lactic acid as well as Ca (II), Mg (II), Na (I) and K (I) ions during a 30-minute perfusion after 24 hours of storage.

Results

All tested markers were released more slowly into HTK + Cys + PRL with less release of K(I) and Mg(II) and greater of Na(I) and Ca(II) ions.

Conclusions

Addition of the Cys and PRL to HTK positively affected 24-hour storage of isolated livers.     

Laparoscopic versus open mesh repair for recurrent inguinal hernia: a meta-analysis of outcomes

Background

The objective of this study was to examine the outcomes of comparisons between laparoscopic and open mesh repairs in the setting of recurrent inguinal hernia.

Methods

The electronic databases MEDLINE, Embase, Pubmed, and the Cochrane Library were used to search for articles from 1990 to 2008. The present meta-analysis pooled the effects of outcomes of a total of 1,542 patients enrolled into 5 randomized controlled trials and 7 comparative studies, using classic and modern meta-analytic methods.

Results

Significantly fewer cases of hematoma/seroma formation were observed in the laparoscopic group in comparison with the Lichtenstein group (odds ratio, .38; .15-.96; P = .04). A matter of great importance is the higher relative risk of overall recurrence in the transabdominal preperitoneal group compared with the totally extraperitoneal group (relative risk, 3.25; 1.32-7.9; P = .01).

Conclusions

Laparoscopic versus open mesh repair for recurrent inguinal hernia was equivalent in most of the analyzed outcomes.     

Impact of Smoking and Smoking Cessation on Outcomes in Bladder Cancer Patients Treated with Radical Cystectomy

Background

Cigarette smoking is the best-established risk factor for urothelial carcinoma development.

Objective

To elucidate the association of pretreatment smoking status, cumulative exposure, and time since smoking cessation on outcomes of patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC).

Design, setting, and participants

We retrospectively collected clinicopathologic and smoking variables, including smoking status, number of cigarettes per day (CPD), duration in years, and time since smoking cessation, for 1506 patients treated with RC for UCB. Lifetime cumulative smoking exposure was categorized as light short-term (≤20 CPD for ≤20 yr), light long-term (≤20 CPD for >20 yr), heavy short-term (>20 CPD for ≤20 yr), and heavy long-term (>20 CPD for >20 yr).

Intervention

RC and bilateral lymph node (LN) dissection without neoadjuvant chemotherapy.

Outcome measurements and statistical analysis

Logistic regression and competing risk analyses assessed the association of smoking with disease recurrence, cancer-specific mortality, and overall mortality.

Results and limitations

There was no difference in clinicopathologic factors between patients who had never smoked (20%), former smokers (46%), and current smokers (34%). Smoking status was associated with the cumulative incidence of disease recurrence (p = 0.004) and cancer-specific mortality (p = 0.016) in univariable analyses and with disease recurrence in multivariable analysis (p = 0.02); current smokers had the highest cumulative incidences. Among ever smokers, cumulative smoking exposure was associated with advanced tumor stages (p < 0.001), LN metastasis (p = 0.002), disease recurrence (p < 0.001), cancer-specific mortality (p = 0.001), and overall mortality (p = 0.037) in multivariable analyses that adjusted for standard characteristics; heavy long-term smokers had the worst outcomes, followed by light long-term, heavy short-term, and light short-term smokers. Smoking cessation ≥10 yr mitigated the risk of disease recurrence (hazard ratio [HR]: 0.44; p < 0.001), cancer-specific mortality (HR: 0.42; p < 0.001), and overall mortality (HR: 0.69; p = 0.012) in multivariable analyses. The study is limited by its retrospective nature.

Conclusions

Smoking is associated with worse prognosis after RC for UCB. This association seems to be dose-dependent, and its effects are mitigated by >10 yr smoking cessation. Health care practitioners should counsel smokers regarding the detrimental effects of smoking and the benefits of smoking cessation on UCB etiology and prognosis.     

Predicting Survival of Patients with Node-positive Prostate Cancer Following Multimodal Treatment

Background

According to the TNM staging system, patients with prostate cancer (PCa) with lymph node invasion (LNI) are considered a single-risk group. However, not all LNI patients share the same cancer control outcomes.

Objective

To develop and internally validate novel nomograms predicting cancer-specific mortality (CSM)–free rate in pN1 patients.

Design, setting, and participants

We evaluated 1107 patients with pN1 PCa treated with radical prostatectomy, pelvic lymph node dissection, and adjuvant therapy at two tertiary care centers between 1988 and 2010.

Outcome measurements and statistical analysis

Univariable and multivariable Cox regression models tested the relationship between CSM and patient clinical and pathologic characteristics, which consisted of prostate-specific antigen (PSA) value, pathologic Gleason score, pathologic tumor stage, status of surgical margins, number of positive lymph nodes, and status of adjuvant therapy. A Cox regression coefficient-based nomogram was developed and internally validated.

Results and limitations

All 1107 patients received adjuvant hormonal therapy (aHT). Additionally, 35% of patients received adjuvant radiotherapy (aRT). The 10-yr CSM-free rate was 84% in the entire cohort and 87% in patients treated with aRT plus aHT versus 82% in patients treated with aHT alone (p = 0.08). At multivariable analyses, PSA value, pathologic Gleason score, pathologic tumor stage, surgical margin status, number of positive lymph nodes, and aRT status were statistically significant predictors of CSM (all p ≤ 0.04). Based on these predictors, nomograms were developed to predict the 10-yr CSM-free rate in the overall patient population and in men with biochemical recurrence. These models showed high discrimination accuracy (79.5–83.3%) and favorable calibration characteristics. These results are limited by their retrospective nature.

Conclusions

Some patients with pN1 PCa have favorable CSM-free rates at 10 yr. We developed and internally validated the first nomograms that allow an accurate prediction of the CSM-free rate in these patients at an individual level.     

Robotic and laparoscopic high extended pelvic lymph node dissection during radical cystectomy: technique and outcomes

Background

With the increasing use of laparoscopic and robotic radical cystectomy (RC), there are perceived concerns about the adequacy of lymph node dissection (LND).

Objective

Describe the robotic and laparoscopic technique and the short-term outcomes of high extended pelvic LND (PLND) up to the inferior mesenteric artery (IMA) during RC.

Design, setting, and participants

From January 2007 through September 2009, we performed high extended PLND with proximal extent up to the IMA (n = 10) or aortic bifurcation (n = 5) in 15 patients undergoing robotic RC (n = 4) or laparoscopic RC (n = 11) at two institutions.

Surgical procedure

We performed robotic extended PLND with the proximal extent up to the IMA or aortic bifurcation. The LND was performed starting from the right external iliac, obturator, internal iliac, common iliac, preaortic and para-aortic, precaval, and presacral and then proceeding to the left side. The accompanying video highlights our detailed technique.

Measurements

Median age was 69 yr, body mass index was 26, and American Society of Anesthesiologists class ≥3 was present in 40% of patients. All urinary diversions, including orthotopic neobladder (n = 5) and ileal conduit (n = 10), were performed extracorporeally.

Results and limitations

All 15 procedures were technically successful without need for conversion to open surgery. Median operative time was 6.7 h, estimated blood loss was 500 ml, and three patients (21%) required blood transfusion. Median nodal yield in the entire cohort was 31 (range: 15-78). The IMA group had more nodes retrieved (median: 42.5) compared with the aortic bifurcation group (median: 20.5). Histopathology confirmed nodal metastases in four patients (27%), including three patients in the IMA group and one patient in the aortic bifurcation group. Perioperative complications were recorded in six cases (40%). During a median follow-up of 13 mo, no patient developed local or systemic recurrence. Limitations of the study include its retrospective design and small cohort of patients.

Conclusions

High extended PLND during laparoscopic or robotic RC is technically feasible. Longer survival data in a larger cohort of patients are necessary to determine the proper place for robotic and laparoscopic surgery in patients undergoing RC for high-risk bladder cancer.     

Human cytokine expression profile in various conditioned media for in vitro expansion bone marrow and umbilical cord blood immunophenotyped mesenchymal stem cells

Introduction

Bone marrow (BM) represents the major source of mesenchymal stem cells (MSCs); however, umbilical cord blood (UCB) MSCs have some advantages over BM, such as a higher differentiation capability and noninvasive collection methods.

Objectives

We compared antigen expression and cytokine-secretion by MSC from BM and UCB expanded with media supplemented with fetal bovine serum (FBS) or human platelet lysate (HPL).

Materials and Methods

We compared protocols for the expansion of hMSC starting from samples of BM or UCB by morphological analysis, calculation of population doubling numbers, and cytometry techniques using monoclonal antibodies (BD Biosciences). Using the last technique, cytokines were detected in brain homogenate supernatant fluids of MSC cultured in various media, using the Bio-Plex cytokine assay system (BD Biosciences).

Results

Calculating the number population doubling (PD) and colony-forming unit-¹fibroblast (CFU-F) assays showed significantly better expansion with HPL compared with a selected batch of FBS and within fewer days: PD about 5 for 10%HPL versus 25 for fibroblast growth factor2 (FGF2) medium. By flow cytometry, we observed a greater number of BM MSCs compared with UCB MSCs, as well as differences in the expression of some MSC antigens, particularly CD105, CD90, and CD31. Analysis of cytokines: FGFb, RANTES, VEGF, IL-6, IL-8, G-CSF, and GM-CSF showed only some of them to be expressed: namely, IL-6, IL-8, and VEGF. MSCs derived from UCB showed low concentrations of these cytokines compared with MSCs derived from BM.     

Risk factors and outcome of early recurrence after resection of small hepatocellular carcinomas

Background

This study aimed to clarify risk factors for early recurrence and examine the subsequent outcome in patients undergoing potentially R0 resection of small hepatocellular carcinomas (HCCs) (≤2 cm in greatest dimension).

Methods

Eighty-nine patients were divided into 2 groups as follows: 26 patients suffering from recurrence within 2 years of surgery (early recurrence group) and 63 patients who were disease-free for at least 2 years (disease-free 2Y group).

Results

Only 7 of 63 patients (11%) from the group that was disease-free for at least 2 years died during the 5-year period after surgery, whereas 13 of 26 patients (50%) from the early recurrence group died. Multivariate analysis showed that the preoperative maximum removal rate of technetium-99m-diethylenetriamine pentaacetic acid-galactosyl human serum albumin and microscopic vascular invasion were independent predictors of the early recurrence of small HCC.

Conclusions

Early recurrence of small HCC is the leading cause of death within 5 years after R0 resection. The preoperative hepatic functional reserve influences early recurrence, even in patients with small tumors.     

Local control, survival, and operative morbidity and mortality after re-resection, and intraoperative radiation therapy for recurrent or persistent primary high-risk neuroblastoma

Background/Purpose

Patients with locally recurrent or persistent high-risk neuroblastoma are difficult to treat. We describe our experience using intraoperative radiation therapy (IORT) after re-resection in this high-risk population.

Methods

We retrospectively reviewed 44 consecutive patients who received IORT at our institution between April 2000 and September 2009 after gross total resection of recurrent/persistent tumor. Specifically, we evaluated local recurrence rates, complications, and overall survival.

Results

The median age at diagnosis was 41.5 months. Median follow-up after IORT was 10.5 months. Each patient received prior chemotherapy and surgery, while 94.5% had previous external beam radiation therapy. MYCN was amplified in 34% of patients. There were no operative or postoperative deaths, and 18 patients (40.9%) had postoperative complications. There was a 50.4% probability of local control. MYCN amplification did not affect local control (local recurrence rate of 53.9% vs 52.4%, P = .89). Median overall survival was 18.7 months (95% confidence interval, 11.7-25.6 months). Mean survival for MYCN-amplified patients was 13.0 vs 39.2 months for those without MYCN amplification (P = .035).

Conclusions

Intraoperative radiation therapy after re-resection of locally recurrent/persistent neuroblastoma results in a reasonable rate of local control with acceptable morbidity and survival. This approach should be considered in this high-risk population.     

External Validation of Online Predictive Models for Prediction of Cancer-specific Mortality and All-cause Mortality in Patients with Urothelial Carcinoma of the Urinary Bladder

Purpose

The objective of the study was to validate the previously reported lookup Table and Bladder Cancer Research Consortium (BCRC) nomogram in predicting cancer-specific mortality (CSM) and all-cause mortality (ACM) after radical cystectomy using an external cohort from South Korea.

Methods

The study comprised 409 patients. Discrimination was quantified with the concordance index. The relationship between the model-derived and actual CSM and ACM was graphically explored within calibration plots. Clinical net benefit was evaluated by decision curve analysis.

Results

Of the 409 patients, 147 (35.9 %) had died from various causes. One hundred two deaths were attributable to bladder cancer. For CSM at 5 years, the bootstrap-corrected concordance indices of the American Joint Committee on Cancer (AJCC) staging system, lookup Table, and BCRC nomogram were 71.8 % (95 % confidence interval [CI] 66.9–76.5), 73.0 % (95 % CI 67.9–78.0), and 76.2 % (95 % CI 71.6–80.9), respectively. For ACM at the same time point, the discrimination accuracies of these models were 70.7 % (95 % CI 66.7–74.6), 72.8 % (95 % CI 68.5–76.9), and 76.2 % (95 % CI 72.3–80.2), respectively. The calibration plots tended to exaggerate both survival outcomes in all models. When compared to the lookup Table as well as the AJCC staging system, the BCRC nomogram performed well across a wide range of threshold probabilities using decision curve analysis.

Conclusions

The BCRC nomogram was characterized by higher accuracy and larger potential clinical benefit compared to the lookup Table. However, there is a great need for additional models that consider outcomes of patients for whom the existing models do not apply.     

Prediction of prostate cancer risk: the role of prostate volume and digital rectal examination in the ERSPC risk calculators

Background

The European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculators (RCs) are validated tools for prostate cancer (PCa) risk assessment and include prostate volume (PV) data from transrectal ultrasound (TRUS).

Objective

Develop and validate an RC based on digital rectal examination (DRE) that circumvents the need for TRUS but still includes information on PV.

Design, setting, and participants

For development of the DRE-based RC, we studied the original ERSPC Rotterdam RC population including 3624 men (885 PCa cases) and 2896 men (547 PCa cases) detected at first and repeat screening 4 yr later, respectively. A validation cohort consisted of 322 men, screened in 2010-2011 as participants in ERSPC Rotterdam.

Measurements

Data on TRUS-assessed PV in the development cohorts were re-coded into three categories (25, 40, and 60 cm³) to assess the loss of information by categorization of volume information. New RCs including PSA, DRE, and PV categories (DRE-based RC) were developed for men with and without a previous negative biopsy to predict overall and clinically significant PCa (high-grade [HG] PCa) defined as T stage >T2b and/or Gleason score ≥7. Predictive accuracy was quantified by the area under the receiver operating curve. We compared performance with the Prostate Cancer Prevention Trial (PCPT) RC in the validation study.

Results and limitations

Areas under the curve (AUC) of prostate-specific antigen (PSA) alone, PSA and DRE, the DRE-based RC, and the original ERSPC RC to predict PCa at initial biopsy were 0.69, 0.73, 0.77, and 0.79, respectively. The corresponding AUCs for predicting HG PCa were higher (0.74, 0.82, 0.85, and 0.86). Similar results were seen in men previously biopsied and in the validation cohort. The DRE-based RC outperformed the PCPT RC (AUC 0.69 vs 0.59; p = 0.0001) and a model based on PSA and DRE only (AUC 0.69 vs 0.63; p = 0.0075) in the relatively small validation cohort. Further validation is required.

Conclusions

An RC should contain volume estimates based either on TRUS or DRE. Replacing TRUS measurements by DRE estimates may enhance implementation in the daily practice of urologists and general practitioners.