Complication Rates of Tension-Free Midurethral Slings in the Treatment of Female Stress Urinary Incontinence: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Comparing Tension-Free Midurethral Tapes to Other Surgical Procedures and Different Devices

Objectives

To evaluate the complication rates of tension-free midurethral slings compared with other surgical treatments for stress urinary incontinence, including other tension-free midurethral slings.

Methods

A systematic review of the literature using MEDLINE, EMBASE, and Web of Science was performed in January 2007. Meta-analysis was conducted by using the Review Manager software 4.2.

Results

Our search identified 33 randomized controlled trials reporting data on complication rates. Our meta-analysis showed that complication rates were similar after tension-free vaginal tape (TVT) and Burch colposuspension, with the exclusion of bladder perforation, which was more common after TVT (p = 0.0001), and reoperation rate, which was significantly higher after Burch colposuspension (p = 0.02). TVT and pubovaginal sling were followed by similar complication rates. With regards to the comparisons among retropubic tapes, TVT and intravaginal slingplasty had similar complication rates, whereas suprapubic arc sling (SPARC) was complicated by higher rates of voiding lower urinary tract symptoms (LUTS) (p = 0.02) and reoperations (p = 0.04). Comparing retropubic and transobturator tapes, the occurrence of bladder perforations (p = 0.007), pelvic haematoma (p = 0.03), and storage LUTS (p = 0.01) was significantly less common in patients treated by transobturator tapes.

Conclusions

Tension-free slings were followed by lower risk of reoperation compared with Burch colposuspension, whereas pubovaginal sling and tension-free midurethral slings had similar complication rates. With regards to different tension-free tapes, voiding LUTS and reoperations were more common after SPARC, whereas bladder perforations, pelvic haematoma, and storage LUTS were less common after transobturator tapes. The quality of many evaluated studies was limited.     

The Long Term (5-Years) Objective TVT Success Rate Does Not Depend on Predictive Factors at Multivariate Analysis: A Multicentre Retrospective Study

Objectives

We evaluated the predictive risk factors that could affect the long-term efficacy of the tension-free vaginal tape (TVT) procedure for the treatment of female stress urinary incontinence (SUI).

Methods

One hundred thirty-eight (mean age, 52.4 ± 9.3 yr) women who underwent the TVT procedure for SUI were selected and followed up for at least 5 yr (mean, 67.2 mo; range, 60–76) after the surgery. We analyzed the preoperative and intraoperative parameters using univariate and multivariate regression for cure rates and patients’ satisfaction.

Results

The overall 5-yr cure rate was 76.8%, with a satisfaction rate of 86.9%. The cure rates were lower in patients with high body mass index (BMI ≥ 25 kg/m²/BMI < 25 kg/m² = 68.3%:83.3%, p = 0.044), low abdominal leak point pressure (ALPP < 60 cm H₂O/ALPP ≥ 60 cm H₂O = 51.6%:82.8%, p = 0.003), and high grade of SUI (40.0% in grade III; 69.7% in grade II; 86.6% in grade I, p = 0.012). On multivariate analysis, there were no independent risk factors related to cure rate, and urgency was the only factor independently associated with patients’ satisfaction (p = 0.017; odds ratio = 4.114).

Conclusions

This study demonstrates that the TVT procedure is effective for female SUI without any independent predictive factors affecting long-term cure rate. Urgency was the only predictive factor affecting patient satisfaction. However, high BMI, low ALPP, and high grade of incontinence may impair the cure rate of the TVT.     

TVT-O for the Treatment of Pure Urodynamic Stress Incontinence: Efficacy,Adverse Effects,and Prognostic Factors at 5-Year Follow-up

Background

Inside-out tension-free vaginal transobturator tape (TVT-O) is currently one of the most effective and popular procedures for the surgical treatment of female stress urinary incontinence (SUI), but data reporting long-term outcomes are scarce.

Objective

To evaluate the efficacy and safety of TVT-O 5-yr implantation for management of pure SUI in women.

Design, setting, and participants

A prospective observational study was conducted in four tertiary reference centers. Consecutive women presenting with urodynamically proven, pure SUI treated by TVT-O were included. Patients with mixed incontinence and/or anatomic evidence of pelvic organ prolapse were excluded.

Intervention

TVT-O implantation without any associated procedure.

Outcome measurements and statistical analysis

Data regarding subjective outcomes (International Consultation on Incontinence-Short Form [ICIQ-SF], Patient Global Impression of Improvement, patient satisfaction scores), objective cure (stress test) rates, and adverse events were collected during follow-up. Multivariable analyses were performed to investigate outcomes.

Results and limitations

Of the 191 women included, 21 (11.0%) had previously undergone a failed anti-incontinence surgical procedure. Six (3.1%) patients were lost to follow-up. The 5-yr subjective and objective cure rates were 90.3% and 90.8%, respectively. De novo overactive bladder (OAB) was reported by 24.3% of patients at 5-yr follow-up. Median ICIQ-SF score significantly improved from 17 (interquartile range [IQR]:16–17) preoperatively to 0 (IQR: 0–2) (p < 0.0001).Failure of a previous anti-incontinence procedure was the only independent predictor of subjective recurrence of SUI (hazard ratio [HR]: 4.4; p = 0.009) or objective (HR: 3.7; p = 0.02). No predictive factor of de novo OAB was identified.

Conclusions

TVT-O implantation is a highly effective option for the treatment of women with pure SUI, showing a very high cure rate and a low incidence of complications after 5-yr follow-up.     

A Randomized Comparison of a Single-incision Midurethral Sling and a Transobturator Midurethral Sling in Women with Stress Urinary Incontinence: Results of 12-mo Follow-up

Background

Midurethral sling procedures have become the prime surgical treatment for women with stress urinary incontinence (SUI). Single-incision mini-slings (SIMS) potentially offer similar efficacy with reduced morbidity. This international multicenter trial compared the efficacy and morbidity of a SIMS (MiniArc) and a transobturator standard midurethral sling (SMUS) (Monarc).

Objective

To compare subjective and objective cure, morbidity, and surgery-related discomfort following SIMS and transobturator SMUS.

Design, setting, and participants

Prospective randomized controlled trial with an initial follow-up period of 12 mo. Women with symptomatic SUI were eligible.

Outcome measurements and statistical analysis

Primary outcome was subjective cure, defined as an improvement on the Patient Global Impression of Improvement (PGI-I). Coprimary outcome was the mean visual analog scale (VAS) pain score (0–100) during 3 d after surgery. Secondary outcomes were objective cure based on the cough stress test (CST), disease-specific quality of life determined by the Urogenital Distress Inventory (UDI-6) score, surgical parameters, and physical performance during recovery. Analysis was by intent to treat. Differences between the MiniArc and Monarc groups on dichotomous variables were chi-square tested and presented as relative risks (RR) with corresponding 95% confidence intervals. We hypothesized that MiniArc was noninferior to Monarc concerning subjective cure and superior concerning postoperative pain.

Results and limitations

We randomized 97 women to MiniArc and 96 to Monarc. At 12-mo follow-up, subjective cure was 83% following MiniArc and 86% following Monarc (p = 0.46). Objective cure was 89% following MiniArc and 91% following Monarc (p = 0.65). The mean pain VAS score during the first three postoperative days was 9 following MiniArc and 22 following Monarc (Mann-Whitney U test, p < 0.01).

Conclusions

At 1-yr follow-up, MiniArc was noninferior to Monarc with respect to subjective and objective cure and superior with respect to postoperative pain.

Patient summary

This 1-yr randomized clinical trial showed that MiniArc, a single-incision midurethral sling, is noninferior to Monarc, a transobturator sling, with respect to cure and superior with respect to pain and recovery.     

Surgical Treatment of Recurrent Stress Urinary Incontinence in Women: A Systematic Review and Meta-analysis of Randomised Controlled Trials

Context

Recurrent stress urinary incontinence (R-SUI) represents a management dilemma; however, only a limited number of randomised controlled trials (RCTs) have assessed the various surgical procedures used for its treatment.

Objective

To assess the effectiveness and complications of various surgical procedures for the treatment of female R-SUI.

Evidence acquisition

A prospective peer-reviewed protocol was prepared a priori. A systematic literature review of all published RCTs comparing surgical procedures for treatment of R-SUI was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Data were analysed using RevMan 5.

Evidence synthesis

We conducted a literature search from 1945 to February 2013. Data were available for a total of 350 women in 10 RCTs with a mean follow-up of 18.1 mo. Meta-analysis was possible for the comparison of retropubic tension-free vaginal tape (RP-TVT) versus transobturator tension-free vaginal tape (TO-TVT) in five RCTs (n = 135). There was no statistically significant difference between RP-TVT and TO-TVT in the patient-reported improvement (odds ratio [OR]: 0.84, 95% confidence interval [CI], 0.41–1.69) or objective cure/improvement (OR: 1.75; 95% CI, 0.86–3.54). One RCT showed a trend towards a higher rate of patient-reported and objective cure/improvement with the inside-out TO-TVT compared with the outside-in; however, it was not statistically significant (OR: 3.00; 95% CI, 0.85–10.57, and OR: 3.32; 95% CI, 0.96–11.41, respectively). There was no significant difference between Burch colposuspension and RP-TVT (one RCT) in patient-reported improvement (OR: 0.33; 95% CI, 0.01–8.57) or objective cure/improvement (OR: 0.52; 95% CI, 0.13–2.05).

Conclusions

This meta-analysis shows no evidence of a significant difference in patient-reported and objective cure/improvement rates between RP-TVT and TO-TVT in the surgical treatment of women with R-SUI. However, due to the relatively low number of patients, the analysis might be underpowered. This review highlights the poor level of evidence in this field and the need for well-designed clinical trials to address this important clinical dilemma.     

Tension-free vaginal tape for the treatment of urodynamic stress incontinence: efficacy and adverse effects at 10-year follow-up

Background

One of the most effective and popular current procedures for the surgical treatment of stress urinary incontinence (SUI) is tension-free midurethral slings.

Objective

To evaluate the outcomes of women with retropubic tension-free vaginal tape (TVT) for urodynamic stress incontinence (USI) after 10-yr follow-up.

Design, setting, and participants

This was a prospective observational study. Consecutive women with proven USI were treated with TVT. Patients with mixed incontinence and/or anatomic evidence of pelvic organ prolapse were excluded.

Intervention

Standard retropubic TVT.

Measurements

Patients underwent preoperative clinical and urodynamic evaluations. During follow-up examinations, women were assessed for subjective satisfaction and objective cure rates. Multivariable analyses were performed to investigate outcomes.

Results and limitations

A total of 63 women were included. After 10 yr, 5 patients (8%) were lost or no longer evaluable. The 10-yr subjective, objective, and urodynamic cure rates were 89.7%, 93.1%, and 91.4%, respectively. These rates were stable across the whole study period (p > 0.99). De novo overactive bladder was reported by 30.1% and 18.9% of patients at 3-mo and 10-yr follow-up, respectively (p for trend = 0.19). A total of 84.2% of women with detrusor overactivity received antimuscarinic drugs, but 43.8% were nonresponders 12 wk later. At multivariable analysis, maximum detrusor pressure during the filling phase >9 cm H₂O (hazard ratio [HR]: 16.2; p = 0.01) and maximum detrusor pressure during the voiding phase ≤29 cm H₂O (HR: 8.0; p = 0.01) were independent predictors for the recurrence of SUI, as well as obesity was for the recurrence of objective SUI (HR: 17.1; p = 0.01) and of USI (HR: 8.9; p = 0.02), respectively. Intraoperatively, bladder perforation occurred in two cases; no severe bleeding or other complications occurred.

Conclusions

The 10-yr results of this study seem to demonstrate that TVT is a highly effective option for the treatment of female SUI, recording a very high cure rate with low complications after a 10-yr follow-up.     

Temporal Trends,Practice Patterns,and Treatment Outcomes for Infected Upper Urinary Tract Stones in the United States

Background

The incidence of infected urolithiasis is unknown, and evidence describing the optimal management strategy for obstruction is equivocal.

Objective

To examine the trends of infected urolithiasis in the United States, the practice patterns of competing treatment modalities, and to compare adverse outcomes.

Design, setting, and participants

A weighted estimate of 396 385 adult patients hospitalized with infected urolithiasis was extracted from the Nationwide Inpatient Sample, 1999–2009.

Outcome measurements and statistical analysis

Time trend analysis examined the incidence of infected urolithiasis and associated sepsis, as well as rates of retrograde ureteral catheterization and percutaneous nephrostomy (PCN) for urgent/emergent decompression. Propensity-score matching compared the rates of adverse outcomes between approaches.

Results and limitations

Between 1999 and 2009, the incidence of infected urolithiasis in women increased from 15.5 (95% confidence interval [CI], 15.3–15.6) to 27.6 (27.4–27.8)/100 000); men increased from 7.8 (7.7–7.9) to 12.1 (12.0–12.3)/100 000. Rates of associated sepsis increased from 6.9% to 8.5% (p = 0.013), and severe sepsis increased from 1.7% to 3.2% (p < 0.001); mortality rates remained stable at 0.25–0.20% (p = 0.150). Among those undergoing immediate decompression, 113 459 (28.6%), PCN utilization decreased from 16.1% to 11.2% (p = 0.001), with significant regional variability. In matched analysis, PCN showed higher rates of sepsis (odds ratio [OR]: 1.63; 95% CI, 1.52–1.74), severe sepsis (OR: 2.28; 95% CI, 2.06–2.52), prolonged length of stay (OR: 3.18; 95% CI, 3.01–3.34), elevated hospital charges (OR: 2.71; 95%CI, 2.57–2.85), and mortality (OR: 3.14; 95%CI, 13–4.63). However, observational data preclude the assessment of timing between outcome and intervention, and disease severity.

Conclusions

Between 1999 and 2009, women were twice as likely to have infected urolithiasis. Rates of associated sepsis and severe sepsis increased, but mortality rates remained stable. Analysis of competing treatment strategies for immediate decompression demonstrates decreasing utilization of PCN, which showed higher rates of adverse outcomes. These findings should be viewed as preliminary and hypothesis generating, demonstrating the pressing need for further study.     

Systematic Review and Meta-Analysis of Robotic-Assisted versus Conventional Laparoscopic Pyeloplasty for Patients with Ureteropelvic Junction Obstruction: Effect on Operative Time,Length of Hospital Stay,Postoperative Complications,and Success Rate

Background

Although robotic-assisted procedures may theoretically be more advantageous than conventional laparoscopic ones, few studies have shown clear superiority of robotic-assisted laparoscopic pyeloplasty (RAP) over conventional laparoscopic pyeloplasty (CLP) for ureteropelvic junction obstruction (UPJO).

Objective

To undertake a systematic review and meta-analysis to evaluate the effect of RAP versus CLP for patients with UPJO, focusing on operative time, length of hospital stay, postoperative complications, and success rate.

Design, setting, and participants

We searched four electronic bibliographic databases, including the related articles PubMed feature, reference lists from articles, and program abstracts from scientific meetings. Consequently, 58 citations were identified. Two individuals independently screened the titles and abstracts of each citation to select the articles (90% agreement).

Intervention

Studies that compared RAP with CLP for treatment of UPJO were included. Case series on RAP or CLP were excluded because of large heterogeneity.

Measurements

We utilized weighted mean difference (WMD) to measure operative time and length of hospital stay and odds ratio (OR) and risk difference (RD) to measure complication and success rates. These ORs were pooled using a random effects model and were tested for heterogeneity.

Results

We identified eight publications that strictly met our eligibility criteria. Meta-analysis of extractable data showed that RAP was associated with a 10-min operative time reduction (WMD: −10.4 min; 95% CI: −24.6–3; p = 0.15) and significantly shorter hospital stay compared with CLP (WMD: −0.5 d; 95% CI: −0.6–−0.4; p < 0.01). There were no differences between the approaches with regard to rates of complication (OR: 0.7; 95% CI: 0.3–1.6; p = 0.40) and success (OR: 1.3; 95% CI: 0.5–3.5; p = 0.62).

Conclusions

RAP and CLP appear to be equivalent with regard to postoperative urinary leaks, hospital readmissions, success rates, and operative time.     

The Clinical Effectiveness of Retropubic (IVS-02) and Transobturator (IVS-04) Midurethral Slings: Randomized Trial

Background

Few series comparing the clinical efficacy of retropubic slings versus transobturator slings for the treatment of female stress urinary incontinence (SUI) are available.

Objective

To compare clinical efficacy of retropubic tape operations and transobturator suburethral tape operations for the surgical treatment of female SUI.

Design, setting, and participants

From January 2003 to December 2005, 611 patients underwent clinical and urodynamic evaluation before surgical treatment for SUI. Patients with advanced urogenital prolapse (pelvic organ prolapse-quantification scale [POP-Q] scale grade >1) were excluded, and 537 patients were included in this study. After 18 mo, 398 women were available for follow-up efficacy evaluation at a tertiary academic center.

Intervention

All patients underwent either a retropubic sling procedure or a transobturator sling procedure. Patients were randomly allocated into two study groups at a ratio of 1:1.

Measurements

After 18 mo all enrolled patients were clinically checked for clinical efficacy of both procedures.

Results and limitations

Demographic and urodynamic parameters of patients were similar in both groups. No bladder injury occurred in the transobturator sling group (IVS-04), whereas 13 intraoperational bladder perforations (6.5%) occurred in the retropubic sling group (IVS-02) (p < 0.001). The tape erosion rate was <2.5% in both groups (p = 0.7). After 18 mo, 398 patients (201 in the IVS-02 group and 197 in the IVS-04 group) were evaluated in terms of clinical efficacy of the procedures. We found out that there was no statistically significant difference in clinical efficacy between these two procedures (χ² = 1.88, p = 0.39). In the IVS-02 group, 75.1% of patients (n = 151) remained dry (cured), 16.9% of patients (n = 34) reported significant improvement, and 8.0% of patients (n = 16) were considered as failures. In the IVS-04 group, 74.1% of patients (n = 146) remained dry, 14.2% of patients (n = 28) reported significant improvement, and 11.7% (n = 23) were considered as failures.

Conclusions

Based on an 18-mo follow-up, the efficacies of both techniques are comparable; however, the retropubic route appears to be more efficient in the intrinsic sphincter deficiency (ISD) group.     

Tension-Free Vaginal Tape Versus Transobturator Suburethral Tape: Five-Year Follow-up Results of a Prospective,Randomised Trial

Background

Many studies have assessed the equivalent effectiveness of tension-free vaginal tape (TVT) and transobturator suburethral tape (TVT-O) at short- to medium-term follow-up, but no long-term randomised trials appear in the literature.

Objective

We compared the use of TVT to TVT-O, providing a longer follow-up than currently appears in the literature.

Design, setting, and participants

Seventy-two consecutive patients affected by stress urinary incontinence (SUI) were included in this randomised, controlled trial. Patients were randomly allocated to the TVT or TVT-O procedure using a predetermined, computer-generated randomisation code.

Intervention

After preoperative assessment, patients were randomly allocated to the TVT or TVT-O procedure.

Measurements

This 5-yr study represents the extension of our original randomised trial, which was designed to assess the incidence of long-term complications (primary end point) and successes (secondary end point) for both techniques.

Results and limitations

At 60-mo follow-up, 52 patients (72%) were objectively cured of SUI (72.9% after TVT-O and 71.4% after TVT), but only 44 patients (61%) were satisfied. The late complication rate was 16.6% (10 women): five women (16.1%) in the TVT-O group and five women (17.2%) in the TVT group (p = 1). In this follow-up, 62% of the patients from the TVT-O group and 60% from the TVT group (p = 1) expressed that they were satisfied or very satisfied with the results. The mean cause of dissatisfaction was the development of sexual dysfunction resulting from dyspareunia or incontinence during intercourse, which was found in 6 of 16 dissatisfied patients (37.5%). The limitations of our study included the adequate but small sample size and the lack of questionnaires.

Conclusions

Both surgical techniques are safe, with similar results (72.9% and 71% of patients objectively cured after TVT-O and TVT, respectively) and low complication rates (16.6%: 16.1% and 17.2%, respectively, for TVT-0 and TVT), even after 5-yr follow-up.     

A randomized comparison of transobturator tape and Burch colposuspension in the treatment of female stress urinary incontinence

This study was performed to compare the efficacy of transobturator tape (TOT) and Burch colposuspension in the treatment of female stress urinary incontinence (SUI). This is a prospective randomized single blind study of 100 women diagnosed as with urodynamic SUI who were randomized either to TOT procedure (n = 49) or Burch procedure (n = 51). The outcome was evaluated at 1 and 2 years. The mean operation time and hospital stay were significantly shorter in the TOT group compared to Burch group (p < 0.001). Procedure-related complications and postoperative voiding problems including postoperative urinary retention, de novo voiding difficulties and de novo urge incontinence were similar in the two groups. Both the subjective and objective cure rates of SUI at 1 year were 85.7 and 87.5%, respectively, in the TOT group. This was similar to subjective and objective cure rates at one year of 84.3% (p = 0.8) and 80.3% (p = 0.4) in the Burch group, respectively. At the end of 2 years, 32 patients were available in the TOT group and 31 patients were available in the Burch group for analysis. Both the subjective and objective cure rates of SUI at 2 years were 87.5 and 87.5% in the TOT group which was similar to the 87% (p = 0.9) and 83.8% (p = 0.6) in the Burch group, respectively. TOT procedure results in similar cure rates of SUI at 1 and 2 years compared to Burch procedure. The TOT procedure has a shorter operative time and length of hospital stay.     

A Prospective Multicenter Randomized Comparative Study Between the U- and H-type Methods of the TVT SECUR Procedure for the Treatment of Female Stress Urinary Incontinence: 1-Year Follow-Up

Background

No studies have been published comparing the U- and H-type methods of the TVT SECUR (TVT-S) procedure.

Objective

Our aim was to compare the efficacy and safety of the two types of TVT-S for female stress urinary incontinence (SUI).

Design, setting, and participants

Women with urodynamic SUI were enrolled in this 12-mo multicenter randomized study.

Intervention

Subjects were randomly allocated to either the U- or H-type method of TVT-S.

Measurements

Pre- and postoperative evaluations included a standing stress test, the Sandvik questionnaire, the Incontinence Quality of Life (I-QOL) questionnaire, and the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS). Patients’ satisfaction and complications were evaluated. Objective and subjective cures were defined as no leakage on the stress test and responses on the Sandvik questionnaire, respectively. We compared the surgical outcomes between the two methods.

Results and limitations

Of 285 women, 144 had the U-type method and 141 had the H-type method. Objective cure rates were 87.5% for the U-type method and 80.1% for the H-type method (p = 0.091). Subjective cure rates were 77.1% for the U-type method and 75.7% for the H-type method (p = 0.786). Improvement in I-QOL and domain scores of the ICIQ-FLUTS (filling and incontinence sum, QOL score), and patients’ satisfaction favored the U-type method. There were three cases of intraoperative vaginal wall perforation, one case of increased bleeding, and three cases of temporary postoperative retention. A power calculation was not performed, and some baseline characteristics were not balanced between the two methods.

Conclusions

Both methods of TVT-S provided comparable cure rates for female SUI. However, QOL and treatment satisfaction favored the U-type method.

Trial registration

The protocol of this study was not registered.     

Meta-analysis of plasma to red blood cell ratios and mortality in massive blood transfusions for trauma

Background

The current military paradigm for blood transfusion in major trauma favours high plasma:RBC ratios. This study aimed determine whether high plasma:red blood cell (RBC) ratios during massive transfusion for trauma decrease mortality, using meta-analysis of contemporaneous groups matched for injury severity score.

Methods

A systemic review of the published literature for massive blood transfusions in trauma was performed. Patients were categorised into groups based on plasma:RBC transfusion ratios. Meta-analysis was only performed when there were no significant differences in Injury Severity Score (ISS) between ratio groups within studies. The main endpoint was 30-day mortality.

Results

Six observational studies reporting outcomes for 1885 patients were included in this meta-analysis. Five studies were from civilian environments and one from a military setting. Ratio cut-offs at 1:2 were the most commonly reported, demonstrating a survival advantage with higher ratios (OR 0.49, 95% CI 0.31–0.80, p = 0.004). Ratios ≥ 1:2 showed a significant reduction in mortality compared to lower ratios (OR 0.56, 95% CI 0.40–0.78, p < 0.001). Reducing the cut-off level was still protective (ratios between 1:2.5 and 1:4, OR 0.41), although the confidence interval was wide (0.16–1.00, p = 0.05) and data heterogenous (I² = 78%). Ratios of 1:1 were not proven to confer additional benefit beyond ratios of 1:2 (OR 0.50, 95% CI 0.37–0.68, p < 0.001).

Conclusions

In groups matched for ISS, there was a survival benefit with high plasma:RBC resuscitation ratios. No additional benefits of 1:1 over 1:2 ratios were identified.     

Developing a burn injury severity score (BISS): Adding age and total body surface area burned to the injury severity score (ISS) improves mortality concordance

Background

There is limited research validating the injury severity score (ISS) in burns. We examined the concordance of ISS with burn mortality. We hypothesized that combining age and total body surface area (TBSA) burned to the ISS gives a more accurate mortality risk estimate.

Methods

Data from the Royal Perth Hospital Trauma Registry and the Royal Perth Hospital Burns Minimum Data Set were linked. Area under the receiver operating characteristic curve (AUC) measured concordance of ISS with mortality. Using logistic regression models with death as the dependent variable we developed a burn-specific injury severity score (BISS).

Results

There were 1344 burns with 24 (1.8%) deaths, median TBSA 5% (IQR 2–10), and median age 36 years (IQR 23–50). The results show ISS is a good predictor of death for burns when ISS ≤ 15 (OR 1.29, p = 0.02), but not for ISS > 15 (ISS 16–24: OR 1.09, p = 0.81; ISS 25–49: OR 0.81, p = 0.19). Comparing the AUCs adjusted for age, gender and cause, ISS of 84% (95% CI 82–85%) and BISS of 95% (95% CI 92–98%), demonstrated superior performance of BISS as a mortality predictor for burns.

Conclusion

ISS is a poor predictor of death in severe burns. The BISS combines ISS with age and TBSA and performs significantly better than the ISS.     

Combination of CK20 and Ki-67 Immunostaining Analysis Predicts Recurrence,Progression, and Cancer-Specific Survival in pT1 Urothelial Bladder Cancer

Background

The prognostic value of CK20, Ki-67, and p53 has been investigated for non–muscle-invasive urothelial bladder cancers but not for the distinct and clinically challenging subset of pT1 bladder cancers.

Objective

To evaluate the prognostic value of CK20, Ki-67, and p53 within the largest series of pT1 urothelial bladder cancers.

Design, setting, and participants

Data from 309 patients with pT1 urothelial bladder cancer from one single urologic centre were collected.

Intervention

Adjuvant instillation of bacillus Calmette-Guérin was performed in each patient. A second resection was performed after 4–8 wk. A total of 76 patients underwent cystectomy.

Outcome measurements and statistical analysis

We conducted histomorphologic analysis; immunohistochemistry for CK20, Ki-67, and p53; and univariate and multivariate Cox regression models including recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS).

Results and limitations

At a median follow-up of 49 mo, we found recurrence and progression and disease-specific mortality rates of 22.7%, 20.1%, and 15.9%, respectively. CK20 expression was significantly correlated with RFS in multivariate analysis (hazard ratio [HR]: 5.89; 95% confidence interval [CI], 1.44–24.15; p = 0.014). In multivariate analysis, Ki-67 was the only marker significantly correlated with PFS (HR: 2.80; 95% CI, 1.45–5.43, p = 0.002). Ki-67 (HR: 3.83; 95% CI, 1.59–9.26; p = 0.003), and CK20 (HR: 8.44; 95% CI,1.16–61.34; p = 0.035) were significantly correlated with CSS in multivariate analysis. The combination of CK20 and Ki-67 showed significantly worse RFS (p = 0.026), PFS (p = 0.003), and CSS (p < 0.001) in tumours with a high proliferation index and abnormal CK20 expression. A retrospective study design was the major limitation of this study.

Conclusions

Our present analysis of the largest series of patients with pT1 urothelial bladder cancer published to date found Ki-67 and CK20 to be potential prognostic markers improving the risk stratification of pT1 bladder tumours. They are reliable indicators of biologic aggressiveness and may contribute to decision making on therapeutic strategy for pT1 bladder carcinomas.     

The Application of Artificial Intelligence to Microarray Data: Identification of a Novel Gene Signature to Identify Bladder Cancer Progression

Background

New methods for identifying bladder cancer (BCa) progression are required. Gene expression microarrays can reveal insights into disease biology and identify novel biomarkers. However, these experiments produce large datasets that are difficult to interpret.

Objective

To develop a novel method of microarray analysis combining two forms of artificial intelligence (AI): neurofuzzy modelling (NFM) and artificial neural networks (ANN) and validate it in a BCa cohort.

Design, setting, and participants

We used AI and statistical analyses to identify progression-related genes in a microarray dataset (n = 66 tumours, n = 2800 genes). The AI-selected genes were then investigated in a second cohort (n = 262 tumours) using immunohistochemistry.

Measurements

We compared the accuracy of AI and statistical approaches to identify tumour progression.

Results and limitations

AI identified 11 progression-associated genes (odds ratio [OR]: 0.70; 95% confidence interval [CI], 0.56–0.87; p = 0.0004), and these were more discriminate than genes chosen using statistical analyses (OR: 1.24; 95% CI, 0.96–1.60; p = 0.09). The expression of six AI-selected genes (LIG3, FAS, KRT18, ICAM1, DSG2, and BRCA2) was determined using commercial antibodies and successfully identified tumour progression (concordance index: 0.66; log-rank test: p = 0.01). AI-selected genes were more discriminate than pathologic criteria at determining progression (Cox multivariate analysis: p = 0.01). Limitations include the use of statistical correlation to identify 200 genes for AI analysis and that we did not compare regression identified genes with immunohistochemistry.

Conclusions

AI and statistical analyses use different techniques of inference to determine gene–phenotype associations and identify distinct prognostic gene signatures that are equally valid. We have identified a prognostic gene signature whose members reflect a variety of carcinogenic pathways that could identify progression in non–muscle-invasive BCa.     

Use of Potentially Curative Therapies for Muscle-invasive Bladder Cancer in the United States: Results from the National Cancer Data Base

Background

Despite its lethal potential, many patients with muscle-invasive bladder cancer (MIBC) do not receive aggressive, potentially curative therapy consistent with established practice standards.

Objective

To characterize the treatments received by patients with MIBC and analyze their use according to sociodemographic, clinical, pathologic, and facility measures.

Design, setting, and participants

Using the National Cancer Data Base, we analyzed 28 691 patients with MIBC (stages II–IV) treated between 2004 and 2008, excluding those with cT4b tumors or distant metastases. Treatments included radical or partial cystectomy with or without chemotherapy (CT), chemoradiotherapy (CRT), radiation therapy (RT), or CT alone and observation following biopsy. Aggressive therapy (AT) was defined as radical or partial cystectomy or definitive RT/CRT (total dose ≥50 Gy).

Outcome measurements and statistical analysis

AT use and correlating variables were assessed by multivariable, generalized estimating equation models adjusted for facility clustering.

Results and limitations

According to the database, 52.5% of patients received AT; 44.9% were treated surgically, 7.6% received definitive CRT or RT, and 25.9% of patients received observation only. AT use decreased with advancing age (odds ratio [OR]: 0.34 for age 81–90 yr vs ≤50 yr; p < 0.001). AT use was also lower in racial minorities (OR: 0.74 for black race; p < 0.001), the uninsured (OR: 0.73; p < 0.001), Medicaid-insured patients (OR: 0.81; p = 0.01), and at low-volume centers (OR: 0.64 vs high-volume centers; p < 0.001). Use of AT was higher with increasing tumor stage (OR: 2.23 for T3/T4a vs T2; p < 0.001) and nonurothelial histology (OR: 1.25 and 1.43 for squamous and adenocarcinoma, respectively; p < 0.001). Study limitations include retrospective design and lack of information about patient and provider motivations regarding therapy selection.

Conclusions

AT for MIBC appears underused, especially in the elderly and in groups with poor socioeconomic status. These data point to a significant unmet need to inform policy makers, payers, and physicians regarding appropriate therapies for MIBC.     

Laparoendoscopic Single-site Partial Nephrectomy: A Multi-institutional Outcome Analysis

Background

Laparoendoscopic single-site surgery (LESS) has been developed in an attempt to further reduce the surgical trauma associated with conventional laparoscopy. Partial nephrectomy (PN) represents a challenging indication for LESS.

Objective

To report a large multi-institutional series of LESS-PN and to analyze the predictors of outcomes after LESS-PN.

Design, setting, and participants

Consecutive cases of LESS-PN done between November 2007 and March 2012 at 11 participating institutions were included in this retrospective analysis.

Intervention

Each group performed LESS-PN according to its own protocols, entry criteria, and techniques.

Outcome measurements and statistical analysis

Demographic data, main perioperative outcome parameters, and perioperative complications were gathered and analyzed. A multivariable analysis was used to assess the factors predicting a short (≤20 min) warm ischemia time (WIT), the occurrence of postoperative complication of any grade, and a favorable outcome, arbitrarily defined as a combination of the following events: short WIT plus no perioperative complications plus negative surgical margins plus no conversion to open surgery or standard laparoscopy.

Results and limitations

A total of 190 cases were included in this analysis. Mean renal tumor size was 2.6, and PADUA score 7.2. Median operative time was 170 min, with median estimated blood loss (EBL) of 150 ml. A clampless technique was adopted in 70 cases (36.8%), and the median WIT was 16.5 min. PADUA score independently predicted length of WIT (low vs high score: odds ratio [OR]: 5.11 [95% confidence interval (CI), 1.50–17.41]; p = 0.009; intermediate vs high score: OR: 5.13 [95% CI, 1.56–16.88]; p = 0.007). The overall postoperative complication rate was 14.7%. The adoption of a robotic LESS technique versus conventional LESS (OR: 20.92 [95% CI, 2.66–164.64]; p = 0.003) and the occurrence of lower (≤250 ml) EBL (OR: 3.60 [95% CI, 1.35–9.56]; p = 0.010) were found to be independent predictors of no postoperative complications of any grade. A favorable outcome was obtained in 83 cases (43.68%). On multivariate analysis, the only predictive factor of a favorable outcome was the PADUA score (low vs high score: OR: 4.99 [95% CI, 1.98–12.59]; p < 0.001). Limitations of the study were the retrospective design and different selection criteria for the participating centers.

Conclusions

LESS-PN can be safely and effectively performed by experienced hands, given a high likelihood of a single additional port. Anatomic tumor characteristics as determined by the PADUA score are independent predictors of a favorable surgical outcome. Thus patients presenting tumors with low PADUA scores represent the best candidates for LESS-PN. The application of a robotic platform is likely to reduce the overall risk of postoperative complications.     

Analgesia in the management of paediatric and adolescent trauma during the resuscitative phase: The role of the pediatric trauma centre

Background

The objective of this study was to evaluate the use of analgesia in the resuscitative phase of severely injured children and adolescents.

Methods

A retrospective cohort of paediatric (age < 18 years), severely injured (ISS ≥ 12) patients were identified from the London Health Sciences Centre's Trauma Registry from 2007 to 2010. Variables were compared between Analgesia and Non-analgesia groups with Pearson Chi-square and Mann–Whitney U tests. Resuscitative analgesia use was assessed through multivariable logistic regression controlling for age, gender, mechanism, arrival and Trauma Team Activation (TTA).

Results

Analgesia was used in 32% of cases. Univariate analysis did not reveal any differences in gender, age, injury type, injury profile and arrival patterns. Significant differences were found with analgesia used more frequently in patients injured in a motor vehicle collision (58% vs. 42%, p = 0.026) and having parents in the resuscitation room (17% vs. 6%, p = 0.01). Analgesia patients were more injured (median ISS 22 vs. 17, p = 0.027) and had 2.25 times more TTA (39% vs. 17%). Logistic regression revealed patients arriving directly to a trauma centre had a higher incidence of receiving analgesia (OR 2.01, 95% CI: 1.03–3.93), as did TTA (OR 2.18, 95% CI: 1.01–4.73) and having parents in resuscitation room (3.56, 95% CI: 1.23–10.33). Narcotics were most commonly used (85%), followed by benzodiazepines (16%), with 66% given during the primary survey.

Conclusion

Use of analgesia is important in the acute management of paediatric trauma. Direct presentation to a level I trauma centre, TTA and the presence of parents lead to higher appropriate use of analgesia in paediatric trauma resuscitation.     

Photodynamic Diagnosis of Non–muscle-invasive Bladder Cancer with Hexaminolevulinate Cystoscopy: A Meta-analysis of Detection and Recurrence Based on Raw Data

Background

Studies on hexaminolevulinate (HAL) cystoscopy report improved detection of bladder tumours. However, recent meta-analyses report conflicting effects on recurrence.

Objective

To assess available clinical data for blue light (BL) HAL cystoscopy on the detection of Ta/T1 and carcinoma in situ (CIS) tumours, and on tumour recurrence.

Design, setting, and participants

This meta-analysis reviewed raw data from prospective studies on 1345 patients with known or suspected non–muscle-invasive bladder cancer (NMIBC).

Intervention

A single application of HAL cystoscopy was used as an adjunct to white light (WL) cystoscopy.

Outcome measurements and statistical analysis

We studied the detection of NMIBC (intention to treat [ITT]: n = 831; six studies) and recurrence (per protocol: n = 634; three studies) up to 1 yr. DerSimonian and Laird's random-effects model was used to obtain pooled relative risks (RRs) and associated 95% confidence intervals (CIs) for outcomes for detection.

Results and limitations

BL cystoscopy detected significantly more Ta tumours (14.7%; p < 0.001; odds ratio [OR]: 4.898; 95% CI, 1.937–12.390) and CIS lesions (40.8%; p < 0.001; OR: 12.372; 95% CI, 6.343–24.133) than WL. There were 24.9% patients with at least one additional Ta/T1 tumour seen with BL (p < 0.001), significant also in patients with primary (20.7%; p < 0.001) and recurrent cancer (27.7%; p < 0.001), and in patients at high risk (27.0%; p < 0.001) and intermediate risk (35.7%; p = 0.004). In 26.7% of patients, CIS was detected only by BL (p < 0.001) and was also significant in patients with primary (28.0%; p < 0.001) and recurrent cancer (25.0%; p < 0.001). Recurrence rates up to 12 mo were significantly lower overall with BL, 34.5% versus 45.4% (p = 0.006; RR: 0.761 [0.627–0.924]), and lower in patients with T1 or CIS (p = 0.052; RR: 0.696 [0.482–1.003]), Ta (p = 0.040; RR: 0.804 [0.653–0.991]), and in high-risk (p = 0.050) and low-risk (p = 0.029) subgroups. Some subgroups had too few patients to allow statistically meaningful analysis. Heterogeneity was minimised by the statistical analysis method used.

Conclusions

This meta-analysis confirms that HAL BL cystoscopy significantly improves the detection of bladder tumours leading to a reduction of recurrence at 9–12 mo. The benefit is independent of the level of risk and is evident in patients with Ta, T1, CIS, primary, and recurrent cancer.