Homicide Among American Indians/Alaska Natives, 1999-2009: Implications for Public Health Interventions.

OBJECTIVE: We determined estimates of homicide among American Indians/Alaska Natives (AI/ANs) compared with non-Hispanic white people to characterize disparities and improve AI/AN classification in incidence and mortality reporting. METHODS: We linked 1999-2009 death certificate data with Indian Health Service (IHS) patient registration data to examine death rates from homicide among AI/AN and non-Hispanic white people. Our analysis focused primarily on residents of IHS Contract Health Service Delivery Area counties and excluded Hispanic people to avoid underestimation of incidence and mortality in AI/ANs and for consistency in our comparisons. We used age-adjusted death rates per 100,000 population and stratified our analyses by sex, age, and IHS region. RESULTS: Death rates per 100,000 population from homicide were four times higher among AI/ANs (rate = 12.1) than among white people (rate = 2.8). Homicide rates for AI/ANs were highest in the Southwest (25.6 and 6.9 for males and females, respectively) and in Alaska (17.7 and 10.3 for males and females, respectively). Disparities between AI/ANs and non-Hispanic white people were highest in the Northern Plains region among men (rate ratio [RR] = 9.8, 95% confidence interval [CI] 8.5, 11.3) and among those aged 25-44 years (RR59.0, 95% CI 7.5, 10.7) and 0-24 years (RR57.4, 95% CI 6.1, 8.9). CONCLUSION: Death rates from homicide among AI/ANs were higher than previously reported and varied by sex, age, and region. Violence prevention efforts involving a range of stakeholders are needed at the community level to address this important public health issue.

Long-term oncological outcomes of a phase II trial of neoadjuvant chemohormonal therapy followed by radical prostatectomy for patients with clinically localised, high-risk prostate cancer.

OBJECTIVE: To determine long-term oncological outcomes of radical prostatectomy (RP) after neoadjuvant chemohormonal therapy (CHT) for clinically localised, high-risk prostate cancer. PATIENTS AND METHODS: In this phase II multicentre trial of patients with high-risk prostate cancer (PSA level >20 ng/mL, Gleason ≥8, or clinical stage ≥T3), androgen-deprivation therapy (goserelin acetate depot) and paclitaxel, carboplatin and estramustine were administered before RP. We report the long-term oncological outcomes of these patients and compared them to a contemporary cohort who met oncological inclusion criteria but received RP only. RESULTS: In all, 34 patients were enrolled and followed for a median of 13.1 years. Within 10 years most patients had biochemical recurrence (BCR-free probability 22%; 95% confidence interval [CI] 10-37%). However, the probability of disease-specific survival at 10 years was 84% (95% CI 66-93%) and overall survival was 78% (95% CI 60-89%). The CHT group had higher-risk features than the comparison group (123 patients), with an almost doubled risk of calculated preoperative 5-year BCR (69% vs 36%, P < 0.01). After adjusting for these imbalances the CHT group had trends toward improvement in BCR (hazard ratio [HR] 0.76, 95% CI 0.43-1.34; P = 0.3) and metastasis-free survival (HR 0.55, 95% CI 0.24-1.29; P = 0.2) although these were not statistically significant. CONCLUSIONS: Neoadjuvant CHT followed by RP was associated with lower rates of BCR and metastasis compared with the RP-only group; however, these results were not statistically significant. Because this treatment strategy has known harms and unproven benefit, this strategy should only be instituted in the setting of a clinical trial.

Comparison of perioperative outcomes of retroperitoneal and transperitoneal minimally invasive partial nephrectomy after adjusting for tumor complexity.

OBJECTIVE: To evaluate and compare perioperative outcomes of transperitoneal and retroperitoneal (RP) laparoscopic and robotic partial nephrectomies (LPNs) while adjusting for tumor complexity. MATERIALS AND METHODS: Retrospective review was conducted of 191 patients who underwent transperitoneal (n = 116) or RP (n = 75) LPN. To adjust for tumor complexity, individual components of the radius, exophytic or endophytic properties, nearness to the collecting system or sinus, anterior or posterior location, and location in reference to polar lines (R.E.N.A.L.) nephrometry score were used in multivariate linear and logistic regression models to compare perioperative outcomes between the 2 groups. A propensity approach was also used to adjust for multiple covariates. Investigated outcomes included estimated blood loss (EBL), ischemia and operative times, length of hospital stay, margin status, opioid use, postoperative estimated glomerular filtration rate, complications within 30 days, and readmission rates. RESULTS: Tumors resected by RPLPN were more likely to have lower complexity score by nephrometry (P = .04). Four of the 5 components of the R.E.N.A.L. nephrometry score were significantly different between the groups. After adjustment for these factors, a lower EBL was noted in the RP group (ß, -97; 95% confidence interval, -156 to -39; P = .001). Risk of readmission for the RP group was significantly lower (odds ratio, 0.15; P = .024) using propensity analysis. CONCLUSION: Using adjustment for tumor complexity, RPLPN was associated with lower EBL and readmission rates supporting the potential clinical advantage for this approach when feasible.

Characteristics of acupuncture treatment associated with outcome: an individual patient meta-analysis of 17,922 patients with chronic pain in randomised controlled trials.

BACKGROUND: Recent evidence shows that acupuncture is effective for chronic pain. However we do not know whether there are characteristics of acupuncture or acupuncturists that are associated with better or worse outcomes. METHODS: An existing dataset, developed by the Acupuncture Trialists' Collaboration, included 29 trials of acupuncture for chronic pain with individual data involving 17,922 patients. The available data on characteristics of acupuncture included style of acupuncture, point prescription, location of needles, use of electrical stimulation and moxibustion, number, frequency and duration of sessions, number of needles used and acupuncturist experience. We used random-effects meta-regression to test the effect of each characteristic on the main effect estimate of pain. Where sufficient patient-level data were available, we conducted patient-level analyses. RESULTS: When comparing acupuncture to sham controls, there was little evidence that the effects of acupuncture on pain were modified by any of the acupuncture characteristics evaluated, including style of acupuncture, the number or placement of needles, the number, frequency or duration of sessions, patient-practitioner interactions and the experience of the acupuncturist. When comparing acupuncture to non-acupuncture controls, there was little evidence that these characteristics modified the effect of acupuncture, except better pain outcomes were observed when more needles were used (p=0.010) and, from patient level analysis involving a sub-set of five trials, when a higher number of acupuncture treatment sessions were provided (p<0.001). CONCLUSION: There was little evidence that different characteristics of acupuncture or acupuncturists modified the effect of treatment on pain outcomes. Increased number of needles and more sessions appear to be associated with better outcomes when comparing acupuncture to non-acupuncture controls, suggesting that dose is important. Potential confounders include differences in control group and sample size between trials. Trials to evaluate potentially small differences in outcome associated with different acupuncture characteristics are likely to require large sample sizes.

TMPRSS2-ERG rearrangement in dominant anterior prostatic tumours: incidence and correlation with ERG immunohistochemistry.

AIM: To study prostate cancer zonal differences in TMPRSS2-ERG gene rearrangement. METHODS AND RESULTS: We examined 136 well-characterized dominant anterior prostatic tumours, including 61 transition zone (TZ) and 75 anterior peripheral zone (PZ) lesions, defined using strict anatomical considerations. TMPRSS2-ERG FISH and ERG protein immunohistochemistry were performed on tissue microarrays. FISH results, available for 56 TZ and 71 anterior PZ samples, were correlated with ERG staining and TZ-associated 'clear cell' histology. Fewer TZ cancers (four of 56; 7%) were rearranged than anterior PZ cancers (18 of 71; 25%) (P = 0.009); deletion was the sole mechanism of TZ cancer rearrangement. ERG protein overexpression was present in 4% (two of 56; both FISH+) and 30% (21 of 71; 17 FISH+) of TZ and anterior PZ tumours, respectively. 'Clear cell' histology was present in 21 of 56 (38%) TZ and eight of 71 (11%) anterior PZ tumours. Seven per cent of cancers with and 21% without this histology had rearrangement, regardless of zonal origin. CONCLUSIONS: TMPRSS2-ERG rearrangement occurs in dominant TZ and anterior PZ prostate cancers, with all rearranged TZ cancers in this cohort showing deletion. ERG immunohistochemistry demonstrated excellent sensitivity (86%) and specificity (96%) for TMPRSS2-ERG rearrangement. TMPRSS2-ERG fusion is rare in TZ tumours and present at a low frequency in tumours displaying 'clear cell' histology.

Responses to the Acupuncture Trialists' Collaboration individual patient data meta-analysis.

In September 2012 the Acupuncture Trialists' Collaboration published the results of an individual patient data meta-analysis of almost 18 000 patients in high quality randomised trials. The results favoured acupuncture. Although there was little argument about the findings in the scientific press, a controversy played out in blog posts and the lay press. This controversy was characterised by ad hominem remarks, anonymous criticism, phony expertise and the use of opinion to contradict data, predominantly by self-proclaimed sceptics. There was a near complete absence of substantive scientific critique. The lack of any reasoned debate about the main findings of the Acupuncture Trialists' Collaboration paper underlines the fact that mainstream science has moved on from the intellectual sterility and ad hominem attacks that characterise the sceptics' movement.

Urine neutrophil gelatinase-associated lipocalin as a marker of acute kidney injury after kidney surgery.

PURPOSE: We evaluated urine NGAL as a marker of acute kidney injury in patients undergoing partial nephrectomy. We sought to identify the preoperative clinical features and surgical factors during partial nephrectomy that are associated with renal injury, as measured by increased urine NGAL vs controls. MATERIALS AND METHODS: Using patients treated with radical nephrectomy or thoracic surgery as controls, we prospectively collected and analyzed urine and serum samples from patients treated with partial or radical nephrectomy, or thoracic surgery between April 2010 and April 2012. Urine was collected preoperatively and at multiple time points postoperatively. Differences in urine NGAL levels were analyzed among the 3 surgical groups using a generalized estimating equation model. The partial nephrectomy group was subdivided based on a preoperative estimated glomerular filtration rate of less than 60, or 60 ml/minute/1.73 m(2) or greater. RESULTS: Of 162 patients included in final analysis more than 65% had cardiovascular disease. The median estimated glomerular filtration rate was greater than 60 ml/minute/1.73 m(2) in the radical and partial nephrectomy, and thoracic surgery groups (61, 78 and 84.5 ml/minute/1.73 m(2), respectively). Preoperatively, a 10 unit increase in the estimated glomerular filtration rate was associated with a 4 unit decrease in urine NGAL in the partial nephrectomy group. Postoperatively, urine NGAL in the partial nephrectomy group was not higher than in controls and did not correlate with ischemia time. Patients with partial nephrectomy with a preoperative estimated glomerular filtration rate of less than 60 ml/minute/1.73 m(2) had higher urine NGAL postoperatively than those with a higher preoperative estimated rate. CONCLUSIONS: Urine NGAL does not appear to be a useful marker for detecting renal injury in healthy patients treated with partial nephrectomy. However, patients with poorer preoperative renal function have higher baseline urine levels and appear more susceptible to acute kidney injury, as detected by urine levels and Acute Kidney Injury Network criteria, than those with a normal estimated glomerular filtration rate.

Urinary diversion practice patterns among certifying American urologists.

PURPOSE: We investigated trends in urinary diversion use and surgeon characteristics in the performance of incontinent and continent urinary diversion using American Board of Urology data. MATERIALS AND METHODS: Annualized case log data for urinary diversion were obtained from the American Board of Urology for urologists who certified or recertified from 2002 to 2010. We evaluated the association between surgeon characteristics and the performance of any urinary diversion or the type of urinary diversion. RESULTS: Of the 5,096 certifying or recertifying urologist case logs examined 1,868 (37%) urologists performed any urinary diversion. The median number of urinary diversions was 4 per year (IQR 2, 6) and 222 urologists (4%) performed 10 or more per year. On multivariate analysis younger urologists, those self-identified as oncologists or female urologists, those who certified in more recent years and those in larger practice areas or outside the Northeast region of the United States were more likely to perform any urinary diversion. Only 9% of the total cohort (471 urologists) performed any continent urinary diversion. The likelihood of performing any continent urinary diversion increased with the number of urinary diversions (p <0.0001). As urinary diversion volume increased, the proportion representing continent urinary diversion also increased (p <0.0005). Surgeons in private practice settings and those in the Northeast were less likely to perform continent urinary diversion. CONCLUSIONS: Few urologists perform any urinary diversion. Continent urinary diversion is most frequently done by high volume surgeons. The type of urinary diversion that a patient receives may depend in part on surgeon characteristics.

Prognostic impact of subclassification of radical prostatectomy positive margins by linear extent and Gleason grade.

PURPOSE: We evaluated the relationship of progression to positive surgical margin linear length and Gleason grade at a positive surgical margin. MATERIALS AND METHODS: We studied 2,150 prostatectomies done for pT2 or pT3a disease to determine grade, stage and surgical margin status. In patients with positive surgical margins we recorded the location, number, positive margin linear length and highest Gleason grade at a positive margin. The Kaplan-Meier method and log rank test were used to determine differences in progression-free probability among positive margin features. The concordance index was used to discriminate the accuracy of grouping surgical margin status as negative/positive vs positive margin linear length/highest Gleason grade. RESULTS: A total of 207 cases (10%) showed positive surgical margins, including 93 (45%) that were pT2+ and 114 (55%) that were pT3a. Patients with pT3a and positive margins had greater prostate specific antigen and tumor volume, and Gleason score 7 or greater than those with pT2+. A total of 45 patients with positive margins progressed. We then subcategorized positive margins. Of the patients 164 (79%) had 1 positive margin. Positive margin linear length was 1 mm or less, 1.1 to 3 and greater than 3 in 104 (50%), 55 (27%) and 48 cases (23%), respectively. Two-year progression-free probability was 95%, 91%, 83% and 47% in patients with negative margins and the 3 positive margin linear length groups, respectively (p <0.001). Gleason grade at a positive margin was 3 and 4/5 in 154 (74%) and 53 patients (26%), respectively. The latter group was significantly more likely to progress (p <0.001). The overall margin status concordance index was 0.636. It was not considerably enhanced by categorizing by positive surgical margin linear length/highest Gleason grade at positive margins. CONCLUSIONS: The linear extent of and highest Gleason grade at a positive surgical margin are associated with progression. However, subcategorization does not importantly add to predictive models using margin status only. More robust markers are needed in patients with positive surgical margins to warrant routine reporting and identify those at risk for biochemical recurrence.

Clinically significant prostate cancer is rarely missed by ablative procedures of the prostate in men with prostate specific antigen less than 4 ng/ml.

PURPOSE: Laser vaporization of the prostate is widely used to treat lower urinary tract symptoms. It may decrease the hospital cost and morbidity associated with transurethral resection of the prostate. However, prostate cancer may go undetected because tissue is not taken at laser vaporization. To our knowledge the rate of clinically significant prostate cancer missed by laser vaporization has not been assessed to date. We determined the rate of clinically significant prostate cancer detected by transurethral resection of the prostate compared to the estimated number of cancers missed by laser vaporization. MATERIALS AND METHODS: A total of 74,505 men diagnosed with stage T1 prostate cancer between 2004 and 2006 were identified from the SEER (Surveillance, Epidemiology and End Results) program in the United States. The total number of laser vaporizations and transurethral resections were calculated based on Medicare claims for the same period. Clinically significant cancer was defined as that with a Gleason score of 7 or greater in men 40 to 75 years old. RESULTS: If prostate specific antigen screening were used uniformly (excluding men with prostate specific antigen greater than 4 ng/ml), only 1 of 382 transurethral resections of the prostate would identify clinically significant prostate cancer for a total of 390 in the American population in 3 years. Based on Medicare reported laser vaporization use a total of only 163 clinically significant cancers would be missed in more than 60,000 procedures. CONCLUSIONS: The incidence of T1a and T1b prostate cancer remains low and few patients have clinically significant prostate cancer. When prostate specific antigen screening is used, the number of clinically significant tumors missed by ablative procedures is low (average of 0.26% of all procedures) and can be identified by prostate specific antigen screening.

Contemporary practice patterns of endoscopic surgical management for benign prostatic hyperplasia among urologists in the United States.

PURPOSE: We describe contemporary trends in endoscopic surgical management for benign prostatic hyperplasia. We examined case logs submitted by urologists for American Board of Urology certification or recertification. We compared electrosurgical transurethral resection of the prostate vs laser vaporization or laser enucleation and determined the impact of surgeon age on practice patterns. MATERIALS AND METHODS: We analyzed case logs from 2004 to 2010 for trends and used logistic regression models to assess the impact of surgeon age on endoscopic surgery use. RESULTS: A total of 3,955 urologists included at least 1 endoscopic surgical management in the case logs, while 2,334 (59%) exclusively performed electrosurgical transurethral resection of the prostate and 309 (8%) exclusively performed laser vaporization or laser enucleation. We observed a large increase in the number and proportion of laser procedures from 11% in 2004 to 44% in 2010. Although there was no difference in median age between urologists who performed exclusively electrosurgical transurethral resection and those who performed laser procedures, the latter had a substantially higher case volume. Older urologists were significantly less likely to perform laser vaporization or enucleation when undergoing the second recertification (OR 0.56/10 years of age, 95% CI 0.36-0.87, p = 0.009), but not the initial certification. CONCLUSIONS: There was a substantial increase in laser vaporization or laser enucleation procedures performed by urologists who underwent board certification or recertification in 2004 to 2010. However, of those undergoing the second recertification older age was significantly associated with a lower likelihood of performing laser procedures. These data provide estimates of current practice patterns and further our understanding of evolving surgical treatment for benign prostatic hyperplasia.

Acupuncture for chronic pain: individual patient data meta-analysis.

BACKGROUND: Although acupuncture is widely used for chronic pain, there remains considerable controversy as to its value. We aimed to determine the effect size of acupuncture for 4 chronic pain conditions: back and neck pain, osteoarthritis, chronic headache, and shoulder pain. METHODS: We conducted a systematic review to identify randomized controlled trials (RCTs) of acupuncture for chronic pain in which allocation concealment was determined unambiguously to be adequate. Individual patient data meta-analyses were conducted using data from 29 of 31 eligible RCTs, with a total of 17 922 patients analyzed. RESULTS: In the primary analysis, including all eligible RCTs, acupuncture was superior to both sham and no-acupuncture control for each pain condition (P < .001 for all comparisons). After exclusion of an outlying set of RCTs that strongly favored acupuncture, the effect sizes were similar across pain conditions. Patients receiving acupuncture had less pain, with scores that were 0.23 (95% CI, 0.13-0.33), 0.16 (95% CI, 0.07-0.25), and 0.15 (95% CI, 0.07-0.24) SDs lower than sham controls for back and neck pain, osteoarthritis, and chronic headache, respectively; the effect sizes in comparison to no-acupuncture controls were 0.55 (95% CI, 0.51-0.58), 0.57 (95% CI, 0.50-0.64), and 0.42 (95% CI, 0.37-0.46) SDs. These results were robust to a variety of sensitivity analyses, including those related to publication bias. CONCLUSIONS: Acupuncture is effective for the treatment of chronic pain and is therefore a reasonable referral option. Significant differences between true and sham acupuncture indicate that acupuncture is more than a placebo. However, these differences are relatively modest, suggesting that factors in addition to the specific effects of needling are important contributors to the therapeutic effects of acupuncture.

International variation in artificial urinary sphincter use.

OBJECTIVE: To analyze international trends in artificial urinary sphincter (AUS) use, indications for placement, and application by gender. METHODS: We conducted a retrospective review of data derived from patient information forms sent to American Medical Systems. There were 86 140 unique cases from March 1975 through December 2008, including all indications. RESULTS: AUS use increased worldwide from 1975 (90 procedures) through 2008 (4818 procedures). In 2008, patients with postprostatectomy incontinence (PPI) accounted for 61% (2907/4751) of AUS use compared to 12% (8/66) in 1975. Artificial urinary sphincter annual implant rates in women were much lower than in men, decreasing from 298 procedures in 1990 to 67 in 2008. Artificial urinary sphincter implants in the United States for men alone accounted for the majority (62%, 2995/4818) of worldwide artificial urinary sphincter use in 2008. Conversely, artificial urinary sphincter use has recently started declining in other areas, including South America and Canada. Frequency of artificial urinary sphincter surgery varied dramatically from less than 0.01 per 100 000 population in Brazil to 0.99 in the United States. Of surgeons performing artificial urinary sphincter implants in 2008, case volumes in and outside of the United States were similarly low: 56% in the United States and 52% outside the United States performed only 1 artificial urinary sphincter implant, whereas 76% in the United States and 73% outside the United States did fewer than 3. CONCLUSION: Artificial urinary sphincter use has continued to increase internationally over the study period, especially for patients with PPI. However, artificial urinary sphincter use exhibits considerable regional variation, and most surgeons performed very low annual case volumes of implants.

Surgical practice patterns for male urinary incontinence: analysis of case logs from certifying American urologists.

PURPOSE: Several options exist for the surgical correction of male stress urinary incontinence including periurethral bulking agents, artificial urinary sphincters and the recently introduced male urethral slings. We investigated contemporary trends in the use of these treatments. MATERIALS AND METHODS: Annualized case log data for incontinence surgeries from certifying and recertifying urologists were obtained from the ABU (American Board of Urology), ranging from 2004 to 2010. Chi-square tests and logistic regression models were used to evaluate the association between surgeon characteristics (type of certification, annual volume, practice type and practice location) and the use of incontinence procedures. RESULTS: Among the 2,036 nonpediatric case logs examined the number of incontinence treatments reported for certification has steadily increased over time from 1,936 to 3,366 treatments per year from 2004 to 2010 (p = 0.008). Nearly a fifth of urologists reported placing at least 1 sling. The proportion of endoscopic procedures decreased from 80% of all incontinence procedures in 2004 to 60% in 2010, but they remained the exclusive incontinence procedure performed by 49% of urologists. A urologist's increased use of endoscopic treatments was associated with a decreased likelihood of performing a sling procedure (OR 0.5, p <0.0005). Artificial urinary sphincter use remained stable, accounting for 12% of procedures. CONCLUSIONS: Incontinence procedures are on the rise. Urethral slings have been widely adopted and account for the largest increase among treatment modalities. Endoscopic treatments continue to be commonly performed and may represent overuse in the face of improved techniques. Further research is required to validate these trends.

Systematic classification and prediction of complications after nephrectomy in patients with metastatic renal cell carcinoma (RCC).

UNLABELLED: Study Type - Harm (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Radical nephrectomy for patients with metastatic renal cell carcinoma results in greater rates of morbidity than for those with less advanced disease. This study systematically characterizes complications associated with nephrectomy for metastatic RCC and identifies patient and disease characteristics that are associated with a greater risk of developing complications. Overall complications were relatively frequent, but major complications (grade 3 or greater) were rare. Increasing age and worsening performance status were associated with increased probability of complications. When complications were sustained, patients were less likely to receive systemic therapy in a timely fashion. These observations may influence the timing or patient selection for surgery or systemic therapy. OBJECTIVE: • To evaluate and identify factors predictive for morbidity after radical nephrectomy in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: • We identified patients with mRCC who underwent nephrectomy at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1989 and 2009. • Postoperative complications were characterised using a modified version of the Clavien-Dindo classification system. • Patient and disease characteristics, including a previously validated MSKCC risk-stratification system using calcium, haemoglobin (Hb), lactate dehydrogenase, and Karnofsky Performance Status (KPS), were evaluated as predictors of postoperative complications using univariate and multivariable logistic regression models. • The area under the receiver operating characteristic curve (AUC) was calculated for each model to assess predictive accuracy and corrected for overfit using 10-fold cross validation. RESULTS: • Over the study period, 195 patients with mRCC underwent nephrectomy; 53 (27%) developed grade ≥ 2 complications within 8 weeks of surgery. • Pulmonary, thromboembolic events and anaemia requiring transfusion were the most common types of complications after nephrectomy in the metastatic setting. • In univariate analysis, age, low albumin, low KPS, high corrected serum calcium, low serum Hb, and unfavourable MSKCC risk score were predictive of complications. • Patients who sustained postoperative complications were less likely to receive systemic therapy within 56 days (odds ratio [OR] 0.32; 95% confidence interval [CI] 0.12-0.86; P= 0.024). • A multivariable model containing KPS (OR 14.5; 95%CI 4.34-48.6; P < 0.001) and age (OR 1.04; 95%CI 1.01-1.08; P= 0.014) showed the greatest predictive accuracy (corrected AUC 0.72; 95%CI 0.63-0.80) for postoperative complications. CONCLUSIONS: • Postoperative complications after radical nephrectomy in the setting of mRCC are common and occur frequently in older patients and those with worse KPS. • These complications are important because they may delay or deny receipt of subsequent systemic therapy.

Intraoperative mannitol use does not improve long-term renal function outcomes after minimally invasive partial nephrectomy.

OBJECTIVE: To evaluate intravenous mannitol during minimally invasive partial nephrectomy (PN) by comparing the renal function outcomes of the patients who received it versus those who did not. METHODS: Of 285 consecutive elective minimally invasive PN cases from February 2005 to July 2010, 164 patients (58%) were treated with mannitol. We compared the renal function recovery using a multivariate generalized estimating equation linear model of estimated glomerular filtration rate (eGFR) controlling for nephrometry complexity, preoperative eGFR, American Society of Anesthesiologists score, ischemia time, estimated blood loss, age, and sex. Sensitivity analyses were performed to adjust for cold ischemia and individual surgeon differences corrected for year of surgery. RESULTS: Of the 285 patients who underwent minimally invasive treatment, 164 received mannitol and 121 did not. Those who received mannitol had a better preoperative eGFR (median 72 vs 69 mL/min/m(2), P = .046), less complex nephrometry scores (P = 0.051), and were less likely to have an American Society of Anesthesiologists score of ≥ 3 (42% vs 54%, P = .005). Renal function recovery was similar in both groups (estimated effect of mannitol -0.7 mL/min/m(2), 95% confidence interval -3.6-2.2, P = .6). At no point in the postoperative period did mannitol make a significant difference in the eGFR according to the generalized estimating equation model after adjusting for multiple potential renal function confounders. CONCLUSION: Mannitol use did not influence renal function recovery within 6 months of minimally invasive PN as measured by the eGFR in our analysis. An appropriately designed prospective study of mannitol is being conducted to validate its use during PN.

Evaluating the utility of a preoperative nomogram for predicting 90-day mortality following radical cystectomy for bladder cancer.

OBJECTIVE: To evaluate the performance of the Isbarn nomogram for predicting 90-day mortality following radical cystectomy in a contemporary series. PATIENTS AND METHODS: We identified 1141 consecutive radical cystectomy patients treated at our institution between 1995 and 2005 with at least 90 days of follow-up. We applied the published nomogram to our cohort, determining its discrimination, with the area under the receiver operating characteristic curve (AUC), and calibration. We further compared it with a simple model using age and the Charlson comorbidity score. RESULTS: Our cohort was similar to that used to develop the Isbarn nomogram in terms of age, gender, grade and histology; however, we observed a higher organ-confined (≤pT2, N0) rate (52% vs 24%) and a lower overall 90-day mortality rate [2.8% (95% confidence interval 1.9%, 3.9%) vs 3.9%]. The Isbarn nomogram predicted individual 90-day mortality in our cohort with moderate discrimination [AUC 73.8% (95% confidence interval 64.4%, 83.2%)]. In comparison, a model using age and Charlson score alone had a bootstrap-corrected AUC of 70.2% (95% confidence interval 67.2%, 75.4%). CONCLUSIONS: The Isbarn nomogram showed moderate discrimination in our cohort; however, the exclusion of important preoperative comorbidity variables and the use of postoperative pathological stage limit its utility in the preoperative setting. The use of a simple model combining age and Charlson score yielded similar discriminatory ability and underscores the significance of individual patient variables in predicting outcomes. An accurate tool for predicting postoperative morbidity/mortality following radical cystectomy would be valuable for treatment planning and counselling. Future nomogram design should be based on preoperative variables including individual risk factors, such as comorbidities.

The surgical learning curve for artificial urinary sphincter procedures compared to typical surgeon experience.

BACKGROUND: The artificial urinary sphincter (AUS) is a well-established treatment for male stress urinary incontinence. OBJECTIVE: We aimed to characterize the surgical learning curve for reoperation rates after AUS implantation. DESIGN, SETTING, AND PARTICIPANTS: The study cohort consisted of 65 602 adult males who received an AUS between 1988 and 2008, constituting close to 90% of all operations conducted during that time. Data on reoperations were obtained from the manufacturer, which requires documentation for warranty coverage. MEASUREMENTS: Surgeon experience was calculated as the number of original AUS implants performed prior to the index patient's surgery. Multivariable logistic regression models were used to examine the association between experience and reoperative rates, adjusted for case mix. RESULTS AND LIMITATIONS: There was a slow but steady decrease in reoperative rates with increasing surgeon experience (p=0.020), showing no plateau through 200 procedures. The risk of reoperation for a surgeon with five prior cases was 24.0%, which decreased to 18.1% for a surgeon with 100 prior implants (absolute risk difference [ARD]: 5.9%; 95% confidence interval [CI], 1.3-10.1%) and to 13.2% for a surgeon with 200 prior implants (ARD: 10.7%; 95% CI, 2.6-16.6%). Two-thirds of contemporary patients (having AUS procedure between years 2000 and 2008) saw a surgeon who had done ≤25 prior AUS implants; only 9% saw a surgeon with ≥100 prior procedures. CONCLUSIONS: The learning curve for AUS surgery appears to be very long and without an obvious plateau. This is in contrast to typical surgeon experience, suggesting a considerable burden of avoidable reoperations. Efforts to flatten the learning are urgently needed.

Prognostic significance of lymphovascular invasion in radical prostatectomy specimens.

UNLABELLED: Study Type - Prognosis (case series). LEVEL OF EVIDENCE: 4. What's known on the subject? and What does the study add? The reported incidence of lymphovascular invasion (LVI) in radical prostatectomy specimens ranges from 5% to 53%. Although LVI has a strong and significant association with adverse clinicopathologic features, it has almost uniformly not been found to be a predictor of biochemical recurrence (BR) on multivariate analysis. This study confirms that LVI is associated with features of aggressive disease and is an independent predictor of BCR. Given that LVI may play a role in the metastatic process, it may be useful in clinical decision-making regarding adjuvant therapy for patients treated with RP. OBJECTIVES: To determine whether lymphovascular invasion (LVI) in radical prostatectomy (RP) specimens has prognostic significance. The study examined whether LVI is associated with clinicopathological characteristics and biochemical recurrence (BCR). PATIENTS AND METHODS: LVI was evaluated based on routine pathology reports on 1298 patients treated with RP for clinically localized prostate cancer between 2004 and 2007. LVI was defined as the unequivocal presence of tumour cells within an endothelium-lined space. The association between LVI and clinicopathological features was assessed with univariate logistic regression. Cox regression was used to test the association between LVI and BCR. RESULTS: LVI was identified in 10% (129/1298) of patients. The presence of LVI increased with advancing pathological stage: 2% (20/820) in pT2N0 patients, 16% (58/363) in pT3N0 patients and 17% (2/12) in pT4N0 patients; and was highest in patients with pN1 disease (52%; 49/94). Univariate analysis showed an association between LVI and higher preoperative prostate-specific antigen levels and Gleason scores, and a greater likelihood of extraprostatic extension, seminal vesicle invasion, lymph node metastasis and positive surgical margins (all P < 0.001). With a median follow-up of 27 months, LVI was significantly associated with an increased risk of BCR after RP on univariate (P < 0.001) and multivariate analysis (hazard ratio, 1.77; 95% confidence interval, 1.11-2.82; P = 0.017). As a result of the relatively short follow-up, the predictive accuracy of the standard clinicopathological features was high (concordance index, 0.880), and inclusion of LVI only marginally improved the predictive accuracy (0.884). CONCLUSIONS: Although associated with features of aggressive disease and BCR, LVI added minimally to established predictors on short follow-up. Further study of cohorts with longer follow-up is warranted to help determine its prognostic significance.

Individual patient data meta-analysis of acupuncture for chronic pain: protocol of the Acupuncture Trialists' Collaboration.

BACKGROUND: The purpose of clinical trials of acupuncture is to help clinicians and patients make decisions about treatment. Yet this is not straightforward: some trials report acupuncture to be superior to sham (placebo) acupuncture while others show evidence that acupuncture is superior to usual care but not sham, and still others conclude that acupuncture is no better than usual care. Meta-analyses of these trials tend to come to somewhat indeterminate conclusions. This appears to be because, until recently, acupuncture research was dominated by small trials of questionable quality. The Acupuncture Trialists' Collaboration, a group of trialists, statisticians and other researchers, was established to synthesize patient-level data from several recently published large, high-quality trials. METHODS: There are three distinct phases to the Acupuncture Trialists Collaboration: a systematic review to identify eligible studies; collation and harmonization of raw data; statistical analysis. To be eligible, trials must have unambiguous allocation concealment. Eligible pain conditions are osteoarthritis; chronic headache (tension or migraine headache); shoulder pain; and non-specific back or neck pain. Once received, patient-level data will undergo quality checks and the results of prior publications will be replicated. The primary analysis will be to determine the effect size of acupuncture. Each trial will be evaluated by analysis of covariance with the principal endpoint as the dependent variable and, as covariates, the baseline score for the principal endpoint and the variables used to stratify randomization. The effect size for acupuncture from each trial--that is, the coefficient and standard error from the analysis of covariance--will then be entered into a meta-analysis. We will compute effect sizes separately for comparisons of acupuncture with sham acupuncture, and acupuncture with no acupuncture control for each pain condition. Other analyses will investigate the impact of different sham techniques, styles of acupuncture or frequency and duration of treatment sessions. DISCUSSION: Individual patient data meta-analysis of high-quality trials will provide the most reliable basis for treatment decisions about acupuncture. Above all, however, we hope that our approach can serve as a model for future studies in acupuncture and other complementary therapies.