Media reporting of ProtecT: a disconnect in information dissemination?

BACKGROUND: Given the central role of the media in disseminating information to the public, we analyzed news coverage of the recent publication from ProtecT to assess views on treatment, the level of detail presented and degree of bias. METHODS: We applied a predefined search strategy to identify all news articles reporting on ProtecT within 30 days of its publication. Articles were independently assessed by two urologists and two lay persons using five-point Likert scales. Descriptive statistics and analysis of variance were used. RESULTS: Of 33 unique articles identified, 20 (61%) conveyed negative views on definitive treatment for localized prostate cancer (PCa), while 29 (88%) expressed favorable views of active surveillance/monitoring (AM). Nevertheless, fewer than half of the articles described what AM entails (n=15; 46%) or the rate of treatment in the AM arm (n=12; 36%). Moreover, while 32 (97%) articles highlighted the absence of a difference in cancer-specific mortality at 10 years, only 17 (52%) mentioned the need for longer follow-up. A total of 17 (52%) articles had a notable degree of perceived bias (⩾4/5 on Likert scale), with shorter articles (P=0.02), articles covering few content areas (P=0.03) and articles that did not detail what AM entails (P=0.003) containing significantly increased bias. CONCLUSIONS: The majority of news articles regarding ProtecT presented an adverse view of definitive treatment for localized PCa relative to AM, but failed to highlight key nuances of the trial. Healthcare professionals and the lay public should be cautious in acquiring medical news through the general media. Additionally, the urologic community must continue to improve the quality of disseminated information, for example, through proactively engaging with the media, through social media and/or through participation in continuing education lecture series, so as to guide the knowledge translation process, especially upon publication of such potentially influential studies.

Gleason grading after neoadjuvant hormonal therapy retains prognostic value for systemic progression following radical prostatectomy.

BACKGROUND: The Gleason grading system in prostatectomy specimens following receipt of neoadjuvant therapy has been considered inaccurate. However, with continuing expansion of novel therapeutics, it is important to understand whether the Gleason system can be effectively utilized in this setting. The aim of this study was to assess the ability of the Gleason grading system to predict systemic progression among prostatectomy specimens treated with neoadjuvant hormone therapy (NHT). METHODS: This was a single-institution retrospective analysis from 1987 to 2009 of 13,427 patients who underwent radical prostatectomy (RP) without NHT and 1148 patients with NHT. NHT consisted of leuprolide alone (n = 415), antiandrogen therapy alone (n = 400) and combined treatment (n = 333). Kaplan-Meier analysis estimated 15-year systemic progression-free survival among NHT and non-NHT patients. Cox proportional hazard regression models estimated risk of systemic progression following RP according to NHT use and nonuse. RESULTS: Median duration of NHT was 3 months (interquartile range (IQR) 2-4) whereas median follow-up after RP was 8.3 years (IQR 5-10.8). NHT patients were more likely to be D'Amico high risk, have locally advanced pathologic T stage (≥ pT3), pathologic Gleason scores (GS) of 8-10 and lymph node involvement (P<0.0001 for all). NHT use was associated with lower rates of positive surgical margins, more downgrading to pT0 and less GS upgrading from biopsy (P ≤ 0.001 for all). GS could not be assigned to only 3% of NHT patients. On multivariate analysis, pathologic GS remained a predictor of systemic progression (SP) following NHT (hazard ratio (HR) 1.6, P = 0.005), but the association was less strong compared with non-NHT patients (HR 2.9, P < 0.0001). CONCLUSIONS: Utilization of the Gleason system appears feasible among hormonally pretreated prostatectomy specimens and shows continued prognostication for systemic progression. Confirmatory investigations are needed before the Gleason system can be reliably applied in the setting of neoadjuvant therapy.

Association between neuraxial analgesia, cancer progression, and mortality after radical prostatectomy: a large, retrospective matched cohort study.

BACKGROUND: Systemic opioids are immunosuppressive, which could promote tumour recurrence. We, therefore, test the hypothesis that supplementing general anaesthesia with neuraxial analgesia improves long-term oncological outcomes in patients having radical prostatectomy for adenocarcinoma. METHODS: Patients who had general anaesthesia with neuraxial analgesia (n=1642) were matched 1:1 based on age, surgical year, pathological stage, Gleason scores, and presence of lymph node disease with those who had general anaesthesia only. Medical records were reviewed. Outcomes of interest were systemic cancer progression, recurrence, prostate cancer mortality, and all-cause mortality. Data were analysed using stratified proportional hazards regression, the Kaplan-Meier method, and log-rank tests. The median follow-up was 9 yr. RESULTS: After adjusting for comorbidities, positive surgical margins, and adjuvant hormonal and radiation therapies within 90 postoperative days, general anaesthesia only was associated with increased risk for systemic progression [hazard ratio (HR)=2.81, 95% confidence interval (CI) 1.31-6.05; P=0.008] and higher overall mortality (HR=1.32, 95% CI 1.00-1.74; P=0.047). Although not statistically significant, similar findings were observed for the outcome of prostate cancer deaths (adjusted HR=2.2, 95% CI 0.88-5.60; P=0.091). CONCLUSIONS: This large retrospective analysis suggests a possible beneficial effect of regional anaesthetic techniques on oncological outcomes after prostate surgery for cancer; however, these findings need to be confirmed (or refuted) in randomized trials.

Laparoendoscopic single-site and transvaginal nephrectomy.

Significant energy has been applied to development of minimally-invasive techniques in surgery to decrease morbidity, improve cosmesis, and hasten postoperative convalescence without compromising surgical outcomes. The evolution of laparoscopy has revolutionized simple, radical and donor nephrectomy in appropriately selected patients, exchanging large flank and abdominal incisions for small "keyhole" incisions. Surgeons continue to pursue innovative approaches to minimize the morbidity of procedures. Natural orifice translumenal endoscopic surgery (NOTES) eliminates entirely the need for abdominal incisions, while laparoendoscopic single-site (LESS) surgery permits placement of multiple instruments through a single incision. Together, they represent two novel approaches developed within the last decade that have been successfully applied to nephrectomy in both the laboratory and clinical settings. Here, the transvaginal and LESS approaches to nephrectomy are reviewed.

Robotic partial nephrectomy: a multi-institutional analysis.

Laparoscopic partial nephrectomy for kidney tumors has demonstrated durable oncologic and functional outcomes. The feasibility of robotic partial nephrectomy (RPN) has been demonstrated in several small, single-institution studies. We performed a large, multi-institutional analysis to determine early oncologic results and perioperative outcomes after RPN. Between October, 2002 and September, 2007, 148 patients underwent RPN at six different centers by nine different primary surgeons for localized renal tumors. Medical and operative records were reviewed for clinical characteristics, pathologic findings, and follow-up information. A total of 148 patients underwent RPN. Mean tumor size was 2.8 cm. Renal hilar clamping was utilized in 120 patients, with a mean warm ischemia time of 27.8 min. Positive surgical margins were identified in six patients (4%), of which two had cautery artifact obscuring the margin after off-clamp cautery excision and one underwent completion radical nephrectomy with no evidence of cancer. There is no evidence of tumor recurrence at mean follow-up of 7.2 months (range 2-54 months) overall, and mean follow-up of 18 months (range 12-23 months) for patients with positive surgical margin. Complications occurred in nine patients (6.1%), including hematoma requiring drainage (n = 1), prolonged ileus (n = 3), pulmonary embolus (n = 2), prolonged urine leak (n = 2), and rhabdomyolysis (n = 1). Two patients underwent open conversion for failure to progress, one patient with morbid obesity and one patient with adhesions from prior ureterolithotomy. Mean hospital stay was 1.9 days. In this multi-institutional series of surgeons beginning their initial experience in RPN, the procedure is a feasible option for minimally invasive, nephron-sparing surgery, with immediate oncologic results and perioperative outcomes comparable with more mature laparoscopic series.

Renal stone epidemiology in Rochester, Minnesota: an update.

Studies in Western countries have suggested an increasing incidence of nephrolithiasis (NL) in the latter part of the 20th century. Therefore, we updated NL epidemiology data for the Rochester population over the years 1970-2000. All Rochester residents with any diagnostic code that could be linked to NL in the years of 1970, 1980, 1990, and 2000 were identified, and the records reviewed to determine if they met the criteria for a symptomatic kidney stone as defined in a previous Rochester, MN study. Age-adjusted incidence (+/-s.e.) of new onset symptomatic stone disease for men was 155.1 (+/-28.5) and 105.0 (+/-16.8) per 100,000 per year in 1970 and 2000, respectively. For women, the corresponding rates were 43.2 (+/-14.0) and 68.4 (+/-12.3) per 100,000 per year, respectively. On average, rates for women increased by about 1.9% per year (P=0.064), whereas rates for men declined by 1.7% per year (P=0.019). The overall man to woman ratio decreased from 3.1 to 1.3 during the 30 years (P=0.006). Incident stone rates were highest for men aged 60-69 years, whereas for women, they plateaued after age 30. Therefore, since 1970 overall NL incidence rates in Rochester have remained relatively flat. However, NL rates for men have declined, whereas rates for women appear to be increasing. The reasons remain to be determined.

Ureteroscopic treatment of upper tract urinary calculi.

Ureteroscopic treatment of upper urinary tract calculi is continuously evolving. Initial reports were limited to the treatment of distal ureteral stones. These cases had mixed success, and compared to modern ureteroscopy, had significant associated morbidity. The entire urinary tract can now be safely accessed via ureteroscopy almost always. Improvements in ureteroscope technology have certainly made this possible. These advances include smaller steerable scopes and sharper optics and video. The enhanced view of the upper urinary tract in combination with advances in lithotripsy, in particular, the holmium laser, has resulted in increased treatment success and reduced procedure related morbidity. This review describes the advances in ureteroscopic technology and provides data regarding treatment success and associated complications.

Complete solo laparoscopic radical prostatectomy: initial experience.

OBJECTIVES: To demonstrate the feasibility of "complete solo" (CS) laparoscopic radical prostatectomy (LRP) performed solely with robotic manipulation of the laparoscope and without any human assistant at all. A comparison was made between CS LRP and the standard technique to identify the advantages and drawbacks. METHODS: Sixteen consecutive patients undergoing CS LRP were compared with the last 16 patients undergoing standard LRP. The standard procedure was performed with five trocars and one human assistant. Therefore, the surgeon had three instruments immediately available and could switch quickly from one to another, while the assistant held the laparoscope and a retractor. The CS method used a voice-controlled robotic arm to manipulate the laparoscope and a mechanical arm for the assisting instrument. RESULTS: The mean operative time in the CS and standard groups was 324 and 347 minutes, respectively (P >0.5). An additional human assistant was required, for 1 hour, in 3 patients of each group. No significant difference was noted between the two groups in terms of catheterization time, hospital stay, positive margin rate, complications, short-term cancer control, or functional results. The CS method has been demonstrated to be highly cost-effective compared with the standard technique. CONCLUSIONS: The CS LRP is feasible and compares favorably with the standard technique. It offers unique advantages in terms of direct control of the operative view, standardization of the assistance, and higher stability of the laparoscope, thus greatly enhancing the surgeon's comfort. The diminished need for human operative assistance provides significant economic and organizational benefits.

The impact of intense laparoscopic skills training on the operative performance of urology residents.

PURPOSE: As laparoscopy has become more commonplace in urology, increased emphasis has been placed on laparoscopic education. We assessed the impact of laparoscopic skills training on the operative performance of urological surgeons inexperienced with laparoscopy. MATERIALS AND METHODS: Urology residents were prospectively randomized to undergo laparoscopic skills training (6) or no training (6). Baseline assessment of operative performance (scale 0 to 35) during porcine laparoscopic nephrectomy was completed by all subjects. Cumulative time to complete laparoscopic tasks using an inanimate trainer was also recorded. The skills training group then practiced inanimate trainer tasks for 30 minutes daily for 10 days. The 2 groups then repeated the timed inanimate trainer tasks and underwent repeat assessment of the ability to perform porcine laparoscopic nephrectomy. RESULTS: At baseline no statistical difference was noted in laparoscopic experience, inanimate trainer time or overall operative assessment in the 2 groups. In the skills training group mean cumulative time to complete inanimate trainer tasks decreased from 341 to 176 seconds (p = 0.003), while in the control group it decreased from 365 to 301 (p = 0.15). Operative assessment improved from initial to repeat porcine laparoscopic nephrectomy regardless of the trained versus control randomization grouping (22.0 to 27.8, p = 0.0008 and 20.8 to 26.5, p = 0.00007, respectively). CONCLUSIONS: In vivo experience enables urological surgeons inexperienced with laparoscopy to improve significantly in all aspects of complex laparoscopic procedures. In this pilot study the magnitude of improvement was independent of additional training in laparoscopic skills. Educational curriculum should include in vivo practice in addition to skills training.

Laparoscopic radiofrequency thermal ablation of renal tissue with and without hilar occlusion.

PURPOSE: Few studies have evaluated the effect of radiofrequency thermal ablation on renal tissue, although it has been used clinically to treat small renal masses. We studied the size and histology of lesions created with radiofrequency thermal ablation administered via the laparoscopic approach with and without hilar occlusion in a porcine model. MATERIALS AND METHODS: The lower pole of each kidney was exposed laparoscopically in 11 farm pigs. In each kidney a 7-electrode dry radiofrequency thermal ablation probe was inserted at an identical location and deployed to a diameter of 2 cm. Energy was applied for 8 minutes at an average temperature of 100C. The left renal hilum of each pig was clamped during radiofrequency thermal ablation. Two pigs were sacrificed immediately, and 3 each were sacrificed at 24 hours, 2 and 4 weeks. The size and shape of the lesions created were measured and examined histologically. RESULTS: There were no intraoperative or postoperative complications. Laparoscopic ultrasound confirmed probe placement but did not monitor lesion progression. Acutely lesions were firm and white with a small adjacent hemorrhagic zone. Histological evaluation revealed preserved renal architecture but the loss of distinct cytoplasmic features. Nicotinamide adenine dinucleotide staining demonstrated no viable cells within the lesions. In surviving animals pelvicaliceal integrity was preserved. In the 2 and 4-week survival groups kidneys treated with hilar occlusion had larger lesions than nonoccluded kidneys but the differences were not significant at 4 weeks (3.2 x 2.7 x 2.5 cm. and 3.5 x 1.7 x 2.0, respectively, p >0.05). Histologically untreated parenchyma of hilar occluded kidneys demonstrated changes consistent with chronic pyelonephritis. In 1 kidney radiofrequency thermal ablation with hilar occlusion resulted in complete lower pole loss at 4 weeks. CONCLUSIONS: In the porcine model renal radiofrequency thermal ablation creates rapid and completely devitalized lesions of consistent size and shape. Hilar occlusion may result in slightly larger lesions but risks damage to the whole renal unit.

Hemostatic laparoscopic partial nephrectomy: initial experience with the radiofrequency coagulation-assisted technique.

OBJECTIVES: The techniques for hemostasis after renal tumor excision have limited the widespread application of laparoscopic partial nephrectomy (LPN). To improve hemostasis and aid visualization, we report our experience with a novel radiofrequency coagulation (RFC) technique for LPN. METHODS: Ten patients underwent RFC-assisted LPN. The demographic and perioperative data were tabulated. Patients were positioned as for laparoscopic nephrectomy, and laparoscopic ports were placed. The kidney within Gerota's fascia was mobilized, and the fat overlying the tumor was carefully removed for pathologic evaluation. Under laparoscopic guidance, a radiofrequency probe was percutaneously inserted into the lesion and deployed to coagulate the lesion and a margin of normal parenchyma. Laparoscopic scissors were used to excise the lesion; additional hemostatic maneuvers were used selectively. RESULTS: The mean renal tumor size was 2.1 cm (range 1.0 to 3.2). The median operative time was 170 minutes and the median blood loss was 125 mL. The RFC technique resulted in complete tissue coagulation within the treated volume, thereby facilitating intraoperative visualization, minimizing blood loss, and permitting rapid and controlled tumor resection. The renal architecture was preserved, allowing accurate diagnosis of renal cell carcinoma and angiomyolipoma in 9 and 1 cases, respectively. No perioperative complications occurred. CONCLUSIONS: The use of RFC is an effective method to facilitate LPN of both exophytic and endophytic masses. By coagulating a margin of normal parenchyma, the technique minimizes blood loss and improves visualization during LPN. We anticipate this technique will broaden the clinical application for LPN.

Current evaluation and management of renal and ureteral stones.

A systematic clinical approach is required for the diagnosis and management of renal and ureteral stones. The presenting symptoms, past medical history, medications, and physical examination all provide clues to the diagnosis of urinary stones. In the acute setting, noncontrast helical computerized tomography has emerged as the first line imaging test for renal colic. More traditional imaging tests are also important in the management of stone disease. After making the diagnosis of a urinary stone, the urologist should discuss the advantages and disadvantages of all treatment options with the patient. For most stone patients today, many equally effective treatment approaches can exist for the same problem. To help direct surgical management, guidelines for stone management have been devised. With technologic advances, stone treatment has improved and complications have decreased. While patient care has been significantly impacted by use of effective endourologic techniques, patients should complete imaging tests following surgery to assure a stone-free state. In addition, recurrent stone formers should complete a medical stone evaluation to identify treatable causes of their stones.

Pathologic staging of renal cell carcinoma: significance of tumor classification with the 1997 TNM staging system.

BACKGROUND: The TNM staging system for renal cell carcinoma was revised by the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) in 1997. The 1997 TNM staging system for renal cell carcinoma reclassifies tumors using criteria for size and for extent of renal vein/vena cava involvement that are different from the criteria used in the 1987 staging system. The current study investigated the prognostic significance of tumor classification and other factors using the new staging system. METHODS: Records from 1547 renal cell carcinoma patients (1039 males and 508 females; mean age, 63.4 years; mean follow-up, 7.1 years) who underwent surgical resection between 1970 and 1998 were analyzed retrospectively. Tumors were staged using the 1987 and 1997 TNM criteria, and Kaplan-Meier estimates of survival and disease recurrence were compared for both staging systems. The Peto-Peto log rank test and the generalized Wilcoxon test were used to assess univariate significance of prognostic factors on survival. Cox proportional hazards regression analysis was then completed to assess the significance of the revised staging system. RESULTS: Tumor classification using the 1987 TNM staging system (P = 0.0001) and the 1997 TNM staging system (P = 0.0001) was a significant predictor of cause specific survival. Using 1997 TNM staging criteria, 641 patients were reclassified from the T2 classification to the T1 classification, 114 patients were reclassified from the T3c classification to the T3b classification, 11 patients were reclassified from the T4b classification to the T3c classification, and 3 patients were reclassified from the T4b classification to the T3b classification. Patients with reclassified tumors had outcomes similar to patients with tumors that remained in the same tumor classification. Patient stratification was improved using the new staging system. Prognostic discrimination for cause specific survival at 10 years was noted for the 1987 and 1997 TNM classifications (T1, 97% vs. 91%; T2, 84% vs. 70%; T3a, 53% vs. 53%; T3b, 48% vs. 42%; and T3c, 29% vs. 43%). CONCLUSIONS: The revised classification of renal cell carcinoma was a significant predictor of cause specific survival for the cohort of patients described in this report. Using the new system, the stratification of patients was improved. Patients who had their tumors reclassified as a result of the new staging system had outcomes similar to those of patients who had tumors that remained in the same classification. Based on an analysis of this cohort, tumor classification is valid, and the T1 subclassification is warranted. However, additional revision may be required to optimize staging.

Struvite stones: diagnosis and current treatment concepts.

Effective management of struvite calculi requires a comprehensive approach to eliminate the stone burden and prevent stone recurrence. These stones occur more frequently in women, infants, and the elderly, as these patients are at greater risk for urinary tract infections. All patients should have routine laboratory testing as well as an excretory urogram. Appropriate urine cultures should be completed. Definitive management should promptly follow diagnosis. Percutaneous nephrolithotomy with or without SWL is the usual treatment. Appropriate antibiotic use is helpful; magnesium and phosphorus restriction and administration of urease inhibitors are less valuable.

Role of microvessel density in predicting recurrence in pathologic Stage T3 prostatic adenocarcinoma.

OBJECTIVES: Extraprostatic extension of prostatic adenocarcinoma (pathologic Stage T3) increases the risk of recurrence after radical prostatectomy compared with organ-confined prostate cancer. Use of microvessel density in predicting cancer recurrence in Stage pT3 cancer is poorly understood. We evaluated known predictors of recurrence, including Gleason grade, preoperative serum prostate-specific antigen (PSA), DNA ploidy, seminal vesicle involvement, and surgical margin status in comparison with optimized microvessel density (OMVD) and area-weighted microvessel density (AWMVD) in patients with Stage pT3 prostate cancer. METHODS: Between 1987 and 1989, 290 previously untreated patients underwent radical prostatectomy and were found to have pathologic Stage T3 adenocarcinoma. No patient received adjuvant therapy. Embedded prostatectomy specimens from 211 patients with sufficient tissue for immunohistochemical staining with factor VIII-related antigen were studied by computer-assisted digital image analysis for OMVD and AWMVD. The correlation of Gleason grade, preoperative PSA, DNA ploidy, seminal vesicle involvement, surgical margin positivity, OMVD, and AWMVD with clinical or biochemical failure was assessed using the Cox proportional hazards model. Biochemical failure was defined as a postoperative increase in PSA greater than 0.2 ng/mL, and clinical failure was defined as a positive biopsy or metastasis on bone scan. RESULTS: The mean follow-up +/- SD for all patients was 7.1 +/- 1.8 years, with 43 deaths (9 due to prostate cancer) and 124 cases of clinical and/or biochemical recurrence. The mean OMVD was 65.0 +/- 17.3, and the mean AWMVD was 8.2 +/- 5.3. OMVD and AWMVD were not predictors of cancer recurrence or significantly associated with DNA ploidy or preoperative PSA. AWMVD was associated with Gleason grade (P = 0.003). The estimated relative risk (adjusted for other cancer variables) of clinical and biochemical recurrence associated with a change in OMVD from the 25th percentile (53.5) to the 75th percentile (75.4) was 1.14 (95% confidence interval 0.92 to 1.42). The estimated relative risk (adjusted) of clinical and biochemical recurrence associated with a change in AWMVD from the 25th percentile (4.8) to the 75th percentile (10.4) was 1.17 (95% confidence interval 0.97 to 1.42). Gleason grade, preoperative PSA, DNA ploidy, and seminal vesicle involvement were predictors of clinical and/or biochemical recurrence in univariate and multivariate analyses. CONCLUSIONS: Microvessel density, assessed by OMVD and AWMVD, did not predict recurrence in patients with pathologic Stage T3 adenocarcinoma of the prostate (TNM Stage T3N0M0). DNA ploidy, Gleason grade, preoperative PSA, and seminal vesicle involvement remained the best predictors of clinical and/or biochemical recurrence in this group of patients.

Transforming growth factor-beta1 (TGF-beta1) is sufficient to induce fibrosis of rabbit corpus cavernosum in vivo.

PURPOSE: The pleotropic cytokine TGF-beta1 which induces connective tissue synthesis, and inhibits the growth of smooth muscle cells, has been implicated in corpus cavernosum fibrosis. The objective of this study was to determine the dose and time dependence of TGF-beta1 as an active agent in penile corporal fibrosis in an animal model. MATERIALS AND METHODS: A time release method of delivery was developed using sodium alginate microspheres containing recombinant human (rh) TGF-beta1. New Zealand White rabbits were injected intracorporally with a single alginate microsphere either with or without rh-TGF-beta1. Dosage was varied from 325 to 1500 ng./bead. Animals were sacrificed at either three or five days post injection and the penises removed en bloc, examined, and processed for quantitative histomorphometric analysis, staining the sections with Masson's trichrome. RESULTS: Alginate microspheres containing [125I]-rh-TGF-beta1 showed slow-release kinetics (t1/2 = 10.5 hours). Histomorphometric analysis of 60 sets of high powered fields/treatment/ animal showed dose dependent decreases in percentage of corporal smooth muscle with TGF-beta1 treatment (750 to 1500 ng./bead). Placebo (alginate microspheres alone) had trabecular smooth muscle content comparable to values previously reported for untreated rabbit corpus cavernosum. CONCLUSIONS: This study confirms that TGF-beta1 induces fibrosis in situ by altering connective tissue synthesis and hence the structure of the corpus cavernosum. Injection of rh-TGF-beta1 impregnated alginate microspheres into the corpus cavernosum resulted in dose-dependent decreases in percentage of corporal smooth muscle.