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Background: Despite revisions in 2005 and 2014, the Gleason prostate cancer (PCa) grading system still has major deficiencies. Combining of Gleason scores into a three-tiered grouping (6, 7, 8-10) is used most frequently for prognostic and therapeutic purposes. The lowest score, assigned 6, may be misunderstood as a cancer in the middle of the grading scale, and 3+4=7 and 4+3=7 are often considered the same prognostic group., Objective: To verify that a new grading system accurately produces a smaller number of grades with the most significant prognostic differences, using multi-institutional and multimodal therapy data., Design, Setting, and Participants: Between 2005 and 2014, 20,845 consecutive men were treated by radical prostatectomy at five academic institutions; 5501 men were treated with radiotherapy at two academic institutions., Outcome Measurements and Statistical Analysis: Outcome was based on biochemical recurrence (BCR). The log-rank test assessed univariable differences in BCR by Gleason score. Separate univariable and multivariable Cox proportional hazards used four possible categorizations of Gleason scores., Results and Limitations: In the surgery cohort, we found large differences in recurrence rates between both Gleason 3+4 versus 4+3 and Gleason 8 versus 9. The hazard ratios relative to Gleason score 6 were 1.9, 5.1, 8.0, and 11.7 for Gleason scores 3+4, 4+3, 8, and 9-10, respectively. These differences were attenuated in the radiotherapy cohort as a whole due to increased adjuvant or neoadjuvant hormones for patients with high-grade disease but were clearly seen in patients undergoing radiotherapy only. A five-grade group system had the highest prognostic discrimination for all cohorts on both univariable and multivariable analysis. The major limitation was the unavoidable use of prostate-specific antigen BCR as an end point as opposed to cancer-related death., Conclusions: The new PCa grading system has these benefits: more accurate grade stratification than current systems, simplified grading system of five grades, and lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa., Patient Summary: We looked at outcomes for prostate cancer (PCa) treated with radical prostatectomy or radiation therapy and validated a new grading system with more accurate grade stratification than current systems, including a simplified grading system of five grades and a lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa., Competing Interests: Financial disclosures: Jonathan I. Epstein certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Radiotherapy or radical hysterectomy with salpingo-oophorectomy (SOE) as treatment for uterine cervical cancer causes estrogen deprivation in premenopausal women. The effects on androgen production have rarely been examined but could be relevant for survivors of cervical cancer because insufficiency has been associated with low sexual function., Aim: To investigate the effects of pelvic radiotherapy, hysterectomy with SOE, or surgery without SOE on androgen levels and to explore potential associations with sexual function., Methods: Patients with cervical cancer (N = 60) were prospectively examined through blood sampling and questionnaires before and 1 year after treatments., Main Outcome Measures: Serum testosterone (measured by liquid chromatography and tandem mass spectrometry), sex hormone-binding globulin, androstenedione, dehydroepiandrosterone sulfate, follicle-stimulating hormone, luteinizing hormone, and estradiol levels and Female Sexual Function Index scores., Results: In women treated with radiotherapy (n = 38), median total and free testosterone levels were significantly decreased at 1-year follow-up compared with baseline in premenopausal women (n = 16; total testosterone -29%, P = .01; free testosterone -22%, P = .007) and postmenopausal women (n = 22; total testosterone -25%, P = .03; free testosterone -29%, P = .03). Androstenedione was decreased in premenopausal women only and dehydroepiandrosterone sulfate was decreased in postmenopausal women only after radiotherapy. In women treated with hysterectomy and SOE (n = 10), testosterone levels were lower but not significantly lower, and there was no change in those having surgery without SOE (n = 12). Female Sexual Function Index scores lower than 26.5 in sexually active women were reported by 80% 1 year after radiotherapy, by 44% after hysterectomy with SOE, and by 40% after surgery without SOE, with no significant differences compared with baseline values. No direct correlation between androgen levels and Female Sexual Function Index scores were found at 1-year follow-up., Conclusion: Total and free testosterone levels decreased slightly but significantly after pelvic radiotherapy in pre- and postmenopausal women. The clinical importance of this decrease is unclear, but androgen levels were not directly related to sexual function in this pilot setting., (Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to assess the effect of introducing an enhanced recovery programme (ERP) to an established robot-assisted radical cystectomy (RARC) service., Materials and Methods: Data were prospectively collected on 221 consecutive patients undergoing totally intracorporeal RARC between December 2003 and May 2014. The ERP was specifically designed to support an evolving RARC service, where increasing proportions of patients requiring radical cystectomy underwent RARC. Patient demographics and outcomes before and after implementation of the ERP were compared. The primary endpoint was length of stay (LOS). Secondary outcomes included age, American Society of Anesthesiologists (ASA) score, preoperative staging, operative time, complications and readmissions. Differences in outcomes between patients before and after implementation of ERP were tested with the Jonckheere-Terpstra trend test and quantile regression with backward selection., Results: Following implementation of the ERP, the demographics of the patients (n = 135) changed, with median age increasing from 66 to 70 years (p < 0.01), higher ASA grade (p < 0.001), higher preoperative stage cancer (pT ≥ 2, p < 0.05) and increased likelihood of undergoing an ileal conduit diversion (p < 0.001). Median LOS before ERP was 9 days [interquartile range (IQR) 8-13 days] and after ERP was 8 days (IQR 6-10 days) (p < 0.001). ASA grade and neoadjuvant chemotherapy also affected LOS (p < 0.05 and p < 0.01, respectively). There was no significant difference in 30 day complication rates, readmission rates or 90 day mortality, with 59% experiencing complications before ERP implementation and 57% after implementation. The majority of complications were low grade., Conclusions: Patient demographics changed as the RARC service evolved from selected patients to a general service. Despite worsening demographics, LOS decreased following ERP implementation. This evidence-based ERP safely standardized perioperative care, resulting in decreased LOS and decreased variability in LOS.

Background: We aimed to investigate cancer-bereaved youths' opinions and experiences of being told about a parent's imminent death from cancer and of barriers to this communication., Material and Methods: This nationwide population-based survey included 622/851 (73%) youths (aged 18-26) who at age 13-16, 6-9 years earlier had lost a parent to cancer., Results: In total 595 of 610 (98%) of the participants stated that teenage children should be informed when the parent's death was imminent (i.e. a matter of hours or days, not weeks). 59% stated that they themselves had been told this, 37% by the parents, 7% by parents and healthcare professionals together and 8% by professionals only. Frequent reasons for why the teenager and parents did not talk about imminent death before loss were that one (n=106) or both (n=25) of the parents together with the teenage child had pretended that the illness was not that serious, or that none of the parents had been aware that death was imminent (n=80). Up to a couple of hours before the loss, 43% of participants had not realized that death was imminent., Conclusion: In this population-based study virtually all youth who at ages 13-16 had lost a parent to cancer afterwards stated that teenagers should be told when loss is near, i.e. a matter of hours or days, not weeks. Many stated that they had not been given this information and few were informed by professionals, with implications for future improvements in end-of-life care of patients with teenage children.

Objective: This study aims to assess use of hormone therapy (HT) after cervical cancer treatment in women of premenopause age., Methods: We identified 837 women aged 45 years or younger at diagnosis of cervical cancer in the Swedish Cancer Register from January 1, 2005 to September 30, 2009 with a minimal follow-up of 1.5 years. Information on cancer treatment (surgical operation, radiotherapy, and/or chemotherapy) was obtained through the National Patient Register. Use of HT was estimated through HT dispensing during follow-up as recorded in the Prescribed Drug Register. Percentage of recommended dose was assessed by frequency of HT dispensing at half-year intervals up to April 1, 2011 or a maximal age of 50 years., Results: A total of 257 women (31%) received acute estrogen deprivation due to bilateral salpingo-oophorectomy and/or radiotherapy. Among these women, 171 (67%) of 257 had at least one dispensing of HT during the period 0.5 to 1 year after diagnosis, and 118 (46%) of 257 were dispensed 75% or more of the recommended dose. Proportion users decreased to 39% at 4.5 to 5 years after diagnosis (21% with ≥ 75% of the recommended dose). Women younger than 40 years had a higher prevalence of HT use at 0.5 to 1 year (79%), decreasing to 45% after 4.5 to 5 years. The results did not vary by cancer histology., Conclusions: Fewer than half of cervical cancer survivors with therapy-induced early menopause used HT at or close to the recommended dose, and the use decreased during follow-up. Increased awareness of the health benefits of HT for this patient group is needed among professionals and women.

There are few studies showing that physical exercise can improve secondary lymphedema. We hypothesized that water exercise would be more effective than land exercise in reducing limb volume. Secondary objectives were joint movement, BMI, daily function, well-being, and body image. Limb volume was measured with circumference or was volumetric. Well-being and body image were measured with a study-specific questionnaire and daily function with DASH and HOOS questionnaires. Eighty-eight eligible patients with secondary lymphedema after breast or gynecological cancer participated in this controlled clinical intervention study. There was a higher proportion of women who participated in water exercises who reduced their secondary arm limb volume (p = 0.029), and there were also significant differences for BMI (p = 0.047) and self-reported frequency of swelling (p = 0.031) in the water exercise group after intervention. Women with arm lymphedema in the land exercise group improved DASH scores (p = 0.047) and outer rotation in the shoulder (p = 0.001). Our results suggest that to reduce objective and self-reported swelling, lymphedema patients may be offered water exercise training while to improve daily shoulder function, land exercises are preferred. To guide female cancer survivors with lymphedema to effective exercise resulting in reduced limb volume and improved function, adequate evidenced-based programs are needed.

Background: Robotic-assisted laparoscopic radical prostatectomy is a current standard treatment for localized prostate cancer, with treatment failure defined by biochemical recurrence (BCR). Open radical prostatectomy series have identified the presence of a positive surgical margin (PSM) as a predictor of long-term recurrence, a measure that is affected by the surgeon׳s skill. We evaluate the effect of PSM parameters on BCR rates from robotic-assisted laparoscopic radical prostatectomy, across 3 high-volume institutions., Methods: De-identifiable clinicopathological and histopathological data were prospectively collected for 4,001 patients with at least 3 years of follow-up. Kaplan-Meier plots and 3 statistical models were used to evaluate the effect of margin parameters on BCR, via crude rates, traditional multivariable Cox regression, and a propensity-adjusted Cox regression model., Results: Overall, 37% of men with a PSM developed BCR compared with 10% of men with negative margins (hazard ratio [HR] = 1.81, 95% CI: 1.47-2.22). Length ≥3 mm or a multifocal positive margin was associated with a higher risk of BCR compared with negative margin cases. On multivariable Cox regression analysis of the positive margin cohort, only apical margins significantly predicted BCR relative to basal margins (HR = 2.03, 95% CI: 1.01-4.09), whereas there was no significant difference in BCR rates for posterolateral margins relative to basal margins (HR = 1.62, 95% CI: 0.84-3.11). Propensity-adjusted modeling confirmed a greater effect of apical compared with posterolateral PSM., Conclusions: A PSM length ≥3 mm is predictive of BCR, as is to a lesser extent multiple positive margins. In contrast to open prostatectomy series, posterolateral margins carry a smaller risk of BCR compared with apical margins., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To evaluate the role of positive surgical margin (PSM) size/focality and location in relation to risk of biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP)., Patients and Methods: Clinicopathological data were collected from 904 patients who underwent RARP at a single European institution from 2002 to 2006. PSM status after RARP was defined as cancer cells at the inked margin, and was stratified by size/focality and location. The outcome variable was BCR, defined as a postoperative PSA level of ≥0.2 ng/mL. We modelled clinicopathological covariates including PSM size/focality and location using Cox proportional hazards regression. In subgroup analyses, we assessed the effect of PSM size and location at different pathological stages and grades of disease., Results: Compared with negative SM, a PSM of >3 mm/multifocal was associated with an increased risk of BCR in the entire cohort (hazard ratio [HR] 2.84, 95% confidence interval 1.76-4.59), while unifocal PSMs of ≤3 mm were not significantly associated with BCR. In subgroup analyses, the negative impact of >3 mm/multifocal PSM appeared greatest in those with lower postoperative stage and grade of disease. The prognostic role of PSM location was unconfirmed, although data indicated that posterolateral PSMs may be of lower significance in RARP patients. The study is limited by lack of central pathology review, and lack of statistical adjustment for tumour volume, lymph node status, and surgeon volume., Conclusion: We found that men with >3 mm/multifocal PSMs have a higher risk of BCR than those with unifocal PSMs of ≤3 mm or negative SMs, especially if they have lower risk disease. Posterolateral margins may be of little significance in a RARP population., (© 2013 The Authors. BJU International © 2013 BJU International.)

Purpose: Lymph node dissection in patients with prostate cancer may increase complications. An association of lymph node dissection with thromboembolic events was suggested. We compared the incidence and investigated predictors of deep venous thrombosis and pulmonary embolism among other complications in patients who did or did not undergo lymph node dissection during open and robot-assisted laparoscopic radical prostatectomy., Materials and Methods: Included in study were 3,544 patients between 2008 and 2011. The cohort was derived from LAPPRO, a multicenter, prospective, controlled trial. Data on adverse events were extracted from patient completed questionnaires. Our primary study outcome was the prevalence of deep venous thrombosis and/or pulmonary embolism. Secondary outcomes were other types of 90-day adverse events and causes of hospital readmission., Results: Lymph node dissection was performed in 547 patients (15.4%). It was associated with eightfold and sixfold greater risk of deep venous thrombosis and pulmonary embolism events compared to that in patients without lymph node dissection (RR 7.80, 95% CI 3.51-17.32 and 6.29, 95% CI 2.11-18.73, respectively). Factors predictive of thromboembolic events included a history of thrombosis, pT4 stage and Gleason score 8 or greater. Open radical prostatectomy and lymph node dissection carried a higher risk of deep venous thrombosis and/or pulmonary embolism than robot-assisted laparoscopic radical prostatectomy (RR 12.67, 95% CI 5.05-31.77 vs 7.52, 95% CI 2.84-19.88). In patients without lymph node dissection open radical prostatectomy increased the thromboembolic risk 3.8-fold (95% CI 1.42-9.99) compared to robot-assisted laparoscopic radical prostatectomy. Lymph node dissection induced more wound, respiratory, cardiovascular and neuromusculoskeletal events. It also caused more readmissions than no lymph node dissection (14.6% vs 6.3%)., Conclusions: Among other adverse events we found that lymph node dissection during radical prostatectomy increased the incidence of deep venous thrombosis and pulmonary embolism. Open surgery increased the risks more than robot-assisted surgery. This was most prominent in patients who were not treated with lymph node dissection., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Lack of trust in the health-care system after losing a child to suicide may prevent bereaved parents from seeking professional treatment when needed, thus diminishing their chances of recovery., Aims: This is the first large study to aim at evaluating the incidence of lack of trust in the health-care system and associated variables in suicide-bereaved parents., Method: This nationwide population-based survey included 569 parents who lost a child to suicide 2-5 years earlier and a matched comparison group of 326 nonbereaved parents. Using a study-specific questionnaire, we asked bereaved and nonbereaved parents if they trusted the health-care system and measured psychological and background variables., Results: Prevalence of lack of trust in the health-care system differed between the bereaved (46.5%) and the nonbereaved parents (18.3%), giving a relative risk of 2.5 (95% CI = 2.0-3.3). After multivariable modeling, high scores of depression, living in big cities, and being single were identified as variables associated with lack of trust in suicide-bereaved parents., Conclusion: Suicide-bereaved parents show lack of trust in the health-care system. We present possible effect modifiers that may be considered in professional interventions aiming at influencing suicide-bereaved parents' level of trust.

Purpose: We present a 2-institution experience with completely intracorporeal robotic orthotopic ileal neobladder after radical cystectomy in 132 patients., Materials and Methods: Established open surgical techniques were duplicated robotically with all neobladders suture constructed intracorporeally in a globular configuration. Nerve sparing was performed in 56% of males. Lymphadenectomy was extended (up to aortic bifurcation in 51, 44%) and superextended (up to the inferior mesenteric artery in 20, 17%). Ureteroileal anastomoses were Wallace-type (86, 65%) or Bricker-type (46, 35%). The learning curve at each institution was assessed using chronological subgroups and by trends across the entire cohort. Data were prospectively collected and retrospectively queried., Results: Mean operating time was 7.6 hours (range 4.4 to 13), blood loss was 430 cc (range 50 to 2,200) and hospital stay was 11 days (median 8, range 3 to 78). Clavien grade I, II, III, IV and V complications within 30 days were 7%, 25%, 13%, 2% and 0%, respectively, and between 30 and 90 days were 5%, 9%, 11%, 1% and 2%, respectively. Mean nodal yield was 29 (range 7 to 164) and the node positivity rate was 17%. Operative time, blood loss, hospital stay and prevalence of late complications improved with experience. During a mean followup of 2.1 years (range 0.1 to 9.8) cancer recurred in 20 patients (15%). Five-year overall, cancer specific and recurrence-free survival was 72%, 72% and 71%, respectively., Conclusions: We developed a refined technique of robotic intracorporeal orthotopic neobladder diversion, duplicating open principles. Operative efficiency and outcomes improved with experience. Going forward, we propose a prospective randomized comparison between open and robotic intracorporeal neobladder surgery., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Since 2003, Karolinska University Hospitals have performed totally intracorporeal robotic-assisted radical cystectomy (RARC) in carefully selected patients. As our technique has evolved, the proportion of patients undergoing RARC has progressively increased. Whilst open radical cystectomy remains the gold standard, several high-volume centres have now demonstrated that RARC is both feasible and safe. RARC comprises three stages: radical cystectomy, extended lymph node dissection and urinary diversion. The majority of centres in the United States currently perform RARC utilizing an extracorporeal approach for the urinary diversion stage, perceiving this to be a more accessible option with a reduced risk of complications. We assess the evidence for this perception, reviewing the literature and reporting the functional outcomes and complication rates for a totally intracorporeal RARC approach. We also describe our technique for both intracorporeal orthotopic neobladder and intracorporeal ileal conduit, identifying the potential hazard steps and the 'tips and tricks' to optimize outcomes.

Background: Self-injury, a manifestation of severe psychological distress, is increased in cancer-bereaved youths. Little is known about the potential influence on the risk for self-injury of factors that could be clinically relevant to and modifiable by the health-care professionals involved in the care of the dying parent., Methods: In a nationwide population-based anonymous study, 622 (73.1%) youths (aged 18-26) who, 6 to 9 years earlier at ages 13 to 16, had lost a parent to cancer answered study-specific questions about self-injury and factors related to the family and parental health care., Results: Univariable analyses showed that the risk for self-injury was increased among cancer-bereaved youths who reported poor family cohesion the years before (relative risk [RR], 3.4, 95% confidence interval [CI], 2.5-4.6) and after the loss (RR, 3.3, 95% CI, 2.4-4.4), distrust in the health care provided to the dying parent (RR, 1.7, 95% CI, 1.2-2.4), perceiving poor health-care efforts to cure the parent (RR 1.5, 95% CI, 1.1-2.1) and poor efforts to prevent suffering (RR, 1.6, 95% CI, 1.1-2.4), that at least one of their parents had been depressed or had troubles in life (RR, 1.5, CI, 1.1-2.1) and believing 3 days before the loss that the treatment would probably cure the parent (RR, 1.6, CI, 1.1-2.3). In the total multivariable models, only poor family cohesion before and after the loss remained statistically significantly associated with self-injury., Conclusion: Poor family cohesion before and after the loss of a parent to cancer is associated with an increased risk of self-injury in teenage children., (Copyright © 2014 John Wiley & Sons, Ltd.)

Background: Research on the assumed, positive and negative, psychological effects of viewing the body after a suicide loss is sparse. We hypothesized that suicide-bereaved parents that viewed their childs body in a formal setting seldom regretted the experience, and that viewing the body was associated with lower levels of psychological morbidity two to five years after the loss., Methods and Findings: We identified 915 suicide-bereaved parents by linkage of nationwide population-based registries and collected data by a questionnaire. The outcome measures included the Patient Health Questionnaire (PHQ-9). In total, 666 (73%) parents participated. Of the 460 parents (69%) that viewed the body, 96% answered that they did not regret the experience. The viewing was associated with a higher risk of reliving the child's death through nightmares (RR 1.61, 95% CI 1.13 to 2.32) and intrusive memories (RR 1.20, 95% CI 1.04 to 1.38), but not with anxiety (RR 1.02, 95% CI 0.74 to 1.40) and depression (RR 1.25, 95% CI 0.85 to 1.83). One limitation of our study is that we lack data on the informants' personality and coping strategies., Conclusions: In this Swedish population-based survey of suicide-bereaved parents, we found that by and large everyone that had viewed their deceased child in a formal setting did not report regretting the viewing when asked two to five years after the loss. Our findings suggest that most bereaved parents are capable of deciding if they want to view the body or not. Officials may assist by giving careful information about the child's appearance and other details concerning the viewing, thus facilitating mental preparation for the bereaved person. This is the first large-scale study on the effects of viewing the body after a suicide and additional studies are needed before clinical recommendations can be made.

Introduction: The aim of this report is to describe our surgical technique of totally intracorporeal robotic assisted radical cystectomy (RARC) with neobladder formation., Materials and Methods: Between December 2003 and March 2013, a total of 147 patients (118 male, 29 female) underwent totally intracorporeal RARC for urinary bladder cancer. We also performed a systematic search of Medline, Embase and PubMed databases using the terms RARC, robotic cystectomy, robot-assisted, totally intracorporeal RARC, intracorporeal neobladder, intracorporeal urinary diversion, oncological outcomes, functional outcomes, and complication rates., Results: The mean age of our patients was 64 years (range 37-87). On surgical pathology 47% had pT1 or less disease, 27% had pT2, 16% had pT3 and 10% had pT4. The mean number of lymph nodes removed was 21 (range 0-60). 24% of patients had lymph node positive dAQ1isease. Positive surgical margins occurred in 6 cases (4%). Mean follow-up was 31 months (range 4-115 months). Two patients (1.4%) died within 90 days of their operation. Using Kaplan-Meier analysis, overall survival and cancer specific survival at 60 months was 68% and 69.6%, respectively. 80 patients (54%) received a continent diversion with totally intracorporeal neobladder formation. In the neobladder subgroup median total operating time was 420 minutes (range 265-760). Daytime continence and satisfactory sexual function or potency at 12 months ranged between 70-90% in both men and women., Conclusions: Our experience with totally intracorporeal RARC demonstrates acceptable oncological and functional outcomes that suggest this is a viable alternative to open radical cystectomy.

The response of cells and tissues to elevated temperatures is highly important in several research areas, especially in the area of infrared neural stimulation. So far, only the heat response of neurons has been considered. In this study, primary rat astrocytes were exposed to infrared laser pulses of various pulse lengths and the resulting cell morphology changes and cell migration was studied using light microscopy. By using a finite element model of the experimental setup the temperature distribution was simulated and the temperatures and times to induce morphological changes and migration were extracted. These threshold temperatures were used in the commonly used first-order reaction model according to Arrhenius to extract the kinetic parameters, i.e., the activation energy, E a, and the frequency factor, A c, for the system. A damage signal ratio threshold was defined and calculated to be 6% for the astrocytes to change morphology and start migrating.

Objective: To evaluate the effect of the learning curve on operative, postoperative, and pathological outcomes of the first 67 totally intracorporeal robot-assisted radical cystectomies (RARCs) with neobladders performed by two lead surgeons at Karolinska University Hospital., Patients and Methods: Between December 2003 and October 2012, 67 patients (61 men and six women) underwent RARC with orthotopic urinary diversion by two main surgeons. Data were collected prospectively on patient demographics, peri- and postoperative outcomes including operation times, conversion rates, blood loss, complication rates, pathological data and length of stay (LOS) for these 67 consecutive patients. The two surgeons operated on 47 and 20 patients, respectively. The patients were divided into sequential groups of 10 in each individual surgeon's series and assessed for effect of the learning curve., Results: Patient demographics and clinical characteristics were similar in both surgeons' groups. The overall total operation times trended down in both surgeons' series from a median time of 565 min in the first group of 10 cases, to a median of 345 min in the last group for surgeon A (P < 0.001) and 413 to 385 min for surgeon B (not statistically significant). Risk of conversion to open surgery also decreased with a 30% conversion rate in the first group to zero in latter groups (P < 0.01). Overall complications decreased as the learning curve progressed from 70% in the first group to 30% in the later groups (P < 0.05), although major complications were not statistically different when compared between the groups. Patient demographics did not change over time. The mean estimated blood loss was unchanged across groups with increasing experience. The pathological staging, mean total lymph node yield and number of positive margins were also unchanged across groups. There was a decrease in LOS from a mean of 19 days in the first group to a mean (range) of 9 (4-78) days in the later groups, although the median LOS was unchanged and therefore not statistically significant., Conclusions: Totally intracorporeal RARC with intracorporeal neobladder is a complex procedure, but it can be performed safely, with a structured approach, at a high-volume established robotic surgery centre without compromising perioperative and pathological outcomes during the learning curve for surgeons. An experienced robotic team and mentor can impact the learning curve of a new surgeon in the same centre resulting in decreased operation times early in their personal series, reducing conversion rates and complication rates., (© 2013 The Authors. BJU International © 2013 BJU International.)

Background: Robot-assisted radical cystectomy (RARC) with totally intracorporeal neobladder diversion is a complex procedure that has been reported with good outcomes in small series., Objective: To present complications and oncologic and functional outcomes of this procedure., Design, Setting, and Participants: Between 2003 and 2012 in a tertiary referral center, 70 patients were operated on by two experienced robotic surgeons. Data were collected prospectively and reviewed retrospectively., Intervention: RARC with totally intracorporeal modified Studer ileal neobladder formation., Outcome Measurements and Statistical Analysis: The overall outcome of RARC with a totally intracorporeal neobladder was presented by assessing (1) surgical margins, (2) recurrence or cancer-specific death at 24 mo, (3) 30-d and 90-d complications graded according to the modified Clavien-Dindo system, (4) daytime and nighttime continence (no or one pad per day) at 6 and 12 mo, and (5) satisfactory sexual activity or potency at 6 mo and 12 mo. Survival rates were estimated by Kaplan-Meier plots., Results and Limitations: Median follow-up of the cohort was 30.3 mo (interquartile range: 12.7-35.6). We recorded negative margins in 69 of 70 patients (98.6%). Clavien 3-5 complications occurred in 22 of 70 patients (31.4%) at 30 d and 13 of 70 (18.6%) at >30 d. At 90 d, the overall complication rate was 58.5%. Clavien <3 and Clavien ≥3 complications were recorded in 15 of 70 patients (21.4%) and 26 of 70 (37.1%), respectively. Kaplan-Meier estimates for recurrence-free, cancer-specific, and overall survival at 24 mo were 80.7%, 88.9%, and 88.9%, respectively. Daytime continence and satisfactory sexual function or potency at 12 mo ranged between 70% and 90% in both men and women. Limitations of this study include its retrospective design, selection bias due to the learning curve phase, and missing data., Conclusions: In this expert center for RARC, outcomes after RARC with totally intracorporeal neobladder diversion appear satisfactory and in line with contemporary open series., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: To assess adolescent and young adult siblings' perception of social support prior to and following the loss of their brother or sister to cancer, 2 to 9 years earlier, and their anxiety at follow-up., Method: In 2009, 174 (73%) bereaved siblings (12-25 years) participated in a nationwide, long-term follow-up study in Sweden using an anonymous study-specific questionnaire. The Hospital Anxiety and Depression Scale was used to measure self-assessed anxiety., Results: Siblings had a higher risk of anxiety if they perceived their need for social support was unsatisfied during their brother or sisters' last month before death, relative risk (RR) = 3.6 (95% confidence interval [CI] = 1.8-7.3); time after death, RR = 2.9 (95% CI = 1.5-5.6); and at follow-up, RR = 3.8 (95% CI = 2.0-7.2). Furthermore, a higher risk for anxiety was shown for siblings if they did not perceive that their parents and neighbors cared for them after their brother or sisters' death, RR = 2.7 (95% CI = 1.3-5.5), RR = 5.4 (95% CI = 1.3-21.9), respectively., Conclusion: Bereaved siblings had a greater probability to report self-assessed anxiety if they perceived that their need for social support was not satisfied prior to and following death. Information from both nurses and other health care professionals to families about the impact of social support may contribute to lessen the siblings' risk of anxiety.

Purpose: Lower limb lymphedema (LLL) is a common condition after pelvic cancer treatment but few studies have evaluated its effect on the quality of life and its consequences on daily life activities among gynecological cancer survivors., Methods: We identified a cohort of 789 eligible women, treated with pelvic radiotherapy alone or as part of combined treatment of gynecological cancer, from 1991 to 2003 at two departments of gynecological oncology in Sweden. As a preparatory study, we conducted in-depth interviews with gynecological cancer survivors and constructed a study-specific questionnaire which we validated face-to-face. The questionnaire covered physical symptoms originating in the pelvis, demographic, psychological, and quality of life factors. In relation to the lymph system, 19 questions were asked., Results: Six hundred sixteen (78 %) gynecological cancer survivors answered the questionnaire and participated in the study. Thirty-six percent (218/606) of the cancer survivors reported LLL. Overall quality of life was significantly lower among cancer survivors with LLL. They were also less satisfied with their sleep, more worried about recurrence of cancer, and more likely to interpret symptoms from the body as recurrence. Cancer survivors reported that LLL kept them from physical activity (45 %) and house work (29 %) and affected their ability to partake in social activities (27 %) or to meet friends (20 %)., Conclusion: Lower limb lymphedema has a negative impact on quality of life among gynecological cancer survivors, affecting sleep and daily life activities, yet only a few seek professional help.

HPV-DNA positive (HPVDNA+) oropharyngeal squamous cell carcinoma (OSCC) has better clinical outcome than HPV-DNA negative (HPVDNA-) OSCC. Current treatment may be unnecessarily extensive for most HPV+ OSCC, but before de-escalation, additional markers are needed together with HPV status to better predict treatment response. Here the influence of HLA class I/HLA class II expression was explored. Pre-treatment biopsies, from 439/484 OSCC patients diagnosed 2000-2009 and treated curatively, were analyzed for HLA I and II expression, p16(INK4a) and HPV DNA. Absent/weak as compared to high HLA class I intensity correlated to a very favorable disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) in HPVDNA+ OSCC, both in univariate and multivariate analysis, while HLA class II had no impact. Notably, HPVDNA+ OSCC with absent/weak HLA class I responded equally well when treated with induction-chemo-radiotherapy (CRT) or radiotherapy (RT) alone. In patients with HPVDNA- OSCC, high HLA class I/class II expression correlated in general to a better clinical outcome. p16(INK4a) overexpression correlated to a better clinical outcome in HPVDNA+ OSCC. Absence of HLA class I intensity in HPVDNA+ OSCC suggests a very high survival independent of treatment and could possibly be used clinically to select patients for randomized trials de-escalating therapy.

Background: Although open radical cystectomy (ORC) remains the gold standard of care for muscle-invasive bladder cancer, robot-assisted radical cystectomy (RARC) continues to gain wider acceptance. In this article, we focus on the steps of RARC, describing our approach, which has been developed over the past 10 yr. Totally intracorporeal RARC aims to offer the benefits of a complete minimally invasive approach while replicating the oncologic outcomes of open surgery., Objective: We report our outcomes of a totally intracorporeal RARC procedure, describing step by step our technique and highlighting the variations on this standard template of nerve-sparing and female organ-preserving approaches in men and women., Design, Setting, and Participants: Between December 2003 and October 2012, a total of 113 patients (94 male and 19 female) underwent totally intracorporeal RARC., Surgical Procedure: We performed RARC, extended pelvic lymph node dissection, and a totally intracorporeal urinary diversion (UD) in all patients. In the accompanying video, we focus on the standard template for RARC, also describing nerve-sparing and female organ-preserving approaches., Outcome Measurements and Statistical Analysis: Complications and oncologic outcomes are reported, including overall survival (OS) and cancer-specific survival (CSS) using Kaplan-Meier analysis., Results and Limitations: RARC with intracorporeal UD was performed in 113 patients. Mean age was 64 yr (range: 37-84). Forty-three patients underwent intracorporeal ileal conduit, and 70 had intracorporeal neobladder. On surgical pathology, 48% of patients had ≤ pT1 disease, 27% had pT2 disease, 13% had pT3 disease, and 12% had pT4 disease. The mean number of lymph nodes removed was 21 (range: 0-57). Twenty percent of patients had lymph node-positive disease. Positive surgical margins occurred in six cases (5.3%). Median follow-up was 25 mo (range: 3-107). We recorded a total of 70 early complications (0-30 d) in 54 patients (47.8%), with 37 patients (32.7%) having Clavien grade ≥ 3. Thirty-six late complications (>30 d) were recorded in 30 patients (26.5%), with 20 patients (17.7%) having Clavien grade ≥ 3. One patient (0.9%) died within 90 days of operation from pulmonary embolism. Using Kaplan-Meier analysis, CSS was 81% at 3 yr and 67% at 5 yr., Conclusions: Our structured approach to RARC has enabled us to develop this complex service while maintaining patient outcomes and complication rates comparable with ORC series. Our results demonstrate acceptable oncologic outcomes and encouraging long-term CSS rates., (Copyright © 2013 European Association of Urology. All rights reserved.)

Background and Objective: Infrared neural stimulation (INS) has recently evoked interest as an alternative to electrical stimulation. The mechanism of activation is the heating of water, which induces changes in cell membrane potential but may also trigger heat sensitive receptors. To further elucidate the mechanism, which may be dependent on cell type, a detailed description of the temperature distribution is necessary. A good control of the resulting temperature during INS is also necessary to avoid excessive heating that may damage the cells. Here we present a detailed model for the heating during INS and apply it for INS of in vitro neural networks of rat cerebral cortex neurons., Study Design/materials and Methods: A model of the heating during INS of a cell culture in a non-turbid media was prepared using multiphysics software. Experimental parameters such as initial temperature, beam distribution, pulse length, pulse duration, frequency and laser-cell distance were used. To verify the model, local temperature measurements using open pipette resistance were conducted. Furthermore, cortical neurons in culture were stimulated by a 500  mW pulsed diode laser (wavelength 1,550  nm) launched into a 200  µm multimodal optical fiber positioned 300  µm from the glass surface. The radiant exposure was 5.2 J/cm(2) ., Results: The model gave detailed information about the spatial and temporal temperature distribution in the heated volume during INS. Temperature measurements using open pipette resistance verified the model. The peak temperature experienced by the cells was 48°C. Cortical neurons were successfully stimulated using the 1,550  nm laser and single cell activation as well as neural network inhibition were observed., Conclusion: The model shows the spatial and temporal temperature distribution in the heated volume and could serve as a useful tool for future studies of the heating during INS., (Copyright © 2013 Wiley Periodicals, Inc.)

Objective: To determine how psychological premorbidity affects the risk of depression in parents who lost a child through suicide., Design: Population-based survey., Setting: Sweden, between 2009 and 2010., Participants: All parents who lost a child, age 15-30, through suicide between 2004 and 2007 according to National population registries. Non-bereaved parents matched for age, sex, living area, marital status, number of children., Exclusion Criteria: born outside a Nordic country, not Swedish speaking, contact details missing. Participants: 666 of 915 (73%) suicide-bereaved and 377 of 508 (74%) non-bereaved parents., Main Outcome Measures: Depression measured by the nine-item depression scale of the Patient Health Questionnaire (PHQ-9) and study-specific questions to assess psychological premorbidity and experience of the child's presuicidal morbidity., Results: In all, 94 (14%) suicide-bereaved and 51 (14%) non-bereaved parents (relative risk 1.0; 95% CI 0.8 to 1.4) had received their first treatment for psychological problems or had been given a psychiatric diagnosis more than 10 years earlier. The prevalence of moderate-to-severe depression was 115 (18%) in suicide-bereaved versus 28 (7%) in non-bereaved parents (RR 2.3; 95% CI 1.6 to 3.5). For those without psychological premorbidity, the relative risk was 2.3 (95% CI 1.4 to 3.6). 339 (51%) suicide-bereaved parents expressed worry over the child's psychological health during the month preceding the suicide and 259 (39%) had anticipated the suicide., Conclusions: In parents who lost a child through suicide in Sweden we did not find a higher prevalence of long-term psychological premorbidity than among parents who had not lost a child; the more than twofold risk of depression among the bereaved can probably be explained by the suicide and the stressful time preceding the suicide.

Purpose: To assess children's trust in the care provided to a dying parent during the final week of life in relation to end-of-life medical information about disease, treatment, and death., Methods: This nationwide population-based survey included 622 (73%) of 851 youths who, 6 to 9 years earlier, at age 13 to 16 years, lost a parent to cancer. We asked about the children's reception of end-of-life professional information and trust in the care provided. We also asked about depression and several potential risk factors of distrust in the care provided., Results: A majority (82%) reported moderate/very much trust in the care provided. Compared with children who received end-of-life medical information before their loss, the risk of distrust in the care provided was higher in those who received no information (risk ratio [RR], 2.5; 95% CI, 1.5 to 4.1), in those who only received information afterward (RR, 3.2; 95% CI, 1.7 to 5.9), and in those who did not know or remember if end-of-life medical information was provided (RR, 1.7; 95% CI, 1.1 to 2.5). Those reporting distrust in the care provided had an RR of 2.3 (95% CI, 1.5 to 3.5) for depression. Furthermore, the risk of distrust in the care provided was higher among children reporting poor efforts to cure (RR, 5.1; 95% CI, 3.6 to 7.3), and/or a poor relationship with the surviving parent (RR, 2.9; 95% CI, 2.0 to 4.1)., Conclusion: Our study suggests that children's trust in the care provided to a dying parent was highest when they received end-of-life medical information before their loss.

Patients with human papillomavirus (HPV) positive tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC, respectively) have a better clinical outcome than those with HPV negative tumours, irrespective of treatment. However, to better individualise treatment, additional biomarkers are needed together with HPV status. In a pilot study, we showed that high numbers of CD8(+) tumour infiltrating lymphocytes (TILs) in HPVDNA+ p16(INK4a+) TSCC indicated a better outcome. Here this study was extended. Totally 203 TSCC and 77 BOTSCC formalin fixed paraffin embedded tumour biopsies, earlier tested for HPV DNA (79% HPVDNA+) and p16(INK4a) from patients treated with curative intention, were analysed for CD8(+) and CD4(+) TILs by immunohistochemistry. Data obtained for 275 patients were correlated to HPVDNA and p16(INK4a) status, overall survival (OS) and disease free survival (DFS). In both HPVDNA+ and HPVDNA+ p16(INK4a+) tumours higher CD8(+) TIL counts correlated to a better 3-year OS (logrank test, both p<0.001) and 3-year DFS (logrank test, p = 0.003 and p = 0.004 respectively) as compared to the lowest quartile in the groups. A similar pattern was observed when analysing TSCC alone, while for BOTSCC significance was obtained only for 3-year OS. In HPVDNA- tumours the trend was similar, but significance was obtained again only for 3-year OS. The number of CD4(+) TILs did not generally correlate to survival. In conclusion, in HPVDNA+ and/or HPVDNA+ p16(INK4a+) tumours high CD8(+) TIL counts indicated a better 3-year OS. This suggests that high CD8(+) TIL counts together with HPVDNA+ or HPVDNA+ p16(INK4a+) could be used when selecting patients for more individualised treatment., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Introduction: Erectile dysfunction has been widely investigated as the major factor responsible for sexual bother in patients after radical prostatectomy (RP); painful orgasm (PO) is one element of this bother, but little is known about its prevalence and its effects on sexual health., Aim: This study aims to investigate the prevalence of PO and to identify potential risk factors., Main Outcome Measures: A total of 1,411 consecutive patients underwent open (radical retropubic prostatectomy) or robot-assisted laparoscopic RP between 2002 and 2006. The patients were asked to complete a study-specific questionnaire., Methods: Of a total of 145 questions, 5 dealt with the orgasmic characteristics. The questionnaire was also administered to a comparison group of 442 persons, matched for age and area of residency., Results: The response rate was 91% (1,288 patients). A total of 143 (11%) patients reported PO. Among the 834 men being able to have an orgasm, the prevalence was 18% vs. 6% in the comparison group (relative risk [RR] 2.8, 95% confidence interval [CI] 1.7-4.5). When analyzed as independent variables, bilateral seminal vesicle (SV)-sparing approach (RR 2.33, 95% CI 1.0-5.3, P = 0.045) and age <60 years were significantly related to the presence of PO (95% CI 0.5-0.9, P = 0.019). After adjustment for age, bilateral SV-sparing still remained a significant predictor for occurrence of PO., Conclusions: We found that PO occurs significantly more often in patients undergoing bilateral SV-sparing RP when compared with age-matched comparison population., (© 2013 International Society for Sexual Medicine.)

Purpose: The aim of this study was to investigate what bowel organ and delivered dose levels are most relevant for the development of 'emptying of all stools into clothing without forewarning' so that the related dose-responses could be derived as an aid in avoiding this distressing symptom in the future., Material and Methods: Of the 77 gynecological cancer survivors treated with radiotherapy (RT) for gynecological cancer, 13 developed the symptom. The survivors were treated between 1991 and 2003. The anal-sphincter region, the rectum, the sigmoid and the small intestines were all delineated and the dose-volume histograms were exported for each patient. The dose-volume parameters were estimated fitting the data to the Relative Seriality (RS), the Lyman and the generalized Equivalent Uniform Dose (gEUD) model., Results: The dose-response parameters for all three models and four organs at risk (OARs) were estimated. The data from the sigmoid fits the studied models best: D50 was 58.8 and 59.5 Gy (RS, Lyman), γ50 was 1.60 and 1.57 (RS, Lyman), s was 0.32, n was 0.13 and a was 7.7 (RS, Lyman, gEUD). The estimated volume parameters indicate that the investigated OARs behave serially for this endpoint. Our results for the three models studied indicate that they have the same predictive power (similar LL values) for the symptom as a function of the dose for all investigated OARs., Conclusions: In our study, the anal-sphincter region and sigmoid fit our data best, but all OARs were found to have steep dose-responses for 'emptying of all stools into clothing without forewarning' and thus, the outcome can be predicted with an NTCP model. In addition, the dose to the four studied OARs may be considered when minimizing the risk of the symptom.

Background: The objective of this study was to assess long-term psychological distress in siblings who lost a brother or sister to cancer 2 to 9 years earlier, as compared with a control group of non-bereaved siblings from the general population., Methods: During 2009, we conducted a nationwide follow-up study in Sweden by using an anonymous study-specific questionnaire. Siblings who had lost a brother or sister to cancer between the years 2000 and 2007 and also a control group of non-bereaved siblings from the general population were invited to participate. The Hospital Anxiety and Depression Scale (HADS) was used to measure psychological distress, and to test for differences in the ordinal outcome responses between the groups, we used Wilcoxon-Mann-Whitney rank-sum test., Results: Among the bereaved siblings, 174/240 (73%) participated and 219/293 (75%) among the non-bereaved. Self-assessed low self-esteem (p = 0.002), difficulties falling asleep (p = 0.005), and low level of personal maturity (p = 0.007) at follow-up were more prevalent among bereaved siblings. However, anxiety (p = 0.298) and depression (p = 0.946), according to HADS, were similar., Conclusion: Bereaved siblings are at increased risk of low self-esteem, low level of personal maturity and difficulties falling asleep as compared with non-bereaved peers. Yet, the bereaved were not more likely to report anxiety or depression., (Copyright © 2012 John Wiley & Sons, Ltd.)

Objective: To investigate the risk of self-injury in parentally cancer-bereaved youth compared with their nonbereaved peers., Design: Population-based study of cancer-bereaved youth and a random sample of matched population controls., Setting: Sweden in 2009 and 2010., Participants: A total of 952 youth (74.8%) confirmed to be eligible for the study returned the questionnaire: 622 (73.1%) of 851 eligible young adults who lost a parent to cancer between the ages of 13 and 16 years, in 2000 to 2003, and 330 (78.4%) of 451 nonbereaved peers., Main Exposure: Cancer bereavement or nonbreavement during the teenage years., Main Outcome Measures: Unadjusted and adjusted odds ratios (ORs) of self-injury after January 1, 2000., Results: Among cancer-bereaved youth, 120 (19.5%) reported self-injury compared with 35 (10.6%) of their nonbereaved peers, yielding an OR of 2.0 (95% CI, 1.4-3.0). After controlling for potential confounding factors in childhood (eg, having engaged in self-destructive behavior, having been bullied, having been sexually or physically abused, having no one to share joys and sorrows with, and sex), the adjusted OR was 2.3 (95% CI, 1.4-3.7). The OR for suicide attempts was 1.6 (95% CI, 0.8-3.0)., Conclusions: One-fifth of cancer-bereaved youth reported self-injury, representing twice the odds for self-injury in their nonbereaved peers, regardless of any of the adjustments we made. Raised awareness on a broad basis in health care and allied disciplines would enable identification and support provision to this vulnerable group.

The post-translational modification of proteins with N-acetylglucosamine (O-GlcNAc) is involved in the regulation of a wide variety of cellular processes and associated with a number of chronic diseases. Despite its emerging biological significance, the systematic identification of O-GlcNAc proteins is still challenging. In the present study, we demonstrate a significantly improved O-GlcNAc protein enrichment procedure, which exploits metabolic labeling of cells by azide-modified GlcNAc and copper-mediated Click chemistry for purification of modified proteins on an alkyne-resin. On-resin proteolysis using trypsin followed by LC-MS/MS afforded the identification of around 1500 O-GlcNAc proteins from a single cell line. Subsequent elution of covalently resin bound O-GlcNAc peptides using selective β-elimination enabled the identification of 185 O-GlcNAc modification sites on 80 proteins. To demonstrate the practical utility of the developed approach, we studied the global effects of the O-GlcNAcase inhibitor GlcNAcstatin G on the level of O-GlcNAc modification of cellular proteins. About 200 proteins including several key players involved in the hexosamine signaling pathway showed significantly increased O-GlcNAcylation levels in response to the drug, which further strengthens the link of O-GlcNAc protein modification to cellular nutrient sensing and response.

Objective: The objective of the present study is to examine bereaved siblings' perception of research participation., Methods: A Swedish nationwide study on avoidable and modifiable health care-related factors in paediatric oncology among bereaved siblings who lost a brother or sister to cancer between the years 2000 and 2007 was conducted. Data are presented as proportions, and the differences between groups were statistically tested at the 5% significant level using Fisher's exact test., Results: Out of 240 eligible siblings, 174 responded (73 %). None of the siblings (0/168) thought their participation would affect them negatively in the long term. However, 13% (21/168) stated it was a negative experience to fill out the questionnaire, whereas 84% (142/169) found it to be a positive experience. Women were more likely to report their participation as positive in a long-term perspective compared with men (p = 0.018)., Conclusions: None of the bereaved siblings in this Swedish nationwide study anticipated any long-term negative effect from their research participation. A majority reported it as positive to revisit their needs and experiences throughout their brother or sister's illness and death 2-9 years following the loss. We believe that the stepwise approach used in this study contributed to the high acceptance., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: Robot-assisted radical prostatectomy (RARP) is an increasingly commonly used surgical treatment option for prostate cancer (PCa); however, its longer-term oncologic results remain uncertain., Objective: To report biochemical recurrence-free survival (BRFS) outcomes for men who underwent RARP ≥5 yr ago at a single European centre., Design, Setting, and Participants: A total of 944 patients underwent RARP as monotherapy for PCa from January 2002 to December 2006 at Karolinska University Hospital, Stockholm, Sweden. Standard clinicopathologic variables were recorded and entered into a secure, ethics-approved database made up of those men with registered domiciles in Stockholm. The median follow-up time was 6.3 yr (interquartile range: 5.6-7.2)., Outcome Measurements and Statistical Analysis: The outcome of this study was biochemical recurrence (BCR), defined as a confirmed prostate-specific antigen (PSA) of ≥0.2 ng/ml. Kaplan-Meier survival plots with log-rank tests, as well as Cox univariable and multivariable regression analyses, were used to determine BRFS estimates and determine predictors of PSA relapse, respectively., Results and Limitations: The BRFS for the entire cohort at median follow-up was 84.8% (95% confidence interval [CI], 82.2-87.1); estimates at 5, 7, and 9 yr were 87.1% (95% CI, 84.8-89.2), 84.5% (95% CI, 81.8-86.8), and 82.6% (95% CI, 79.0-85.6), respectively. Nine and 19 patients died of PCa and other causes, respectively, giving end-of-follow-up Kaplan-Meier survival estimates of 98.0% (95% CI, 95.5-99.1) and 94.1% (95% CI, 90.4-96.4), respectively. Preoperative PSA >10, postoperative Gleason sum ≥4 + 3, pathologic T3 disease, positive surgical margin status, and lower surgeon volume were associated with increased risk of BCR on multivariable analysis. This study is limited by a lack of nodal status and tumour volume, which may have confounded our findings., Conclusions: This case series from a single, high-volume, European centre demonstrates that RARP has satisfactory medium-term BRFS. Further follow-up is necessary to determine how this finding will translate into cancer-specific and overall survival outcomes., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The postoperative effect on penile length after radical prostatectomy has been the subject of studies with conflicting results. We analyzed self-perceived penile shortening, quality of life and self-esteem after radical prostatectomy. In this cross-sectional study of a cohort of 1411 men who underwent a radical prostatectomy at Karolinska University Hospital between 2002 and 2006, we used a study-specific questionnaire. Patients and controls were asked about their perceived penile shortening by comparing present penile length now and at age 30 years. All subjects were also asked about their present quality of life and self-esteem. Patients were compared with 442 age-matched population-based controls. Among 1288 who underwent radical prostatectomy and answered the questionnaire (response rate 91%), 663 patients reported self-perceived penile shortening (55%), as compared with 85 (26%) of 350 men in the control group, corresponding to a relative risk (RR) of 2.1 (95% confidence interval (CI) 1.8-2.6) of self-perceived penile shortening compared with the age-matched control group. Age, grade of erectile dysfunction and angina were correlated with self-perceived penile shortening in both the operated and the control group. After adjustments for all of these mentioned potential confounders, we obtained a RR of 1.7 (95% CI 1.4-2.1) of self-perceived penile shortening compared with the controls. We also found that self-assessed penile shortening was associated with a RR of 1.2 (95% CI 1.1-1.3) for a low-to-moderate self-assessed quality of life and a RR of 1.2 (95% CI 1.1-1.4) for a low-to-moderate self estimation of self-esteem. Extensive nerve-sparing technique seems to be associated with less self-perceived penile shortening compared with radical prostatectomy with lower degree of nerve-sparing approach. These data indicate that radical prostatectomy is associated with self-perceived penile shortening and suggests that erectile function is a key factor in penile shortening.

Purpose: To better understand clinically significant definitions of urinary incontinence we investigated the relationship between urinary leakage and patient reported bother from urinary leakage., Materials and Methods: A consecutive series of 1,411 men who underwent radical prostatectomy at Karolinska University Hospital, Stockholm, Sweden, from 2002 to 2006 were invited to complete a study specific questionnaire with questions on pad status, urinary leakage and bother from urinary leakage., Results: Questionnaires were received from 1,179 men with a followup of greater than 1 year (median 2.2). Results showed that even a small amount of urinary leakage resulted in a high risk of urinary bother. Of 775 survivors 46 (6%) reporting 0 pads indicated moderate or much bother compared to 38 of 123 (31%) who reported using a security pad. When comparing the 2 groups, the risk of bother from urinary leakage was more than 5 times higher in the safety pad vs the 0 pad group (RR 5.2, 95% CI 3.5-7.7). As the number of pads increased, we noted a higher bother risk. Cross-tabulation of pad use and urinary leakage revealed wide variation in pad requirements despite the same answer to urinary leakage questions., Conclusions: If the definition of continence is based on pad use, for example safety pads, a certain number of men who report moderate or much bother from urinary leakage will be defined as continent. Our results also show that for each stated rate of urinary leakage men prove to have a major variation in the pad requirement., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To identify predictors for long-term urinary leakage after radical prostatectomy., Patients and Methods: A consecutive series of 1411 patients who underwent radical prostatectomy (open surgery or robot-assisted laparoscopic surgery) at Karolinska University Hospital between 2002 and 2006 were invited to complete a study-specific questionnaire. Urinary leakage was defined as use of two or more pads per day., Results: Questionnaires were received from 1288 (91%) patients with a median follow-up of 2.2 years. Age at surgery predicts in an exponential manner long-term urinary incontinence at follow-up with an estimated relative increase of 6% per year. Among the oldest patients, 19% had urinary incontinence compared with 6% in the youngest age group, translating to a prevalence ratio of 2.4 (95% confidence interval [CI], 1.5-8.1). Low educational level, as compared with high, yielded an increased age-adjusted prevalence ratio of 2.5 (95% CI, 1.7-3.9). Patients who had undergone salvage radiation therapy had an increased prevalence of urinary incontinence (2.5; 95% CI, 1.6-3.8), as did those with respiratory disease (2.4; 95% CI, 1.3-4.4). Body mass index, prostate weight, presence of diabetes or previous transurethral resection did not appear to influence the prevalence of urinary incontinence., Conclusions: In this series, a patient's age at radical prostatectomy influenced, in an exponential manner, his risk of long-term urinary incontinence. Other predictors are low educational level, salvage radiation therapy and respiratory disease. Intervention studies are needed to understand if these data are relevant to the prevalence of urinary leakage if a radical prostatectomy is postponed in an active monitoring programme., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: The aim of this study was to analyse whether the exonic Ser608Leu (rs2297518) polymorphism in nitric oxide synthase-2 (NOS2) influences urinarybladder cancer risk and pathogenesis., Material and Methods: Genotyping of 359 bladder cancer patients from a population-based cohort and 164 population controls was carried out by allelic discrimination and sequencing. Genotypes were combined with information on tumour stage, grade, stage progression and cancer-specific death, from a 5-year clinical follow-up., Results: For the Ser608Leu polymorphism, TT homozygotes had three-fold higher odds for bladder cancer (p = 0.081), but once ill, a lower risk for stage progression (p = 0.031) and a better prognosis., Conclusions: The data indicate that the Tallele of the NOS2 Ser608Leu polymorphism is an initial risk factor for developing urinary bladder cancer. Among bladder cancer patients, however, individuals who are TT homozygous have a lower risk of developing muscle-invasive disease and a higher cancer-specific survival. Depending on the cellular context, nitric oxide can induce proliferation as well as apoptosis. The results from this and previous studies suggest that NOS2 polymorphisms may influence both the risk of contracting bladder cancer and the aggressiveness of the disease.

Nitric oxide (NO) is an important biological messenger known to influence several types of human cancers. NO formation is catalyzed by three different nitric oxide synthase (NOS) enzymes. In this study we analyzed if the NOS3 promoter polymorphism -786T>C (rs2070744) and the NOS3 Glu298Asp polymorphism in exon 7 (rs1799983) influence risk and pathogenesis of urinary-bladder cancer. Allelic discrimination and DNA sequencing were used to determine the -786T>C and the Glu298Asp NOS3 genotypes in 359 urinary-bladder cancer patients, from a population-based patient material, and 164 population controls. Patient genotypes were combined with information on tumor stage, grade, stage and grade progression and cancer-specific death, using a 5-year clinical follow-up. A threefold increased odds ratio for bladder cancer was found in homozygous carriers of the C allele of the -786T>C promoter polymorphism (p=0.017). No increased bladder cancer risk was found for the Glu298Asp polymorphism, but there was an association between the Glu298Asp and tumor grade (p=0.040). Our results suggest that the NOS3 promoter polymorphism -786T>C may influence bladder cancer risk., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Involuntary release of urine during sexual climax, orgasm-associated urinary incontinence, occurs frequently after radical prostatectomy. We know little about its prevalence and its effect on sexual satisfaction., Aim: To determine the prevalence of orgasm-associated incontinence after radical prostatectomy and its effect on sexual satisfaction., Methods: Consecutive series, follow-up at one point in calendar time of men having undergone radical prostatectomy (open surgery or robot-assisted laparoscopic surgery) at Karolinska University Hospital, Stockholm, Sweden, 2002-2006. Of the 1,411 eligible men, 1,288 (91%) men completed a study-specific questionnaire., Main Outcome Measure: Prevalence rate of orgasm-associated incontinence., Results: Of the 1,288 men providing information, 691 were sexually active. Altogether, 268 men reported orgasm-associated urinary incontinence, of whom 230 (86%) were otherwise continent. When comparing them with the 422 not reporting the symptom but being sexually active, we found a prevalence ratio (with 95% confidence interval) of 1.5 (1.2-1.8) for not being able to satisfy the partner, 2.1 (1.1-3.5) for avoiding sexual activity because of fear of failing, 1.5 (1.1-2.1) for low orgasmic satisfaction, and 1.4 (1.2-1.7) for having sexual intercourse infrequently. Prevalence ratios increase in prostate-cancer survivors with a higher frequency of orgasm-associated urinary incontinence., Conclusion: We found orgasm-associated urinary incontinence to occur among a fifth of prostate cancer survivors having undergone radical prostatectomy, most of whom are continent when not engaged in sexual activity. The symptom was associated with several aspects of sexual life., (© 2011 International Society for Sexual Medicine.)

Multiple length scales are involved in the development of traumatic brain injury, where the global mechanics of the head level are responsible for local physiological impairment of brain cells. In this study, a relation between the mechanical state at the tissue level and the cellular level is established. A model has been developed that is based on pathological observations of local axonal injury. The model contains axons surrounding an obstacle (e.g., a blood vessel or a brain soma). The axons, which are described by an anisotropic fiber-reinforced material model, have several physically different orientations. The results of the simulations reveal axonal strains being higher than the applied maximum principal tissue strain. For anisotropic brain tissue with a relatively stiff inclusion, the relative logarithmic strain increase is above 60%. Furthermore, it is concluded that individual axons oriented away from the main axonal direction at a specific site can be subjected to even higher axonal strains in a stress-driven process, e.g., invoked by inertial forces in the brain. These axons can have a logarithmic strain of about 2.5 times the maximum logarithmic strain of the axons in the main axonal direction over the complete range of loading directions. The results indicate that cellular level heterogeneities have an important influence on the axonal strain, leading to an orientation and location-dependent sensitivity of the tissue to mechanical loads. Therefore, these effects should be accounted for in injury assessments relying on finite element head models.

Objectives: To assess the surgery-related complications at robot-assisted radical cystectomy with total intracorporeal urinary diversion during our learning curve in treating 45 patients with bladder cancer., Methods: A total of 45 patients were pooled in 3 consecutive groups of 15 cases each to evaluate the complications according to the Clavien classification. As a surrogate for our learning curve, the following parameters were assessed: operative time, blood loss, urinary diversion type, lymph node yield, surgical margin status, and length of hospital stay., Results: Early surgery-related complications were noted in 40% of the patients and late complications in 30%. The early Clavien grade III complications remained significant (27%) and did not decline with time. Overall, fewer complications were observed between the groups over time, with a significant decrease in late versus early complications (P = .005 and P = .058). The mean operative times declined from the first group to the second and third groups (P = .005) and the hospital stays shortened (P = .006). No significant difference was observed between groups regarding the lymph node yield at cystectomy (P = .108), with a mean of 22.5 nodes (range 10-52) removed. More patients received an orthotopic bladder substitute (Studer) in each of the latter 2 groups than in the first., Conclusions: Although robot-assisted radical cystectomy with total intracorporeal urinary diversion is a complex procedure, we observed decreased surgery-related complications and improved outcomes over time in the present series. Our results need to be confirmed by others before robot-assisted radical cystectomy with totally intracorporeal urinary diversion can be accepted as a treatment option for patients with bladder cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Root hairs secrete ATP as they grow, and extracellular ATP and ADP can trigger signaling pathways that regulate plant cell growth. In several plant tissues the level of extracellular nucleotides is limited in part by ectoapyrases (ecto-NTPDases), and the growth of these tissues is strongly influenced by their level of ectoapyrase expression. Both chemical inhibition of ectoapyrase activity and suppression of the expression of two ectoapyrase enzymes by RNAi in Arabidopsis resulted in inhibition of root hair growth. As assayed by a dose-response curve, different concentrations of the poorly hydrolysable nucleotides, ATPγS and ADPβS, could either stimulate (at 7.5-25 μM) or inhibit (at ≥ 150 μM) the growth rate of root hairs in less than an hour. Equal amounts of AMPS, used as a control, had no effect on root hair growth. Root hairs of nia1nia2 mutants, which are suppressed in nitric oxide (NO) production, and of atrbohD/F mutants, which are suppressed in the production of H(2)O(2), did not show growth responses to applied nucleotides, indicating that the growth changes induced by these nucleotides in wild-type plants were likely transduced via NO and H(2)O(2) signals. Consistent with this interpretation, treatment of root hairs with different concentrations of ATPγS induced different accumulations of NO and H(2)O(2) in root hair tips. Two mammalian purinoceptor antagonists also blocked the growth responses induced by extracellular nucleotides, suggesting that they were initiated by a receptor-based mechanism.

Background: Observational data indicate that retropubic radical prostatectomy (RRP) for prostate cancer (PCa) may induce inguinal hernia (IH) formation. Little is known about the influence of robot-assisted radical prostatectomy (RALP) on IH risk., Objective: To compare the incidence of IH after RRP and RALP to that of nonoperated patients with PCa and to a population control., Design, Setting, and Participants: We studied two groups. All 376 men included in the Scandinavian Prostate Cancer Group Study Number 4 constitute study group 1. Patients were randomly assigned RRP or watchful waiting (WW). The 1411 consecutive patients who underwent RRP or RALP at Karolinska University Hospital constitute study group 2. Men without PCa, matched for age and residence to each study group, constitute controls., Measurements: Postoperative IH incidence was detected through a validated questionnaire. The participation rates were 82.7% and 88.4% for study groups 1 and 2, respectively., Results and Limitations: The Kaplan-Meier cumulative occurrence of IH development after 48 mo in study group 1 was 9.3%, 2.4%, and 0.9% for the RRP, the WW, and the control groups, respectively. There were statistically significant differences between the RRP group and the WW and control groups, but not between the last two. In study group 2 the cumulative risk of IH development at 48 mo was 12.2%, 5.8%, and 2.6% for the RRP, the RALP, and the control group, respectively. There were statistically significant differences between the RRP group and the RALP and control groups, but not between the last two., Conclusions: RRP for PCa leads to an increased risk of IH development. RALP may lower the risk as compared to open surgery., (Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: We analyzed whether the NOS2 promoter microsatellite (CCTTT)n polymorphism influences bladder cancer pathogenesis., Materials and Methods: We genotyped 359 patients with bladder cancer in a population based cohort and 164 population controls by DNA fragment analysis and sequencing. Genotypes were combined with information on tumor stage, grade and stage, grade progression and cancer specific death. Clinical followup was 5 years., Results: We divided (CCTTT)n alleles into short-10 or fewer, intermediate-11 or 12 and long-13 or greater repeats. Patients homozygous for 13 or longer (CCTTT)n repeats were at decreased odds ratio for bladder cancer (p = 0.010). However, after illness developed they were at 3-fold increased hazard ratio for stage progression (p = 0.062) and 4-fold increased hazard ratio for death from bladder cancer (p = 0.056). We discovered what is to our knowledge a previously undescribed polymorphism at position 23105343 (C/T). There was no difference in frequency between bladder cancer cases and population controls for this polymorphism. No associations were found between tumor stage, grade or stage and grade progression. However, patients with bladder cancer with the heterozygous CT genotype were at 3-fold increased hazard ratio of death from cancer (p = 0.011)., Conclusions: Nitric oxide can induce proliferation or apoptosis depending on the cellular context. Results suggest that the (CCTTT)n NOS2 microsatellite may influence bladder cancer risk and aggressiveness. This polymorphism may have an impact on disease pathogenesis, possibly by affecting intracellular nitric oxide levels., (Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Fecal incontinence is a symptom reported by cancer survivors after pelvic radiotherapy and is recognized to be one of the most troubling symptom-induced sources of distress to patients., Objective: To investigate how fecal incontinence, patient-reported as emptying of all stools into clothing without forewarning, impact self-assessed quality of life from a social, psychological, sexual, and functional aspect among gynecological cancer survivors treated with pelvic radiotherapy., Methods: We identified a cohort of 789 eligible women in the Stockholm and Gothenburg areas treated with pelvic radiotherapy alone or as combined treatment of gynecological cancer. From the Swedish Population Registry, we identified 478 control women. Data were collected using a study-specific, validated, postal questionnaire including questions covering symptoms from the pelvic region, demographics, social functioning, psychological, and quality-of-life issues., Results: Participation was 78% for cancer survivors and 72% for control women. The fecal incontinence symptom emptying of all stools into clothing without forewarning was reported by 70 cancer survivors (12%), with lowered quality of life in 74% of the 70 cancer survivors. This symptom kept the survivors from going to parties (relative risk [RR], 11.8; 95% confidence interval [CI], 6.6-21.1), kept the survivors from traveling (RR, 9.3; 95% CI, 5.3-16.5), affected their work ability (RR, 7.9; 95% CI, 3.8-16.4), hindered their sexual life (RR, 9.2; 95% CI, 4.8-17.6), and changed them as persons (RR, 4.9; 95% CI, 2.9-8.1). The prevalence of the symptom emptying of all stools into clothing without forewarning among control women was 3 (1%) of 344., Conclusions: Among gynecological cancer survivors having undergone pelvic radiotherapy alone or as part of a combined treatment, fecal incontinence is associated with social, psychological, sexual, and functional consequences.

A recently developed proteomic strategy, the "GG-azide"-labeling approach, is described for the detection and proteomic analysis of geranylgeranylated proteins. This approach involves metabolic incorporation of a synthetic azido-geranylgeranyl analog and chemoselective derivatization of azido-geranylgeranyl-modified proteins by the "click" chemistry, using a tetramethylrhodamine-alkyne. The resulting conjugated proteins can be separated by 1-D or 2-D and pH fractionation, and detected by fluorescence imaging. This method is compatible with downstream LC-MS/MS analysis. Proteomic analysis of conjugated proteins by this approach identified several known geranylgeranylated proteins as well as Rap2c, a novel member of the Ras family. Furthermore, prenylation of progerin in mouse embryonic fibroblast cells was examined using this approach, demonstrating that this strategy can be used to study prenylation of specific proteins. The "GG-azide"-labeling approach provides a new tool for the detection and proteomic analysis of geranylgeranylated proteins, and it can readily be extended to other post-translational modifications.

We have examined the stimulation and recording properties of conjugated polymer microelectrode arrays as interfaces with neural networks of dissociated cortical cells. In particular the stimulation properties were investigated as a means of supplying a neural network with information. The stimulation efficiency at low stimulation voltages was evaluated and referenced to bare indium tin oxide (ITO) electrodes. The polymer electrodes were electrochemically polymerized from a blend of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) and ethylenedioxythiophene (EDOT) onto ITO microelectrodes. Dissociated cortical cells were then plated on the electrodes and cultivated to form neural networks. Polymer electrode stimulation evoked a much greater response from the network than stimulation from ITO electrodes. Neural interfaces using polymer electrodes could be maintained for several months.

The functional outcome of microsurgical repair of divided nerves is disappointing since many regenerating axons fail to reach appropriate targets. Sorting of regenerating axons according to target tissue might be used to improve functional regeneration. The aim of the present study is to see if regenerating axons can be sorted into functionally different bundles with target-derived molecules. The proximal stump of the adult rat sciatic nerve was sutured into the inlet of a silicon Y-tube. The two branches of the Y-tube were filled with agarose primed with filtrates prepared from skin and muscle homogenates from the operated rat. The tibial and sural nerves were inserted in the two branches of the Y-tube. Six weeks later the sciatic nerve axons showed vigorous regeneration into both branches. Electron microscopic examination of regenerated nerve segments showed numerous myelinated and unmyelinated axons. The proportion of myelinated axons was significantly larger in the muscle-gel branch than in the skin-gel branch. Retrograde tracing from the nerve regenerates with Fast Blue and Fluoro-Ruby showed that ventral horn neurons at L4-L5 segmental levels were preferentially labeled from the muscle-gel branch. Neurons in corresponding dorsal root ganglia were labeled from both Y-tube branches (no significant numerical difference). A few neurons of both types contained both tracers. Measurements revealed that sensory neurons labeled from the muscle-gel branch were significantly larger (mean perikaryal area 870 microm(2)) than neurons labeled from the skin-gel branch (mean area 580 microm(2)). We conclude that regenerating motor and sensory axons can be sorted with target-derived molecules., (Copyright 2001 Academic Press.)

Three years after launching the team-based Quality For All program, Top Chemical Company CEO Sam Verde was searching for a team-based compensation system that would reflect his company's new philosophy. With a committee gathered to discuss the issue, Verde confronts the fact that changing pay plans is an issue few people can agree on. "Very simply," explains vice president for compensation Gilbert Porterfield, "the plan is designed to give employees working on teams real incentives for constant improvement and overall excellence. The variable aspect of the system pays employees for the performance of their group." This doesn't sit well with the others. "It's going to punish teams like mine for the failings of others instead of rewarding us for the work we do and have already done," says packaging team representative Ruth Gibson. Another committee member feels that team-based anything is a "motivational happy land that doesn't square with how people really work." While Verde likes the proposed pay plan, he has doubts over whether his employees will accept the risk. Upper management has no problem basing 60% of its pay on TopChem's performance. But getting line employees to risk part of their salaries--even as little as 4%--on the ups and downs of the chemical industry may be more trouble than it's worth. Four experts on compensation reveal where Top Chemical went wrong in its plan and how Sam Verde might bring about change successfully.