ProFertil study protocol for the investigation of gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy aiming at fertility protection of young women and teenagers with cancer in Sweden-a phase III randomised double-blinded placebo-controlled study.

BACKGROUND: Gonadotropin-releasing hormone agonists (GnRHa) cotreatment used to transiently suppress ovarian function during chemotherapy to prevent ovarian damage and preserve female fertility is used globally but efficacy is debated. Most clinical studies investigating a beneficial effect of GnRHa cotreatment on ovarian function have been small, retrospective and uncontrolled. Unblinded randomised studies on women with breast cancer have suggested a beneficial effect, but results are mixed with lack of evidence of improvement in markers of ovarian reserve. Unblinded randomised studies of women with lymphoma have not shown any benefit regarding fertility markers after long-term follow-up and no placebo-controlled study has been conducted so far. The aim of this study is to investigate if administration of GnRHa during cancer treatment can preserve fertility in young female cancer patients in a double-blind, placebo-controlled clinical trial. METHODS AND ANALYSIS: A prospective, randomised, double-blinded, placebo-controlled, phase III study including 300 subjects with breast cancer. In addition, 200 subjects with lymphoma, acute leukemias and sarcomas will be recruited. Women aged 14-42 will be randomised 1:1 to treatment with GnRHa (triptorelin) or placebo for the duration of their gonadotoxic chemotherapy. Follow-up until 5 years from end of treatment (EoT). The primary endpoint will be change in anti-Müllerian hormone (AMH) recovery at follow-up 12 months after EoT, relative to AMH levels at EoT, comparing the GnRHa group and the placebo group in women with breast cancer. ETHICS AND DISSEMINATION: This study is designed in accordance with the principles of Good Clinical Practice (ICH-GCP E6 (R2)), local regulations (ie, European Directive 2001/20/EC) and the ethical principles of the Declaration of Helsinki. Within 6 months of study completion, the results will be analysed and the study results shall be reported in the EudraCT database. STUDY REGISTRATION: The National Institutional review board in Sweden dnr:2021-03379, approval date 12 October 2021 (approved amendments 12 June 2022, dnr:2022-02924-02 and 13 December 2022, dnr:2022-05565-02). The Swedish Medical Product Agency 19 January 2022, Dnr:5.1-2021-98927 (approved amendment 4 February 2022). Manufacturing authorisation for authorised medicinal products approved 6 December 2021, Dnr:6.2.1-2020-079580. Stockholm Medical Biobank approved 22 June 2022, RBC dnr:202 253. TRIAL REGISTRATION NUMBER: NCT05328258; EudraCT number:2020-004780-71.

The Late Effects of Cancer Treatment on Female Fertility and the Current Status of Fertility Preservation-A Narrative Review.

Fertility counseling should be offered to all individuals of young reproductive age early in the patient's trajectory following a cancer diagnosis. Systemic cancer treatment and radiotherapy often have an inherent gonadotoxic effect with the potential to induce permanent infertility and premature ovarian failure. For the best chances to preserve a patient's fertility potential and to improve future quality of life, fertility preservation methods should be applied before cancer treatment initiation, thus multidisciplinary team-work and timely referral to reproductive medicine centers specialized in fertility preservation is recommended. We aim to review the current clinical possibilities for fertility preservation and summarize how infertility, as a late effect of gonadotoxic treatment, affects the growing population of young female cancer survivors.

Trends and outcomes of fertility preservation for girls, adolescents and young adults with Turner syndrome: A prospective cohort study.

Background: In Scandinavian countries, programs for fertility preservation (FP) are offered free of charge at tertiary-care university hospitals to all patients facing infertility risks due to malignant diagnoses or benign conditions. In this prospective study we aimed to investigate trends and outcomes of FP indicated by a diagnosis of Turner syndrome. Methods: Prospective cohort study of patients with Turner karyotype receiving fertility preservation counselling at the Karolinska University Hospital between 1 January 1999 and 31 December 2021. Results: The cohort included 100 women and girls that received counselling, whereof 27% were prepubertal girls, 59% were adolescents and 14% of adult age. Before 2006 all patients were referred for fertility counselling at the time of Turner diagnosis. Based on updated guidelines, mainly patients who showed signs of puberty were referred after 2006. As a result, spontaneous menarche was more common in the later period. In total, 39% of the cohort had monosomal karyotype (45X), 20% had 45X/46XX or 45X/47XXX mosaicisms and 36% had an X-chromosomal structural anomaly. Ovarian tissue cryopreservation was planned for 73% of all patients, and oocyte cryopreservation following gonadotropin stimulation was planned for 10% of the patients. Follicles were present in 25% of all biopsies analyzed. Adolescents were more likely to have follicles present (30%) than prepubertal girls (16%) or adult women (17%). The ten patients that underwent gonadotropin stimulation for oocyte cryopreservation underwent a total of 15 cycles and eight patients successfully preserved oocytes. In total, 26% of the cohort has undergone fertility treatment or expressed further interest in fertility preservation. Six women have given birth using donated oocytes and three following spontaneous conception. Two women have undergone re-transplantation of cryopreserved ovarian tissue, without regaining ovarian function, and none of the women that have cryopreserved oocytes has returned to use them. Conclusion: Fertility counselling for girls with Turner syndrome should ideally be offered at onset of spontaneous puberty to improve the chances of fertility preservation. Since the girls and women in this cohort are still young, the return rate and utilization of the preserved tissue and oocytes is expected to increase with time. Clinical Trial Registration: ClinicalTrials.gov, identifier NTC04602962.

A Prospective Study on Fertility Preservation in Prepubertal and Adolescent Girls Undergoing Hematological Stem Cell Transplantation.

BACKGROUND: Hematological stem cell transplantation (HSCT) is an established method which has markedly increased the survival rate of hematologic malignancies since its introduction in the 1980's. The conditioning for HSCT has known gonadotoxic effects and often leads to premature loss of fertility. In this study we have prospectively followed a cohort of girls undergoing HSCT and studied the outcomes of fertility preservation treatments performed before or after HSCT, as well as the long-term reproductive outcome. METHODS: In this one-center prospective study, 39 girls counselled for fertility preservation prior to or after conditioning for HSCT for malignant or benign diseases at childhood or adolescence between 1990 and 2017 were included. The patients were presented with the option to undergo cryopreservation of ovarian tissue or oocytes depending on their age and the time available. Follicle counts of the ovarian tissue and number of oocytes collected before or after HSCT were compared between patients treated for benign and malignant diseases. Hormone measurements post HSCT treatment, including FSH and AMH, reproductive outcomes and overall survival until January 2021 were investigated. RESULTS: In total, 34 girls and adolescents underwent fertility preservation before or after HSCT. Before HSCT, ovarian tissue was cryopreserved in 15 patients and two patients had oocytes preserved. Thirteen patients cryopreserved ovarian tissue after HSCT and seven patients returned to cryopreserve oocytes. Follicles were present in all tissue samples collected prior to HSCT, and in more than half of the samples collected post-HSCT. Half of the patients had spontaneous menarche or resumed menstruation post HSCT. Overall, 35 patients had survived at end of follow up and 7 patients had achieved parenthood. CONCLUSIONS: Since fertility loss is common following HSCT, fertility preservation should be offered to all patients. Fertility preservation treatments can be performed both before and after HSCT. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/show/NCT04602962, identifier NTC04602962.

Do negative intrusive thoughts at diagnosis predict impaired quality of life, depressed mood and waking up with anxiety 3, 12 and 24 months after radical prostatectomy? - a longitudinal study.

Objective: To evaluate the effect of intrusive thoughts at diagnosis on quality of life, depressed mood and waking up with anxiety up to two years after radical prostatectomy.Method: The Laparoscopic Prostatectomy Robot Open (LAPPRO) trial was a prospective, longitudinal multicenter study of 4003 patients undergoing radical prostatectomy. Questionnaire data were collected preoperatively, at 3, 12 and 24 months after surgery.Results: The group of patients with intrusive thoughts at diagnosis had a statistically significant higher postoperative prevalence of impaired quality of life, depressed mood and waking up with anxiety as compared with the group of patients with no or minor intrusive thoughts. The highest risk increase for impaired QoL, depressed mood and waking up with anxiety ≥1/week was at 12, 3 and 3 months, respectively, where the three outcomes increased by 38% (RR: 1.38; 95%CI: 1.27-1.49)), 136% (RR: 2.36; 95%CI: 1.74-3.19)) and 165% (RR: 2.65; 95%CI: 2.22-3.17)), respectively.Conclusions: The demonstrated link between intrusive thoughts and quality of life, depressed mood and waking up with anxiety deliver is further evidence to the idea that intrusive thoughts has potential as an endpoint for assessing and predicting psychological distress among men with prostate cancer diagnosis.Trial registration number: ISRCTN06393679 (www.isrctn.com). Date of registration: 07/02/2008. Retrospectively registered.

Effects of a home-based exercise program on the insulin-like growth factor axis in patients operated for colorectal cancer in Sweden: Results from the randomised controlled trial PHYSSURG-C.

OBJECTIVES: We report results from a subgroup within the ongoing PHYSSURG-C trial with the aim to examine effects of exercise on IGF-1 and IGFBP-3 in patients undergoing colorectal cancer surgery. DESIGN: Randomised controlled trial. SETTING: A Swedish university hospital. PARTICIPANTS: Between 2015 and 2016, 217 patients were enrolled (I = 106, C = 111), with 122 patients that had given blood samples at baseline and at least at one follow-up (I = 51, C = 71). Patients 20 year or older with colorectal cancer were eligible. Exclusion criteria were emergency surgery, local surgery, language problems or inability to perform intervention. INTERVENTIONS: Patients were computer-randomised to either a daily home-based aerobic exercise intervention (I), or to usual care (C). The intervention lasted two weeks before surgery and four weeks after discharge from hospital and consisted of medium-intensity aerobic exercise and inspiratory muscle training. Circulating concentrations of IGF-1 and IGFBP-3 were determined by blinded personnel at baseline, time of surgery and 4-6 weeks postoperatively. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome of this subpopulation report was change in IGF-1/IGFBP-3 ratio, IGF-1 and IGFBP-3 concentrations from baseline to surgery, and 4-6 weeks postoperatively. RESULTS: The IGF-1/IGFBP-3 ratio increased from baseline to surgery by 11% in I and 8% in C with no difference between groups (I vs. C: 1.04, 95%CI: 0.97-1.11; p = 1.000). Postoperative change was 5% in I and 3% in C with no difference between groups (I vs. C:1.03, 95%CI: 0.96-1.10; p = 1.000). Results concerning IGF-1 and IGFBP-3 also showed statistically significant dynamics over time with no difference between groups. No adverse events were reported. CONCLUSIONS: The home-based exercise program in our trial did not have any effect on IGF-1, or IGFBP-3. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov with identifier NCT02299596. This work was funded externally.

Chronic pain after two laparoendoscopic inguinal hernia repairs compared with laparoendoscopic repair followed by the Lichtenstein repair: an international questionnaire study.

BACKGROUND: The best repair of a recurrent inguinal hernia after primary laparoendoscopic repair is debatable. The aim was to assess chronic pain after two laparoendoscopic repairs in the same groin compared with Lichtenstein reoperation preceded by a laparoendoscopic repair. METHODS: This cohort study included adult patients who had received two laparoendoscopic repairs (Lap-Lap) or a laparoendoscopic repair followed by the Lichtenstein repair (Lap-Lich). Eligible patients were identified in the Danish and the Swedish hernia databases. Lap-Lap was matched 1:3 with Lap-Lich, and patients were sent validated questionnaires. The primary outcome was the proportion with chronic pain-related functional impairment, compared between the two groups. Secondary outcomes included chronic pain during various activities. RESULTS: In total, 74% (546 patients) responded to the questionnaires with a median follow-up since the second repair of 4.9 years (0.9-21.9 years). Regarding the primary outcome, 21% in Lap-Lap and Lap-Lich had chronic pain-related functional impairment of daily activities (p = 0.94). More patients in Lap-Lap compared with Lap-Lich reported pain ≥ 20 mm measured by the visual analog scale, 11% versus 5%, p = 0.04. However, there was no difference in the median VAS score or in the vast majority of the remaining secondary outcomes. CONCLUSIONS: There was no overall difference in chronic pain between patients who had received Lap-Lap compared with Lap-Lich. Choice of operative strategy for the second repair should, therefore, not be based on risk of chronic pain.

Chronic pain and risk for reoperation for recurrence after inguinal hernia repair using self-gripping mesh.

BACKGROUND: Improved recurrence rates after groin hernia surgery have led to chronic pain becoming the most troublesome postoperative complication. Self-gripping mesh was developed to decrease the risk for development of chronic pain. The aim of this nationwide cohort study was to compare recurrence rate and chronic pain 1 year after an open, anterior mesh repair of inguinal hernias with either a self-gripping mesh or other lightweight mesh. METHOD: All operations registered as open anterior mesh repair (Lichtenstein) in the Swedish Hernia Registry between September 2012 and October 2016 were selected. At 1 year after repair, patients were sent a pain questionnaire assessing chronic pain. We compared the prevalence of chronic pain and reoperation for recurrence using lightweight, sutured mesh or self-gripping mesh. RESULTS: We analyzed the 1,803 repairs using self-gripping mesh and 16,567 repairs using lightweight mesh. We found no difference in the prevalence of chronic pain 1 year after the hernia repair between self-gripping mesh and sutured lightweight mesh (OR 0.92, CI 95% 0.80-1.06, P = .257). There was no increase in reoperation for recurrence when using self-gripping mesh (HR 0.71, CI 95% 0.45-1.14, P = .156). Mean operation time was considerably less when using self-gripping mesh (43 vs 70 minutes; P > .001). CONCLUSION: The use of self-gripping mesh does not decrease the incidence of chronic pain and reoperation for recurrence compared with lightweight, sutured mesh for open anterior mesh repair of inguinal hernias. Furthermore, the use of self-gripping mesh is associated with a clinically important, lesser operation time.

Quality of life in patients treated for anal carcinoma-a systematic literature review.

PURPOSE: Anal cancer is a mainly treated with chemoradiotherapy. A small number of patients undergo salvage surgery. There are few published studies investigating quality of life and functional outcome after treatment for anal cancer. The aim of this review was to explore the literature and identify areas for further research. METHODS: A search was conducted in Medline using MESH terms related to anal cancer and quality of life. Two investigators selected and reviewed articles based on titles and abstracts. Three investigators read and reviewed the included articles and collected relevant data. The included articles were evaluated using the minimum standard checklist, and key findings were summarised in a chart. RESULTS: Some 15 articles, and a total of 802 patients, were deemed eligible. The results differed slightly among the studies. The incidence of symptoms such as fatigue, nausea, insomnia and appetite loss was higher than among healthy volunteers. Bowel function, urinary function and sexual function were negatively affected. Some studies found that, compared with the normal population, anal cancer survivors scored clinically significant worse in the functional scales in QLQ-C30. CONCLUSION: In conclusion, it is apparent that several functional problems affect the quality of life of patients with anal cancer. There are few studies which have investigated quality of life after treatment for anal cancer. Interventions to address issues related to anal cancer treatment may improve long-term quality of life in this patient group. TRIAL REGISTRATION: CRD42017059787.

Self-assessed preoperative level of habitual physical activity predicted postoperative complications after colorectal cancer surgery: A prospective observational cohort study.

INTRODUCTION: There is a growing interest in physical activity in relation to recovery after surgery. One important aspect of measuring recovery after surgical procedures is postoperative complications. The aim of this study was to determine if there is an association between the preoperative level of habitual physical activity and postoperative complications in patients undergoing elective surgery for colorectal cancer. MATERIALS AND METHODS: 115 patients scheduled for elective surgery due to colorectal cancer between February 2014 and September 2015 answered a questionnaire regarding physical activity and other baseline variables. Physical activity was assessed using the Saltin-Grimby physical activity level scale. Complications within 30 days after surgery were classified according to Clavien-Dindo, and the Comprehensive Complications Index (CCI) was calculated. Primary outcome was difference in CCI and key secondary outcome was risk for CCI ≥20. RESULTS: Physically inactive individuals had a CCI that was 12 points higher than individuals with light activity (p = 0.002) and 17 points higher than regularly active individuals (p = 0.0004). Inactive individuals had a relative risk for a CCI ≥20 that was 65% higher than for individuals reporting light activity (95% confidence interval (CI) for relative risk (RR) = 1.1-2.5) and 338% higher than for regularly active individuals (95% CI for RR = 2.1-9.4). CONCLUSION: Self-assessed level of habitual physical activity before colorectal cancer surgery was associated with fewer postoperative complications measured with CCI, in a dose-response relationship.

90-Day readmission after radical prostatectomy-a prospective comparison between robot-assisted and open surgery.

Purpose: All types of surgery are associated with complications. The debate is ongoing whether robot-assisted radical prostatectomy can lower this risk compared to open surgery. The objective of the present study was to evaluate post-operative adverse events leading to readmissions, using clinical records to classify these adverse events systematically. Materials and methods: A prospective controlled trial of men who underwent robot-assisted laparoscopic (RALP) or retropubic radical prostatectomy (RRP) at 14 departments of Urology (LAPPRO) between 2008 and 2011. Data on all readmissions within 3 months of surgery were collected from the Patient registry, Swedish Board of Health and Welfare. For each readmission the highest Clavien-Dindo grade was listed. Results: A total of 4003 patients were included in the LAPPRO trial and, after applying exclusion criteria, 3706 patients remained for analyses. The results showed no statistically significant difference in the overall readmission rates (8.1 vs. 7.1%) or readmission due to major complications (Clavien-Dindo ≥3b, 1.7 vs. 1.9%) between RALP and RRP within 90 days after surgery. Patients subjected to lymph-node dissection (LND) had twice the risk for readmission as men not undergoing LND, irrespective RALP or RRP technique. Blood transfusion was significantly more frequent during and within 30 days of RRP surgery (16 vs. 4%). Abdominal symptoms were more common after RALP. Conclusions: There is a substantial risk for hospital readmission after prostate-cancer surgery, regardless of technique; although major complications are rare. Regardless of surgical technique, attention should be focused on specific types of complications.

Groin hernia repair in women - A nationwide register study.

INTRODUCTION: The aim of this study was to investigate reoperation for recurrence in men and women with respect to method of repair, hernia anatomy and year of operation. METHOD: Since 1992, groin hernia repairs performed in Sweden are prospectively registered in the Swedish Hernia Register, (SHR). Reoperations are noted, regardless of where the reoperation is performed. Risk of reoperation for recurrence is calculated for men and women with respect of method of repair, hernia anatomy and year of operation. RESULTS: Out of 221 108 eligible operations registered between 1992-2013, 17 545 (8%) were performed on women. The risk of being operated for recurrence after laparoscopic surgery was lowered in women, RR 0,4(95%CI 0.3-0.7) and increased in men, RR 2.3(95% CI 2.0-2.7), compared to the Lichtenstein technique. DISCUSSION: The reoperation for recurrence rate differed significantly between men and women. As regards the technique used for primary repair, laparoscopic groin hernia repair lowered the risk of reoperation for recurrence in women whereas it doubled the risk in men.

The effect of pre- and post-operative physical activity on recovery after colorectal cancer surgery (PHYSSURG-C): study protocol for a randomised controlled trial.

BACKGROUND: Surgery for colorectal cancer is associated with a high risk of post-operative adverse events, re-operations and a prolonged post-operative recovery. Previously, the effect of prehabilitation (pre-operative physical activity) has been studied for different types of surgery, including colorectal surgery. However, the trials on colorectal surgery have been of limited methodological quality and size. The aim of this trial is to compare the effect of a combined pre- and post-operative intervention of moderate aerobic physical activity and inspiratory muscle training (IMT) with standard care on post-operative recovery after surgery for colorectal cancer. METHODS/DESIGN: We are conducting a randomised, controlled, parallel-group, open-label, multi-centre trial with physical recovery within 4 weeks after cancer surgery as the primary endpoint. Some 640 patients planned for surgery for colorectal cancer will be enrolled. The intervention consists of pre- and post-operative physical activity with increased daily aerobic activity of moderate intensity as well as IMT. In the control group, patients will be advised to continue their normal daily exercise routine. The primary outcome is patient-reported physical recovery 4 weeks post-operatively. Secondary outcomes are length of sick leave, complication rate and severity, length of hospital stay, re-admittances, re-operations, post-operative mental recovery, quality of life and mortality, as well as changes in insulin-like growth factor 1 and insulin-like growth factor-binding protein 3, perception of pain and a health economic analysis. DISCUSSION: An increase in moderate-intensity aerobic physical activity is a safe, cheap and feasible intervention that would be possible to implement in standard care for patients with colorectal cancer. If shown to be effective, this lifestyle intervention could be a clinical parallel to pre-operative smoke cessation that has already been implemented with good clinical results. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02299596 . Registered on 17 November 2014.

Is preoperative physical activity related to post-surgery recovery?-a cohort study of colorectal cancer patients.

INTRODUCTION: An increasing interest is seen in the role of preoperative physical activity (PA) in enhancing postoperative recovery. The short-term effect of preoperative PA on recovery after colorectal cancer is unknown. The aim of this study was to evaluate the association of the preoperative level of PA with postoperative recovery after surgery due to colorectal cancer disease. METHODS: This is a prospective observational cohort study, with 115 patients scheduled to undergo elective colorectal surgery. The self-reported level of preoperative PA was compared to measures of recovery. RESULTS: Regular self-reported preoperative PA was associated with a higher chance of feeling highly physically recovered 3 weeks after surgery (relative chance 3.3, p = 0.038), compared to physical inactivity. No statistically significant associations were seen with length of hospital stay, self-assessed mental recovery, re-admittances or with re-operations. DISCUSSION: In clinical practice, evaluating the patients' level of PA is feasible and may potentially be used as a prognostic tool for patients undergoing colorectal cancer surgery. Given the study design, the results from this study cannot prove causality. CONCLUSION: The present study found that the preoperative level of PA was associated with a faster self-assessed physical recovery after colorectal cancer surgery. PA did not show any associations with the primary outcome measure length of hospital stay or any of the other secondary outcome measures. Assessment of PA level preoperatively could be used for prognostic reasons. If systematic preoperative/postoperative physical training will enhance recovery, this remains to be studied in a randomized controlled study. HIGHLIGHTS: We examined preoperative physical activity and the recovery after colorectal cancer surgery. Physically active individuals had faster self-assessed physical recovery. Assessment of preoperative physical activity may provide prognostic clinical information.

Is preoperative physical activity related to post-surgery recovery? A cohort study of patients with breast cancer.

OBJECTIVE: The aim of our study is to assess the association between preoperative level of activity and recovery after breast cancer surgery measured as hospital stay, length of sick leave and self-assessed physical and mental recovery. DESIGN: A prospective cohort study. SETTING: Patients included were those scheduled to undergo breast cancer surgery, between February and November 2013, at two participating hospitals in the Western Region of Sweden. PARTICIPANTS: Patients planned for breast cancer surgery filled out a questionnaire before, as well as at 3 and 6 weeks after the operation. The preoperative level of activity was self-assessed and categorised into four categories by the participants using the 4-level Saltin-Grimby Physical Activity Level Scale (SGPALS). MAIN OUTCOME MEASURE: Our main outcome was postoperative recovery measured as length of sick leave, in-hospital stay and self-assessed physical and mental recovery. RESULTS: 220 patients were included. Preoperatively, 14% (31/220) of participants assessed themselves to be physically inactive, 61% (135/220) to exert some light physical activity (PA) and 20% (43/220) to be more active (level 3+4). Patients operated with mastectomy versus partial mastectomy and axillary lymph node dissection versus sentinel node biopsy were less likely to have a short hospital stay, relative risk (RR) 0.88 (0.78 to 1.00) and 0.82 (0.70 to 0.96). More active participants (level 3 or 4) had an 85% increased chance of feeling physically recovered at 3 weeks after the operation, RR 1.85 (1.20 to 2.85). No difference was seen after 6 weeks. CONCLUSIONS: The above study shows that a higher preoperative level of PA is associated with a faster physical recovery as reported by the patients 3 weeks post breast cancer surgery. After 6 weeks, most patients felt physically recovered, diminishing the association above. No difference was seen in length of sick leave or self-assessed mental recovery between inactive or more active patients.

The preoperative level of physical activity is associated to the postoperative recovery after elective cholecystectomy - A cohort study.

INTRODUCTION: There is an increasing interest in the role of preoperative physical activity for postoperative recovery. The effect of preoperative physical activity and recovery after cholecystectomy is unknown. The aim of this study was to evaluate the association of self-reported leisure-time preoperative physical activity with postoperative recovery and complications after elective cholecystectomy due to gallstone disease. METHODS: Prospective observational cohort study with 200 patients scheduled to undergo elective cholecystectomy. Level of self-assessed leisure-time physical activity was compared with recovery. RESULTS: Regular physical activity was associated with a higher degree of return to work within three weeks post-operatively (relative chance (RC) 1.26, p = 0.040); with a higher chance of leaving hospital within one day post-op (RC 1.23, p = 0.001), as well as with better mental recovery (RC 1.18, p = 0.049), compared to physically inactive. No statistically significant association was seen with return to work within one week or with self-assessed physical recovery. DISCUSSION: In clinical practice, evaluating the patients' level of physical activity is feasible, and may potentially be used to identify patients being more suitable for same-day surgery. Given the study design, the results from this study cannot prove causality. CONCLUSION: The present study shows that the preoperative leisure-time physical activity-level, is positively associated with less sick leave, a shorter hospital stay and with better mental recovery, three weeks post-elective cholecystectomy. We recommend assessing the physical activity-level preoperatively for prognostic reasons. If preoperative/postoperative physical training will increase recovery remains to be shown in a randomized controlled study.

Incidence of groin hernia repair after radical prostatectomy: a population-based nationwide study.

OBJECTIVE: To assess the incidence of groin hernia repair after radical prostatectomy for prostate cancer compared with the incidence in a control population without prostate cancer in a nationwide, population-based study. BACKGROUND: Recent reports indicate an increase in the incidence of groin hernia repair after radical prostatectomy. Inadequate knowledge of the incidence of groin hernia in the general population makes this information hard to interpret. METHODS: Information was retrieved from the Prostate Cancer Database (PCBaSe) and Swedish Hernia Register for events between 1998 and 2010. The incidence of groin hernia surgery was calculated for a group of men treated with radical prostatectomy (open and minimally invasive) and for a group treated with radiation therapy, and these were compared with the incidence in a control cohort of men matched for age and county of residence. Multivariate analysis was used to assess the hazard ratio (HR) of groin hernia repair according to age, tumor risk category, and Charlson Comorbidity Index. RESULTS: A total of 28,608 cases and 105,422 controls were included in the study. Men treated with radical prostatectomy and radiation therapy had a significantly higher incidence of groin hernia repair than the control cohort: HR: 3.95 (95% confidence interval: 3.70-4.21) for retropubic prostatectomy, HR: 3.37 (95% confidence interval: 2.95-3.87) for minimally invasive prostatectomy, and HR: 1.84 (95% confidence interval: 1.66-2.04) for radiation therapy. CONCLUSIONS: An almost 4-fold increase in groin hernia repair was observed after radical prostatectomy compared with controls, and men who received radiation therapy had an almost 2-fold increase in incidence. As well as postoperative changes in the abdominal wall, increased vigilance for groin hernia seems to be important for the increased incidence of groin hernia repair seen after radical prostatectomy or radiation therapy for prostate cancer.

Adsorption of α-synuclein to supported lipid bilayers: positioning and role of electrostatics.

An amyloid form of the protein α-synuclein is the major component of the intraneuronal inclusions called Lewy bodies, which are the neuropathological hallmark of Parkinson's disease (PD). α-Synuclein is known to associate with anionic lipid membranes, and interactions between aggregating α-synuclein and cellular membranes are thought to be important for PD pathology. We have studied the molecular determinants for adsorption of monomeric α-synuclein to planar model lipid membranes composed of zwitterionic phosphatidylcholine alone or in a mixture with anionic phosphatidylserine (relevant for plasma membranes) or anionic cardiolipin (relevant for mitochondrial membranes). We studied the adsorption of the protein to supported bilayers, the position of the protein within and outside the bilayer, and structural changes in the model membranes using two complementary techniques-quartz crystal microbalance with dissipation monitoring, and neutron reflectometry. We found that the interaction and adsorbed conformation depend on membrane charge, protein charge, and electrostatic screening. The results imply that α-synuclein adsorbs in the headgroup region of anionic lipid bilayers with extensions into the bulk but does not penetrate deeply into or across the hydrophobic acyl chain region. The adsorption to anionic bilayers leads to a small perturbation of the acyl chain packing that is independent of anionic headgroup identity. We also explored the effect of changing the area per headgroup in the lipid bilayer by comparing model systems with different degrees of acyl chain saturation. An increase in area per lipid headgroup leads to an increase in the level of α-synuclein adsorption with a reduced water content in the acyl chain layer. In conclusion, the association of α-synuclein to membranes and its adsorbed conformation are of electrostatic origin, combined with van der Waals interactions, but with a very weak correlation to the molecular structure of the anionic lipid headgroup. The perturbation of the acyl chain packing upon monomeric protein adsorption favors association with unsaturated phospholipids preferentially found in the neuronal membrane.