Incidence of genitourinary complications following radiation therapy for localised prostate cancer.

PURPOSE: Studies of genitourinary toxicity following radiotherapy for prostate cancer are mainly from high volume single institutions and the incidence and burden of treatment remain uncertain. Hence we determine the cumulative incidence of treatment-related genitourinary toxicity in patients with localised prostate cancer treated with primary external beam radiotherapy (EBRT) at a state population level. METHODS: We analysed data from a prospective population-based cohort, including hospital admission and cancer registry data, for men with localised prostate cancer who underwent primary EBRT without nodal irradiation between 1998 and 2019 in South Australia. The 10-year cumulative incidence of genitourinary toxicity requiring hospitalisation or procedures was determined. Clinical predictors of toxicity and the volume of admissions, non-operative, minor operative and major operative procedures were determined. RESULTS: All the included patients (n = 3350) had EBRT, with a median (IQR) of 74 Gy (70-78) in 37 fractions (35-39). The 10-year cumulative incidence of was 28.4% (95% CI 26.3-30.6) with a total of 2545 hospital admissions, including 1040 (41%) emergency and 1893 (74%) readmissions. The 10-year cumulative incidence of patients in this cohort requiring a urological operative procedure was 18% (95% CI 16.1-19.9), with a total of 106 (4.2%) non-operative, 1044 (41%) minor operative and 57 (2.2%) major operative urological procedures. CONCLUSIONS: Genitourinary toxicity after radiotherapy for prostate cancer is common. Although there continue to be advancements in radiotherapy techniques, patients and physicians should be aware of the risk of late toxicity when considering EBRT.

Predicting post-radiation genitourinary hospital admissions in patients with localised prostate cancer.

PURPOSE: The risk of treatment-related toxicity is important for patients with localised prostate cancer to consider when deciding between treatment options. We developed a model to predict hospitalisation for radiation-induced genitourinary toxicity based on patient characteristics. METHODS: The prospective South Australian Prostate Cancer Clinical Outcomes registry was used to identify men with localised prostate cancer who underwent curative intent external beam radiotherapy (EBRT) between 1998 and 2019. Multivariable Cox proportional regression was performed. Model discrimination, calibration, internal validation and utility were assessed using C-statistics and area under ROC, calibration plots, bootstrapping, and decision curve analysis, respectively. RESULTS: There were 3,243 patients treated with EBRT included, of which 644 (20%) patients had a treated-related admission. In multivariable analysis, diabetes (HR 1.35, 95% CI 1.13-1.60, p < 0.001), smoking (HR 1.78, 95% CI 1.40-2.12, p < 0.001), and bladder outlet obstruction (BOO) without transurethral resection of prostate (TURP) (HR 7.49, 95% CI 6.18-9.08 p < 0.001) followed by BOO with TURP (HR 4.96, 95% CI 4.10-5.99 p < 0.001) were strong independent predictors of hospitalisation (censor-adjusted c-statistic = 0.80). The model was well-calibrated (AUC = 0.76). The global proportional hazards were met. In internal validation through bootstrapping, the model was reasonably discriminate at five (AUC 0.75) years after radiotherapy. CONCLUSIONS: This is the first study to develop a predictive model for genitourinary toxicity requiring hospitalisation amongst men with prostate cancer treated with EBRT. Patients with localised prostate cancer and concurrent BOO may benefit from TURP before EBRT.

The bidirectional association between depression and lower urinary tract symptoms (LUTS) in men: A systematic review and meta-analysis of observational studies.

BACKGROUND: Recent evidence from observational studies suggests a bidirectional association between lower urinary tract symptoms (LUTS) and depression in men. We sought to systematically quantify the effect of the presence of LUTS on depression symptoms, compared to those without LUTS, in adult males, and vice versa. METHODS: Electronic databases (MEDLINE, PsycINFO, SCOPUS, Embase) were examined for articles in English before March 2021. Observational studies of men aged over 18 years; reporting an association between LUTS and depression; including a validated scale for LUTS and depression symptoms were eligible for study inclusion. RESULTS: Seventeen studies out of 1787 records identified 163 466 men with reported depression symptoms by LUTS status, while 10 studies reported 72 363 men with LUTS by depression symptoms. Pooled estimates showed a strong effect of LUTS presence on depression risk (OR: 2.89, 95% CI: 2.50-3.33), with a high degree of heterogeneity among the examined studies (I2 = 83%; τ2 = 0,06; p < 0.001). Subgroup analyses demonstrated differences by study region (Q value:13.7, df:4, p = 0.003), setting (7.8(2), p = 0.020), design (7.2(1), p = 0.003), quality (6.2(1), p = 0.013), and LUTS measure (40.9(3), p < 0.001). Pooled estimates also showed a strong effect of depression presence on LUTS risk in men (OR: 3.13, 95% CI: 2.72-3.60), with only moderate heterogeneity between studies (I2 = 58%; τ2 = 0,02; p = 0.001). CONCLUSIONS: The strong relationship observed between LUTS and depression implies shared risk factors that cannot be solely attributed to the prostate. This has immediate implications for future studies and the assessment and management of patients with either condition.

Pelvic Radiation Disease.

Pelvic radiation is increasingly being used for the neoadjuvant and definitive treatment of pelvic organ malignancy. While this treatment can be highly effective, and may assist in organ sparing, it is also associated with significant toxicity and devastating adverse events that need to be considered. In broad terms, pelvic radiation disease affects both the primary target organ as well as adjacent organs and soft tissue structures, with complications that can be classified and graded according to consensus criteria. The complication grade is often modality, dose, and area dependent. The most common manifestations are proctitis, cystitis, recto-urethral fistula, ureteric stricture, and bone involvement. Toxicity can be misdiagnosed for many years, resulting in significant management delays. Complications can be difficult to prevent and challenging to treat, requiring specialized multi-disciplinary input to achieve the best possible strategy to minimize impact and improve patient quality of life.

Classification systems for anterior urethral stricture disease in men: a systematic review.

OBJECTIVE: To identify and explore the various classification systems that have been proposed for anterior urethral stricture disease (AUSD) and to identify the advantages and disadvantages of each. METHODS: A comprehensive systematic review was conducted in MEDLINE, EMBASE, SCOPUS and COCHRANE databases with a search strategy created appropriately. Titles and abstracts of search results were screened by two authors and selected for full-text review. Studies exploring urethral stricture classification, clinical scoring or staging systems used in men over the age of 18 with benign anterior urethral stricture disease were included. RESULTS: The search identified 3113 articles, of which 10 were selected for inclusion after scrutiny. Four classification systems were identified. These include ULTRA score, urethral stricture score, cystoscopy-based staging system and Gombe Urethrographic score. These were based on various modalities, including cystoscopy, retrograde urethrogram (RUG) and sonourethrogram (SUG). From the scoring systems identified, the urethral stricture scoring system has multiple external validation studies and is predictive of operative complexity, operative time, recurrence and postoperative complications. CONCLUSIONS: Several classification systems have been proposed for AUSD. Each has its advantages and disadvantages. The urethral stricture score has been externally validated and shown to been predictive of surgical outcomes and recurrence. There are no scores that incorporate patient-related outcome measures (PROMs). Many classification systems have yet to provide sufficient external validation. Further external validation studies are needed before the general adoption of a particular system.

Buccal mucosal ureteroplasty for the management of ureteric strictures: A systematic review of the literature.

OBJECTIVE: To review the published literature evaluating the efficacy and safety of buccal mucosa ureteroplasty. METHODS: A systematic literature review was carried out using a protocol devised a priori. The review was registered with the Joanna Briggs Institute. Results were scrutinized and full text of all relevant articles was obtained for review. RESULTS: A systematic search resulted in 1092 articles, with scrutiny resulting in 1079 exclusions. Two additional articles were identified from references, resulting in a total of 15 included studies containing a total of 72 buccal mucosal ureteroplasty procedures. A total of 34 cases were carried out using the open approach, and 38 were carried out using the robot assisted approach. The overall reported success rate was reported to be 66 out of 72 (91.6%), being 32 out of 34 (94.1%) and 34 out of 38 (89.5%) open and robotic cases, respectively. The complication rate was reported in 60 cases, being 15 out of 60 (25%) for all complications, with a 5% (3/60) rate for complications graded as Clavien-Dindo score ≥3. CONCLUSIONS: Buccal mucosa ureteroplasty appears to have high success rates and low rates of serious complications in both open and robot assisted approaches. However, the current available literature is limited to 72 cases, and further studies with larger patient populations and ongoing longitudinal review are warranted.

Intraurethral catheter placement does not change the external circumferential measurement of the urethra during AUS placement: A prospective observational trial.

AIMS: Measuring the urethral circumference accurately during artificial urethral sphincter (AUS) placement is an important technical aspect to optimize the selection of cuff size. Differing methods exist for this step with some experts recommending measurement with no urethral catheter in place. In this prospective observational trial, we compared urethral measurements with and without an indwelling catheter to determine if the presence of a catheter affects the circumferential measurement. METHODS: With IRB approval, we prospectively collected data on consecutive cases of transperineal male AUS implantation. Urethral circumference was measured with no urethral catheter (0 French [Fr]), 12Fr, and 16Fr Foley catheters in the urethra. The final measurements and cuff size chosen were recorded. A comparison was made between each measurement using Spearman's correlation coefficient. RESULTS: A total of 54 patients were included, the majority of whom (92.6%) underwent AUS placement for postprostatectomy incontinence. The three urethral circumference measurements were highly correlated (0Fr vs 12Fr, ρ = 0.96, P < .001, mean difference 1 mm) (0Fr vs 16Fr, ρ = 0.94, P < .001, mean difference 2 mm) (12Fr vs 16Fr, ρ = 0.96, P < .001, mean difference 1 mm). Patients with a history of radiation had a lower mean urethral circumference than those who had never been radiated (4.78 cm vs 5.3 cm, P = .01). CONCLUSIONS: Urethral circumference measurement during AUS implantation is not influenced by the presence of a 12 or 16Fr Foley catheter when compared to no catheter in the urethra. Measurement of the urethral circumference can, therefore, be accurately performed with or without a catheter in place, depending on the surgeon's preference.

A Critical Analysis of Bulbar Urethroplasty Stricture Recurrence: Characteristics and Management.

PURPOSE: We evaluated the management of recurrent bulbar urethral stricture disease after urethroplasty at our institution. MATERIALS AND METHODS: We performed an institution review board approved, retrospective case study of our urethroplasty database to collect stricture related and postoperative information with an emphasis on bulbar urethral stricture disease recurrence after urethroplasty between 1996 and 2012. Repair types included primary anastomotic, augmented anastomotic and onlay repair. Recurrence, which was defined as the need for intervention, was diagnosed with cystoscopy or retrograde urethrogram. RESULTS: We identified 437 men who underwent urethroplasty of bulbar urethral stricture disease as performed by 2 surgeons from January 1996 to December 2012. Of the men 395 had available followup data. Recurrence was identified in 25 men (6.3%), of whom all presented with symptoms, including a weak stream in 23, urinary tract infection in 1 and pyelonephritis in 1. Median time to recurrence was 10 months. Recurrence was initially treated endoscopically in 23 of 25 cases (92%), dilatation in 12 and visual urethrotomy in 11. In 5 patients (22%) further recurrence developed after endoscopic treatment, which was managed by repeat urethroplasty in 2, self-calibration only in 2 and visual urethrotomy with subsequent self-calibration in 1. We identified 2 distinct phenotypes of recurrent stricture, including type A-short focal recurrence, which may be salvaged with an endoscopic procedure, and type B-the long graft length type, which is less likely to be salvaged with endoscopy. CONCLUSIONS: Recurrence after urethroplasty is most likely to develop within the first 12 months. Type A short focal recurrence may be managed by a salvage endoscopic procedure, including dilation or visual urethrotomy. These data on the phenotype of recurrence may be useful for patient treatment.

Aquablation - image-guided robot-assisted waterjet ablation of the prostate: initial clinical experience.

OBJECTIVE: To assess the safety and feasibility of aquablation in a first-in-man study. Aquablation is a novel minimally invasive water ablation therapy combining image guidance and robotics (AquaBeam(®) ) for the targeted and heat-free removal of prostatic tissue in men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: A prospective, non-randomised, single-centre trial in men aged 50-80 years with moderate-to-severe LUTS was conducted. Under real-time image-based ultrasonic guidance, AquaBeam technology enables surgical planning and mapping, and leads to a controlled heat-free resection of the prostate using a high-velocity saline stream. Patients were evaluated at 1, 3, and 6 months after aquablation. RESULTS: In all, 15 patients were treated with aquablation under general anaesthesia. The mean (range) age was 73 (59-86) years and prostate size was 54 (27-85) mL. A substantial median lobe was present in six of the 15 patients. The mean International Prostate Symptom Score (IPSS) was 23 and the maximum urinary flow rate (Qmax ) was 8.4 mL/s at baseline. The mean procedural time was 48 min with a mean aquablation treatment time of 8 min. All procedures were technically successful with no serious or unexpected adverse events (AEs). All but one patient had removal of catheter on day 1, and most of the patients were discharged on the first postoperative day. No patient required a blood transfusion, and postoperative sodium changes were negligible. There were no serious 30-day AEs. One patient underwent a second aquablation treatment within 90 days of the first procedure. The mean IPSS score statistically improved from 23.1 at baseline to 8.6 at 6 months (P < 0.001) and the Qmax increased from 8.6 mL/s at baseline to 18.6 mL/s at the 6-month follow-up (P < 0.001). At 6 months, the mean detrusor pressure at Qmax decreased to 45 cmH2 0 from 66 cmH2 0 at baseline (P < 0.05), and the mean prostate size was reduced to 36 mL, a 31% reduction in size vs baseline (P < 0.001). No cases of urinary incontinence or erectile dysfunction were reported. CONCLUSIONS: These preliminary results from this initial study show aquablation of the prostate is technically feasible with a safety profile comparable to other BPH technologies. The combination of surgical mapping by the operating surgeon and the high-velocity saline provides a promising technique delivering a conformal, quantifiable, and standardised heat-free ablation of the prostate. Advantages of this technique include reduction in resection time compared with other endoscopic methods, as well as the potential to preserve sexual function.

Gastrografin in Prolonged Postoperative Ileus: A Double-blinded Randomized Controlled Trial.

OBJECTIVE: To investigate the therapeutic value of Gastrografin in shortening duration of prolonged postoperative ileus (PPOI) after elective colorectal surgery. BACKGROUND: Gut wall edema is central to the pathogenesis of PPOI. Hyperosmotic, orally administered, water-soluble contrast media such as Gastrografin are theoretically capable of mitigating this edema. METHODS: A double-blinded, placebo-controlled, randomized trial was conducted. Participants were allocated to receive 100 mL of Gastrografin (Exposure Group) or flavored distilled water (Control Group) administered enterally. Other aspects of management were standardized. Resolution of PPOI was assessed 12-hourly. RESULTS: Eighty patients were randomized equally, with 5 in the Exposure Group and 4 in the Control Group excluded from analysis. Participants were evenly matched at baseline. Mean duration of PPOI did not differ between Exposure and Control Groups (83.7 vs 101.3 hours; P = 0.191). When considering individual markers of PPOI resolution, Gastrografin did not affect time to resolution of nausea and vomiting (64.5 vs 74.3 hours; P = 0.404) or consumption of oral diet (75.8 vs 90.0 hours; P = 0.297). However, it accelerated time to flatus or stool (18.9 vs 32.7 hours; P = 0.047) and time to resolution of abdominal distension (52.8 vs 77.7 hours; P = 0.013). There were no significant differences between groups in nasogastric output; analgesia, antiemetic, or fluid requirement; complications; or length of stay. CONCLUSIONS: Gastrografin is not clinically useful in shortening an episode of PPOI characterized by upper and lower gastrointestinal symptoms. It may however be of therapeutic benefit in the subset of PPOI patients who display lower gastrointestinal symptoms exclusively after surgery.

Enucleation techniques for benign prostate obstruction: which one and why?

PURPOSE OF REVIEW: Endoscopic enucleation of the prostate is the most advanced form of surgical management of benign prostate hyperplasia. The purpose of this review is to update the reader on various modalities currently in use, and in trial, for endoscopic enucleation. RECENT FINDINGS: A recent paradigm shift has occurred for the proponents of electrosurgery technology to utilizes the advantages offered by laser enucleation with interest in bipolar enucleation. Holmium laser enucleation still has the greatest randomized evidence with the longest follow-up among all the various lasers used to perform enucleation. SUMMARY: Randomized trials with longer follow-up are required to demonstrate whether nonholmium types of energy really have advantages in enucleation (speed, ease of use and hemostasis) and durability (decade plus) as compared to the holmium laser.

Non-steroidal anti-inflammatory drugs for lower urinary tract symptoms in benign prostatic hyperplasia: systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the effects of non-steroidal anti-inflammatory drugs (NSAIDs) in men with benign prostatic hyperplasia (BPH) using systematic review and meta-analysis of clinical trials. SUBJECTS: Men treated with NSAIDs in comparison with placebo or other BPH medications. METHODS: All aspects of the Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) statement were followed. Trials were eligible for inclusion provided they (i) randomized men with BPH to receive NSAIDs in comparison with placebo or other BPH medications, and (ii) included clinical outcomes such as urological symptom scales, symptoms or urodynamic measurements. Data analysis was performed using REVIEW MANAGER Version 5.0 software. Study weight was calculated by the inverse variances of the study effect estimates. RESULTS: In all, 183 men from three randomized, placebo-controlled trials (lasting 4-24 weeks) were assessed. NSAIDs improved urinary symptom scores and flow measures. The weighted mean difference for the International Prostate Symptom Score (IPSS) was -2.89 IPSS points (95% CI -3.84 to -1.95, P < 0.001, n = 3 studies). The weighted mean difference for peak urine flow was 0.89 mL/s (95% CI 0.21-1.58, P = 0.01, n = 3 studies) and for reported adverse effects was 1.51 (95% CI 0.66-3.43, P = 0.32, n = 3 studies,). All patients assigned to NSAIDs continued the treatment. There were no serious adverse effects and there were no withdrawals or losses to follow-up. CONCLUSION: The evidence suggests that NSAIDs improve urinary symptoms and flow measures. Their long-term effectiveness, safety and ability to prevent BPH complications are not known.

The Surgical Recovery Score correlates with the development of complications following elective colectomy.

BACKGROUND: The Surgical Recovery Score (SRS) is a validated, comprehensive recovery assessment tool used to measure functional recovery after major surgery. To further evaluate its clinical applicability, this study investigated whether the SRS correlates with clinical outcomes and the occurrence of complications after elective colectomy. MATERIALS AND METHODS: We conducted a retrospective review of prospectively collected data for consecutive patients undergoing elective colonic resection within an enhanced recovery program at our institution from September 2008 to September 2011. We administered the 31-item SRS questionnaire preoperatively (baseline) and on postoperative days 1, 3, 7, 14, and 30. We scored individual questionnaires as a percentage of the maximum possible score, with a higher SRS indicating improved functional recovery (range, 17-100). We prospectively recorded clinical outcomes and graded 30-d complications as per the Clavien-Dindo classification. We conducted univariate and logistic regression analysis to determine the correlation of the SRS to the development of complications. RESULTS: We evaluated 134 patients, 62 of whom developed minor complications (grades 1-2) (46%) and 21 of whom developed major complications (grades 3-5) (16%). The SRS was similar at baseline in the complicated and uncomplicated groups but significantly lower on postoperative days 3, 7, 14, and 30 in patients who developed major complications, and on days 7 and 14 in patients who developed minor complications. In a logistic regression analysis, the SRS on postoperative day 3 was independently associated with the development of any complication, as well as major complications specifically. CONCLUSIONS: In addition to measuring functional recovery, the SRS closely correlates with the development of complications after elective colectomy and offers a reliable outcome measure to assess overall postoperative recovery.

Which laser works best for benign prostatic hyperplasia?

The advantages offered by lasers compared to older technologies for endoscopic surgery for symptomatic benign prostate hyperplasia (BPH) are reviewed. Laser treatments for the endoscopic management of patients with bladder outlet obstruction (BOO) resulting from BPH can be divided into three basic techniques. These techniques are vaporisation (removal of tissue), resection of tissue (excision of small chips and subsequent irrigation from bladder) and enucleation (dissection of the adenoma from the surgical capsule and subsequent morcellation). The decision to offer a transurethral laser approach to patients with BPH depends on their comorbidities, the surgeon's expertise with the different procedures, and the availability of the relevant technology.

Goal-directed fluid therapy- a survey of anaesthetists in the UK, USA, Australia and New Zealand.

BACKGROUND: Goal-directed fluid therapy (GDFT) has been shown to reduce complications and hospital length of stay following major surgery. However, there has been no assessment regarding its use in clinical practice. METHODS: An electronic survey was administered to randomly selected anaesthetists from the United Kingdom (UK, n = 2000) and the United States of America (USA, n = 2000), and 500 anaesthetists from Australia/New Zealand (AUS/NZ). Preferences, clinical use and attitudes towards GDFT were investigated. Results were collated to examine regional differences. RESULTS: The response rates from the UK (n = 708) and AUS/NZ (n = 180) were 35%, and 36% respectively. The response rate from the USA was very low (n = 178; 9%). GDFT use was significantly more common in the UK than in AUS/NZ (p < 0.01). The Oesophageal Doppler Monitor was the most preferred instrument in the UK (n = 362; h76%) with no clear preferences in other regions. GDFT was most commonly utilised in major abdominal surgery and for patients with significant comorbidities. The commonest reasons stated for not using GDFT were either lack of availability of monitoring tools (AUS/NZ: 57 (70%); UK: 94 (64%)) or a lack of experience with instruments (AUS/NZ: 43 (53%); UK: 51 (35%)). A subset of respondents (AUS/NZ: 22(27%); UK: 45 (30%)) felt GDFT provided no perceived benefit. Enthusiasm towards the use of GDFT in the absence of existing barriers was high. CONCLUSION: Several hypotheses were generated regarding important differences in the use of GDFT between anaesthetists from the UK and AUS/NZ. There is significant interest in utilising GDFT in clinical practice and existing barriers should be addressed.

Long term genitourinary toxicity following curative intent intensity-modulated radiotherapy for prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Recent studies have shown that radiation-induced pelvic toxicity often requires urological consultation. However, the 10-year incidence of genitourinary toxicity following intensity-modulated radiotherapy (IMRT) amongst patients with localised prostate cancer remains unclear. Hence, we conducted a systematic review and meta-analysis to determine the incidence of late genitourinary toxicity relying on Radiation Therapy Oncology Group (RTOG) and Common Terminology Criteria for Adverse Events (CTCAE) grade as well as the incidence of specific genitourinary toxicity. Secondary objectives involved quantifing the number of studies reporting 120-month follow-up endpoints, time to event analysis, predictive factors or economic evaluation. METHODS: Articles published from January 2008 to December 2021 describing prospective studies were systematically searched in MEDLINE, EMBASE and Cochrane (PROSPERO protocol CRD42019133320). Quality assessment was performed by use of the Cochrane Risk of Bias 2 Tool for RCTs and the Newcastle Ottowa Scale for non-RCTs. Meta-analysis was performed on the 60-month incidence of RTOG and CTCAE Grade ≥2 genitourinary toxicity, haematuria, urinary retention and urinary incontinence. RESULTS: We screened 4721 studies and six studies met our inclusion criteria. All included studies involved normofractionation, three included a hypofractionation comparator arm and none involved nodal irradiation. The pooled 60-month cumulative incidence of RTOG and CTCAE Grade ≥2 genitourinary toxicity were 17% (95% CI: 5-20%, n = 678) and 33% (95% CI: 27-38%, n = 153), respectively. The pooled 60-month cumulative incidence of Haematuria was 5% (95% CI: -4-14%, n = 48), Urinary incontinence 12% (95% CI: 6-18%, n = 194), Urinary retention 24% (95% CI: 9-40%, n = 10). One study reported time to event analyses, one reported predictive factors, no studies reported economic analysis or 120-month toxicity. There was considerable heterogeneity amongst the studies. CONCLUSION: There are few high-quality studies reporting 60-month toxicity rates after IMRT. Conservative estimates of 60-month toxicity rates are high and there is need for longer follow-up and consistent toxicity reporting standards.

Risk of secondary malignancy following radiation therapy for prostate cancer.

We investigated whether prostate cancer patients treated with external beam radiation therapy (EBRT) have a higher cumulative incidence of secondary cancer compared with patients treated with radical prostatectomy (RP). We used state-wide linked data from South Australia to follow men with prostate cancer diagnosed from 2002 to 2019. The cumulative incidence of overall and site-specific secondary cancers between 5 and 15 years after treatment was estimated. Fine-Gray competing risk analyses were performed with additional sensitivity analyses to test different scenarios. A total of 7625 patients were included (54% underwent RP and 46% EBRT). Characteristics of the two groups differed significantly, with the EBRT group being older (71 vs. 64 years), having higher comorbidity burden and being more likely to die during follow-up than the RP group. Fifteen-year cumulative incidence for all secondary cancers was 27.4% and 22.3% in EBRT and RP groups, respectively. In the adjusted models, patients in the EBRT group had a significantly higher risk of genitourinary (adjusted subhazard ratio (aSHR), 2.29; 95%CI 1.16-4.51) and lung (aSHR, 1.93; 95%CI 1.05-3.56) cancers compared with patients in the RP group. However, there was no statistically significant difference between the two groups for risk of any secondary cancer, gastro-intestinal, skin or haematologic cancers. No statistically significant differences in overall risk of secondary cancer were observed in any of the sensitivity analyses and patterns for risk at specific cancer sites were relatively consistent across different age restriction and latency/time-lag scenarios. In conclusion, the increased risk of genitourinary and lung cancers among men undergoing EBRT may relate partly to treatment effects and partly to unmeasured residual confounding.

A brief relaxation intervention reduces stress and improves surgical wound healing response: a randomised trial.

Psychological stress has been shown to impair wound healing, but experimental research in surgical patients is lacking. This study investigated whether a brief psychological intervention could reduce stress and improve wound healing in surgical patients. This randomised controlled trial was conducted at a surgical centre. Inclusion criteria were English-speaking patients over 18 years booked to undergo elective laparoscopic cholecystectomy; exclusion criteria were cancellation of surgery, medical complications, and refusal of consent. Seventy five patients were randomised and 15 patients were excluded; 60 patients completed the study (15 male, 45 female). Participants were randomised to receive standard care or standard care plus a 45-min psychological intervention that included relaxation and guided imagery with take-home relaxation CDs for listening to for 3 days before and 7 days after surgery. In both groups ePTFE tubes were inserted during surgery and removed at 7 days after surgery and analysed for hydroxyproline as a measure of collagen deposition and wound healing. Change in perceived stress from before surgery to 7-day follow-up was assessed using questionnaires. Intervention group patients showed a reduction in perceived stress compared with the control group, controlling for age. Patients in the intervention group had higher hydroxyproline deposition in the wound than did control group patients (difference in means 0.35, 95% CI 0.66-0.03; t(43)=2.23, p=0.03). Changes in perceived stress were not associated with hydroxyproline deposition. A brief relaxation intervention prior to surgery can reduce stress and improve the wound healing response in surgical patients. The intervention may have particular clinical application for those at risk of poor healing following surgery.

Perioperative use of statins in elective colectomy.

BACKGROUND: Statins have many beneficial effects and may attenuate the proinflammatory and metabolic stress response to surgery and consequently reduce postoperative morbidity. OBJECTIVE: This study investigated whether perioperative use of statins improved short-term outcomes after elective colectomy. DESIGN: This study is a retrospective review of prospectively collected data. SETTINGS AND PATIENTS: This study was conducted in consecutive patients undergoing elective colonic resection within an enhanced recovery program at a tertiary hospital (Manukau Surgery Centre, Middlemore Hospital, Auckland, New Zealand) from January 2005 to December 2010. MAIN OUTCOME MEASURES: Complications, hospital stay, and readmissions were recorded for 30 days postoperatively. Postoperative functional recovery was measured by the use of the validated Surgical Recovery Score. Serum proinflammatory cytokines were measured on postoperative day 1. RESULTS: There were 269 patients; 86 patients were on a statin perioperatively, whereas 183 patients had no statin. Members of the statin group were older (median age, 72 vs 69 years; p = 0.021), included more men (53% vs 40%; p = 0.049), and included a higher number of patients with an ASA score of 3 (55% vs 22%; p < 0.001). Patients on statin therapy had a significantly lower number of anastomotic leaks (1% vs 7%; p = 0.031). However, there was no significant difference in total complications or median hospital stay. The 2 groups had comparable functional recovery, and there was no significant difference in serum cytokine levels. LIMITATIONS: This retrospective study did not analyze type, duration, or dose of statins given perioperatively. CONCLUSION: Patients on perioperative statins had greater baseline perioperative risks compared with nonusers, but they achieved equivalent outcomes overall. Statin use was associated with reduced anastomotic leaks. Thus, perioperative statin use may reduce morbidity after elective colectomy, and this finding warrants further investigation.

A prospective case-control study of the local and systemic cytokine response after laparoscopic versus open colonic surgery.

BACKGROUND: There is a sequential, high concentration cytokine response after major abdominal surgery. The magnitude of this response has been directly linked to postoperative metabolic derangement, ileus, adhesions, and oncological outcomes. We aimed to compare the local and systemic cytokine response in laparoscopic and open colonic surgery and relate this to postoperative recovery parameters. METHODS: Using a prospectively collected patient database, we compared a Study Group (n = 50) of patients undergoing elective laparoscopic colonic resection with a Control Group (n = 25) of patients undergoing equivalent open colonic surgery within an ERAS program. Patients were matched for age, gender, BMI, ASA, Cr Possum, side of resection, diagnosis, and histologic stage. Plasma and peritoneal fluid concentrations of IL-6, IL-8, IL-10, and TNFα were measured at 20-24 h after surgery. The Surgical Recovery Score was determined pre-operatively and at 3, 7, 30, and 60 d postoperatively. All data were prospectively collected, and a priori definitions were used for discharge parameters, complications, and complication severity. RESULTS: Peritoneal fluid IL-6 concentration was lower after laparoscopic surgery. There were no significant differences in the other cytokines measured, or in any postoperative recovery outcomes. Significant correlations were found between cytokine levels and discharge criteria achievement, day stay, postoperative complications, and the Surgical Recovery Score. CONCLUSION: With the exception of a lower peritoneal IL-6 level, the systemic and peritoneal cytokine response at 20-24 h is similar after laparoscopic versus open colonic resection within an ERAS program, with corresponding equivalent rates of postoperative recovery.