The contradictory role of febuxostat in ABCG2 expression and potentiating hypericin-mediated photodynamic therapy in colorectal cancers.

Photodynamic Therapy (PDT) is an emerging method to treat colorectal cancers (CRC). Hypericin (HYP) is an effective mediator of PDT and the ABCG2 inhibitor, Febuxostat (FBX) could augment PDT. HT29 and HEK293 cells showed light dependant cytotoxic response to PDT in both 2D and 3D cell models. FBX co-treatment was not found to improve PDT cytotoxicity. Next, ABCG2 protein expression was observed in HT29 but not in HEK293 cells. However, ABCG2 gene expression analysis did not support protein expression results as ABCG2 gene expression results were found to be higher in HEK293 cells. Although HYP treatment was found to significantly reduce ABCG2 gene expression levels in both cell lines, FBX treatment partially restored ABCG2 gene expression. Our findings indicate that FBX co-treatment may not be suitable for augmenting HYP-mediated PDT in CRC but could potentially be useful for other applications.

Tissue morphometric measurements do not predict survival following colorectal cancer surgery.

BACKGROUND: Ex vivo tissue morphometric (TM) measurements have been proposed as a quality marker for colorectal cancer (CRC) surgery. However, their survival associations require clarification. This study aimed to evaluate the feasibility of capturing TM measurements based on ex vivo fresh specimen images and explore the association between these TM measurements and survival outcomes. METHODS: A prospective cohort study at Concord Hospital, Sydney was conducted with Stage I to III CRC patients (2009-2019) who underwent an anterior resection (AR) or right hemicolectomy (RH). Using high-resolution digital photographs of fresh CRC specimens, ex vivo tissue morphometric (TM) measurements-resected mesentery area (TM A), distances from high vascular tie to tumour (TM B) and bowel wall (TM C), and bowel length (TM D)-were recorded using Image J. Overall survival (OS) and disease-free survival (DFS) estimates and their associations to clinicopathological variables were investigated with Kaplan-Meier and Cox regression analyses. Linear regression models tested association between TM measurements and lymph node (LN) yield. RESULTS: Of the 1,425 patients who underwent CRC surgery, TM measurements were performed on 312 patients, with an average age of 69.4 years (SD 12.3), of whom 52.9% were male. The majority had an AR (57.8%). Among AR patients, a 5-year OS rate of 77.4% and a DFS rate of 70.1% were observed, with TM measurements bearing no relationship to survival outcomes. Similarly, RH patients exhibited a 5-year OS rate of 67.2% and a DFS rate of 63.1%, with TM measurements again showing no association with survival. Only TM D (P = 0.02) measurements were associated with the number of LNs examined. CONCLUSION: This study successfully demonstrates the feasibility of measuring TM measurements on photographs of ex vivo fresh specimens following CRC surgery. The lack of association with survival outcomes questions the utility of TM measurements as a quality metric of CRC surgery.

Impact of in-hospital postoperative complications on quality of life up to 12 months after major abdominal surgery.

BACKGROUND: Postoperative complications are common, but there are limited data regarding their implications on patients' quality of life. This study aimed to address this gap in the literature by analysing the impact of postoperative complications on patients' health-related quality of life. METHODS: Data from the Perioperative Quality Improvement Programme were analysed, and included patient-level data for 19 685 adults who underwent elective major abdominal procedures in England since 2016. Postoperative complications were graded using the Clavien-Dindo classification. Quality of life was assessed by responses to the EuroQol five-dimension five-levels-of-response (EQ-5D-5L™) questionnaire before surgery, and at 6 and 12 months after operation. Ordinal logistic regression was used to estimate the association between Clavien-Dindo grades and quality of life. Tobit and ordinary least squares regression analyses were used to estimate the quality-adjusted life-year (QALY) loss resulting from postoperative complications between admission and 12 months after surgery. RESULTS: At 6 and 12 months after surgery, increasingly severe postoperative complications were significantly associated with poorer health-related quality of life. The effect of postoperative complications on quality of life was sustained until at least 12 months after operation. Between admission and 12 months after surgery, 0.012, 0.026, 0.033, and 0.086 QALYs were lost for those experiencing a grade I, II, III, or IV postoperative complication respectively. CONCLUSION: Postoperative complications have a significant and sustained effect on patients' quality of life after surgery; this effect worsens as the severity of the complications increases.

A digitally driven manufacturing process for high resolution patterning of cell formations.

This paper presents the engineering and validation of an enabling technology that facilitates new capabilities in in vitro cell models for high-throughput screening and tissue engineering applications. This is conducted through a computerized system that allows the design and deposition of high-fidelity microscale patterned coatings that selectively alter the chemical and topographical properties of cell culturing surfaces. Significantly, compared to alternative methods for microscale surface patterning, this is a digitally controlled and automated process thereby allowing scientists to rapidly create and explore an almost infinite range of cell culture patterns. This new capability is experimentally validated across six different cell lines demonstrating how the precise microscale deposition of these patterned coatings can influence spatiotemporal growth and movement of endothelial, fibroblast, neuronal and macrophage cells. To further demonstrate this platform, more complex patterns are then created and shown to guide the behavioral response of colorectal carcinoma cells.

Participants' Perspectives of Their Involvement in Medical Device Trials: A Focus Groups Study.

BACKGROUND: Medical technologies have the potential to improve quality and efficiency of healthcare. The design of clinical trials should consider participants' perspectives to optimise enrolment, engagement and satisfaction. This study aims to assess patients' perceptions of their involvement in medical device trials, to inform the designs of future medical technology implementation and evaluation. METHODS: Four focus groups were undertaken with a total of 16 participants who had participated in a study testing hospital inpatient remote monitoring devices. Interviews were audio-recorded, transcribed verbatim and underwent thematic analysis. RESULTS: Four main themes emerged: patients' motivations for participating in medical device research; patients' perceptions of technology in medicine; patients' understanding of trial methodology; and patients' perceptions of the benefits of involvement in medical device trials. The appeal of new technology is a contributing factor to the decision to consent, although concerns remain regarding risks associated with technology in healthcare settings. Perceived benefits of participating in device trials include extra care, social benefits and comradery with other participants seen using the devices, although there is a perceived lack of confidence in using technology amongst older patients. CONCLUSION: Future device trials should prioritise information sharing with participants both before and after the trial. Verbal and written information alongside practical demonstrations can help to combat a lack of confidence with technology. Randomised trials and those with placebo- or sham-controlled arms should not be considered as barriers to participation. Study results should be disseminated to participants in lay format as soon as possible, subject to participant permission.

The Incidence of Low Anterior Resection Syndrome as Assessed in an International Randomized Controlled Trial (MRC/NIHR ROLARR).

OBJECTIVE: To investigate the incidence of LARS in patients undergoing elective anterior resection within the MRC/NIHR ROLARR trial and to explore perioperative variables that might be associated with major LARS. SUMMARY BACKGROUND DATA: Sphincter-preserving rectal cancer surgery is frequently accompanied by defaecatory dysfunction known as Low anterior resection syndrome (LARS). This is distressing for patients and is an unmet clinical challenge. METHODS: An international, retrospective cohort study of patients undergoing anterior resection within the ROLARR trial was undertaken. Trial participants with restoration of gastrointestinal continuity and free from disease recurrence completed the validated LARS questionnaire between August 2015 and April 2017. The primary outcome was the incidence of LARS and secondary outcome was severity (minor versus major). RESULTS: LARS questionnaires were received from 132/155 (85%) eligible patients. The median time from surgery to LARS assessment was 1065 days (range 174-1655 d). The incidence of LARS was 82.6% (n = 109/132), which was minor in 26/132 (19.7%) and major in 83/132 (62.9%). The most common symptoms were incontinence to flatus (n = 86/132; 65.2%) and defaecatory clustering (88/132; 66.7%). In a multivariate model, predictors of major LARS were: 1 cm decrease in tumor height above the anal verge (OR = 1.290, 95% CI: 1.101,1.511); and an ASA grade greater than 1 (OR = 2.920, 95% CI: 1.239, 6.883). Treatment allocation (laparoscopic vs robotic) did not predict major LARS. CONCLUSIONS: LARS is a common after rectal cancer surgery and patients should be appropriately counselled preoperatively, particularly before surgery for low tumors or in comorbid populations.

A Multicenter Randomized Controlled Trial Comparing Safety, Efficacy, and Cost-effectiveness of the Surgisis Anal Fistula Plug Versus Surgeon's Preference for Transsphincteric Fistula-in-Ano: The FIAT Trial.

OBJECTIVE: To undertake a randomized comparison of the Biodesign Surgisis anal fistula plug against surgeon's preference in treating cryptoglandular transsphincteric fistula-in-ano. SUMMARY BACKGROUND DATA: The efficacy of the Biodesign Surgisis anal fistula plug in healing anal fistulae is uncertain. METHODS: Participants were randomized to the fistula plug with surgeon's preference (advancement flap, cutting seton, fistulotomy, Ligation of the Intersphincteric Fistula Tract procedure). The primary outcome was faecal incontinence quality of life (FIQoL) at 12-months. Secondary outcomes were fistula healing, incontinence rates, and complication and reintervention rates. RESULTS: Between May 2011 and March 2016, 304 participants were randomized to fistula plug or surgeon's preference. No differences were seen in FIQoL between the 2 groups at 12 months. Clinical fistula healing was reported in 66/122 (54%) of the fistula plug and 66/119 (55%) of the surgeon's preference groups at 12 months. Fecal incontinence rates improved marginally in both the groups. Complications and reinterventions were frequent, with significantly more complications in the fistula plug group at 6-weeks (49/142, 35% vs 25/137, 18%; P=0.002). The mean total costs were £2738 (s.d. £1151) for the fistula plug and £2308 (s.d. £1228) for the surgeon's preference group (mean difference +£430, P=0.0174). The average total quality adjusted life years (QALYs) gained was marginally higher in the fistula plug group. The fistula plug was 35% to 45% likely to be cost-effective across a willingness to pay threshold of £20,000 to £30,000 / QALY. CONCLUSIONS: The Biodesign Surgisis anal fistula plug is associated with similar FIQoL and healing rates to surgeon's preference at 12 months. Higher costs and highly uncertain gains in QALYs mean that the fistula plug may not be considered as a cost-effective treatment in the UK NHS.

The utility of c-Met as a diagnostic tissue biomarker in primary colorectal cancer.

The transmembrane protein, c-Met, is thought to be overexpressed and activated in colorectal cancer (CRC). This study explored its potential as a diagnostic tissue biomarker for CRC in a large human CRC tissue collection obtained from a randomized clinical trial. Tissue microarrays of matched normal colorectal epithelium and primary cancer were prepared from specimens obtained from 280 patients recruited to the MRC CLASICC trial (ISRCTN 74883561) and interrogated using immunohistochemistry for c-Met expression. The distribution and intensity of immunopositivity was graded using a validated, semi-quantifiable score, and differences in median scores analysed using the Wilcoxon signed-rank test. A receiver operating characteristic (ROC) curve was plotted to measure the diagnostic accuracy of c-Met as a biomarker in CRC. Epithelial cell membrane expression of c-Met differed significantly between CRC and normal colorectal tissue: median 12.00 (Interquartile range (IQR) 6-15) versus median 6.00 (IQR 2.70-12.00) respectively (P = <.0001). ROC-AUC analysis of c-Met expression yielded a CRC diagnostic probability of 0.66 (95% CI: 0.61 to 0.70; P < .0001). A score of ≥14.50 showed high specificity at 85.32% (95% CI 80.33%-89.45%) but sensitivity of only 30.92% (CI 25.37%-36.90%). Thus c-Met is consistently overexpressed in human CRC as compared to normal colorectal epithelium tissue. c-Met expression may have a role in diagnosis and prognostication if combined with other biomarkers.

Noninvasive vagus nerve stimulation to reduce ileus after major colorectal surgery: early development study.

AIM: Vagus nerve stimulation has emerged as a plausible intervention to reduce ileus after surgery. An early development study was undertaken with the aim of exploring the feasibility of self-administered, noninvasive vagus nerve stimulation (nVNS) after major colorectal surgery. METHOD: A parallel-group, randomized controlled trial was undertaken between 1 January 2018 and 31 August 2019. Forty patients undergoing colorectal surgery for malignancy were allocated equally to Sham and Active stimulation groups. Electrical vagus nerve stimulation was self-administered bilaterally over the cervical surface landmarks for 5 days before and after surgery. Outcomes of interest were postoperative complications and adverse events measured using the Clavien-Dindo scale, treatment compliance, device usability according to the Systems Usability Scale (SUS) and clinical measures of bowel recovery. RESULTS: Forty patients were randomized and one withdrew, leaving 39 for analysis. Postoperative complications occurred in 9/19 (47.4%) participants receiving Sham and 11/20 (55.0%) receiving Active stimulation and were mostly minor. Compliance with treatment before surgery was 4.7 ± 0.9 days out of 5 days in the Sham group and 4.7 ± 1.1 in the Active group. Compliance with treatment after surgery was 4.1 ± 1.1 and 4.4 ± 1.5, respectively. Participants considered the intervention to be 'acceptable' according to the SUS. The most prominent differences in bowel recovery were days to first flatus (2.35 ± 1.32 vs 1.65 ± 0.88) and tolerance of solid diet (2.18 ± 2.21 vs 1.75 ± 0.91) for Sham and Active groups, respectively. CONCLUSION: This study supports the safety, treatment compliance and usability of self-administered nVNS in patients undergoing major colorectal surgery.

Information needs for recovery after colorectal surgery: a patient focus group study.

AIM: The provision of information to patients is an important part of recovery after colorectal surgery. This study aimed to define patient information needs, barriers to effective understanding and insights into how information provision may be improved. METHOD: A patient focus group was convened. This comprised a broad, convenience sample of 11 participants from across the United Kingdom with experience of major colorectal surgery. A semistructured topic guide was used to facilitate discussion about previous experiences of information provision and how this may be improved. Data were analysed thematically and are presented as major themes. RESULTS: Overall, participants felt that their information needs are poorly prioritized by healthcare professionals. Barriers to understanding and retaining information include highly emotional situations (such as receiving bad news) and inappropriate information design (such as the use of inaccessible language). Participants expressed how information resources should: (a) address patients' individual information needs; (b) empower patients to take an active role in their recovery; (c) support patients with meaningful education and sign-posted resources; and (d) recognize patients' heightened need for information during recovery at home. CONCLUSION: This study provides key insights into the information needs of patients undergoing colorectal surgery. These should inform the development of future information resources, whose format, timing and design are currently supported by low-quality evidence.

What factors determine specimen quality in colon cancer surgery? A cohort study.

PURPOSE: Tenets of 'good quality' colon cancer surgery include mesocolic plane dissection to preserve an intact mesocolic fascia/peritoneum, and excision of sufficient mesocolon for adequate lymphadenectomy. However, it remains controversial what clinicopathological factors determine 'good quality' surgery, and whether quality of surgery influences morbidity/mortality. This study documents the quality of colon cancer surgery at a quaternary referral centre and identifies factors that influence quality of surgery and post-operative outcomes. METHODS: Consecutive patients who underwent resection for colon adenocarcinoma at St. James's University Hospital, Leeds, UK (2015-2017), were included. Primary outcome measures included (i) plane of mesocolic dissection, prospectively assessed; and (ii) tissue morphometry (area of mesentery and vascular pedicle length). Other histopathological data were extracted from a prospective database. Clinical data were obtained from the National Bowel Cancer Audit and individual records. RESULTS: Four hundred five patients were included (mean 69.6 years). The majority (67.4%) of specimens were mesocolic plane dissections. Median area of mesentery excised was 12,085.4 mm2. Median vascular pedicle length was 89.3 mm. Post-operative complication was recorded in one-third of patients. Mesocolic plane excision was associated with open surgery (OR 1.80, 95% CI 1.05-3.09), especially in emergency colectomy. Open resections also had a greater mesentery excised (P = 0.002), but incurred more post-operative complication (OR 2.11, 95% CI 1.12-3.99). Post-operative complication was not associated with plane of excision or tissue morphometry. CONCLUSION: Majority of resections were 'optimal' mesocolic plane dissections. Open resections yielded better quality specimens, but incurred more morbidity. There is room for improvement in the quality of laparoscopic colon cancer surgery, particularly those performed as emergency.

Global academic response to COVID-19: Cross-sectional study.

This study explores the response to COVID-19 from investigators, editors, and publishers and seeks to define challenges during the early stages of the pandemic. A cross-sectional bibliometric review of COVID-19 literature was undertaken between 1 November 2019 and 24 March 2020, along with a comparative review of Middle East respiratory syndrome (MERS) literature. Investigator responsiveness was assessed by measuring the volume and type of research published. Editorial responsiveness was assessed by measuring the submission-to-acceptance time and availability of original data. Publisher-responsiveness was assessed by measuring the acceptance-to-publication time and the provision of open access. Three hundred and ninety-eight of 2,835 COVID-19 and 55 of 1,513 MERS search results were eligible. Most COVID-19 studies were clinical reports (n = 242; 60.8%). The submission-to-acceptance [median: 5 days (IQR: 3-11) versus 71.5 days (38-106); P < .001] and acceptance-to-publication [median: 5 days (IQR: 2-8) versus 22.5 days (4-48·5-; P < .001] times were strikingly shorter for COVID-19. Almost all COVID-19 (n = 396; 99.5%) and MERS (n = 55; 100%) studies were open-access. Data sharing was infrequent, with original data available for 104 (26.1%) COVID-19 and 10 (18.2%) MERS studies (P = .203). The early academic response was characterized by investigators aiming to define the disease. Studies were made rapidly and openly available. Only one-in-four were published alongside original data, which is a key target for improvement. Key points: COVID-19 publications show rapid response from investigators, specifically aiming to define the disease.Median time between submission and acceptance of COVID-19 articles is 5 days demonstrating rapid decision-making compared with the median of 71.5 days for MERS articles.Median time from acceptance to publication of COVID-19 articles is 5 days, confirming the ability to introduce rapid increases at times of crisis, such as during the SARS outbreak.The majority of both COVID-19 and MERS articles are available open-access.

Systematic Review and Meta-analysis of Nonsteroidal Anti-inflammatory Drugs to Improve GI Recovery After Colorectal Surgery.

BACKGROUND: The management of delayed GI recovery after surgery is an unmet challenge. Uncertainty over its pathophysiology has limited previous research, but recent evidence identifies intestinal inflammation and activation of µ-opioid receptors as key mechanisms. Nonsteroidal anti-inflammatory drugs are recommended by enhanced recovery protocols for their opioid-sparing and anti-inflammatory properties. OBJECTIVES: The purpose of this study was to explore the safety and efficacy of nonsteroidal anti-inflammatory drugs to improve GI recovery and to identify opportunities for future research. DATA SOURCES: MEDLINE, Embase, and the Cochrane Library were systematically searched from inception up to January 2018. STUDY SELECTION: Randomized controlled trials assessing the effect of nonsteroidal anti-inflammatory drugs on GI recovery after elective colorectal surgery were eligible. MAIN OUTCOME MEASURES: Postoperative GI recovery, including first passage of flatus, stool, and oral tolerance, were measured. RESULTS: Six randomized controlled trials involving 563 participants were identified. All of the participants received patient-controlled morphine and either nonsteroidal anti-inflammatory drug (nonselective: n = 4; cyclooxygenase-2 selective: n = 1; either: n = 1) or placebo. Patients receiving the active drug had faster return of flatus (mean difference: -17.73 h (95% CI, -21.26 to -14.19 h); p < 0.001), stool (-9.52 h (95% CI, -14.74 to -4.79 h); p < 0.001), and oral tolerance (-12.00 h (95% CI, -18.01 to -5.99 h); p < 0.001). Morphine consumption was reduced in the active groups of 4 studies (average reduction, 12.9-30.0 mg), and 1 study demonstrated significantly reduced measures of systemic inflammation. Nonsteroidal anti-inflammatory drugs were not associated with adverse events, but 1 study was temporarily suspended for safety. LIMITATIONS: The data presented are relatively outdated but represent the best available evidence. CONCLUSIONS: Nonsteroidal anti-inflammatory drugs may represent an effective and accessible intervention to improve GI recovery, but hesitancy over their use after colorectal surgery persists. Additional preclinical research to characterize their mechanisms of action, followed by well-designed clinical studies to test safety and patient-reported efficacy, should be considered.

The impact of advancing age on incidence of hepatectomy and post-operative outcomes in patients with colorectal cancer liver metastases: a population-based cohort study.

BACKGROUND: Clinical outcomes for elderly patients undergoing liver resection for colorectal cancer (CRC) liver metastases are poorly characterised. This study aimed to investigate the impact of advancing age on the incidence of liver resection and post-operative outcomes. METHODS: Patients in the National Bowel Cancer Audit undergoing major CRC resection from 2010 to 2016 in England were included. Liver resection was identified from linked Hospital Episode Statistics data. A Cox-proportional hazards model was used to compare 3-year mortality. RESULTS: Of 117,005 patients, 6081 underwent liver resection. For patients <65 years there was 1 liver resection per 12 cases, 65-74, 1 per 17, and ≥75, 1 per 40. 90-day mortality after liver resection increased with advancing age (<65 0.9% (26/2829), 65-74 2.8% (57/2070), ≥75 4.0% (47/1182); P < 0.001). Age was an independent risk factor for 3-year mortality. Patients 65-74 did not have adjusted mortality higher than those <65, yet age ≥75 was associated with increased overall mortality (Hazard ratio (HR) 1.47 (95% CI 1.30-1.68)) and cancer-specific mortality (HR 1.30 (95% CI 1.13-1.49)). CONCLUSION: Although advancing age was associated with higher rates of 90-day mortality following liver resection, 3-year mortality for patients 65-74 years was comparable to younger patients. These results will aid clinicians and patients in pre-operative decision-making.

An in vivo analysis of safe laparoscopic grasping thresholds for colorectal surgery.

BACKGROUND: Analysis of safe laparoscopic grasping thresholds for the colon has not been performed. This study aimed to analyse tissue damage thresholds when the colon is grasped laparoscopically, correlating histological changes to mechanical compressive forces. METHODS: An instrumented laparoscopic grasper was used to measure the forces applied to porcine colon, with data captured and plotted as a force-time (f-t) curve. Haematoxylin and eosin histochemistry of tissue subjected to 10, 20, 40, 50 and 70 N for 5, 30 and 60 s was performed, and the area of colonic circular and longitudinal muscle was compared in grasped and un-grasped regions. The area under the f-t curve was calculated as a measure of the accumulated force applied, known as the force-time product (FTP). RESULTS: FTP ranged from 55.7 to 3793 N.s. Significant differences were observed between the muscle area of the grasped and un-grasped regions in both longitudinal and circular muscle at 50 N and above for all grasping times. For the longitudinal muscle, significant differences were observed between grasped and un-grasped areas at 20 N force for 30 s (mean difference = 59 mm2, 95% CI 41-77 mm2, P = 0.04), 20 N force for 60 s (mean difference = 31 mm2, 95% CI 21.5-40.5 mm2, P = 0.006) and 40 N force for 30 s (mean difference 37 mm2, 95% CI 27-47 mm2, P = 0.006). Changes in histology correlated with mechanical forces applied to the longitudinal muscle at a FTP over 300 N s. CONCLUSIONS: This study characterizes the grasping forces that result in histological changes to the colon and correlates these with a mechanical measurement of the applied force. The findings will contribute to the development of smart laparoscopic graspers with active constraints to prevent excessive grasping and tissue injury.

Continuous Versus Intermittent Vital Signs Monitoring Using a Wearable, Wireless Patch in Patients Admitted to Surgical Wards: Pilot Cluster Randomized Controlled Trial.

BACKGROUND: Vital signs monitoring is a universal tool for the detection of postoperative complications; however, unwell patients can be missed between traditional observation rounds. New remote monitoring technologies promise to convey the benefits of continuous monitoring to patients in general wards. OBJECTIVE: The aim of this pilot study was to evaluate whether continuous remote vital signs monitoring is a practical and acceptable way of monitoring surgical patients and to optimize the delivery of a definitive trial. METHODS: We performed a prospective, cluster-randomized, parallel-group, unblinded, controlled pilot study. Patients admitted to 2 surgical wards at a large tertiary hospital received either continuous and intermittent vital signs monitoring or intermittent monitoring alone using an early warning score system. Continuous monitoring was provided by a wireless patch, worn on the patient's chest, with data transmitted wirelessly every 2 minutes to a central monitoring station or a mobile device carried by the patient's nurse. The primary outcome measure was time to administration of antibiotics in sepsis. The secondary outcome measures included the length of hospital stay, 30-day readmission rate, mortality, and patient acceptability. RESULTS: Overall, 226 patients were randomized between January and June 2017. Of 226 patients, 140 were randomized to continuous remote monitoring and 86 to intermittent monitoring alone. On average, patients receiving continuous monitoring were administered antibiotics faster after evidence of sepsis (626 minutes, n=22, 95% CI 431.7-820.3 minutes vs 1012.8 minutes, n=12, 95% CI 425.0-1600.6 minutes), had a shorter average length of hospital stay (13.3 days, 95% CI 11.3-15.3 days vs 14.6 days, 95% CI 11.5-17.7 days), and were less likely to require readmission within 30 days of discharge (11.4%, 95% CI 6.16-16.7 vs 20.9%, 95% CI 12.3-29.5). Wide CIs suggest these differences are not statistically significant. Patients found the monitoring device to be acceptable in terms of comfort and perceived an enhanced sense of safety, despite 24% discontinuing the intervention early. CONCLUSIONS: Remote continuous vital signs monitoring on surgical wards is practical and acceptable to patients. Large, well-controlled studies in high-risk populations are required to determine whether the observed trends translate into a significant benefit for continuous over intermittent monitoring. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number ISRCTN60999823; http://www.isrctn.com /ISRCTN60999823 (Archived by WebCite at http://www.webcitation.org/73ikP6OQz).

Systematic Review and Meta-analysis of Prophylactic Mesh During Primary Stoma Formation to Prevent Parastomal Hernia.

BACKGROUND: Implantation of mesh at the time of stoma formation may reduce the rate of parastomal hernia. Until recently, the evidence has been limited to only a few small randomized controlled trials. OBJECTIVE: We present an updated systematic review and meta-analysis to assess the effect of mesh prophylaxis on rates of parastomal hernia. We examine ongoing and unpublished trials via online registries and propose recommendations for future research. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Library were searched up to March 2016 for published randomized controlled trials. Sixteen international trial registries were inspected for ongoing and unpublished trials. STUDY SELECTION: Randomized controlled trials comparing mesh versus no mesh on the incidence of parastomal hernia after colostomy or ileostomy formation were selected. MAIN OUTCOME MEASURES: The primary outcome measure was rate of parastomal hernia at least 12 months after stoma formation. Secondary outcomes included rates of stoma-related complications. RESULTS: Of 3005 studies identified, 7 randomized controlled trials (432 patients) were eligible for inclusion in the final analysis. All were at high risk of bias. Mesh reduced the incidence of clinically detected parastomal hernia (10.8% vs 32.4%; p = 0.001) (risk ratio, 0.34; 95% CI, 0.18-0.65; I = 39%) and the rate of radiologically detected parastomal hernia (34.6% vs 55.3%; p = 0.01) (risk ratio, 0.61; 95% CI, 0.42-0.89; I = 44%). No increase in the incidence of stoma-related complications was observed with the use of prophylactic mesh. Results from ongoing and unpublished randomized controlled trials are expected, but few will report on alternative mesh types or surgical techniques. LIMITATIONS: Heterogeneity of interventions, small patient populations, and a high risk of bias seen in all studies implicate cautious interpretation of the results. CONCLUSION: Mesh prophylaxis at the time of stoma formation appears safe and effective in preventing parastomal hernia; however, limitations of the primary evidence justify larger, more rigorous randomized controlled trials.

A Cross-Sectional Review of Reporting Variation in Postoperative Bowel Dysfunction After Rectal Cancer Surgery.

BACKGROUND: Postoperative bowel dysfunction affects quality of life after sphincter-preserving rectal cancer surgery, but the extent of the problem is not clearly defined because of inconsistent outcome measures used to characterize the condition. OBJECTIVE: The purpose of this study was to assess variation in the reporting of postoperative bowel dysfunction and to make recommendations for standardization in future studies. If possible, a quantitative synthesis of bowel dysfunction symptoms was planned. DATA SOURCES: MEDLINE and EMBASE databases, as well as the Cochrane Library, were queried systematically between 2004 and 2015. STUDY SELECTION: The studies selected reported at least 1 component of bowel dysfunction after resection of rectal cancer. MAIN OUTCOME MEASURES: The main outcome measures were reporting, measurement, and definition of postoperative bowel dysfunction. RESULTS: Of 5428 studies identified, 234 met inclusion criteria. Widely reported components of bowel dysfunction were incontinence to stool (227/234 (97.0%)), frequency (168/234 (71.8%)), and incontinence to flatus (158/234 (67.5%)). Urgency and stool clustering were reported less commonly, with rates of 106 (45.3%) of 234 and 61 (26.1%) of 234. Bowel dysfunction measured as a primary outcome was associated with better reporting (OR = 3.49 (95% CI, 1.99-6.23); p < 0.001). Less than half of the outcomes were assessed using a dedicated research tool (337/720 (46.8%)), and the remaining descriptive measures were infrequently defined (56/383 (14.6%)). LIMITATIONS: Heterogeneity in the reporting, measurement, and definition of postoperative bowel dysfunction precluded pooling of results and limited interpretation. CONCLUSIONS: Considerable variation exists in the reporting, measurement, and definition of postoperative bowel dysfunction. These inconsistencies preclude reliable estimates of incidence and meta-analysis. A broadly accepted outcome measure may address this deficit in future studies.

Core Outcomes for Colorectal Cancer Surgery: A Consensus Study.

BACKGROUND: Colorectal cancer (CRC) is a major cause of worldwide morbidity and mortality. Surgical treatment is common, and there is a great need to improve the delivery of such care. The gold standard for evaluating surgery is within well-designed randomized controlled trials (RCTs); however, the impact of RCTs is diminished by a lack of coordinated outcome measurement and reporting. A solution to these issues is to develop an agreed standard "core" set of outcomes to be measured in all trials to facilitate cross-study comparisons, meta-analysis, and minimize outcome reporting bias. This study defines a core outcome set for CRC surgery. METHODS AND FINDINGS: The scope of this COS includes clinical effectiveness trials of surgical interventions for colorectal cancer. Excluded were nonsurgical oncological interventions. Potential outcomes of importance to patients and professionals were identified through systematic literature reviews and patient interviews. All outcomes were transcribed verbatim and categorized into domains by two independent researchers. This informed a questionnaire survey that asked stakeholders (patients and professionals) from United Kingdom CRC centers to rate the importance of each domain. Respondents were resurveyed following group feedback (Delphi methods). Outcomes rated as less important were discarded after each survey round according to predefined criteria, and remaining outcomes were considered at three consensus meetings; two involving international professionals and a separate one with patients. A modified nominal group technique was used to gain the final consensus. Data sources identified 1,216 outcomes of CRC surgery that informed a 91 domain questionnaire. First round questionnaires were returned from 63 out of 81 (78%) centers, including 90 professionals, and 97 out of 267 (35%) patients. Second round response rates were high for all stakeholders (>80%). Analysis of responses lead to 45 and 23 outcome domains being retained after the first and second surveys, respectively. Consensus meetings generated agreement on a 12 domain COS. This constituted five perioperative outcome domains (including anastomotic leak), four quality of life outcome domains (including fecal urgency and incontinence), and three oncological outcome domains (including long-term survival). CONCLUSION: This study used robust consensus methodology to develop a core outcome set for use in colorectal cancer surgical trials. It is now necessary to validate the use of this set in research practice.

SaFaRI: sacral nerve stimulation versus the FENIX magnetic sphincter augmentation for adult faecal incontinence: a randomised investigation.

PURPOSE: Faecal incontinence is a physically, psychologically and socially disabling condition. NICE guidance (2007) recommends surgical intervention, including sacral nerve stimulation (SNS), after failed conservative therapies. The FENIX magnetic sphincter augmentation (MSA) device is a novel continence device consisting of a flexible band of interlinked titanium beads with magnetic cores that is placed around the anal canal to augment anal sphincter tone through passive attraction of the beads. Preliminary studies suggest the FENIX MSA is safe, but efficacy data is limited. Rigorous evaluation is required prior to widespread adoption. METHOD AND DESIGN: The SaFaRI trial is a National Institute of Health Research (NIHR) Health Technology Assessment (HTA)-funded UK multi-site, parallel group, randomised controlled, unblinded trial that will investigate the use of the FENIX MSA, as compared to SNS, for adult faecal incontinence resistant to conservative management. Twenty sites across the UK, experienced in the treatment of faecal incontinence, will recruit 350 patients randomised equally to receive either SNS or FENIX MSA. Participants will be followed-up at 2 weeks post-surgery and at 6, 12 and 18 months post-randomisation. The primary endpoint is success, as defined by device in use and ≥50 % improvement in the Cleveland Clinic Incontinence Score (CCIS) at 18 months post-randomisation. Secondary endpoints include complications, quality of life and cost effectiveness. DISCUSSION: SaFaRI will rigorously evaluate a new technology for faecal incontinence, the FENIX™ MSA, allowing its safe and controlled introduction into current clinical practice. These results will inform the future surgical management of adult faecal incontinence.