Analysis of the B cell receptor repertoire in six immune-mediated diseases.

B cells are important in the pathogenesis of many, and perhaps all, immune-mediated diseases. Each B cell expresses a single B cell receptor (BCR)1, and the diverse range of BCRs expressed by the total B cell population of an individual is termed the 'BCR repertoire'. Our understanding of the BCR repertoire in the context of immune-mediated diseases is incomplete, and defining this could provide new insights into pathogenesis and therapy. Here, we compared the BCR repertoire in systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, Crohn's disease, Behçet's disease, eosinophilic granulomatosis with polyangiitis, and immunoglobulin A (IgA) vasculitis by analysing BCR clonality, use of immunoglobulin heavy-chain variable region (IGHV) genes and-in particular-isotype use. An increase in clonality in systemic lupus erythematosus and Crohn's disease that was dominated by the IgA isotype, together with skewed use of the IGHV genes in these and other diseases, suggested a microbial contribution to pathogenesis. Different immunosuppressive treatments had specific and distinct effects on the repertoire; B cells that persisted after treatment with rituximab were predominately isotype-switched and clonally expanded, whereas the inverse was true for B cells that persisted after treatment with mycophenolate mofetil. Our comparative analysis of the BCR repertoire in immune-mediated disease reveals a complex B cell architecture, providing a platform for understanding pathological mechanisms and designing treatment strategies.

Reporting of health-related quality of life in emergency laparotomy trials: a systematic review and narrative synthesis.

PURPOSE: Emergency laparotomy is associated with high morbidity for the surgical patient. Understanding patients' health-related quality of life after their surgery is important to enhance the informed consent process, and to enable the evaluation and improvement of surgical care. This review aims to summarise the use of health-related quality of life tools in clinical trials involving patients undergoing emergency laparotomy. METHODS: A systematic review was undertaken of the scientific literature published in the MEDLINE® and PubMed databases between January 2011 and July 2021. A narrative synthesis approach was chosen to synthesise the diverse range of studies in a structured manner. All included papers were evaluated using the Cochrane Collaboration's tool for assessing risk of bias. RESULTS: Eleven studies were selected for inclusion. Most of the studies had a low risk of bias. Two of the studies used health-related quality of life as the primary outcome measure. A variety of health-related quality of life measurement tools were used; the EQ-5D tool was the most popular questionnaire. Protocol adherence was dependent on the length of time which had elapsed after emergency surgery. CONCLUSION: There are many perceived challenges to collecting health-related quality of life data in the emergency surgery setting. Many of these can be offset with progressive trial designs. There is a need for further research in the systematic development of patient-reported outcomes for use in emergency surgery.

Efficacy and safety of low- versus high-dose glucocorticoid regimens for induction of remission of anti-neutrophil cytoplasm antibody-associated vasculitis: a systematic review and meta-analysis.

OBJECTIVE: Glucocorticoids (GCs) remain a cornerstone of the initial management of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), but have several dose-dependent side effects, in particular infections. The optimal dosing and tapering of oral GCs for remission induction are unknown. A systematic review and meta-analysis was undertaken to determine the efficacy and safety of low- versus high-dose GC regimens. METHOD: A systematic search of MEDLINE, Embase, and PubMed databases was conducted. Clinical studies using a GC-based induction protocol were selected. A daily dose of 0.5 mg/kg or < 30 mg/day oral prednisolone equivalent by the start of week 4 of the induction tapering schedule marked the threshold between high- and low-dose GCs. Risk ratios (RRs) were calculated by the random effects model for outcomes of remission and infection. Relapse events were summarized using risk differences with 95% confidence intervals (CIs). RESULTS: In total, 1145 participants were included in three randomized controlled trials and two observational studies, of whom 543 were assigned to the low-dose GC group and 602 to the high-dose GC group. A low-dose GC regimen was non-inferior to high-dose GCs with respect to outcomes of remission (RR 0.98, 95% CI 0.95-1.02, p = 0.37; I2 = 0%) and relapse (risk difference 0.03, 95% CI -0.01 to 0.06, p = 0.15; I2 = 12%), while significantly reducing the incidence of infection (RR 0.60, 95% CI 0.39-0.91, p = 0.02; I2 = 65%). CONCLUSION: Studies with low-dose GC regimens in AAV are associated with fewer infections while obtaining equivalent efficacy.

Gasless laparoscopy in rural India-registry outcomes and evaluation of the learning curve.

BACKGROUND: A program of gasless laparoscopy (GL) has been implemented in rural North-East India. To facilitate safe adoption, participating rural surgeons underwent rigorous training prior to independent clinical practice. An online registry was established to capture clinical data on safety and efficacy and to evaluate initial learning curves for gasless laparoscopy. METHODS: Surgeons who had completed the GL training program participated in the online RedCap Registry. Patients included in the registry provided informed consent for the use of their data. Data on operative times, conversion rates, perioperative complications, length of stay, and hospital costs were collected. Fixed reference cumulative sum (CUSUM) model was used to evaluate the learning curve based on operative times and conversion rates published in the literature. RESULTS: Four surgeons from three rural hospitals in North-East India participated in the registry. The data were collected over 12 months, from September 2019 to August 2020. One hundred and twenty-three participants underwent GL procedures, including 109 females (88.6%) and 14 males. GL procedures included cholecystectomy, appendicectomy, tubal ligation, ovarian cystectomy, diagnostic laparoscopy, and adhesiolysis. The mean operative time was 75.3 (42.05) minutes for all the surgeries. Conversion from GL to open surgery occurred in 11.4% of participants, with 8.9% converted to conventional laparoscopy. The main reasons for conversion were the inability to secure an operative view, lack of operating space, and adhesions. The mean length of stay was 3 (2.1) days. The complication rate was 5.7%, with one postoperative death. The CUSUM analysis for GL cholecystectomy showed a longer learning curve for operative time and few conversions. The learning curve for GL tubal ligation was relatively shorter. CONCLUSION: Gasless laparoscopy can be safely implemented in the rural settings of Northeast India with appropriate training programs. Careful case selection is essential during the early stages of the surgical learning curve.

Protocol for the ORION trial (RadiO fRequency ablatION for haemorrhoids): a randomised controlled trial.

BACKGROUND: Haemorrhoids are common and can significantly impact the personal and working lives of individuals. Those with more severe symptoms and those not responding to conservative management may require surgery. Current surgical techniques are associated with a degree of postoperative discomfort which may delay return to normal activity. Recurrence is lower in more radical procedures but resulting pain is higher. Radiofrequency ablation (RFA) is a new technique that is gaining popularity and has several hypothesised benefits, including reduced pain and recurrence. However, available evidence is limited. A recent overview from the National Institute for Health and Clinical Excellence recommended more research, in the form of randomised controlled trials, be carried out before further investment is made by national health services. Our aim is to assess whether RFA is at least as good in terms of recurrence as existing surgical interventions, but superior in terms of pain, for patients with symptomatic grade II and III haemorrhoids. METHODS: The RadiO fRequency ablatION for haemorrhoids (ORION) trial will be a pragmatic multicentre patient/assessor-blind parallel group-controlled trial with economic evaluation. The target sample size is 376 participants (188 per arm) and is based on two co-primary endpoints: (i) a non-inferiority design for recurrence and (ii) superiority design for pain at seven days. Participants with grade II or III haemorrhoids will be recruited in 16 National Health Service hospitals and randomised (1:1) to either RFA or surgeon's choice of surgery. CONCLUSIONS: Results will inform future practice for the treatment of grade II-III haemorrhoids and provide evidence for national health services on future investments in RFA. TRIAL REGISTRATION: ISRCTN14474552.

Clinical effectiveness of gasless laparoscopic surgery for abdominal conditions: systematic review and meta-analysis.

BACKGROUND: In high-income countries, laparoscopic surgery is the preferred approach for many abdominal conditions. Conventional laparoscopy is a complex intervention that is challenging to adopt and implement in low resource settings. This systematic review and meta-analysis evaluate the clinical effectiveness of gasless laparoscopy compared to conventional laparoscopy with CO2 pneumoperitoneum and open surgery for general surgery and gynaecological procedures. METHODS: A search of the MEDLINE, EMBASE, Global Health, AJOL databases and Cochrane Library was performed from inception to January 2021. All randomised (RCTs) and comparative cohort (non-RCTs) studies comparing gasless laparoscopy with open surgery or conventional laparoscopy were included. The primary outcomes were mortality, conversion rates and intraoperative complications. SECONDARY OUTCOMES: operative times and length of stay. The inverse variance random-effects model was used to synthesise data. RESULTS: 63 studies were included: 41 RCTs and 22 non-RCTs (3,620 patients). No procedure-related deaths were reported in the studies. For gasless vs conventional laparoscopy there was no difference in intraoperative complications for general RR 1.04 [CI 0.45-2.40] or gynaecological surgery RR 0.66 [0.14-3.13]. In the gasless laparoscopy group, the conversion rates for gynaecological surgery were high RR 11.72 [CI 2.26-60.87] when compared to conventional laparoscopy. For gasless vs open surgery, the operative times were longer for gasless surgery in general surgery RCT group MD (mean difference) 10 [CI 0.64, 19.36], but significantly shorter in the gynaecology RCT group MD - 18.74 [CI - 29.23, - 8.26]. For gasless laparoscopy vs open surgery non-RCT, the length of stay was shorter for gasless laparoscopy in general surgery MD - 3.94 [CI - 5.93, - 1.95] and gynaecology MD - 1.75 [CI - 2.64, - 0.86]. Overall GRADE assessment for RCTs and Non-RCTs was very low. CONCLUSION: Gasless laparoscopy has advantages for selective general and gynaecological procedures and may have a vital role to play in low resource settings.

The alternative complement pathway in ANCA-associated vasculitis: further evidence and a meta-analysis.

We compared the common pathway components C3a, C5a and membrane attack complex (MAC), also known as C5b-9, and the alternative pathway components factor B and properdin in patients with ANCA-associated vasculitis (AAV) and healthy controls, and conducted a meta-analysis of the available clinical evidence for the role of complement activation in the pathogenesis of AAV. Complement components were evaluated in 59 patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis and 36 healthy volunteers. In 28 patients, testing was repeated in remission. Next, we performed a meta-analysis by searching databases to identify studies comparing complement levels in AAV patients and controls. A random-effects model was used for statistical analyses. The median concentrations of MAC, C5a, C3a and factor B were higher in active AAV patients (P < 0·001). Achievement of remission was associated with reductions in C3a (P = 0·005), C5a (P = 0·035) and factor B levels (P = 0·045), whereas MAC and properdin levels did not change. In active AAV, there were no effects of ANCA specificity, disease phenotype, previous immunosuppression or disease severity on complement levels. A total of 1122 articles were screened, and five studies, including this report, were entered into the meta-analysis. Plasma MAC, C5a and factor B in patients with active AAV were increased compared to patients in remission (excluding factor B) and controls. Changes in C3a were of borderline significance. Our findings and the results of the meta-analysis support activation of the complement system predominantly via the alternative pathway in AAV patients.

Patient education about recovery after colorectal surgery: systematic scoping review.

AIM: Enhanced recovery after surgery (ERAS) protocols aim to optimize recovery through a series of evidence-based recommendations. A key component of ERAS is the provision of patient education. Whilst the recommendation for this is strong, the evidence to inform its format, timing and delivery is unclear. The aim of this review was to describe previous educational interventions used to improve recovery after colorectal surgery and to explore opportunities for future research. METHODS: A systematic scoping review was performed. MEDLINE and Embase databases were searched between 1 January 1990 and 12 February 2020. Studies which described or assessed the effectiveness of a patient education or information resource to improve recovery after colorectal surgery were eligible. Outcomes of interest included the format, timing and delivery of interventions, as well as key features of intervention and study design. A narrative synthesis of data was produced through a process of charting and summarizing key results. RESULTS: A total of 1298 papers were inspected, and 11 were eligible for inclusion. Five papers were reports of randomized controlled trials, and others reported a mix of non-randomized and qualitative studies. The design of educational interventions included audio-visual resources (n = 3), smartphone device applications (n = 3) and approaches to facilitate person-to-person counselling (n = 5). Most of the counselling interventions reported positive outcomes (mainly in length of hospital stay), whereas the other types reported mixed results. Patients and the public were seldom involved as collaborators in the design of interventions. CONCLUSIONS: Patient education is generally advantageous, but there is insufficient evidence to optimize its design and delivery in the setting of colorectal surgery.

Establishing core outcome sets for gastrointestinal recovery in studies of postoperative ileus and small bowel obstruction: protocol for a nested methodological study.

INTRODUCTION: Gastrointestinal recovery describes the restoration of normal bowel function in patients with bowel disease. This may be prolonged in two common clinical settings: postoperative ileus and small bowel obstruction. Improving gastrointestinal recovery is a research priority but researchers are limited by variation in outcome reporting across clinical studies. This protocol describes the development of core outcome sets for gastrointestinal recovery in the contexts of postoperative ileus and small bowel obstruction. METHOD: An international Steering Group consisting of patient and clinician representatives has been established. As overlap between clinical contexts is anticipated, both outcome sets will be co-developed and may be combined to form a common output with disease-specific domains. The development process will comprise three phases, including definition of outcomes relevant to postoperative ileus and small bowel obstruction from systematic literature reviews and nominal-group stakeholder discussions; online-facilitated Delphi surveys via international networks; and a consensus meeting to ratify the final output. A nested study will explore if the development of overlapping outcome sets can be rationalized. DISSEMINATION AND IMPLEMENTATION: The final output will be registered with the Core Outcome Measures in Effectiveness Trials initiative. A multi-faceted, quality improvement campaign for the reporting of gastrointestinal recovery in clinical studies will be launched, targeting international professional and patient groups, charitable organizations and editorial committees. Success will be explored via an updated systematic review of outcomes 5 years after registration of the core outcome set.

Research waste in surgical randomized controlled trials.

BACKGROUND: Research waste is a major challenge for evidence-based medicine. It implicates misused resources and increased risks for research participants. The aim of this study was to quantify constituent components of waste in surgical RCTs and explore targets for improvement. METHODS: ClinicalTrials.gov was searched for RCTs registered between January 2011 and December 2012 using the keyword 'surgery'. The primary outcome was research waste, defined as non-publication, inadequate reporting or presence of an avoidable design limitation. Serial systematic searches of PubMed and Scopus databases were performed to determine publication status. Adequacy of reporting was assessed using the CONSORT checklist. Avoidable design limitations were evaluated according to the presence of bias and/or the absence of a cited systematic review of the literature. RESULTS: Of 5617 registered RCTs, 304 met all eligibility criteria. Overall, 259 of 304 (85·2 per cent) demonstrated at least one feature of waste. Of these, 221 (72·7 per cent) were published in a peer-reviewed journal and 219 were accessible for full-text review. Only 73 of 131 (55·7 per cent) RCTs with a pharmacological intervention and 24 of 88 (27 per cent) with a non-pharmacological intervention were reported adequately, and 159 of 219 (72·6 per cent) demonstrated an avoidable design limitation. Multicentre (odds ratio 0·31, 95 per cent c.i. 0·11 to 0·88) and externally funded (OR 0·35, 0·15 to 0·82) RCTs were less associated with research waste. CONCLUSION: This study identified a considerable burden of research waste in surgical RCTs. Future initiatives should target improvements in single-centre, poorly supported RCTs.

ANTECEDENTES: El despilfarro en investigación es uno de los mayores retos para la medicina basada en la evidencia. Conlleva mala utilización de los recursos y aumento de los riesgos para los participantes en las investigaciones. El objetivo de este trabajo fue cuantificar los componentes que conforman este despilfarro en los ensayos aleatorizados y controlados (randomised controlled trials, RCTs) del ámbito quirúrgico y explorar los aspectos clave de mejora. MÉTODOS: Se realizó una búsqueda de los RCTs registrados en la base de datos ClinicalTrials.gov entre enero de 2011 y diciembre de 2012, utilizando la palabra clave cirugía. La variable primaria fue el despilfarro en investigación, definido como la no publicación, el informe inadecuado o la presencia de debilidades del diseño evitables. Para determinar el estado de las publicaciones, se realizaron búsquedas sistemáticas en las bases de datos PubMed y Scopus. La adecuación del informe se evaluó usando la lista de verificación CONSORT. Las debilidades del diseño evitables se evaluaron de acuerdo con la presencia de sesgo y/o la ausencia de citación en revisiones sistemáticas publicadas en la literatura. RESULTADOS: De los 5.617 RCTs registrados, 304 cumplieron con los criterios de elegibilidad. De ellos, 259/304 (85%) cumplieron al menos una de las características de despilfarro. De estos, 221 (73%) se publicaron en una revista con peer review y 219 eran accesibles a texto completo. Únicamente 73/131 (56%) RCTs con una intervención farmacológica y 24/88 (27%) con una intervención no farmacológica presentaban un informe adecuado, y 159/219 (73%) se demostró una debilidad del diseño evitable. Los RCTs multicéntricos (OR: 0,31; i.c. del 95%: 0,11 a 0,88) y con financiación externa (OR: 0,35; i.c. del 95%: 0,15 a 0,82) se asociaron con menos despilfarro de investigación. CONCLUSIÓN: Este estudio constató una carga considerable de despilfarro en investigación en los RCTs quirúrgicos. Se deberían promover iniciativas de mejora, especialmente dirigidas a los RCTs realizados en un solo centro y con menos financiación.

Avoiding, diagnosing and treating well leg compartment syndrome after pelvic surgery.

BACKGROUND: Patients undergoing prolonged pelvic surgery may develop compartment syndrome of one or both lower limbs in the absence of direct trauma or pre-existing vascular disease (well leg compartment syndrome). This condition may have devastating consequences for postoperative recovery, including loss of life or limb, and irreversible disability. METHODS: These guidelines represent the collaboration of a multidisciplinary group of colorectal, vascular and orthopaedic surgeons, acting on behalf of their specialty associations in the UK and Ireland. A systematic analysis of the available peer-reviewed literature was undertaken to provide an evidence base from which these guidelines were developed. RESULTS: These guidelines encompass the risk factors (both patient- and procedure-related), diagnosis and management of the condition. Key recommendations for the adoption of perioperative strategies to facilitate prevention and effective treatment of well leg compartment syndrome are presented. CONCLUSION: All surgeons who carry out abdominopelvic surgical procedures should be aware of well leg compartment syndrome, and instigate policies within their own institution to reduce the risk of this potentially life-changing complication.

Disseminating technology in global surgery.

BACKGROUND: Effective dissemination of technology in global surgery is vital to realize universal health coverage by 2030. Challenges include a lack of human resource, infrastructure and finance. Understanding these challenges, and exploring opportunities and solutions to overcome them, are essential to improve global surgical care. METHODS: This review focuses on technologies and medical devices aimed at improving surgical care and training in low- and middle-income countries. The key considerations in the development of new technologies are described, along with strategies for evaluation and wider dissemination. Notable examples of where the dissemination of a new surgical technology has achieved impact are included. RESULTS: Employing the principles of frugal and responsible innovation, and aligning evaluation and development to high scientific standards help overcome some of the challenges in disseminating technology in global surgery. Exemplars of effective dissemination include low-cost laparoscopes, gasless laparoscopic techniques and innovative training programmes for laparoscopic surgery; low-cost and versatile external fixation devices for fractures; the LifeBox pulse oximeter project; and the use of immersive technologies in simulation, training and surgical care delivery. CONCLUSION: Core strategies to facilitate technology dissemination in global surgery include leveraging international funding, interdisciplinary collaboration involving all key stakeholders, and frugal scientific design, development and evaluation.

Rectal Surgery Evaluation Trial: protocol for a parallel cohort trial of outcomes using surgical techniques for total mesorectal excision with low anterior resection in high-risk rectal cancer patients.

AIM: Total mesorectal excision (TME) is the standard of care for rectal cancer, which can be combined with low anterior resection (LAR) in patients with mid-to-low rectal cancer. The narrow pelvic space and difficulties in obtaining adequate exposure make surgery technically challenging. Four techniques are used to perform the surgery: open laparotomy, laparoscopy, robot-assisted surgery and transanal surgery. Comparative data for these techniques are required to provide clinical data on the surgical management of rectal cancers. METHODS: The Rectal Surgery Evaluation Trial will be a prospective, observational, case-matched, four-cohort, multicentre trial designed to study TME with LAR using open laparotomy, laparoscopy, robot-assisted surgery or transanal surgery in high-surgical-risk patients with mid-to-low non-metastatic rectal cancer. All surgeries will be performed by surgeons experienced in at least one of the techniques. Oncological, morbidity and functional outcomes will be assessed in a composite primary outcome, with success defined as circumferential resection margin ≥ 1 mm, TME Grade III and minimal postoperative morbidity (absence of Clavien-Dindo Grade III-IV complications within 30 days after surgery). Secondary end-points will include the co-primary end-points over the long term (2 years), quality of surgery, quality of life, length of hospital stay, operative time and rate of unplanned conversions. DISCUSSION: This will be the first trial to study all four surgical techniques currently used for TME with LAR in a specific group of high-risk patients. The knowledge obtained will contribute towards helping physicians determine the advantages of each technique and which may be the most appropriate for their patients.

European consensus on the standardization of robotic total mesorectal excision for rectal cancer.

AIM: Surgery for rectal cancer is challenging for both technical and anatomical reasons. The European Academy of Robotic Colorectal Surgery (EARCS) provides a competency-based training programme through a standardized approach. However, there is no consensus on technical standards for robotic surgery when used during surgery for rectal cancer. The aim of this consensus study was to establish operative standards for anterior resection incorporating total mesorectal excision (TME) using robotic techniques, based on recommendations of expert European colorectal surgeons. METHOD: A Delphi questionnaire with a 72-item statement was sent through an electronic survey tool to 24 EARCS faculty members from 10 different countries who were selected based on expertise in robotic colorectal surgery. The task was divided into theatre setup, colonic mobilization and rectal dissection, and each task area was further divided into several subtasks. The levels of agreement (A* > 95% agreement, A > 90%, B > 80% and C > 70%) were considered adequate while agreement of < 70% was considered inadequate. Once consensus was reached, a draft document was compiled and sent out for final approval. RESULTS: The average length of experience of robotic colorectal surgery for participants in this study was 6 years. Initial agreement was 87%; in nine items, it was < 70%. After suggested modifications, the average level of agreement for all items reached 94% in the second round (range 0.75-1). CONCLUSION: This is the first European consensus on the standardization of robotic TME. It provides a baseline for technical standards and structured training in robotic rectal surgery.

Current concepts in imaging for local staging of advanced rectal cancer.

Imaging of rectal cancer has an increasingly pivotal role in the diagnosis, staging, and treatment stratification of patients with the disease. This is particularly true for advanced rectal cancers where magnetic resonance imaging (MRI) findings provide essential information that can change treatment. In this review we describe the rationale for the current imaging standards in advanced rectal cancer for both morphological and functional imaging on the baseline staging and reassessment studies. In addition the clinical implications and future methods by which radiologists may improve these are outlined relative to TNM8.

Postoperative ileus following major colorectal surgery.

BACKGROUND: Postoperative ileus (POI) is characterized by delayed gastrointestinal recovery following surgery. Current knowledge of pathophysiology, clinical interventions and methodological challenges was reviewed to inform modern practice and future research. METHODS: A systematic search of MEDLINE and Embase databases was performed using search terms related to ileus and colorectal surgery. All RCTs involving an intervention to prevent or reduce POI published between 1990 and 2016 were identified. Grey literature, non-full-text manuscripts, and reanalyses of previous RCTs were excluded. Eligible articles were assessed using the Cochrane tool for assessing risk of bias. RESULTS: Of 5614 studies screened, 86 eligible articles describing 88 RCTs were identified. Current knowledge of pathophysiology acknowledges neurogenic, inflammatory and pharmacological mechanisms, but much of the evidence arises from animal studies. The most common interventions tested were chewing gum (11 trials) and early enteral feeding (11), which are safe but of unclear benefit for actively reducing POI. Others, including thoracic epidural analgesia (8), systemic lidocaine (8) and peripheral µ antagonists (5), show benefit but require further investigation for safety and cost-effectiveness. CONCLUSION: POI is a common condition with no established definition, aetiology or treatment. According to current literature, minimally invasive surgery, protocol-driven recovery (including early feeding and opioid avoidance strategies) and measures to avoid major inflammatory events (such as anastomotic leak) offer the best chances of reducing POI.

The treatment of anal fistula: second ACPGBI Position Statement - 2018.

It is over 10 years since the first ACPGBI Position Statement on the management of anal fistula was published in 2007. This second edition is the result of scrutiny of the literature published during this time; it updates the original Position Statement and reviews the published evidence surrounding treatments for anal fistula that have been developed since the original publication.

The timing of liver resection in patients with colorectal cancer and synchronous liver metastases: a population-based study of current practice and survival.

AIM: There is uncertainty regarding the optimal sequence of surgery for patients with colorectal cancer (CRC) and synchronous liver metastases. This study was designed to describe temporal trends and inter-hospital variation in surgical strategy, and to compare long-term survival in a propensity score-matched analysis. METHOD: The National Bowel Cancer Audit dataset was used to identify patients diagnosed with primary CRC between 1 January 2010 and 31 December 2015 who underwent CRC resection in the English National Health Service. Hospital Episode Statistics data were used to identify those with synchronous liver-limited metastases who underwent liver resection. Survival outcomes of propensity score-matched groups were compared. RESULTS: Of 1830 patients, 270 (14.8%) underwent a liver-first approach, 259 (14.2%) a simultaneous approach and 1301 (71.1%) a bowel-first approach. The proportion of patients undergoing either a liver-first or simultaneous approach increased over the study period from 26.8% in 2010 to 35.6% in 2015 (P < 0.001). There was wide variation in surgical approach according to hospital trust of diagnosis. There was no evidence of a difference in 4-year survival between the propensity score-matched cohorts according to surgical strategy: bowel first vs simultaneous [hazard ratio (HR) 0.92 (95% CI: 0.80-1.06)] or bowel first vs liver first [HR 0.99 (95% CI: 0.82-1.19)]. CONCLUSION: There is evidence of wide variation in surgical strategy in dealing with CRC and synchronous liver metastases. In selected patients, the simultaneous and liver-first strategies have comparable long-term survival to the bowel-first approach.

IntAct: intra-operative fluorescence angiography to prevent anastomotic leak in rectal cancer surgery: a randomized controlled trial.

AIM: Anastomotic leak (AL) is a major complication of rectal cancer surgery. Despite advances in surgical practice, the rates of AL have remained static, at around 10-15%. The aetiology of AL is multifactorial, but one of the most crucial risk factors, which is mostly under the control of the surgeon, is blood supply to the anastomosis. The MRC/NIHR IntAct study will determine whether assessment of anastomotic perfusion using a fluorescent dye (indocyanine green) and near-infrared laparoscopy can minimize the rate of AL leak compared with conventional white-light laparoscopy. Two mechanistic sub-studies will explore the role of the rectal microbiome in AL and the predictive value of CT angiography/perfusion studies. METHOD: IntAct is a prospective, unblinded, parallel-group, multicentre, European, randomized controlled trial comparing surgery with intra-operative fluorescence angiography (IFA) against standard care (surgery with no IFA). The primary end-point is rate of clinical AL at 90 days following surgery. Secondary end-points include all AL (clinical and radiological), change in planned anastomosis, complications and re-interventions, use of stoma, cost-effectiveness of the intervention and quality of life. Patients should have a diagnosis of adenocarcinoma of the rectum suitable for potentially curative surgery by anterior resection. Over 3 years, 880 patients from 25 European centres will be recruited and followed up for 90 days. DISCUSSION: IntAct will rigorously evaluate the use of IFA in rectal cancer surgery and explore the role of the microbiome in AL and the predictive value of preoperative CT angiography/perfusion scanning.

Impact of hepatobiliary service centralization on treatment and outcomes in patients with colorectal cancer and liver metastases.

BACKGROUND: Centralization of specialist surgical services can improve patient outcomes. The aim of this cohort study was to compare liver resection rates and survival in patients with primary colorectal cancer and synchronous metastases limited to the liver diagnosed at hepatobiliary surgical units (hubs) with those diagnosed at hospital Trusts without hepatobiliary services (spokes). METHODS: The study included patients from the National Bowel Cancer Audit diagnosed with primary colorectal cancer between 1 April 2010 and 31 March 2014 who underwent colorectal cancer resection in the English National Health Service. Patients were linked to Hospital Episode Statistics data to identify those with liver metastases and those who underwent liver resection. Multivariable random-effects logistic regression was used to estimate the odds ratio of liver resection by presence of specialist hepatobiliary services on site. Survival curves were estimated using the Kaplan-Meier method. RESULTS: Of 4547 patients, 1956 (43·0 per cent) underwent liver resection. The 1081 patients diagnosed at hubs were more likely to undergo liver resection (adjusted odds ratio 1·52, 95 per cent c.i. 1·20 to 1·91). Patients diagnosed at hubs had better median survival (30·6 months compared with 25·3 months for spokes; adjusted hazard ratio 0·83, 0·75 to 0·91). There was no difference in survival between hubs and spokes when the analysis was restricted to patients who had liver resection (P = 0·620) or those who did not undergo liver resection (P = 0·749). CONCLUSION: Patients with colorectal cancer and synchronous metastases limited to the liver who are diagnosed at hospital Trusts with a hepatobiliary team on site are more likely to undergo liver resection and have better survival.