INTRODUCTION:Acute appendicitis is the most common emergency general surgical condition in pregnancy, affecting around 1 in 1000 pregnancies. Reaching a diagnosis is more challenging in this group because of altered clinical presentations and the limitations of diagnostic tools in pregnancy. There is limited guidance from national bodies in the UK on the management of this condition. This study aims to describe current diagnostic and treatment practices for acute appendicitis in pregnancy in the UK, and associated outcomes, to identify variations in practice and areas for improvement. METHODS AND ANALYSIS:This is a UK-wide observational study. Hospitals providing an emergency general surgical service will be eligible to participate. The study consists of two components: (1) a site resource-profile questionnaire to assess the setup of services to care for the pregnant patient requiring emergency non-obstetric abdominal surgery to be completed by a senior collaborator at each participating site, and (2) a retrospective study of patients diagnosed with appendicitis or who had an appendicectomy for suspected appendicitis during a ten-year study period (2013-2023). Data will be collected on diagnostics, radiological findings, management approach and surgical and obstetric outcomes. The main measure of interest is the management approaches (operative versus non-operative; laparoscopic versus open surgery) and their association with selected outcomes. Multivariable logistic regression analyses will be conducted to identify factors which might predict the management strategy and outcomes. ETHICS AND DISSEMINATION:The protocol for this service evaluation study has been reviewed by the University of Sheffield Research Ethics Committee. The study findings will be discussed in a multistakeholder workshop consisting of general surgeons, obstetricians and gynaecologists, radiologists, anaesthetists and patient representatives with a view to making recommendations for quality improvement work and further research. Key findings and recommendations will be disseminated through specialist societies.

Introduction Anastomotic leak (AL) represents a significant complication following gastrointestinal (GI) surgery, contributing to increased morbidity and mortality. pH monitoring has emerged as a potential diagnostic tool for the early detection of AL, but its effectiveness and clinical utility remain to be fully elucidated. This review aims to summarise the evidence regarding perianastomotic pH monitoring for AL detection. Methods A systematic search of relevant databases was conducted to identify pre-clinical and clinical studies investigating pH monitoring for AL detection following GI surgery. Studies were screened by two independent reviewers based on predefined inclusion and exclusion criteria. Data were extracted and presented as a narrative synthesis. Results A total of 10 studies were included in the review, comprising animal studies (n = 2), and human studies in upper GI (n = 3) and colorectal (n = 5) patients. Consistent findings of lower pH values in patients with AL across various postoperative time points were demonstrated. There was diversity in the pH detection method, in addition to variable frequency and timing of pH monitoring. Four studies reported a shorter time for AL detection with pH monitoring vs conventional methods, although no statistical comparisons were used. No standard pH cut-off value for AL detection was identified. Conclusion pH monitoring shows potential as a diagnostic tool for the early detection of AL following GI surgery. While the existing evidence supports its potential utility, further research is required to establish standardised protocols and assess its clinical impact.

BACKGROUND:Predictors of long-term survival after resection of adenocarcinoma arising from intraductal papillary mucinous neoplasms are unknown. This study determines predictors of long-term (>5 years) disease-free survival and recurrence in adenocarcinoma arising from intraductal papillary mucinous neoplasms and derives a prognostic model for disease-free survival. METHODS:Consecutive patients who underwent pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms in 18 academic pancreatic centers in Europe and Asia between 2010 to 2017 with at least 5-year follow-up were identified. Factors associated with disease-free survival were determined using Cox proportional hazards model. Internal validation was performed, and discrimination and calibration indices were assessed. RESULTS:In the study, 288 patients (median age, 70 years; 52% male) were identified; 140 (48%) patients developed recurrence after a median follow-up of 98 months (interquartile range, 78.4-123), 57 patients (19.8%) developed locoregional recurrence, and 109 patients (37.8%) systemic recurrence. At 5 years after resection, the overall and disease-free survival was 46.5% (134/288) and 35.0% (101/288), respectively. On Cox proportional hazards model analysis, multivisceral resection (hazard ratio, 2.20; 95% confidence interval, 1.06-4.60), pancreatic tail location (hazard ratio, 2.34; 95% confidence interval, 1.22-4.50), poor tumor differentiation (hazard ratio, 2.48; 95% confidence interval, 1.10-5.30), lymphovascular invasion (hazard ratio, 1.74; 95% confidence interval, 1.06-2.88), and perineural invasion (hazard ratio, 1.83; 95% confidence interval, 1.09-3.10) were negatively associated with long-term disease-free survival. The final predictive model incorporated 8 predictors and demonstrated good predictive ability for disease-free survival (C-index, 0.74; calibration, slope 1.00). CONCLUSION:A third of patients achieve long-term disease-free survival (>5 years) after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms. The predictive model developed in the current study can be used to estimate the probability of long-term disease-free survival.

BACKGROUND:Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreas are now considered a separate entity to intraductal papillary mucinous neoplasms (IPMN). Invasive IOPNs are extremely rare, and their recurrence patterns, response to adjuvant chemotherapy and long-term survival outcomes are unknown. METHODS:Consecutive patients undergoing pancreatic resection (2010-2020) for invasive IOPNs or adenocarcinoma arising from IPMN (A-IPMN) from 18 academic pancreatic centers worldwide were included. Outcomes of invasive IOPNs were compared with A-IPMN invasive subtypes (ductal and colloid A-IPMN). RESULTS:415 patients were included: 20 invasive IOPN, 331 ductal A-IPMN and 64 colloid A-IPMN. After a median follow-up of 6-years, 45% and 60% of invasive IOPNs had developed recurrence and died, respectively. There was no significant difference in recurrence or overall survival between invasive IOPN and ductal A-IPMN. Overall survival of invasive IOPNs was inferior to colloid A-IPMNs (median time of survival 24.4 months vs. 86.7, months, p = 0.013), but the difference in recurrence only showed borderline significance (median time to recurrence, 22.5 months vs. 78.5 months, p = 0.132). Adjuvant chemotherapy, after accounting for high-risk features, did not reduce rates of recurrence in invasive IOPN (p = 0.443), ductal carcinoma (p = 0.192) or colloid carcinoma (p = 0.574). CONCLUSIONS:Invasive IOPNs should be considered an aggressive cancer with a recurrence rate and prognosis consistent with ductal type A-IPMN.

INTRODUCTION:There is a lack of consensus on the management of inguinal hernia with limited symptoms. To address this issue a systematic review of existing randomized clinical trials (RCTs) was performed to critically appraise all existing data on asymptomatic hernia management, focusing on generalizability. METHODS:A scoping review to identify all RCTs comparing surgical and conservative management of patients with inguinal hernias was undertaken. Medline, Embase, Cochrane and ClinicalTrials.gov databases were searched. Data collected included study characteristics and definitions of population, intervention/comparator, and outcomes; and limitations of each study were also extracted. The quality and generalizability of included RCTs were evaluated using Cochrane's ROB-2 and the PRECIS-2 tool, respectively. RESULTS:Searches returned 661 papers; 14 full-text papers were assessed and three RCTs were identified. All RCTs included only male patients with a mean age above 55 years. All RCTs included asymptomatic patients and two included those with minimal symptoms. Different definitions for 'minimally symptomatic' were used in RCTs and none provided details of what was meant by conservative treatment. Follow-up periods varied between studies (1, 2, 3 years). All RCTs had an overall high risk of bias. According to PRECIS-2, two RCTs were classified as pragmatic, and one was equally pragmatic and explanatory. DISCUSSION:This systematic review highlights a high risk of bias but a good generalizability of the findings from the RCTs conducted on minimally symptomatic inguinal hernia patients. To improve the guidelines for the management of this group of patients, more generalizable data are needed.

AIM:Ileus is characterized by a period of intestinal dysmotility after surgery, leading to vomiting and constipation. In preclinical models, vagus nerve stimulation reduces intestinal inflammation and prevents smooth muscle dysfunction, accelerating the return of gut function. This study explored the feasibility of a definitive trial of non-invasive vagus nerve stimulation (nVNS) along with an early assessment of efficacy. METHOD:A multicentre, randomized feasibility trial (IDEAL Stage 2B) of self-administered nVNS was performed. Patients undergoing colorectal surgery were randomized to nVNS or sham before and after surgery. Feasibility outcomes comprised assessments of recruitment, compliance, blinding and attrition. Clinical outcomes were measures of intestinal function and adverse events. All participants were followed up for 30 days. Interviews with patients and health professionals explored barriers to feasibility and perspectives around implementation. RESULTS:In all, 125 patients were approached about the study and 97 (77.6%) took part. Across all randomized groups, the median compliance to treatment was 19 out of 20 stimulations (interquartile range 17-20). The incidence of adverse events was similar across groups. In this unpowered feasibility study, the time taken for the return of gut function (such as first passage of stool) was similar between nVNS and sham treatments. According to interviews, patients were highly motivated to use the device because it provided them with an opportunity to engage actively in their care. Health professionals were highly driven to tackle the problem of ileus. CONCLUSION:Powered assessments of clinical efficacy are required to confirm or refute the promise of nVNS, as already demonstrated in preclinical models. This feasibility study concludes that a definitive randomized assessment of the clinical benefits of nVNS is desired and feasible.

OBJECTIVE:The aim of the present study was to compare long-term postresection oncological outcomes between adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) and pancreatic ductal adenocarcinoma (PDAC). BACKGROUND:Knowledge of long-term oncological outcomes (e.g. recurrence and survival) comparing A-IPMN and PDAC is scarce. METHODS:Patients undergoing pancreatic resection (2010-2020) for A-IPMN were identified retrospectively from 18 academic pancreatic centers and compared with PDAC patients from the same time period. Propensity-score matching was performed, and survival and recurrence were compared between A-IPMN and PDAC. RESULTS:In all, 459 A-IPMN patients (median age,70; M:F,250:209) were compared with 476 PDAC patients (median age,69; M:F,262:214). A-IPMN patients had lower T-stage, lymphovascular invasion (51.4% vs. 75.6%), perineural invasion (55.8% vs. 71.2%), lymph node positivity (47.3% vs. 72.3%) and R1 resection (38.6% vs. 56.3%) compared with PDAC ( P <0.001). The median survival and time-to-recurrence for A-IPMN versus PDAC were 39.0 versus 19.5 months ( P <0.001) and 33.1 versus 14.8 months ( P <0.001), respectively (median follow-up, 78 vs. 73 months). Ten-year overall survival for A-IPMN was 34.6% (27/78) and PDAC was 9% (6/67). A-IPMN had higher rates of peritoneal (23.0% vs. 9.1%, P <0.001) and lung recurrence (27.8% vs. 15.6%, P <0.001) but lower rates of locoregional recurrence (39.7% vs. 57.8%; P <0.001). The matched analysis demonstrated inferior overall survival (P=0.005), inferior disease-free survival ( P =0.003), and higher locoregional recurrence ( P <0.001) in PDAC compared to A-IPMN but no significant difference in systemic recurrence rates ( P =0.695). CONCLUSIONS:PDACs have inferior survival and higher recurrence rates compared with A-IPMN in matched cohorts. Locoregional recurrence is higher in PDAC, but systemic recurrence rates are comparable and constituted by their own distinctive site-specific recurrence patterns.

The clinico-oncological outcomes of precursor epithelial subtypes of adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) are limited to small cohort studies. Differences in recurrence patterns and response to adjuvant chemotherapy between A-IPMN subtypes are unknown. Clincopathological features, recurrence patterns and long-term outcomes of patients undergoing pancreatic resection (2010–2020) for A-IPMN were reported from 18 academic pancreatic centres worldwide. Precursor epithelial subtype groups were compared using uni- and multivariate analysis. In total, 297 patients were included (median age, 70 years; male, 78.9

OBJECTIVE:This international multicenter cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasm (IPMN). BACKGROUND:Recurrence patterns and treatment of recurrence postresection of adenocarcinoma arising from IPMN are poorly explored. METHODS:Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 and December 2020 at 18 pancreatic centers were identified. Survival analysis was performed using the Kaplan-Meier log-rank test and multivariable logistic regression by Cox-Proportional Hazards modeling. End points were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). RESULTS:Four hundred fifty-nine patients were included (median, 70 years; interquartile range, 64-76; male, 54%) with a median follow-up of 78.1 months. Recurrence occurred in 209 patients [45.5%; median time to recurrence, 12.8 months; early recurrence (within 1 years), 23.2%]. Eighty-three (18.1%) patients experienced a local regional recurrence, and 164 (35.7%) patients experienced a distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (hazard ratio 1.09; P =0.669) One hundred twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months ( P <0.001), with no significant difference between treatment modalities. There was no significant difference in survival between locations of recurrence ( P =0.401). CONCLUSIONS:Recurrence after pancreatic resection for adenocarcinoma arising from IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.

Abstract Background Pancreatic cancer surgery is a complex intervention, with numerous studies exploring variations in approach to curative resection with the aim of improving outcomes. Multicentre randomised controlled trials (RCTs) represent the gold standard for evaluating these technical modifications. However, variations in how surgical intervention are delivered across trial sites and individual surgeons can influence results. Surgical quality assurance mechanisms within trial designs attempt to mitigate this by ensuring standardised, high-quality technique and reducing heterogeneity of procedures. This systematic review aimed to identify approaches to quality assurance within multicentre randomised controlled trials of surgical interventions for pancreatic cancer. Methods A systematic review was performed by searching MEDLINE and Embase databases between 1st January 2000 and 18th December 2022. Articles were deemed eligible for inclusion if they were a multicentre RCT and evaluated a surgical intervention, technique modification or variation in approach to surgical resection for pancreatic cancer. Data was extracted from included studies using a semi-structured form, with consideration of four prospectively defined quality assurance domains: i) surgical intervention and co-interventions description, ii) surgical technique standardisation, iii) performance monitoring methods, iv) surgeon/ unit credentialing methods. Results A total of 1970 studies were identified from the initial search, of which 44 trials were deemed eligible for inclusion. Thirty-six RCTs (81.8%) provided description of the intervention and/or co-intervention. Attempts to standardise technique were described in 33 RCTs (75.0%). However, only 4 trials (9.1%) deconstructed the intervention into its constituent components. Twelve studies (27.3%) described methods used to monitor performance and adherence to the intervention. The most common approaches used were intra-operative photographs (n=7; 15.9%), surgeon self-declaration (n=3; 6.8%), and pathological specimen review (n=2; 4.5%). Ten studies (22.7%) used credentialing methods based on unit entry criteria. Conclusions This study provides important data on the utilisation of methods of surgical quality assurance within pancreatic RCTs. With the exception of intervention description, compliance to the remaining domains of quality assurance was low. This may compromise the extent to which observed differences in clinical outcomes are due to the technique being evaluated within these trials. Confidence in the results of future RCTs would be improved by enhanced quality assurance across the four domains described.

Abstract Background A spray-based disinfectant (VIRUSENDTM) was developed in collaboration with the British Army to provide protection for its service-people from COVID-19. The Critical evaluation of the implementation of VIRUSENDTM in clinical settings (CLEAN) study sought to assess the potential utility of the spray-based disinfectant to enhance infection prevention and control (IPC) in hospital settings during the COVID-19 pandemic. It is a study of the rapid evaluation of a novel product in a high-pressure environment. Methods We conducted a single centre, prospective, rapid mixed-methods, implementation study. Participants were recruited to use the spray as part of their routine IPC practice and data collection followed. Initial observations and pre-implementation survey informed the framework for the post-implementation survey and interviews. Rapid qualitative analysis methodology was used. The study was conducted at a major tertiary referral teaching hospital in the United Kingdom. One hundred and eighty-two staff participants were recruited from ten different clinical environments, selected to represent a diverse level of COVID-19 infection risk. Results One hundred and two participants completed the first survey, 66 completed the second survey and 23 participated in interviews. The interviews with staff regarding their views and experiences of the spray-based disinfectant illuminated the survey responses. Five themes were identified: Is there a need for a spray-based disinfectant? integration of the spray into IPC processes; issues of cleaning vs disinfection; design and functionality; negative consequences of spray use. Conclusions Most people liked using VIRUSENDTM and said that they would continue to use it at work if it was available to them. A key barrier was that VIRUSENDTM whilst being a multi-organism disinfectant, was marketed specifically at COVID-19. In hospitals cleaning and disinfection needs to address a range of infectious organisms. Furthermore, economic evaluation will be required prior to any wider uptake. A rapid evaluation approach identified key issues related to feasibility and acceptability of a novel product in a high-pressure environment. This approach could be usefully applied to the assessment of other potential healthcare interventions where timely information is needed.

Risk prediction models are frequently used to support decision-making in colorectal surgery but can be inaccurate. Machine learning (ML) is becoming increasingly popular, and its application may increase predictive accuracy. We compared conventional risk prediction models for postoperative mortality (based on regression analysis) with ML models to determine the benefit of the latter approach. The study was registered in PROSPERO(CRD42022364753). Following the PRISMA guidelines, a systematic search of three databases (MEDLINE, EMBASE, WoS) was conducted (from 1/1/2000 to 29/09/2022). Studies were included if they reported the development of a risk model to estimate short-term postoperative mortality for patients undergoing colorectal surgery. Discrimination and calibration performance metrics were compared. Studies were evaluated against CHARMS and TRIPOD criteria. 3,052 articles were screened, and 45 studies were included. The total sample size was 1,356,058 patients. Six studies used ML techniques for model development. Most studies (n = 42) reported the area under the receiver operating characteristic curve (AUROC) as a measure of discrimination. There was no significant difference in the mean AUROC values between regression models (0.833 s.d. ± 0.52) and ML (0.846 s.d. ± 0.55), p = 0.539. Calibration statistics, which measure the agreement between predicted estimates and observed outcomes, were less consistent. Risk of bias assessment found most concerns in the data handling and analysis domains of eligible studies. Our study showed comparable predictive performance between regression and ML methods in colorectal surgery. Integration of ML in colorectal risk prediction is promising but further refinement of the models is required to support routine clinical adoption.

Postoperative ileus is a common and distressing complication after intestinal surgery. It presents clinically as impairment of intestinal motility, characterized by abdominal pain, vomiting, and delayed recovery of defaecatory function. For patients, this increases the risk of serious complications, such as pneumonia, venous thromboembolic events, and malnutrition. For healthcare systems, it leads to a substantial economic burden associated with increased medical, nursing, dietitian, and laboratory costs. Accordingly, postoperative ileus is now recognized as a research priority by expert and public stakeholder groups. Numerous clinical interventions have been evaluated in efforts to prevent postoperative ileus, but few have led to meaningful patient benefit. A key challenge for researchers is the absence of a standardized and agreed framework to describe the effectiveness of new interventions in clinical studies. Common outcomes include the time taken until first passage of flatus/stool, time until tolerance of oral diet, and the return of bowel sounds. It remains unclear, however, whether these are sufficiently relevant to patients and healthcare professionals when evaluating new treatments and implementing them in clinical practice. A solution to this problem is the development of an agreed core outcome set developed through patient–clinician consensus. Core outcome sets provide a minimum set of outcomes that should be reported in all studies of a defined clinical condition and are supported by the Core OutcomeMeasures in Effective Trials (COMET) Initiative. The present report describes the international development and final content of an agreed core outcome set for postoperative ileus relevant to patients undergoing intestinal surgery.

Objectives This study examines the conduct of systematic reviews during the early stages of the COVID-19 pandemic, including compliance to protocol registration and duplication of reviews on similar topics. The methodological and reporting quality were also explored. Methods A cross-sectional, bibliometric study was undertaken of all systematic review manuscripts on a COVID-19 intervention published between January 1st and June 30th, 2020. Protocol registration on a publicly accessible database was recorded. Duplication was determined by systematically recording the number of reviews published on each topic of analysis. Methodological quality and reporting quality were assessed using the AMSTAR-2 and PRISMA 2009 instruments, respectively. Results Thirty-one eligible systematic reviews were identified during the inclusion period. The protocol of only four (12.9%) studies was registered on a publicly accessible database. Duplication was frequent, with 15 (48.4%) of the 31 included studies focusing on either hydroxychloroquine (and/or chloroquine) or corticosteroids. Only one study (3.2%) was of "high" methodological quality, four (12.9%) were "low" quality, and the remainder (n = 26, 83.9%) were of "critically low" quality. The median completeness of reporting was 20 out of 27 items (74.1%) with a range of 5-26 (interquartile range: 14-23). Conclusion Systematic reviews during the early stages of the COVID-19 pandemic were uncommonly registered, frequently duplicated, and mostly of low methodological quality. In contrast, the reporting quality of manuscripts was generally good but varied substantially across published reports. There is a need for heightened stewardship of systematic review research, particularly during times of medical crisis where the generation of primary evidence may be rapid and unstable.

Introduction: Despite surgery being performed with curative intent, approximately 65% of patients with colorectal liver metastases develop recurrence within 3 years. The aim of this study was to examine the impact of positive (R1) and negative (R0) resection margin status on survival, tumour recurrence and site of recurrent disease. Methods: Patients who underwent resection for colorectal liver metastases between 2013-2015 were included, to allow at least 5 years follow-up. Development of recurrent disease and site of tumour recurrence (marginal intrahepatic, distant intrahepatic, extrahepatic) were determined using follow-up radiology. Kaplan-Meier method was used to compare survival differences. Results: A total of 386 patients were included. A positive (R1) resection margin was found in 121 (31.4%) patients. This was associated with reduced overall survival compared with that in patients with a negative (R0) resection margin (p<0.05). R1 status was also associated with poorer recurrence free survival (p<0.05). However, pattern of tumour recurrence (marginal intrahepatic, distant intrahepatic, extrahepatic) was not found to be related to resection margin status (p=0.564). Conclusion: The high R1 rate observed in this cohort likely reflects intense pathological analysis of all tumours taken in multiple metastasectomy cases. Although liver resection with a positive (R1) margin was associated with poorer overall survival and earlier recurrence, disease recurrence patterns were similar between the R1 and R0 groups. Notably, patients with a positive resection did not have an increased risk of marginal intrahepatic recurrence. R1 resection margin status may reflect more aggressive underlying tumour biology rather than technical expertise alone.