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

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

Photodynamic Stromal Depletion in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid malignancies, with a five-year survival of less than 10%. The resistance of the disease and the associated lack of therapeutic response is attributed primarily to its dense, fibrotic stroma, which acts as a barrier to drug perfusion and permits tumour survival and invasion. As clinical trials of chemotherapy (CT), radiotherapy (RT), and targeted agents have not been successful, improving the survival rate in unresectable PDAC remains an urgent clinical need. Photodynamic stromal depletion (PSD) is a recent approach that uses visible or near-infrared light to destroy the desmoplastic tissue. Preclinical evidence suggests this can resensitise tumour cells to subsequent therapies whilst averting the tumorigenic effects of tumour–stromal cell interactions. So far, the pre-clinical studies have suggested that PDT can successfully mediate the destruction of various stromal elements without increasing the aggressiveness of the tumour. However, the complexity of this interplay, including the combined tumour promoting and suppressing effects, poses unknowns for the clinical application of photodynamic stromal depletion in PDAC

Surgical trial design for incorporating the effects of learning: what is the current methodological guidance, and is it sufficient?

Background Surgical interventions are complex. Key elements of this complexity are the surgeon and their learning curve. They pose methodological challenges in the design, analysis and interpretation of surgical RCTs. We identify, summarise, and critically examine current guidance about how to incorporate learning curves in the design and analysis of RCTs in surgery. Examining current guidance Current guidance presumes that randomisation must be between levels of just one treatment component, and that the evaluation of comparative effectiveness will be made via the average treatment effect (ATE). It considers how learning effects affect the ATE, and suggests solutions which seek to define the target population such that the ATE is a meaningful quantity to guide practice. We argue that these are solutions to a flawed formulation of the problem, and are inadequate for policymaking in this setting. Reformulating the problem The premise that surgical RCTs are limited to single-component comparisons, evaluated via the ATE, has skewed the methodological discussion. Forcing a multi-component intervention, such as surgery, into the framework of the conventional RCT design ignores its factorial nature. We briefly discuss the multiphase optimisation strategy (MOST), which for a Stage 3 trial would endorse a factorial design. This would provide a wealth of information to inform nuanced policy but would likely be infeasible in this setting. We discuss in more depth the benefits of targeting the ATE conditional on operating surgeon experience (CATE). The value of estimating the CATE for exploring learning effects has been previously recognised, but with discussion limited to analysis methods only. The robustness and precision of such analyses can be ensured via the trial design, and we argue that trial designs targeting CATE represent a clear gap in current guidance. Conclusion Trial designs that facilitate robust, precise estimation of the CATE would allow for more nuanced policymaking, leading to patient benefit. No such designs are currently forthcoming. Further research in trial design to facilitate the estimation of the CATE is needed

The impact of electrode resistance on the biogalvanic characterisation technique

Measurement of a tissue-specific electrical resistance may offer a discriminatory metric for evaluation of tissue health during cancer surgery. With a move toward minimally-invasive procedures, applicable contact sensing modalities must be scalable, fast and robust. A passive resistance characterisation method utilising a biogalvanic cell as an intrinsic power source has been proposed as a potentially suitable solution. Previous work has evaluated this system with results showing effective discrimination of tissue type and damage (through electroporation). However, aspects of the biogalvanic cell have been found to influence the characterisation performance, and are not currently accounted for within the system model. In particular, the electrode and salt-bridge resistance are not independently determined, leading to over-predictions of tissue resistivity.This paper describes a more comprehensive model and characterisation scheme, with electrode parameters and salt-bridge resistivity being evaluated independently. In a generalised form, the presented model illustrates how the relative resistive contributions from the electrodes and medium relate to the existing characterisation method efficacy. We also describe experiments with physiologically relevant salt solutions (1.71, 17.1, 154 mM), used for validation and comparison. The presented model shows improved performance over the current biogalvanic measurement technique at the median conductivity. Both the proposed and extant system models become unable to predict conductivity accurately at high conductivity due to the dominance of the electrodes. The characterisation techniques have also been applied to data collected on freshly excised human colon tissue (healthy and cancerous). The findings suggest that the resistance of the cell under the test conditions is electrode dominated, leading to erroneous tissue resistance determination. Measurement optimisation strategies and the surgical applicability of the biogalvanic technique are discussed in light of these findings

Fluorescent imaging using novel conjugated polymeric nanoparticles-affimer probes in complex in vitro models of colorectal cancer

We developed a carcinoembryonic antigen (CEA) conjugated polymer nanoparticle (CPN510-CEA-Af) probe to target CEA-expressing CRC cells in vitro. Its efficacy was evaluated in 2D and 3D cultures of LS174T, LoVo, and HT29 CRC cell lines. CPN510-CEA-Af produced greater fluorescent signal intensity than unconjugated particles in both 2D cells and 3D spheriods, indicating its potential as a probe for image-guided colorectal cancer surgery

VITAL: an IDEAL stage 2b feasibility study of a randomised controlled trial evaluating whether virtual reality technology can improve surgical training in Sierra Leone

Background: Training surgeons is costly and resource intensive, often requiring extended periods of expert supervision. Virtual reality (VR) has shown potential in enhancing surgical skill acquisition, but its use in low- and middle-income countries (LMICs) remains limited. This study aimed to evaluate the feasibility of using smartphone VR for surgical training in LMICs. Methods: We conducted a prospective randomised controlled feasibility study involving surgical trainees recruited from a government teaching hospital in Freetown, Sierra Leone. Participants were randomised 1:1 VR vs non-VR and received a 2-day hands-on course on lower limb amputation. The VR group received additional VR training consisting of two 30-minute modules with narrated live surgery videos. Feasibility outcomes included recruitment rates, VR intervention adherence, fidelity and acceptability. Results: A total of 30 participants were randomised, 15 to the VR group and 15 to the control group. The recruitment period lasted 2 days, and 29 participants (96.7%) completed the course. The VR intervention had high fidelity and acceptability, with 100% of participants completing the intervention. There was no unblinding. Compared to the control group, the VR group reported statistically significantly higher engagement during the hands-on course. Conclusion: Our findings suggest that smartphone VR is technically feasible for surgical training in LMICs, and may improve engagement and perceived learning. With minor modifications to the intervention and assessments, a larger-scale trial is feasible. These results highlight the potential for VR to address the challenges of surgical training in LMICs, where access to expert supervision and costly training resources may be limited

Updated meta-analysis of randomized controlled trials comparing conventional excisional haemorrhoidectomy with LigaSure for haemorrhoids

Background:\ud To compare the surgical outcome of haemorrhoidectomy performed using LigaSure bipolar diathermy with conventional haemorrhoidectomy.\ud \ud Methods:\ud Only randomized and alternate allocated studies were included from the major electronic databases using the search terms "ligasure" and "haemorrhoids" Duration of operation, blood loss during operation, postoperative pain score, wound healing, in-hospital stay, time to return to normal activities and complications were assessed.\ud \ud Results:\ud The 11 trials contained a total of 1,046 patients; the largest study was based on 273 patients and two earlier studies were based on 34 patients. No significant gender mismatch between the groups was reported in any of the studies. The patients’ ages were similar between groups in the studies, as was disease severity. All 11 studies reported a shorter duration of the operation when using LigaSure compared to the conventional technique (p<0.001). The postoperative pain score (p=0.001) and blood loss during operation (p=0.001) were significantly reduced. After LigaSure haemorrhoidectomy wound healing (p=0.004) and the return to normal activities (p=0.001) were significantly faster than after conventional haemorrhoidectomy. However, the overall incidence of complications reported was not significantly different (p=0.056).\ud \ud Conclusions:\ud LigaSure is an effective instrument for haemorrhoidectomy which results in less blood loss, quicker wound healing and earlier return to work.\u

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