Faculty Bibliography

INTRODUCTION:Three-dimensional (3D) reconstruction describes the generation of either virtual or physically printed anatomically accurate 3D models from two-dimensional medical images. Their implementation has revolutionised medical practice. Within surgery, key applications include growing roles in operative planning and procedures, surgical education and training, as well as patient engagement and education. In comparison to other surgical specialties, oesophagogastric surgery has been slow in their adoption of this technology. Herein the authors outline a scoping review protocol that aims to analyse the current role of 3D modelling in oesophagogastric surgery and highlight any unexplored avenues for future research. METHODS AND ANALYSIS:The protocol was generated using internationally accepted methodological frameworks. A succinct primary question was devised, and a comprehensive search strategy was developed for key databases (MEDLINE, Embase, Elsevier Scopus and ISI Web of Science). These were searched from their inception to 1 June 2020. Reference lists will be reviewed by hand and grey literature identified using OpenGrey and Grey Literature Report. The protocol was registered to the Open Science Framework (osf.io/ta789).Two independent reviewers will screen titles, abstracts and perform full-text reviews for study selection. There will be no methodological quality assessment to ensure a full thematic analysis is possible. A data charting tool will be created by the investigatory team. Results will be analysed to generate descriptive numerical tabular results and a thematic analysis will be performed. ETHICS AND DISSEMINATION:Ethical approval was not required for the collection and analysis of the published data. The scoping review report will be disseminated through a peer-reviewed publication and international conferences. REGISTRATION DETAILS:The scoping review protocol has been registered on the Open Science Framework (https://osf.io/ta789).

BACKGROUND:Three-dimensional (3D) modelling technology translates the patient-specific anatomical information derived from two-dimensional radiological images into virtual or physical 3D models, which more closely resemble the complex environment encountered during surgery. It has been successfully applied to surgical planning and navigation, as well as surgical training and patient education in several surgical specialties, but its uptake lags behind in colorectal surgery. Rectal cancer surgery poses specific challenges due to the complex anatomy of the pelvis, which is difficult to comprehend and visualise. AIM/OBJECTIVE:To review the current and emerging applications of the 3D models, both virtual and physical, in rectal cancer surgery. METHODS:Medline/PubMed, Embase and Scopus databases were searched using the keywords "rectal surgery", "colorectal surgery", "three-dimensional", "3D", "modelling", "3D printing", "surgical planning", "surgical navigation", "surgical education", "patient education" to identify the eligible full-text studies published in English between 2001 and 2020. Reference list from each article was manually reviewed to identify additional relevant papers. The conference abstracts, animal and cadaveric studies and studies describing 3D pelvimetry or radiotherapy planning were excluded. Data were extracted from the retrieved manuscripts and summarised in a descriptive way. The manuscript was prepared and revised in accordance with PRISMA 2009 checklist. RESULTS:Sixteen studies, including 9 feasibility studies, were included in the systematic review. The studies were classified into four categories: feasibility of the use of 3D modelling technology in rectal cancer surgery, preoperative planning and intraoperative navigation, surgical education and surgical device design. Thirteen studies used virtual models, one 3D printed model and 2 both types of models. The construction of virtual and physical models depicting the normal pelvic anatomy and rectal cancer, was shown to be feasible. Within the clinical context, 3D models were used to identify vascular anomalies, for surgical planning and navigation in lateral pelvic wall lymph node dissection and in management of recurrent rectal cancer. Both physical and virtual 3D models were found to be valuable in surgical education, with a preference for 3D printed models. The main limitations of the current technology identified in the studies were related to the restrictions of the segmentation process and the lack of 3D printing materials that could mimic the soft and deformable tissues. CONCLUSION/CONCLUSIONS:3D modelling technology has potential to be utilised in multiple aspects of rectal cancer surgery, however, it is still at the experimental stage of application in this setting.

Treatment strategies for advanced or recurrent rectal cancer have evolved such that the ultimate surgical goal to achieve a cure is complete pathological clearance. To achieve this where the sacrum is involved, en bloc sacrectomy is the current standard of care. Sacral resection is technically challenging and has been described; however, the technique has yet to be streamlined across units. This comprehensive review aims to outline the surgical approach to en bloc sacrectomy for locally advanced or recurrent rectal cancer, with standardisation of the operative steps of the procedure and to discuss options that enhance the technique.

BACKGROUND:There is strong evidence suggesting that excessive fat distribution, for example, in the bowel mesentery or a reduction in lean body mass (sarcopenia) can influence short-, mid-, and long-term outcomes from patients undergoing various types of surgery. Body composition (BC) analysis aims to measure and quantify this into a parameter that can be used to assess patients being treated for abdominal wall hernia (AWH). This study aims to review the evidence linking quantification of BC with short- and long-term abdominal wall hernia repair outcomes. METHODS:A systematic review was performed according to the PRISMA guidelines. The literature search was performed on all studies that included BC analysis in patients undergoing treatment for AWH using Medline, Google Scholar and Cochrane databases by two independent reviewers. Outcomes of interest included short-term recovery, recurrence outcomes, and long-term data. RESULTS:201 studies were identified, of which 4 met the inclusion criteria. None of the studies were randomized controlled trials and all were cohort studies. There was considerable variability in the landmark axial levels and skeletal muscle(s) chosen for analysis, alongside the methods of measuring the cross-sectional area and the parameters used to define sarcopenia. Only two studies identified an increased risk of postoperative complications associated with the presence of sarcopenia. This included an increased risk of hernia recurrence, postoperative ileus and prolonged hospitalisation. CONCLUSION:There is some evidence to suggest that BC techniques could be used to help predict surgical outcomes and allow early optimisation in AWH patients. However, the lack of consistency in chosen methodology, combined with the outdated definitions of sarcopenia, makes drawing any conclusions difficult. Whether body composition modification can be used to improve outcomes remains to be determined.

BACKGROUND:Neurotensin, originally isolated in 1973 has both endocrine and neuromodulator activity and acts through its three main receptors. Their role in promoting tumour cell proliferation, migration, DNA synthesis has been studied in a wide range of cancers. Expression of Neurotensin and its receptors has also been correlated to prognosis and prediction to treatment. MAIN BODY:The effects of NT are mediated through mitogen-activated protein kinases, epidermal growth factor receptors and phosphatidylinositol-3 kinases amongst others. This review is a comprehensive summary of the molecular pathways by which Neurotensin and its receptors act in cancer cells. CONCLUSION:Identifying the role of Neurotensin in the underlying molecular mechanisms in various cancers can give way to developing new agnostic drugs and personalizing treatment according to the genomic structure of various cancers. Video abstract.

Emergency laparotomies are often required for life-threatening conditions and consequently are associated with high mortality. This risk should be discussed with patients and ideally their next of kin (NOK). Failure to do so denies patients and their relatives the opportunity to prepare, breaches consent guidance, and may result in complaints and negligent claims. Patients who underwent an emergency laparotomy over 6 months were retrospectively studied. Mortality risk discussion with patients and their NOK as evidenced by documentation on consent forms or clinical notes was recorded. Factors influencing these discussions included patient's age, American Society of Anaesthesiologists' score, pre-operative diagnosis, Portsmouth Physiological and Operative Severity Score for the enumeration of Mortality and morbidity (P-POSSUM); seniority of consenting surgeon was also investigated. Seventy-six consecutive patients underwent an emergency laparotomy. Sixty-nine had capacity to give consent. Mortality risk was discussed with 24 (34.8%). These patients were older (median age 77.5 v 65.5 years; P < 0.05) and had a higher median P-POSSUM score (11.5% v 7%; P = 0.313) compared to patient with whom mortality risk was not discussed. Mortality risk was discussed with 14 (18.4%) NOK. This was not influenced by any factor studied. For patients requiring an emergency laparotomy, mortality risk was infrequently discussed with both patients and their NOK. These patients have a higher mortality risk than any other and this "failure to inform" has the potential for serious ramifications.

Sphincter tone examination, as part of digital rectal examination (DRE), can provide essential information to support the early detection of colorectal cancer. Mastering DRE skills for junior doctors is always challenging due to the lack of real training cases. In this article, we developed a soft pneumatic active actuator,made of a compound of silicone rubber materials, to mimic human sphincter muscles and simulate various anal sphincter tones for the purpose of training. Different pumping actuation (syringe and bellows) and driving mechanisms (linear, stepper, and servo motor) were implemented and compared for their effect on the rendered tones. A further comparison was made with a previous prototype based on a cable-driven mechanism. Both quantitative and qualitative assessments were conducted to evaluate the performance of each mechanism. A differential pressure sensor was used to measure applied pressure on a catheter balloon placed inside the sphincter, comparing the readings with anorectal manometry data obtained from real patients. Qualitative feedback was gathered through a user study with ten colorectal expert practitioners. Four questions were asked targeting reaction/response time, pressure level, pressure quality, and similarity to a real case. The results show the capacity and limitation of each mechanism, with the one based on a servo motor and a bellows being the most favourably rated.

PURPOSE/OBJECTIVE:Sporadic colorectal cancer (CRC) amongst adolescents and young adults (AYA) is increasing in incidence. The reasons for this trend are not well understood. Current guidelines do not specifically address this patient cohort. A scoping review was performed to summarise the range of available evidence and identify key areas that need to be addressed in current guidelines. METHODS:A systematic literature search was conducted adhering to the PRISMA statement. All potentially eligible studies were screened, and data extraction was performed by two reviewers independently. The studies were then divided into 5 broad subgroups: (1) risk factors, (2) screening, (3) clinicopathological and molecular features, (4) presentation and (5) management. Descriptive statistics were used for data analysis. RESULTS:A total of 17 studies were included from 2010 to 2019. Overall, young adults with CRC tend to present with non-specific symptoms. The majority of these patients have a delayed diagnosis and more advanced disease at presentation, with a rise in prevalence of distal colon and rectal cancers. AYAs tend to have poorly differentiated tumours and are managed more aggressively. Overall 5-year survival varies between studies. CONCLUSION/CONCLUSIONS:This is, to our knowledge, the first scoping review presenting the range of available evidence on CRC in AYAs. Although the rise in incidence is recognised by specialist bodies, recommendations are limited by the sparsity of available data. We seek to highlight the need for further research, define the role of earlier screening and raise awareness to promote thorough assessment of young patients.

Klotho was first discovered as an anti-ageing protein linked to a number of age-related disease processes, including cardiovascular, renal, musculoskeletal, and neurodegenerative conditions. Emerging research has also demonstrated a potential therapeutic role for Klotho in cancer biology, which is perhaps unsurprising given that cancer and ageing share similar molecular hallmarks. In addition to functioning as a tumour suppressor in numerous solid tumours and haematological malignancies, Klotho represents a candidate therapeutic target for patients with these diseases, the majority of whom have limited treatment options. Here, we examine contemporary evidence evaluating the anti-neoplastic effects of Klotho and describe the modulation of downstream oncogenic signalling pathways, including Wnt/β-catenin, FGF, IGF1, PIK3K/AKT, TGFβ, and the Unfolded Protein Response. We also discuss possible approaches to developing therapeutic Klotho and consider technological advances that may facilitate the delivery of Klotho through gene therapy.

BACKGROUND:Better understanding of the impact of metachronous metastases in locally advanced and recurrent rectal cancer may improve decision-making. The aim of this study was to investigate factors influencing metachronous metastasis and its impact on survival in patients who have a beyond total mesorectal excision (bTME) operation. METHODS:This was a retrospective study of consecutive patients who had bTME surgery for locally advanced and recurrent rectal cancer at a tertiary referral centre between January 2006 and December 2016. The primary outcome was overall survival. Cox proportional hazards regression analyses were performed. The influence of metachronous metastases on survival was investigated. RESULTS:Of 220 included patients, 171 were treated for locally advanced primary tumours and 49 for recurrent rectal cancer. Some 90·0 per cent had a complete resection with negative margins. Median follow-up was 26·0 (range 1·5-119·6) months. The 5-year overall survival rate was 71·1 per cent. Local recurrence and metachronous metastasis rates were 11·8 and 22·2 per cent respectively. Patients with metachronous metastases had a worse overall survival than patients without metastases (median 52·9 months versus estimated mean 109·4 months respectively; hazard ratio (HR) 6·73, 95 per cent c.i. 3·23 to 14·00). Advancing pT category (HR 2·01, 1·35 to 2·98), pN category (HR 2·43, 1·65 to 3·59), vascular invasion (HR 2·20, 1·22 to 3·97) and increasing numbers of positive lymph nodes (HR 1·19, 1·07 to 1·16) increased the risk of metachronous metastasis. Nine of 17 patients (53 per cent) with curatively treated synchronous metastases at presentation developed metachronous metastases, compared with 40 of 203 (19·7 per cent) without synchronous metastases (P = 0·002). Corresponding median length of disease-free survival was 17·5 versus 90·8 months (P < 0·001). CONCLUSION/CONCLUSIONS:As metachronous metastases impact negatively on survival after bTME surgery, factors associated with metachronous metastases may serve as selection tools when determining suitability for treatment with curative intent.