Peter G. Vaughan-Shaw

Aim: This study aimed to assess management pathways and outcomes in sigmoid volvulus (SV). Methods: A retrospective review was performed on patients first admitted with SV between 2019 and 2023 within a tertiary-level colorectal service. Demographic, management, and outcome data, including frailty, ASA (American Society of Anaesthesiologists), and National Emergency Laparotomy Audit (NELA) score, were collected. Comparative statistics were used to compare baseline demographics between those operated on and those not and to identify factors associated with survival. Results: A total of 72 patients were included, median age of 78 years, with 25 undergoing surgery. After index discharge without surgery, 50 patients (88%) were re-admitted with SV at least once, with a total of 212 hospital admissions and 1952 hospital bed days at the end of follow-up. A trend towards lower age, NELA score, ASA score and frailty score was seen in those undergoing surgery, with only two deaths observed during postoperative follow-up. In those who were not palliated at first admission but did not undergo surgery at any point, the mortality rate was 42% (n = 16, median survival 545 days, median age 79), with causes of death generally reflecting conditions of frailty and not volvulus itself. Conclusions: This study demonstrates the burden of sigmoid volvulus in an elderly population with significant mortality and morbidity. While survival was better in those undergoing surgery, this likely represents appropriate case selection reflecting underlying frailty and comorbidities in those not offered surgery rather than a protective effect of surgery. While surgery should be considered and documented at index admission, it should not be considered a panacea for the elderly and frail population. What does this paper add to the literature?: This study highlights the burden of sigmoid volvulus in an ageing population, emphasising complex management challenges. Non-operative treatments showed high recurrence and poor survival, while surgery yielded excellent outcomes in selected patients. The findings advocate for a cautious, individualised approach, balancing frailty and risks, rather than universal reliance on surgery.

Background: There is no consensus on optimal management of pilonidal disease. Surgical practice is varied, and existing literature is mainly single-centre cohort studies of varied disease severity, interventions and outcome assessments. Objectives: A prospective cohort study to determine: disease severity and intervention relationship most valued outcomes and treatment preference by patients recommendations for policy and future research. Design: Observational cohort study with nested mixed-methods case study. Discrete choice experiment. Clinician survey. Three-stage Delphi survey for patients and clinicians. Inter-rater reliability of classification system. Setting: Thirty-one National Health Service trusts. Participants: Patients aged > 16 years referred for elective surgical treatment of pilonidal disease. Interventions: Surgery. Main outcome measures: Pain postoperative days 1 and 7, time to healing and return to normal activities, complications, recurrence. Outcomes compared between major and minor procedures using regression modelling, propensity score-based approaches and augmented inverse probability weighting to account for measured potential confounding features. Results: Clinician survey: There was significant heterogeneity in surgeon practice preference. Limited training opportunities may impede efforts to improve practice. Cohort study: Over half of patients (60%; N = 667) had a major procedure. For these procedures, pain was greater on day 1 and day 7 (mean difference day 1 pain 1.58 points, 95% confidence interval 1.14 to 2.01 points, n = 536; mean difference day 7 pain 1.53 points, 95% confidence interval 1.12 to 1.95 points, n = 512). There were higher complication rates (adjusted risk difference 17.5%, 95% confidence interval 9.1 to 25.9%, n = 579), lower recurrence (adjusted risk difference −10.1%, 95% confidence interval −18.1 to −2.1%, n = 575), and longer time to healing (>34 days estimated difference) and time to return to normal activities (difference 25.9 days, 95% confidence interval 18.4 to 33.4 days). Mixed-methods analysis: Patient decision-making was influenced by prior experience of disease and anticipated recovery time. The burden involved in wound care and the gap between expected and actual time for recovery were the principal reasons given for decision regret. Discrete choice experiment: The strongest predictors of patient treatment choice were risk of infection/persistence (attribute importance 70%), and shorter recovery time (attribute importance 30%). Patients were willing to trade off these attributes. Those aged over 30 years had a higher risk tolerance (22.35–34.67%) for treatment failure if they could experience rapid recovery. There was no strong evidence that younger patients were willing to accept higher risk of treatment failure in exchange for a faster recovery. Patients were uniform in rejecting excision-and-leave-open because of the protracted nursing care it entailed. Wysocki classification analysis: There was acceptable inter-rater agreement (κ = 0.52, 95% confidence interval 0.42 to 0.61). Consensus exercise: Five research and practice priorities were identified. The top research priority was that a comparative trial should broadly group interventions. The top practice priority was that any interventions should be less disruptive than the disease itself. Limitations: Incomplete recruitment and follow-up data were an issue, particularly given the multiple interventions. Assumptions were made regarding risk adjustment. Conclusions and future work: Results suggest the burden of pilonidal surgery is greater than reported previously. This can be mitigated with better selection of intervention according to disease type and patient desired goals. Results indicate a framework for future higher-quality trials that stratify disease and utilise broad groupings of common interventions with development of a patient-centred core outcome set. Trial registration: This trial is registered as ISRCTN95551898. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/17/02) and is published in full in Health Technology Assessment; Vol. 28, No. 33. See the NIHR Funding and Awards website for further award information.

Introduction Robotic-assisted surgery (RAS) offers potential advantages over traditional surgical approaches. This study aimed to assess outcomes from a district general hospital (DGH) robotic colorectal programme against published data. Materials and methods The robotic programme was established following simulator, dry/wet lab training, and proctoring. We performed a case series analysing technical, patient, and oncological outcomes extracted from a prospective database of colorectal RAS cases (2015–2022). A registered systematic review (PROSPERO CRD42022300773; PubMed, Web of Science, EMBASE) of single-centre colorectal series from established robotic centres (n>200 cases) was completed and compared to local data using descriptive summary statistics. Risk of bias assessment was performed using an adapted version of the Cochrane ROBINS-I tool. Results Two hundred thirty-two RAS cases were performed including 122 anterior resections, 56 APERs, 19 rectopexies, and 15 Hartmann’s procedures. The median duration was 325 (IQR 265–400) min. Blood loss was < 100 ml in 97% of cases with 2 (0.9%) cases converted to open. Complications (Clavien-Dindo 3–5) occurred in 19 (8%) patients, with 3 (1.3%) deaths in < 30 days. Length of stay was 7 (IQR 5–11) days. In 169 rectal cancer cases, there were 9 (5.3%) cases with a positive circumferential or distal margin and lymph node yield of 17 (IQR 13–24). A systematic review of 1648 abstracts identified 13 studies from established robotic centres, totaling 4930 cases, with technical, patient, and oncological outcomes comparable to our own case series. Conclusions Outcomes from our robotic colorectal programme at a UK DGH are comparable with the largest published case series from world-renowned centres. Training and proctoring together with rolling audit must accompany the expansion of robotic surgery to safeguard outcomes.

Common genetic variation at 11q23.1 is associated with colorectal cancer (CRC) risk, and exerts local (cis) expression quantitative trait locus (cis-eQTL) effects on POU2AF2, COLCA1 and POU2AF3 genes. However, complex linkage disequilibrium and correlated expression at the 11q23.1 locus has thus far hindered elucidation of the mechanisms by which genetic variants impart CRC risk. Here, we establish that rs3087967 is the likely causal eQTL at this locus, co-localising with expression of POU2AF2 and CRC risk. Furthermore, we show trans-eQTL effects on 21 distant target genes, which are highly enriched for Tuft cell markers. Analysis of available scRNAseq, ChIPseq and scATACseq data implicates POU2AF2 as the primary controller of the tuft cell specific trans-genes through POU2F3-correlated genetic regulation. Immunofluorescence demonstrates that the rs3087967 risk genotype (T) is associated with lower tuft cell abundance in human colonic epithelium. CRISPR-mediated deletion of the 11q23.1 risk locus in the mouse germline exacerbated the Apc ^Min/+ mouse phenotype upon abrogation of Pou2af2 expression specifically. Taken together, we implicate a key protective role of tuft cells in the large bowel and the importance of mis-regulation of POU2AF2 as the prime tuft cell transcriptional activator at this locus.

BACKGROUND: Post-operative vitamin D supplementation improves CRC survival outcomes in randomised trials. The aim of this study was to test the feasibility, safety and efficacy of vitamin D in the pre- and perioperative period in patients undergoing CRC surgery. METHODS: Patients were given 3200IU oral cholecalciferol per day perioperatively. Serial serum 25OHD was measured by liquid chromatography tandem mass spectrometry and compared to untreated CRC controls. 25OHD/CRP levels were compared using adjusted generalized linear mixed-effects models. RESULTS: 122 patients underwent serial perioperative sampling, including 41 patients given high-dose perioperative supplementation. 25OHD was higher in patients given high-dose supplementation compared to controls at all peri-operative timepoints (Pvs . 56%, P=0.003), with multivariate modelling indicating a ∼60nmol/l higher 25OHD compared to control patients (P=1.22E-15). Supplementation was associated with lower peri-operative CRP (P=0.035). DISCUSSIONS: High dose pre-operative vitamin D supplementation is associated with higher perioperative 25OHD levels, lower rates of vitamin D insufficiency and reduced early postoperative CRP. These findings provide compelling rationale for early initiation of vitamin D supplementation after a diagnosis of CRC.

Colorectal cancer (CRC) is characterised by heritable risk that is not well understood. Heritable, genetic variation at 11q23.1 is associated with increased colorectal cancer (CRC) risk, demonstrating eQTL effects on 3 cis- and 23 trans-eQTL targets. We sought to determine the relationship between 11q23.1 cis- and trans-eQTL target expression and test for potential cell-specificity. scRNAseq from 32,361 healthy colonic epithelial cells was aggregated and subject to weighted gene co-expression network analysis (WGCNA). One module (blue) included 19 trans-eQTL targets and was correlated with C11orf53 expression only. Following unsupervised clustering of single cells, the expression of 19 trans-eQTL targets was greatest and most variable in cluster number 11, which transcriptionally resembled tuft cells. 14 trans-eQTL targets were found to demarcate this cluster, 11 of which were corroborated in a second dataset. Intra-cluster WGCNA and module preservation analysis then identified twelve 11q23.1 trans-eQTL targets to comprise a network that was specific to cluster 11. Finally, linear modelling and differential abundance testing showed 11q23.1 trans-eQTL target expression was predictive of cluster 11 abundance. Our findings suggest 11q23.1 trans-eQTL targets comprise a C11orf53- related network that is likely tuft cell-specific and reduced expression of these genes correlates with reduced tuft cell abundance in silico .

Vitamin D deficiency is associated with risk of several common cancers, including colorectal cancer (CRC). Here we have utilized patient derived epithelial organoids (ex vivo) and CRC cell lines (in vitro) to show that calcitriol (1,25OHD) increased the expression of the CRC tumor suppressor gene, CDH1 , at both the transcript and protein level. Whole genome expression analysis demonstrated significant differential expression of a further six genes after 1,25OHD treatment, including genes with established links to carcinogenesis GADD45 , EFTUD1 and KIAA1199 . Furthermore, gene ontologies relevant to carcinogenesis were enriched by 1,25OHD treatment (e.g., ‘regulation of Wnt signaling pathway’ , ‘regulation of cell death’ ), with common enriched processes across in vitro and ex vivo cultures including ‘ negative regulation of cell proliferation’ , ‘regulation of cell migration’ and ‘regulation of cell differentiation’ . Our results identify genes and pathways that are modifiable by calcitriol that have links to CRC tumorigenesis. Hence the findings provide potential mechanism to the epidemiological and clinical trial data indicating a causal association between vitamin D and CRC. We suggest there is strong rationale for further well‐designed trials of vitamin D supplementation as a novel CRC chemopreventive and chemotherapeutic agent.

Background: The risk for several common cancers is influenced by the transcriptomic landscape of the respective tissue-of-origin. Vitamin D influences in vitro gene expression and cancer cell growth. We sought to determine whether oral vitamin D induces beneficial gene expression effects in human rectal epithelium and identify biomarkers of response. Methods: Blood and rectal mucosa was sampled from 191 human subjects and mucosa gene expression (HT12) correlated with plasma vitamin D (25-OHD) to identify differentially expressed genes. Fifty subjects were then administered 3200IU/day oral vitamin D3 and matched blood/mucosa resampled after 12 weeks. Transcriptomic changes (HT12/RNAseq) after supplementation were tested against the prioritised genes for gene-set and GO-process enrichment. To identify blood biomarkers of mucosal response, we derived receiver-operator curves and C-statistic (AUC) and tested biomarker reproducibility in an independent Supplementation Trial (BEST-D). Results: Six hundred twenty-nine genes were associated with 25-OHD level (P < 0.01), highlighting 453 GO-term processes (FDRP < 1.0E−07; downregulated gene-set P < 2.6E−05) and corresponding GO terms (P = 2.90E−02), highlighting gene expression patterns consistent with anti-tumour effects. However, only 9 individual participants (18%) showed a significant response (NM gene-set enrichment P < 0.001) to supplementation. Expression changes in HIPK2 and PPP1CC expression served as blood biomarkers of mucosal transcriptomic response (AUC=0.84 [95%CI 0.66–1.00]) and replicated in BEST-D trial subjects (HIPK2 AUC=0.83 [95%CI 0.77–0.89]; PPP1CC AUC=0.91 [95%CI 0.86–0.95]). Conclusions: Higher plasma 25-OHD correlates with rectal mucosa gene expression patterns consistent with anti-tumour effects, and this beneficial signature is induced by short-term vitamin D supplementation. Heterogenous gene expression responses to vitamin D may limit the ability of randomised trials to identify beneficial effects of supplementation on CRC risk. However, in the current study blood expression changes in HIPK2 and PPP1CC identify those participants with significant anti-tumour transcriptomic responses to supplementation in the rectum. These data provide compelling rationale for a trial of vitamin D and CRC prevention using easily assayed blood gene expression signatures as intermediate biomarkers of response.

This instructional video is the first in a series presented by the Dukes' Club and demonstrates an end‐to‐end sutured bowel anastomosis. After watching this video, the viewer will be able to describe the technical principles and main steps to completing an end‐to‐end ileocolic anastomosis, understand different techniques that are available and fully describe how to perform a sutured anastomosis.