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Aim: Locally advanced and recurrent colorectal cancer represents a complex clinical entity, which requires multidisciplinary decision-making and management. The aim of this work is to understand the provision of clinical services in this cohort of patients across Great Britain and Ireland (GB&I) as a key essential step to help facilitate future service development and improvement., Method: A cross-sectional, organizational survey was sent to all colorectal cancer multidisciplinary teams (MDTs) across GB&I. It consisted of 12 key questions addressing the provision of specialist services and advanced surgical techniques. Results are reported in line with the CHERRIES guideline., Results: One hundred and seventy-five MDTs across GB&I participated, with 142 English, 13 Welsh, 14 Scottish, 3 Northern Irish and 3 Irish MDTs. The overall response rate was 93.5% (175/187). Ninety (51.4%) hospital sites reported having a specialist dedicated or subsection MDT. Specialist advanced nursing support was available in 46 (26.2%) hospitals, with a dedicated advanced colorectal cancer outpatient clinic available in 31 (17.7%) hospitals. One hundred and thirteen MDTs (64.5%) offered surgery for advanced colonic cancer, 82 (46.8%) for recurrent colonic cancer, 58 (33.1%) for advanced rectal cancer and 39 (22.2%) for recurrent rectal cancer. A variable number of MDTs offered specialist surgical techniques, including distal sacrectomy [33 (18.9%)], high sacrectomy [16 (9.1%)], complex vascular resection ± reconstruction [33 (18.9%)] and extended lymphadenectomy (pelvic sidewall or para-aortic) [44 (25.1%)]., Conclusion: The IMPACT organizational survey highlights the current variation in the delivery and provision of clinical services for patients with advanced and recurrent colorectal cancer across Great Britain and Ireland., (© 2024 Association of Coloproctology of Great Britain and Ireland.)

Theranostic nanoparticles hold promise for simultaneous imaging and therapy in colorectal cancer. Carcinoembryonic antigen can be used as a target for these nanoparticles because it is overexpressed in most colorectal cancers. Affimer reagents are synthetic proteins capable of binding specific targets, with additional advantages over antibodies for targeting. We fabricated silica nanoparticles using a water-in-oil microemulsion technique, loaded them with the photosensitiser Foslip, and functionalised the surface with anti-CEA Affimers to facilitate fluorescence imaging and photodynamic therapy of colorectal cancer. CEA-specific fluorescence imaging and phototoxicity were quantified in colorectal cancer cell lines and a LS174T murine xenograft colorectal cancer model. Anti-CEA targeted nanoparticles exhibited CEA-specific fluorescence in the LoVo, LS174T and HCT116 cell lines when compared to control particles ( p < 0.0001). No toxicity was observed in LS174T cancer mouse xenografts or other organs. Following photo-irradiation, the anti-CEA targeted particles caused significant cell death in LoVo (60%), LS174T (90%) and HCT116 (70%) compared to controls ( p < 0.0001). Photodynamic therapy (PDT) at 24 h in vivo showed a 4-fold reduction in tumour volume compared to control mouse xenografts ( p < 0.0001). This study demonstrates the efficacy of targeted fluorescence imaging and PDT using Foslip nanoparticles conjugated to anti-CEA Affimer nanoparticles in in vitro and in vivo colorectal cancer models.

Introduction: The COVID-19 pandemic resulted in a significant disruption of colorectal cancer (CRC) care pathways. This study evaluates the management and outcomes of patients with primary locally advanced or recurrent CRC during the pandemic in a single tertiary referral centre., Methods: Patients undergoing elective surgery for advanced or recurrent CRC with curative intent between March 2020 and March 2021 were identified. Following first multidisciplinary team discussion patients were broadly classified into two groups: straight to surgery ( n =22, 45%) or neoadjuvant therapy followed by surgery ( n =27, 55%). Primary outcome was COVID-19-related complication rate., Results: Forty-nine patients with a median age of 66 years (interquartile range: 54-73) were included. No patients developed a COVID-19 infection or related complication during hospital admission. Significant delays were identified in the treatment pathway of patients in the straight to surgery group, mostly due to delays in referral from external centres. Nine of 22 patients in the straight to surgery group had evidence of tumour progression compared with 3 of 27 in the neoadjuvant group ( p =0.015839). Seven of 27 patients in the neoadjuvant group showed evidence of tumour regression. During the study, surgical waiting times were reduced, and more operations were performed during the second wave of COVID-19., Conclusion: This study suggests that it is possible to mitigate the risks of COVID-19-related complications in patients undergoing complex surgery for locally advanced and recurrent CRC. Delay in surgical intervention is associated with tumour progression, particularly in patients who may not have neoadjuvant therapy. Efforts should be made to prioritise resources for patients requiring time-sensitive surgery for advanced and recurrent CRC.

Aim: The modified Delphi approach is an established method for reaching a consensus opinion among a group of experts in a particular field. We have used this technique to survey the entire membership of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) to reach a consensus on prioritizing clinical research questions in colorectal disease., Method: Three rounds of surveys were conducted using a web-based tool. In the first, the ACPGBI membership was invited to submit research questions. In Rounds 2 and 3 they were asked to score questions on priority. A steering group analysed the results of each round to identify those questions ranked as being of highest priority., Results: Five hundred and two questions were submitted in Round 1. Following two rounds of voting and analysis, a list of 25 priority questions was produced, including 15 cancer-related and 10 noncancer-related questions., Conclusion: It is anticipated that these results will: (i) set the research agenda over the next few years for the study of colorectal disease in the United Kingdom, (ii) promote development and (iii) define funding of new research and prioritize areas of unmet clinical need where the potential clinical impact is greatest., (© 2014 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Background: Previous reports have suggested that the VEGF receptor neuropilin-1 (NRP-1) is expressed in a singly dispersed subpopulation of cells in the normal colonic epithelium, but that expression becomes dysregulated during colorectal carcinogenesis, with higher levels in tumour suggestive of a poor prognosis. We noted that the spatial distribution and morphology if NRP-1 expressing cells resembles that of enteroendocrine cells (EEC) which are altered in response to disease state including cancer and irritable bowel syndrome (IBS). We have shown that NRP-1 is down-regulated by butyrate in colon cancer cell lines in vitro and we hypothesized that butyrate produced in the lumen would have an analogous effect on the colon mucosa in vivo. Therefore we sought to investigate whether NRP-1 is expressed in EEC and how NRP-1 and EEC respond to butyrate and other short-chain fatty acids (SCFA - principally acetate and propionate). Additionally we sought to assess whether there is a field effect around adenomas., Methodology: Biopsies were collected at the mid-sigmoid, at the adenoma and at the contralateral wall (field) of 28 subjects during endoscopy. Samples were fixed for IHC and stained for either NRP-1 or for chromogranin A (CgA), a marker of EEC. Stool sampling was undertaken to assess individuals' butyrate, acetate and propionate levels., Result: NRP-1 expression was inversely related to SCFA concentration at the colon landmark (mid-sigmoid), but expression was lower and not related to SCFA concentration at the field. Likewise CgA+ cell number was also inversely related to SCFA at the landmark, but was lower and unresponsive at the field. Crypt cellularity was unaltered by field effect. A colocalisation analysis showed only a small subset of NRP-1 localised with CgA. Adenomas showed extensive, weaker staining for NRP-1 which contrastingly correlated positively with butyrate level. Field effects cause this relationship to be lost. Adenoma tissue shows dissociation of the co-regulation of NRP-1 and EEC., Conclusion: NRP-1 is inversely associated with levels of butyrate and other SCFA in vivo and is expressed in a subset of CgA expressing cells. EEC number is related to butyrate level in the same way.

Introduction: In 2004, an audit in our unit demonstrated wide variation in liver resection rates for colorectal cancer (CRC) metastases within the cancer network. Subsequently, a network-wide CT-based follow-up and referral policy was introduced for all patients. A second audit was performed to assess the impact of the guidelines on liver resection rates., Subjects and Methods: Analysis of prospective liver resection database between 1997 and 2004 and after the introduction of standardised guidelines between January 2005 and April 2008., Results: A total of 362 patients underwent liver resection for CRC metastases between 1997 and 2008, 237 prior to the introduction of the referral guidelines and 125 after. Liver resection rates according to referring hospital varied from 0.92 to 2.32 per 100,000 population before guidelines were introduced. After 2005, resection rates from the four district hospitals standardised (1.68-1.84 per 100,000 population), but the central unit rate (Sheffield) remained significantly higher (2.67 per 100,000 population). No significant difference in 1-year disease-free survival between patients from Sheffield and the out-lying hospitals was found (P = 0.553)., Conclusions: Introduction of a referral protocol standardised resection rates from the four district hospitals, but these remain lower compared to the specialist centre. The wide-spread adoption of a policy to discuss all patients with liver metastases at an advanced disease multidisciplinary team meeting, in the presence of hepatobiliary specialists, may further increase resection rates across the UK.