Faecal immunochemical testing (FIT) in patients with signs or symptoms of suspected colorectal cancer (CRC): a joint guideline from the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and the British Society of Gastroenterology (BSG).

Faecal immunochemical testing (FIT) has a high sensitivity for the detection of colorectal cancer (CRC). In a symptomatic population FIT may identify those patients who require colorectal investigation with the highest priority. FIT offers considerable advantages over the use of symptoms alone, as an objective measure of risk with a vastly superior positive predictive value for CRC, while conversely identifying a truly low risk cohort of patients. The aim of this guideline was to provide a clear strategy for the use of FIT in the diagnostic pathway of people with signs or symptoms of a suspected diagnosis of CRC. The guideline was jointly developed by the Association of Coloproctology of Great Britain and Ireland/British Society of Gastroenterology, specifically by a 21-member multidisciplinary guideline development group (GDG). A systematic review of 13 535 publications was undertaken to develop 23 evidence and expert opinion-based recommendations for the triage of people with symptoms of a suspected CRC diagnosis in primary care. In order to achieve consensus among a broad group of key stakeholders, we completed an extended Delphi of the GDG, and also 61 other individuals across the UK and Ireland, including by members of the public, charities and primary and secondary care. Seventeen research recommendations were also prioritised to inform clinical management.

COVID-19 and the emergency presentation of colorectal cancer.

AIM: The COVID-19 pandemic led to widespread disruption of colorectal cancer services during 2020. Established cancer referral pathways were modified in response to reduced diagnostic availability. The aim of this paper is to assess the impact of COVID-19 on colorectal cancer referral, presentation and stage. METHODS: This was a single centre, retrospective cohort study performed at a tertiary referral centre. Patients diagnosed and managed with colorectal adenocarcinoma between January and December 2020 were compared with patients from 2018 and 2019 in terms of demographics, mode of presentation and pathological cancer staging. RESULTS: In all, 272 patients were diagnosed with colorectal adenocarcinoma during 2020 compared with 282 in 2019 and 257 in 2018. Patients in all years were comparable for age, gender and tumour location (P > 0.05). There was a significant decrease in urgent suspected cancer referrals, diagnostic colonoscopy and radiological imaging performed between March and June 2020 compared with previous years. More patients presented as emergencies (P = 0.03) with increased rates of large bowel obstruction in 2020 compared with 2018-2019 (P = 0.01). The distribution of TNM grade was similar across the 3 years but more T4 cancers were diagnosed in 2020 versus 2018-2019 (P = 0.03). CONCLUSION: This study demonstrates that a relatively short-term impact on the colorectal cancer referral pathway can have significant consequences on patient presentation leading to higher risk emergency presentation and surgery at a more advanced stage. It is therefore critical that efforts are made to make this pathway more robust to minimize the impact of other future adverse events and to consolidate the benefits of earlier diagnosis and treatment.

The nature of the human T cell response to the cancer antigen 5T4 is determined by the balance of regulatory and inflammatory T cells of the same antigen-specificity: implications for vaccine design.

The oncofoetal antigen 5T4 is a promising T cell target in the context of colorectal cancer, as demonstrated by a recent clinical study where 5T4-specific T cell responses, induced by vaccination or cyclophosphamide, were associated with a significantly prolonged survival of patients with metastatic disease. Whilst Th1-type (IFN-γ+) responses specific to 5T4, and other oncofoetal antigens, are often readily detectable in early stage CRC patients and healthy donors, their activity is suppressed as the cancer progresses by CD4+CD25hiFoxp3+ regulatory T cells (Treg) which contribute to the immunosuppressive environment conducive to tumour growth. This study mapped the fine specificity of Th1 and Treg cell responses to the 5T4 protein. Surprisingly, both immunogenic peptides and those recognised by Tregs clustered in the same HLA-DR transcending epitope-rich hotspots within the 5T4 protein. Similarly, regions of low Th1-cell immunogenicity also did not contain peptides capable of stimulating Tregs, further supporting the notion that Treg and Th1 cells recognise the same peptides. Understanding the rules which govern the balance of Th1 and Treg cells responding to a given peptide specificity is, therefore, of fundamental importance to designing strategies for manipulating the balance in favour of Th1 cells, and thus the most effective anti-cancer T cell responses.

Transferring laparoscopic skills to robotic-assisted surgery: a systematic review.

Robotic-Assisted Surgery (RAS) is experiencing rapid expansion, prompting the integration of robotic technical skills training into surgical education programs. As access to robotic training platforms remains limited, it is important to investigate the transferability of laparoscopic skills to RAS. This could potentially support the inclusion of early years laparoscopic training to mitigate the learning curve associated with robotic surgery. This study aims to assess the transferability of laparoscopic skills to robotic surgery. A systematic search was conducted using the PRISMA checklist to identify relevant articles. PubMed, MEDLINE, Embase, and Cochrane databases were searched, and inclusion and exclusion criteria were applied to collate eligible articles. Included were original articles comparing the performance of comparable tasks on both laparoscopic and robotic platforms written in English. Non-peer reviewed papers, conference abstracts, reviews, and case series were excluded. Seventeen articles met the inclusion criteria. Among these, 10 studies (59%) demonstrated skill transferability from laparoscopic surgery (LS) to robotic surgery (RS); while one study (5.8%) showed no significant transferability. Four studies highlighted the positive impact of prior laparoscopic training on robotic skill, whereas six papers suggested no significant difference between laparoscopic novices and experienced laparoscopists when utilizing a robotic simulator. Five studies evaluated advanced surgical skills such as intracorporeal knot tying and suturing, revealing superior robotic performance among experienced laparoscopists compared to novice learners. Laparoscopic skills appear to be transferrable to robotic surgery, particularly in complex surgical techniques. Robotic simulators demonstrate a significant reduction in the learning curve for surgical novices, albeit to a lesser extent for experienced laparoscopists.

Can wearable technology be used to approximate cardiopulmonary exercise testing metrics?

BACKGROUND: Consumer wrist-worn wearable activity monitors are widely available, low cost and are able to provide a direct measurement of several markers of physical activity. Despite this, there is limited data on their use in perioperative risk prediction. We explored whether these wearables could accurately approximate metrics (anaerobic threshold, peak oxygen uptake and peak work) derived using formalised cardiopulmonary exercise testing (CPET) in patients undergoing high-risk surgery. METHODS: Patients scheduled for major elective intra-abdominal surgery and undergoing CPET were included. Physical activity levels were estimated through direct measures (step count, floors climbed and total distance travelled) obtained through continuous wear of a wrist worn activity monitor (Garmin Vivosmart HR+) for 7 days prior to surgery and self-report through completion of the short International Physical Activity Questionnaire (IPAQ). Correlations and receiver operating characteristic (ROC) curve analysis explored the relationships between parameters provided by CPET and physical activity. DEVICE SELECTION: Our choice of consumer wearable device was made to maximise feasibility outcomes for this study. The Garmin Vivosmart HR+ had the longest battery life and best waterproof characteristics of the available low-cost devices. RESULTS: Of 55 patients invited to participate, 49 (mean age 65.3 ± 13.6 years; 32 males) were enrolled; 37 provided complete wearable data for analyses and 36 patients provided full IPAQ data. Floors climbed, total steps and total travelled as measured by the wearable device all showed moderate correlation with CPET parameters of peak oxygen uptake (peak VO2) (R = 0.57 (CI 0.29-0.76), R = 0.59 (CI 0.31-0.77) and R = 0.62 (CI 0.35-0.79) respectively), anaerobic threshold (R = 0.37 (CI 0.01-0.64), R = 0.39 (CI 0.04-0.66) and R = 0.42 (CI 0.07-0.68) respectively) and peak work (R = 0.56 (CI 0.27-0.75), R = 0.48 (CI 0.17-0.70) and R = 0.50 (CI 0.2-0.72) respectively). Receiver operator curve (ROC) analysis for direct and self-reported measures of 7-day physical activity could accurately approximate the ventilatory equivalent for carbon dioxide (VE/VCO2) and the anaerobic threshold. The area under these curves was 0.89 for VE/VCO2 and 0.91 for the anaerobic threshold. For peak VO2 and peak work, models fitted using just the wearable data were 0.93 for peak VO2 and 1.00 for peak work. CONCLUSIONS: Data recorded by the wearable device was able to consistently approximate CPET results, both with and without the addition of patient reported activity measures via IPAQ scores. This highlights the potential utility of wearable devices in formal assessment of physical functioning and suggests they could play a larger role in pre-operative risk assessment. ETHICS: This study entitled "uSing wearable TEchnology to Predict perioperative high-riSk patient outcomes (STEPS)" gained favourable ethical opinion on 24 January 2017 from the Welsh Research Ethics Committee 3 reference number 17/WA/0006. It was registered on ClinicalTrials.gov with identifier NCT03328039.

Cancer Antigen Discovery Is Enabled by RNA Sequencing of Highly Purified Malignant and Nonmalignant Cells.

PURPOSE: Broadly expressed, highly differentiated tumor-associated antigens (TAA) can elicit antitumor immunity. However, vaccines targeting TAAs have demonstrated disappointing clinical results, reflecting poor antigen selection and/or immunosuppressive mechanisms. EXPERIMENTAL DESIGN: Here, a panel of widely expressed, novel colorectal TAAs were identified by performing RNA sequencing of highly purified colorectal tumor cells in comparison with patient-matched colonic epithelial cells; tumor cell purification was essential to reveal these genes. Candidate TAA protein expression was confirmed by IHC, and preexisting T-cell immunogenicity toward these antigens tested. RESULTS: The most promising candidate for further development is DNAJB7 [DnaJ heat shock protein family (Hsp40) member B7], identified here as a novel cancer-testis antigen. It is expressed in many tumors and is strongly immunogenic in patients with cancers originating from a variety of sites. DNAJB7-specific T cells were capable of killing colorectal tumor lines in vitro, and the IFNγ+ response was markedly magnified by control of immunosuppression with cyclophosphamide in patients with cancer. CONCLUSIONS: This study highlights how prior methods that sequence whole tumor fractions (i.e., inclusive of alive/dead stromal cells) for antigen identification may have limitations. Through tumor cell purification and sequencing, novel candidate TAAs have been identified for future immunotherapeutic targeting.

Transanal endoscopic surgery: past, present and future.

Transanal endoscopic surgery is a safe, established technique to remove lesions in the rectum via the anus. This article reviews its evolution, approaches, indications and evidence for its role in treating benign rectal polyps. The future of transanal endoscopic surgery in rectal cancer and inflammatory bowel disease is also explored.

Lung cancer trend in England for the period of 2002 to 2011 and projections of future burden until 2020.

Lung cancer is the most common cancer in the world, therefore creating a huge public health concern. The aim of this study is to determine the change in age-standardised incidence rate trend of lung cancer in England between 2002 and 2011 and use these findings to anticipate the potential burden of the disease by gender in the year 2020. Lung cancer incidence data (ICD-10 code C33-34) from 2002 and 2011 and mid-year population estimates for the same period were obtained from Office of National Statistics. Age-standardised incidence rates were calculated, by gender and region. Poisson regression analysis was used to describe the time incidence trend and projections were estimated up to year 2020. A total of 318, 417 lung cancer cases were identified. Incidence rates decreased in men by an average annual percentage change (AAPC) of -1.0% and increased in women by +1.9%. Projection analysis showed that by year 2020, provided the rates remain the same, English women will have the same lung cancer incidence rates as their male counterparts. This study demonstrated that there would be 5,848 excess lung cancer cases by 2020 with female population accounting for 85% (4,996) of the excess cases. Therefore, in addition to the development of high quality preventive intervention strategies, future public health also needs to prioritise targets at the implementation phase, in a manner that engage women living in regions that have demonstrated very high AAPC values.

Sexual function, body image, and quality of life after laparoscopic and open ileal pouch-anal anastomosis.

PURPOSE: This study was designed to compare self-reported sexual function, body image, and quality of life outcomes among ulcerative colitis patients undergoing laparoscopic or open ileal pouch-anal anastomosis. METHODS: Between 1978 and 2004, 100 laparoscopic and 189 open operations were performed in patients who were identified from a previously published cohort. Patients were surveyed one year after operation to evaluate sexual function, body image, and quality of life. RESULTS: A total of 125 of 289 patients (43 percent) returned completed surveys. There were no significant differences in terms of demographics, complications, or long-term functional outcomes between those who completed the surveys and those who did not. There were no clinical differences in results between laparoscopic and open patients using the three survey instruments. Orgasmic function scores were lower in men who underwent laparoscopic ileal pouch-anal anastomosis (P < 0.05) compared with open ileal pouch-anal anastomosis. Overall, sexual function scores were equal to or better than normal values for men but were lower in women. Finally, overall body image and quality of life scores were above the means published for the United States. CONCLUSIONS: After ileal pouch-anal anastomosis, men and women reported excellent body image and high cosmetic and quality of life scores regardless of operative approach. Female sexual function was more adversely affected after ileal pouch-anal anastomosis than was male sexual function.

Basic fibroblast growth factor infusion increases tumour vascularity, blood flow and chemotherapy uptake.

Tumour response depends on intratumoural cytotoxic concentration, which varies with tumour vascularity. We determined whether basic fibroblast growth factor (bFGF) infusion increased tumour vascularity, blood flow and cytotoxic drug uptake. The effect of interstitial and systemic bFGF infusion was compared with that of saline-infused controls using animal HSN and K12/TR tumour models. Changes in tumour vascularity were assessed by immunohistochemical staining of tumour sections. Blood flow and drug uptake were studied using a radiotracer method. There were significant increases in tumour vascularity, vessel length density and blood flow with both interstitial and systemic bFGF infusions, and a significant increase in tumour fluorouracil uptake after systemic bFGF infusion of liver tumours. The effects were independent of tumour type, and could be produced by bFGF administration after initial tumour growth. bFGF infusion increased tumour fluorouracil uptake. Further studies are required to determine the risks and benefits with this approach to increasing tumour cytotoxic uptake.