Still too little evidence: the role of diet in colorectal cancer survivorship - a systematic review.

Colorectal cancer incidence (CRC) is influenced by dietary factors, yet the impact of diet on CRC-specific mortality and recurrence-free survival (RFS) remains unclear. This review provides a narrative summary of existing research on dietary factors affecting CRC-specific mortality, RFS, and disease-free survival (DFS). This study searched electronic databases to identify cross-sectional/prospective research investigating dietary intake on CRC-specific mortality, RFS, or DFS. Twenty-eight studies were included in the corpus. Because of high study heterogeneity, we performed a narrative synthesis of studies. Limited, but suggestive evidence indicates beneficial effects of adhering to the American Cancer Society (ACS) guidelines and a plant rich low-carbohydrate diet on risk of CRC-specific mortality, potentially driven by fiber from cereals, vegetables, and wholegrains, but not fruit. For RFS and DFS, a Western dietary pattern, high intake of refined grains, and sugar sweetened beverages correlated with increased risk of CRC recurrence and development of disease/death. Conversely, greater adherence to the ACS dietary and alcohol guidelines, higher ω-3 polyunsaturated fatty acids, and dark fish consumption reduced risk. Our findings underscore the need for (i) standardized investigations into diet's role in CRC survivorship, including endpoints, and (ii) comprehensive analyses to isolate specific effects within correlated lifestyle components.

'I Do It All Alone': The Burdens and Benefits of Being Diagnosed With, and Treated for, Colorectal Cancer During the Covid-19 Pandemic.

INTRODUCTION: The Covid-19 pandemic dramatically altered the way cancer care services were accessed and delivered, including for colorectal cancer (CRC). In the United Kingdom, patients were discouraged from presenting in primary care, many consultations took place remotely, investigative procedures and screening programmes were temporarily suspended, and fewer operations and treatments were delivered. People had to face the practical consequences of having cancer during a pandemic and navigate never before seen pathways, often alone. We examined the experience of being diagnosed and treated for CRC during the pandemic, and the implications of this on people's cancer journeys. METHODS: Semi-structured interviews were undertaken with people diagnosed with CRC during the Covid-19 pandemic (January 2020-May 2021), in the North East of England. An iterative topic guide was used during interviews, which took place remotely (telephone or Zoom), were audio recorded, pseudo-anonymised and transcribed. Initial transcripts were independently coded by two researchers, and a code 'bank' developed for application across transcripts. Development of themes and overarching analytical constructs was undertaken collaboratively by the research team. RESULTS: Interviews were conducted with 19 participants, analysed and four key themes identified: (1) The relative threats of Covid-19 and Cancer were not comparable, with cancer seen as posing a far greater risk than Covid-19; (2) Remote consultations were problematic, affecting patients' abilities to build rapport and trust with clinicians, assess nonverbal communication, and feel able to disclose, comprehend and retain information; (3) Stoma follow-up care was seen to be lacking, with long wait times for stoma reversal experienced by some; Finally, (4) Being alone during consultations negatively impacted some peoples' abilities to absorb information, and left them without the support of loved ones at an emotionally vulnerable time. However, some participants preferred being alone at certain points in their pathways, including receiving a diagnosis, and most frequently when receiving in-patient treatment. CONCLUSION: Being alone brought unexpected benefits, absolving people from undertaking emotions work for others, and instead focus on their recovery, however, remote consultations negatively impacted patients' experiences. This study highlights the complex benefits and burdens of pandemic-located cancer journeys, including how these shifted at different points across cancer pathways. PATIENT OR PUBLIC CONTRIBUTION: Lorraine Angell, a cancer survivor, has been central to this study from idea conception, contributing to: development of study focus and design; securing funding; production of patient-facing materials; development of interview topic guides; analysis and interpretation of data; and drafting of key findings and manuscripts.

The COLO-COHORT (Colorectal Cancer Cohort) study: Protocol for a multi-centre, observational research study and development of a consent-for-contact research platform.

AIM: The COLO-COHORT study aims to produce a multi-factorial risk prediction model for colorectal neoplasia that can be used to target colonoscopy to those at greatest risk of colorectal neoplasia, ensuring that people are not investigated unnecessarily and maximizing the use of limited endoscopy resources. The study will also explore the link between neoplasia and the human gut microbiome. Additionally, the study aims to generate a cohort of colonoscopy patients who are 'research ready' through the development of a consent-for-contact (C4C) platform, to facilitate a range of colorectal cancer prevention studies to be conducted at scale and speed. METHODS AND ANALYSIS: This is a multi-centre observational study involving sites across the UK. Recruitment is over a 6-year period (2019-2025). Patients recruited to the study are those attending for colonoscopy. Patients are recruited into two groups, namely observational group A (10 000 patients) and C4C group B (10 000 patients), known as COLO-SPEED (Colorectal Cancer Screening Prevention Endoscopy and Early Diagnosis; https://colospeed.uk). Patients complete a health questionnaire, provide anthropometric measurements and submit biosamples (blood and stool-depending on the part of the study they are recruited into). Patients' colonoscopy and histology findings are also recorded. Models of factors associated with the presence of neoplasia at colonoscopy will be developed using logistic or multinomial regression. For internal validation, model discrimination and calibration will be assessed and bootstrapping and cross-validation approaches used. To enable long-term follow-up for outcomes related to colorectal cancer and polyps, patients are asked to consent to follow-up through data linkage with national databases. DISSEMINATION: In keeping with good research practice, following analysis by the study team the study investigators will make the anonymized dataset available to other researchers. The C4C platform will also be accessible to other researchers. The study findings will be submitted for publication in peer-reviewed journals and lay summaries will be disseminated to participants and the wider public.

Barriers and facilitators to colonoscopy following fecal immunochemical test screening for colorectal cancer: A key informant interview study.

OBJECTIVES: People who are referred for colonoscopy, following an abnormal colorectal cancer (CRC) screening result, are at increased risk of CRC. Despite this, many individuals decline the procedure. The aim of this study was to investigate why. METHODS: As little is currently known about non-attendance at follow-up colonoscopy, and follow-up of abnormal screening results is a nurse-led process, we decided to conduct key informant interviews with Specialist Screening Practitioners ([SSPs] nurses working in the English Bowel Cancer Screening Program). Interviews were conducted online. Transcripts were assessed using inductive and deductive coding techniques. RESULTS: 21 SSPs participated in an interview. Five main types of barriers and facilitators to colonoscopy were described, namely: Sociocultural, Practical, Psychological, Health-related and COVID-related. Key psychological and sociocultural factors included: 'Fear of pain and discomfort associated with the procedure' and 'Lack of support from family and friends'. Key practical, health-related and COVID-related factors included: 'Family and work commitments', 'Existing health conditions as competing priorities' and 'Fear of getting COVID-19 at the hospital'. CONCLUSIONS: A range of barriers and facilitators to follow-up colonoscopy exist. Future studies conducted with patients are needed to further explore barriers to colonoscopy. PRACTICE IMPLICATIONS: Strategies to reduce non-attendance should adopt a multifaceted approach.

Barriers to Early Presentation amongst Rural Residents Experiencing Symptoms of Colorectal Cancer: A Qualitative Interview Study.

Rural cancer inequalities are evident internationally, with rural cancer patients 5% less likely to survive than their urban counterparts. There is evidence to suggest that diagnostic delays prior to entry into secondary care may be contributing to these poorer rural cancer outcomes. This study explores the symptom appraisal and help-seeking decision-making of people experiencing symptoms of colorectal cancer in rural areas of England. Patients were randomly invited from 4 rural practices, serving diverse communities. Semi-structured interviews were undertaken with 40 people who had experienced symptoms of colorectal cancer in the preceding 8 weeks. Four key themes were identified as influential in participants' willingness and timeliness of consultation: a desire to rule out cancer (facilitator of help-seeking); stoicism and self-reliance (barrier to help-seeking); time scarcity (barrier to help-seeking); and GP/patient relationship (barrier or facilitator, depending on perceived strength of the relationship). Self-employed, and "native" rural residents most commonly reported experiencing time scarcity and poor GP/patient relationships as a barrier to (re-)consultation. Targeted, active safety-netting approaches, and increased continuity of care, may be particularly beneficial to expedite timely diagnoses and minimise cancer inequalities for rural populations.

Reconceptualising Rural Cancer Inequalities: Time for a New Research Agenda.

Evidence has shown for over 20 years that patients residing in rural areas face poorer outcomes for cancer. The inequalities in survival that rural cancer patients face are observed throughout the developed world, yet this issue remains under-examined and unexplained. There is evidence to suggest that rural patients are more likely to be diagnosed as a result of an emergency presentation and that rural patients may take longer to seek help for symptoms. However, research to date has been predominantly epidemiological, providing us with an understanding of what is occurring in these populations, yet failing to explain why. In this paper we outline the problems inherent in current research approaches to rural cancer inequalities, namely how 'cancer symptoms' are conceived of and examined, and the propensity towards a reductionist approach to rural environments and populations, which fails to account for their heterogeneity. We advocate for a revised rural cancer inequalities research agenda, built upon in-depth, community-based examinations of rural patients' experiences across the cancer pathway, which takes into account both the micro and macro factors which exert influence on these experiences, in order to develop meaningful interventions to improve cancer outcomes for rural populations.

Symptoms and patient factors associated with longer time to diagnosis for colorectal cancer: results from a prospective cohort study.

BACKGROUND: The objective of this study is to investigate symptoms, clinical factors and socio-demographic factors associated with colorectal cancer (CRC) diagnosis and time to diagnosis. METHODS: Prospective cohort study of participants referred for suspicion of CRC in two English regions. Data were collected using a patient questionnaire, primary care and hospital records. Descriptive and regression analyses examined associations between symptoms and patient factors with total diagnostic interval (TDI), patient interval (PI), health system interval (HSI) and stage. RESULTS: A total of 2677 (22%) participants responded; after exclusions, 2507 remained. Participants were diagnosed with CRC (6.1%, 56% late stage), other cancers (2.0%) or no cancer (91.9%). Half the cohort had a solitary first symptom (1332, 53.1%); multiple first symptoms were common. In this referred population, rectal bleeding was the only initial symptom more frequent among cancer than non-cancer cases (34.2% vs 23.9%, P=0.004). There was no evidence of differences in TDI, PI or HSI for those with cancer vs non-cancer diagnoses (median TDI CRC 124 vs non-cancer 138 days, P=0.142). First symptoms associated with shorter TDIs were rectal bleeding, change in bowel habit, 'feeling different' and fatigue/tiredness. Anxiety, depression and gastro-intestinal co-morbidities were associated with longer HSIs and TDIs. Symptom duration-dependent effects were found for rectal bleeding and change in bowel habit. CONCLUSIONS: Doctors and patients respond less promptly to some symptoms of CRC than others. Healthcare professionals should be vigilant to the possibility of CRC in patients with relevant symptoms and mental health or gastro-intestinal comorbidities.

Attitudes and beliefs of non-participants in a population-based screening programme for colorectal cancer.

BACKGROUND: Uptake of colorectal cancer screening programmes needs to be improved or at least maintained in order to achieve projected reductions in mortality and morbidity. Understanding the origins of non-participation in screening is therefore important. OBJECTIVE: To explore the beliefs and experiences of individuals who had not responded either to their screening invitation or reminder. DESIGN: A qualitative study using in-depth interviews with non-participants from England's population-based colorectal cancer screening programme. Data collection and analysis were carried out using a grounded theory approach, with an emphasis on the constant comparison method, and continued until saturation (27 interviews). FINDINGS: The interviews provided an in-depth understanding of a range of reasons and circumstances surrounding non-participation in screening, including contextual and environmental influences as well as factors specific to the screening test. Non-participation in screening was not necessarily associated with negative attitudes towards screening or a decision to not return a kit. Reasons for non-participation in screening included not feeling that participation is personally necessary, avoiding or delaying decision making, and having some degree of intention to take part but failing to do so because of practicalities, conflicting priorities or external circumstances. Beliefs, awareness and intention change over time. DISCUSSION AND CONCLUSIONS: A range of approaches may be required to improve screening uptake. Some non-participants may already have a degree of intention to take part in screening in the future, and this group may be more responsive to interventions based on professional endorsement, repeat invitations, reminders and aids to making the test more practical.

Patient delay in cancer diagnosis: what do we really mean and can we be more specific?

BACKGROUND: Early diagnosis is a key focus of cancer control because of its association with survival. Delays in diagnosis can occur throughout the diagnostic pathway, within any one of its three component intervals: the patient interval, the primary care interval and the secondary care interval. DISCUSSION: A key focus for help-seeking research in patients with symptoms of cancer has been the concept of 'delay'. The literature is plagued by definitional and semantic problems, which serve to hinder comparison between studies. Use of the word 'delay' has been criticised as judgemental and potentially stigmatising, because of its implications of intent. However, the suggested alternatives (time to presentation, appraisal interval, help-seeking interval and postponement of help-seeking) still fail to accurately define the concept in hand, and often conflate three quite separate ideas; that of an interval, that of an unacceptably long interval, and that of a specific event which caused delay in the diagnostic process. We discuss the need to disentangle current terminology and suggest the term 'prolonged interval' as a more appropriate alternative. Most studies treat the patient interval as a dichotomous variable, with cases beyond a specified time point classified as 'delay'. However, there are inconsistencies in both where this line is drawn, ranging from one week to three months, and how, with some studies imposing seemingly arbitrary time points, others utilising the median as a divisive tool or exploring quartiles within their data. This not only makes comparison problematic, but, as many studies do not differentiate between cancer site, also imposes boundaries which are not necessarily site-relevant. We argue that analysis of the patient interval should be based on presenting symptom, as opposed to pathology, to better reflect the context of the help-seeking interval, and suggest how new definitional boundaries could be developed. SUMMARY: The word 'delay' is currently (conf)used to describe diverse conceptualisations of 'delay' and more mindful, and discerning language needs to be developed to enable a more sophisticated discussion. By stratifying help-seeking by presenting symptom(s), more accurate and informative analyses could be produced which, in turn, would result in more accurately targeted early diagnosis interventions.

O-Mannosylation and human disease.

Glycosylation of proteins is arguably the most prevalent co- and post-translational modification. It is responsible for increased heterogeneity and functional diversity of proteins. Here we discuss the importance of one type of glycosylation, specifically O-mannosylation and its relationship to a number of human diseases. The most widely studied O-mannose modified protein is alpha-dystroglycan (α-DG). Recent studies have focused intensely on α-DG due to the severity of diseases associated with its improper glycosylation. O-mannosylation of α-DG is involved in cancer metastasis, arenavirus entry, and multiple forms of congenital muscular dystrophy [1, 2]. In this review, we discuss the structural and functional characteristics of O-mannose-initiated glycan structures on α-DG, enzymes involved in the O-mannosylation pathway, and the diseases that are a direct result of disruptions within this pathway.

Impact of doulas on healthy birth outcomes.

Birth outcomes of two groups of socially disadvantaged mothers at risk for adverse birth outcomes, one receiving prebirth assistance from a certified doula and the other representing a sample of birthing mothers who elected to not work with a doula, were compared. All of the mothers were participants in a prenatal health and childbirth education program. Expectant mothers matched with a doula had better birth outcomes. Doula-assisted mothers were four times less likely to have a low birth weight (LBW) baby, two times less likely to experience a birth complication involving themselves or their baby, and significantly more likely to initiate breastfeeding. Communication with and encouragement from a doula throughout the pregnancy may have increased the mother's self-efficacy regarding her ability to impact her own pregnancy outcomes.