Nicola S Fearnhead

Rare variant hypothesis for multifactorial inheritance: susceptibility to colorectal adenomas as a model.

The rare variant hypothesis postulates that genetic susceptibility to colorectal neoplasia within the general population is due to a number of low frequency variants in a variety of different genes. Each variant confers a moderate, but detectable, increase in relative risk of developing the disease. Recent evidence suggests that a quarter of patients with multiple adenomatous polyps are due to rare but functionally important variants in just five genes.

A national patient and public colorectal research agenda: Integration of consumer perspectives in bowel disease through early consultation

There is a recognized need to include the views of patients and the public in prioritizing health research. This study aimed: (i) to explore patients’ views on colorectal research; and (ii) to prioritize research topics with patients and the public.

Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer

Objective Colorectal cancer (CRC) leads to significant morbidity/mortality worldwide. Defining critical research gaps (RG), their prioritisation and resolution, could improve patient outcomes. Design RG analysis was conducted by a multidisciplinary panel of patients, clinicians and researchers (n=71). Eight working groups (WG) were constituted: discovery science; risk; prevention; early diagnosis and screening; pathology; curative treatment; stage IV disease; and living with and beyond CRC. A series of discussions led to development of draft papers by each WG, which were evaluated by a 20-strong patient panel. A final list of RGs and research recommendations (RR) was endorsed by all participants. Results Fifteen critical RGs are summarised below: RG1: Lack of realistic models that recapitulate tumour/tumour micro/macroenvironment; RG2: Insufficient evidence on precise contributions of genetic/environmental/lifestyle factors to CRC risk; RG3: Pressing need for prevention trials; RG4: Lack of integration of different prevention approaches; RG5: Lack of optimal strategies for CRC screening; RG6: Lack of effective triage systems for invasive investigations; RG7: Imprecise pathological assessment of CRC; RG8: Lack of qualified personnel in genomics, data sciences and digital pathology; RG9: Inadequate assessment/communication of risk, benefit and uncertainty of treatment choices; RG10: Need for novel technologies/interventions to improve curative outcomes; RG11: Lack of approaches that recognise molecular interplay between metastasising tumours and their microenvironment; RG12: Lack of reliable biomarkers to guide stage IV treatment; RG13: Need to increase understanding of health related quality of life (HRQOL) and promote residual symptom resolution; RG14: Lack of coordination of CRC research/funding; RG15: Lack of effective communication between relevant stakeholders. Conclusion Prioritising research activity and funding could have a significant impact on reducing CRC disease burden over the next 5 years.

Developing a core outcome set for fistulising perianal Crohn’s disease

Objective Lack of standardised outcomes hampers effective analysis and comparison of data when comparing treatments in fistulising perianal Crohn’s disease (pCD). Development of a standardised set of outcomes would resolve these issues. This study provides the definitive core outcome set (COS) for fistulising pCD. Design Candidate outcomes were generated through a systematic review and patient interviews. Consensus was established via a three-round Delphi process using a 9-point Likert scale based on how important they felt it was in determining treatment success culminating in a final consensus meeting. Stakeholders were recruited nationally and grouped into three panels (surgeons and radiologists, gastroenterologists and IBD specialist nurses, and patients). Participants received feedback from their panel (in the second round) and all participants (in the third round) to allow refinement of their scores. Results A total of 295 outcomes were identified from systematic reviews and interviews that were categorised into 92 domains. 187 stakeholders (response rate 78.5%) prioritised 49 outcomes through a three-round Delphi study. The final consensus meeting of 41 experts and patients generated agreement on an eight domain COS. The COS comprised three patient-reported outcome domains (quality of life, incontinence and a combined score of patient priorities) and five clinician-reported outcome domains (perianal disease activity, development of new perianal abscess/sepsis, new/recurrent fistula, unplanned surgery and faecal diversion). Conclusion A fistulising pCD COS has been produced by all key stakeholders. Application of the COS will reduce heterogeneity in outcome reporting, thereby facilitating more meaningful comparisons between treatments, data synthesis and ultimately benefit patient care.

Association of Coloproctology of Great Britain and Ireland Consensus Exercise on Surgical Management of Fistulating Perianal Crohn's Disease

Management of fistulating perianal Crohns disease (fpCD) is a significant challenge for a colorectal surgeon. A recent survey of surgical practice in this condition showed variation in management approaches. As a result we set out to devise recommendations for practice for UK colorectal surgeons.

Variation in practice of pouch surgery in England - using SWORD data to cut to the chase and justify centralisation

Increasing scrutiny on both individual and unit outcomes after surgical procedures is now expected. In the field of inflammatory bowel disease, this is particularly pertinent for outcomes after ileoanal pouch surgery.

SWORD: a sharp performance and activity tool for inflammatory bowel disease surgeons with a blunt message.

High quality performance and activity data for surgery are paramount in maintaining good clinical practice and for quality improvement initiatives. Clinical Outcome Publication (COP) is an NHS England initiative that publishes quality measures following elective bowel cancer surgery at individual consultant and Trust level using National Audit data. This article is protected by copyright. All rights reserved.

Urgent improvements needed to diagnose and manage Lynch syndrome

Lynch syndrome is currently under-recognised, underdiagnosed, and undermanaged, so opportunities to reduce cancer mortality are often missed. The new guideline from the National Institute for Health and Care Excellence recommends universal testing for Lynch syndrome in all people newly diagnosed as having colorectal cancer.1 This should prevent several hundred colorectal cancers annually, but several issues hinder good care …

Detection of colorectal dysplasia using fluorescently labelled lectins

Colorectal cancer screening using conventional colonoscopy lacks molecular information and can miss dysplastic lesions. We tested here the ability of fluorescently labelled lectins to distinguish dysplasia from normal tissue when sprayed on to the luminal surface epithelium of freshly resected colon tissue from the Apcmin mouse and when applied to fixed human colorectal tissue sections. Wheat germ agglutinin (WGA) showed significantly decreased binding to adenomas in the mouse tissue and in sections of human colon from 47 patients. Changes in WGA binding to the human surface epithelium allowed regions containing normal epithelium (NE) or hyperplastic polyps (HP) to be distinguished from regions containing low-grade dysplasia (LGD), high-grade dysplasia (HGD) or carcinoma (C), with 81% sensitivity, 87% specificity and 93% positive predictive value (PPV). Helix pomatia agglutinin (HGA) distinguished epithelial regions containing NE from regions containing HP, LGD, HGD or C, with 89% sensitivity, 87% specificity and 97% PPV. The decreased binding of WGA and HPA to the luminal surface epithelium in human dysplasia suggests that these lectins may enable more sensitive detection of disease in the clinic using fluorescence colonoscopy.

A Rare Case of Primary Seminoma of the Small Bowel with Lymph Node Involvement

IntroductionOne thousand four hundred new cases of testicular cancer are diagnosed annually in the UK, with peak incidence in men aged 25–35 years old. Seminomas account for over 40% of cases. The involvement of the gastrointestinal tract with seminoma is unusual.Case DescriptionWe present a rare case of primary seminoma of the small bowel with lymph node involvement in a 30-year-old man who presented with iron deficiency anaemia and non-specific postprandial abdominal pain. A computed tomographic scan revealed small bowel wall thickening and mesenteric lymphadenopathy. Laparoscopic jejunal resection was performed and subsequent histology confirmed the diagnosis of primary seminoma of the small bowel. The patient also received three courses of cisplastin-based chemotherapy with good therapeutic outcome.DiscussionThe possible anatomical origins of the seminoma include: the small bowel itself, a result of anomalies during embryogenesis, location of the lymphatic drainage of the testis, an occult testicular metastasis or a viable metastasis from a primary testicular lesion which had already regressed.ConclusionThe investigation of unexplained iron deficiency anaemia in a young male patient requires full investigation of the entire gastrointestinal tract.