Colorectal cancer and the blood loss paradox.

Background: Faecal occult blood (FOB) positivity and iron deficiency anaemia (IDA) are common manifestations of colorectal cancer (CRC) and both potentially facilitate diagnosis at an earlier, more treatable stage. It has been assumed that both are the consequence of low-grade blood loss from the tumour bed. Method: A retrospective analysis of 1121 cases of CRC diagnosed at a single centre between 2010 and 2016, comparing cases presenting via FOB-based Bowel Cancer Screening Programme (BCSP) and IDA pathways for a series of variables including age, sex, tumour location and prevalence of anaemia. Results: The BCSP and IDA pathways each accounted for about 15% of the total case load. There were significant differences between the BCSP and IDA sub-groups in median age (68 vs 78 years: p<0.001), median haemoglobin (138 vs 89 g/L: p<0.001) and proportion of lesions in right colon (31.1% vs 82.5%: p<0.001). The major disparity in the prevalence of anaemia (overall 20.0% vs 98.2%: p<0.001) persisted when controlled for tumour location. Conclusion: Paradoxically, CRC screening through the detection of FOB positivity and IDA identifies distinctly different sub-populations of cases. The theoretical implication is that an additional mechanism may be required to explain the development of IDA in CRC. The practical implication is that detection of IDA may have a complementary role to the BCSP in population screening for CRC.

Evidence for improved prognosis of colorectal cancer diagnosed following the detection of iron deficiency anaemia.

Iron deficiency anaemia (IDA) is common in colorectal cancer (CRC), especially, in right-sided CRC which is known to have an overall worse prognosis. The associations between diagnostic pathway (Bowel Cancer Screening Programme (BCSP), IDA, symptomatic) and tumour side/stage was assessed using logistic regression models in 1138 CRC cases presenting during 2010-2016 at a single secondary-care centre in the UK. In the IDA sub-group, the relationship between CRC stage and the event of having a blood count prior to CRC diagnosis was examined using Bayesian parametric survival model. IDA was found as the only significant predictor of right-sided CRC (OR 10.61, 95% CI 7.02-16.52). Early-stage CRC was associated with both the IDA (OR 1.65, 95% CI 1.18-2.29) and BCSP pathway (OR 2.42, 95% CI 1.75-3.37). At any age, the risk of detecting CRC at late-stage was higher in those without a previous blood count check (hazard ratio 1.53, 95% credibility interval 1.08-2.14). The findings of this retrospective observational study suggest a benefit from diagnosing CRC through the detection of IDA, and warrant further research into the prognosis benefit of systematic approach to blood count monitoring of the at-risk population.

Interspecialty referral of oesophagogastric and pharyngolaryngeal cancers delays diagnosis and reduces patient survival: A matched case-control study.

OBJECTIVES: Pharyngolaryngeal and oesophagogastric cancers present with swallowing symptoms and as such, their clinical evaluation traverses boundaries between different specialties. We studied the incidence and significance of interspecialty cancer referrals (ICRs), that is, pharyngolaryngeal cancers first evaluated by gastroenterology and oesophagogastric cancers first evaluated by otolaryngology. DESIGN: A subset analysis of our Integrated Aerodigestive Partnership's audit dataset, of all ICR patients, and an equal number of controls matched for age, sex and cancer subsite. MAIN OUTCOME MEASURES: Information about patient age and presenting symptoms was recorded. The relationship between symptoms and ICR risk was examined with binary logistic regression. Referral-to-diagnosis latency was compared between ICR and control patients with unpaired Student's t test. Cox regression was used to identify independent predictors of overall survival. RESULTS: Of 1130 patients with pharyngolaryngeal and oesophagogastric cancers between 2008 and 2018, 60 diagnoses (5.3%) were preceded by an ICR. Referral-to-diagnosis latency increased from 43 ± 50 days for control patients to 115 ± 140 days for ICR patients (P < .0001). Dysphagia significantly increased the risk of an ICR (odds ratio 3.34; 95% CI 1.30-8.56), and presence of classic gastroesophageal reflux symptoms (heartburn or regurgitation; OR 0.25; 95% CI 0.08-0.83) and "distal" symptoms (nausea/vomiting, abdominal pain or dyspepsia; OR 0.23; 95% CI 0.08-068) significantly reduced the risk. Eleven pharyngolaryngeal cancers (of 26; 42%) were missed by gastroenterology, and eight (of 34; 24%) oesophageal cancers were missed by otolaryngology. An ICR was an independent adverse prognostic risk factor on multivariable analysis (hazard ratio 1.76; 95% CI 1.11-2.73; P < .02; log-rank test). Two systemic root causes were poor visualisation of pharynx and larynx by per-oral oesophago-gastro-duodenoscopy (OGD) for pharyngolaryngeal cancers, and poor sensitivity (62.5%) of barium swallow when it was used to 'evaluate' oesophageal mucosa. CONCLUSIONS: An interspecialty cancer referral occurs in a significant proportion of patients with foregut cancers. It almost triples the time to cancer diagnosis and is associated with a high incidence of missed cancers and diminished patient survival. It is a complex phenomenon, and its reduction requires an integrated approach between primary and secondary care, and within secondary care, to optimise referral pathways and ensure appropriate and expeditious specialist evaluation.

Infected abdominal aortic aneurysm graft complicated by lumbar discitis.

We present the case of a 68-year-old male, who underwent open abdominal aortic graft in August 2016 owing to a ruptured large infrarenal abdominal aneurysm. He subsequently presented 6 months later with back pain, general weakness, reduced mobility and cachexia. He underwent CT, MRI and fluorodeoxyglucose (PDG)-PET spinal imaging, all modalities showing signs of aortic graft infection complicated by L4/5 discitis. The patient was treated conservatively with intravenous antibiotics and spinal brace support, as his general condition did not allow for surgery. Although he showed initial clinical improvement allowing plans for supported discharge, his improvement was not sustained and he died 4 months after admission.

The development of a nurse-led iron deficiency anaemia service in a district general hospital.

OBJECTIVE: To improve the quality of care provided to patients with iron deficiency anaemia (IDA). DESIGN: Service development. SETTING: District General Hospital. PATIENTS: Adults with IDA. MAIN OUTCOME MEASURES: Descriptive report of the practicalities and benefits of establishing an IDA clinic. CONCLUSIONS: The IDA clinic is a novel service development which enhances the management of patients with this common condition, by facilitating prompt confirmation of the diagnosis, replacement therapy and investigation for serious underlying pathology, in particular gastrointestinal malignancy.

Becoming an effective learner.

The teaching of medicine and the expectations of trainees has changed enormously over the past two decades in parallel to changes in medical technology, advances in information technology and the provision of healthcare. With a shortened time in medical training efficient learning is ever more crucial and the skills with which to optimise and enhance our learning opportunities are discussed.

Image analysis of epicuticular damage to foliage caused by dry deposition of the air pollutant nitric acid.

Nitric acid vapor is produced by the same photochemical processes that produce ozone. In the laboratory, concentrated nitric acid is a strong acid and a powerful oxidant. In the environment, where the concentrations are much lower, it is an innocuous source of plant nitrogen. As an air pollutant, which mode of action does dry deposition of nitric acid follow? We investigated the effects of dry deposition of nitric acid on the foliage of four tree species native to the western United States. A novel controlled environment, fumigation system enabled a four-week exposure at concentrations consistent with ambient diurnal patterns. Scanning electron microscopy and automated image analysis revealed changes in the epicuticular wax layer during fumigation. Exposure to nitric acid resulted in a reproducible suite of damage symptoms that increased with increasing dose. Each tree species tested exhibited a unique set of damage features, including cracks, lesions, and conformation changes to epicuticular crystallite structures. Dry deposition of atmospheric nitric acid caused substantial perturbation to the epicuticular surface of all four tree species investigated, consistent with the chemical oxidation of epicuticular waxes. Automated image analysis eliminated many biases that can trouble microscopy studies. Trade names and commercial enterprises or products are mentioned solely for information. No endorsements by the U.S. Department of Agriculture are implied.

Factors associated with the development of post-infectious functional gastrointestinal diseases: does smoking play a role?

OBJECTIVES: Irritable bowel syndrome (IBS) is associated with psychological stress, alterations in gut motor function and/or visceral perception. Previous studies suggest 7-32% of people develop IBS after bacterial gastroenteritis but the exact mechanisms underlying post-infectious IBS are not clear. The present study's aim was to examine the role of possible causative factors in the development of post-infectious functional gastro-intestinal disorders (FGIDs), including IBS. METHODS: A prospective cohort study where 122 people without a prior FGID under study and with stool-positive bacterial gastroenteritis consented to participate. The presence or not of IBS, functional dyspepsia or functional diarrhoea was diagnosed at the start and on 6-month follow-up using self-complete Rome II modular questionnaires. Demographic data, smoking, alcohol use, anxiety and depression (using the Hospital Anxiety and Depression Scale), and life events and impact (using the Life Events Survey) were collected at the start of the study. RESULTS: One hundred and seven questionnaires were returned with 25 participants (23.4%) developing a FGID and 16 participants presenting symptoms consistent with IBS (15%). Smoking was significantly associated with the development of a post-infectious FGID (odds ratio = 4.8, 95% confidence interval = 1.5-15.2) on regression analysis. CONCLUSIONS: Post-infectious FGIDs appear to be associated with smoking. Smoking is known to moderate gut immunity in other disorders such as ulcerative colitis and Crohn's disease. This study adds to increasing evidence for an organic basis to post-infectious FGIDs, perhaps moderated via inflammatory pathways.

Illness perceptions in people with acute bacterial gastro-enteritis.

Functional gastro-intestinal disorders (FGID) like irritable bowel syndrome (IBS) are common and can develop after gastro-enteritis. Illness representations may be important influences on the development of post-infectious FGIDs. Here, we studied both the relationship between prior chronic symptoms (FGIDs) and illness perception during an acute illness (bacterial gastro-enteritis) as well as the relationship between illness perception during an acute illness (bacterial gastro-enteritis) and the subsequent development of chronic abdominal symptoms. Two hundred and seventeen people with recent gastro-enteritis completed a questionnaire asking about gut symptoms consistent with a diagnosis of IBS, functional dyspepsia or functional diarrhoea and the Illness Perception Questionnaire. Those without a prior FGID were followed up and completed a similar gut questionnaire at six months. People with a prior FGID had significantly more symptoms and scored significantly higher on the timeline and consequence scores than those without. People who developed a FGID had a non-significantly higher number of symptoms and higher consequence and timeline scores than those who did not. Neither comparative group differed in the control/cure scores or causation scores. The implications of the findings are discussed.

Does bacterial gastroenteritis predispose people to functional gastrointestinal disorders? A prospective, community-based, case-control study.

OBJECTIVES: Irritable bowel syndrome (IBS) might develop after gastroenteritis. Most previous studies of this relationship have been uncontrolled, and little is known regarding other functional gastrointestinal disorders (FGIDs) after gastroenteritis. The primary aim of this study was to determine the frequency of IBS, functional dyspepsia, or functional diarrhea 6 months after bacterial gastroenteritis. METHODS: This was a prospective, community-based, case-control study. Cases had proven bacterial gastroenteritis, and controls were community-based. FGIDs were diagnosed with the use of self-completed Rome II modular questionnaires administered at baseline, 3, and 6 months. Subjects with prior FGIDs were excluded. The primary endpoint was the presence of one of the three specific FGIDs at 6 months. RESULTS: A total of 500 cases and 705 controls were identified. Of the 500 cases, 265 (53%) consented, but only 128 cases and 219 community controls who consented were eligible. At 6 months, 108 cases and 206 controls returned the questionnaire. FGIDs were diagnosed in significantly more cases (n = 27, 25%) than controls (n = 6, 2.9%) (OR = 11.11, 95% CI = 4.42-27.92). IBS was diagnosed in 18 cases (16.7%) and four controls (1.9%) (OR = 10.1, 95% CI = 3.32-30.69); functional diarrhea in six cases (5.6%) and no controls. Functional dyspepsia was uncommon in both cases and controls. Similar findings were found at 3 months, with 29% of cases and 2.9% of controls having an FGID. CONCLUSIONS: Symptoms consistent with IBS and functional diarrhea occur more frequently in people after bacterial gastroenteritis compared with controls, even after careful exclusion of people with pre-existing FGIDs. The frequency is similar at 3 and 6 months. Our findings support the existence of postinfectious IBS and give an accurate estimate of its frequency.

Cholangiopathy and the biliary cast syndrome.

Biliary casts are uncommon but are more frequently described in liver transplant patients. To our knowledge there have been only two published cases describing biliary casts in non-liver transplant patients. The aetiology of cast development is not fully known but is likely to be multifactorial with the presence of biliary sludge being a prerequisite for cast formation. Bile duct damage and ischaemia, biliary infection, fasting, parenteral nutrition, abdominal surgery and possibly other factors, are all thought to be implicated in cast pathogenesis via sludge development. Endoscopic management has been shown to be effective in a minority of cases and may act as a temporary measure in others but surgical removal of casts is usually necessary. With a greater understanding and improvement in liver transplant surgical techniques and the management of post-operative complications, the development and severity of biliary sludge and casts have decreased.

Is irritable bowel syndrome more common in patients presenting with bacterial gastroenteritis? A community-based, case-control study.

OBJECTIVE: Irritable bowel syndrome (IBS) has been reported to follow infectious diarrhea. Food-borne infections affect 76 million people in the United States and 9.4 million in England per year; of these, only a small percentage of patients see their doctor, and even fewer will have stool culture confirmation. We hypothesized that patients who present to their doctor with gastroenteritis and have positive stool samples may be different from the normal population with regard to their pre-existing bowel symptoms. Our aim was to determine if patients with bacterial gastroenteritis were more likely to have prior IBS, functional dyspepsia, or functional diarrhea, compared with a control population. METHODS: Between January, 2000 and January, 2001, subjects with stool positive bacterial gastroenteritis and control subjects from the same primary care practice were invited to participate. The main outcome measure was the presence of IBS, functional dyspepsia, or functional diarrhea diagnosed using self-report Rome II modular questionnaires. RESULTS: A total of 217 people with recent bacterial gastroenteritis and 265 community controls consented to participate in the study. Of these, 89/217 cases and 46/265 controls had one of the functional GI disorders (OR = 3.3; 95% CI = 2.17-5.00). IBS was present in 67 cases (31%) and 26 controls (10%) (OR = 4.1; 95% CI = 2.49-6.72). There was no statistically significant difference in the presence of prior functional dyspepsia or functional diarrhea. CONCLUSIONS: IBS is more frequent before diagnosis in people with bacterial gastroenteritis presenting to their primary care physician than in community controls. Studies that examine the rate of IBS after bacterial gastroenteritis need to carefully exclude people with prior IBS in a systematic way.

Is lactose intolerance implicated in the development of post-infectious irritable bowel syndrome or functional diarrhoea in previously asymptomatic people?

OBJECTIVE: The relationship between lactose intolerance and post-infectious irritable bowel syndrome (IBS) in adults is uncertain. Bowel symptoms may persist after bacterial gastroenteritis and as post-infectious IBS. Acquired lactose intolerance may follow viral enteric infections in children. We compared the frequency of lactose intolerance after bacterial gastroenteritis in adults with and without symptoms of IBS or functional diarrhoea at 3-6-months' follow-up. DESIGN: A prospective cohort study was conducted. METHODS: All subjects with bacterial gastroenteritis confirmed by stool culture from the microbiology laboratory and without prior IBS or functional diarrhoea were eligible to participate. IBS and functional diarrhoea were diagnosed via self-completed Rome II modular questionnaires. Lactose intolerance was determined from a rise in breath hydrogen and plasma glucose and symptoms. RESULTS: One hundred and twenty-eight subjects with bacterial gastroenteritis were followed prospectively, from which a smaller cohort of 42 subjects took part in this study. The cohort was comprised of 24/25 subjects who developed post-infectious IBS (n = 16) or functional diarrhoea (n = 8) (9 male, 15 female) and 18 random controls (8 male, 10 female) chosen from the group without IBS or functional diarrhoea. The mean age of the subjects was 44.4 years (range 25-76 years). In the group with functional diarrhoea or IBS, four subjects had failure of the plasma glucose to rise but none had abnormal glucose hydrogen breath tests. In the control subjects, one had a positive combined test and six had failure of plasma glucose to rise alone. No subject developed symptoms during the test. CONCLUSIONS: Bacterial gastroenteritis did not cause persistent lactose intolerance in our study population. Lactose intolerance does not appear to be implicated in the aetiology of post-infectious bowel symptoms, including IBS. Advice to avoid dairy products in patients presenting with post-infectious IBS on the basis that they may have lactose intolerance appears unnecessary in patients from northern England.

Push enteroscopy in a UK district general hospital: experience of 51 cases over 2 years.

OBJECTIVES: To determine the number of patients referred for enteroscopy in a district general hospital (DGH), the indication, enteroscopic +/- histological diagnosis, and to compare findings with other series from tertiary referral centres or outside the UK. DESIGN: Retrospective case series over a 2-year period. RESULTS: In the 2-year period, 52 patients were referred for enteroscopy. All except one underwent enteroscopy. The mean age of the patients was 60 years (range 31-84 years). The main indications for enteroscopy were obscure gastrointestinal haemorrhage in 31 (61%) patients (19 with acute and 12 with chronic bleeding) and 7 (14%) patients with arteriovenous malformations (AVMs) on initial oesophagogastroduodenoscopy (OGD). Other indications included clinical deterioration in known coeliac disease in four (8%) patients and abnormal small-bowel follow-through in five (10%) patients. More than half (51%) of the enteroscopies were reported as abnormal, but 10 (38%) had pathology in the stomach or first part of the duodenum (D1) not diagnosed on initial OGD. Diagnoses of two T-cell lymphomas and one of pre-lymphomatous monoclonal T-cell proliferation were made in the refractory coeliac disease group. CONCLUSIONS: Indications (obscure gastrointestinal bleeding), most frequent findings (small-bowel AVMs), and 'missed' lesions within reach of a gastroscope (20%) were in keeping with other series. Enteroscopy is a useful tool in investigating patients with refractory coeliac disease. Its value in investigating patients with abnormal small-bowel radiology was not confirmed. The current need for push enteroscopy in a DGH is small (approximately 1 per 8000 population per year), but it would take only small changes in referral practice to escalate. Criteria for enteroscopy should be developed and refined with improving knowledge of the diagnostic yield for each indication and clinical outcome.