Trends in pathology diagnoses during 10 years of a colorectal cancer screening programme.

AIMS: We report pathology findings from the first 10 years of the faecal-occult blood-based Northern Ireland Bowel Cancer Screening Programme, presenting summary data and trends in pathology diagnoses and clinicopathological features of screen-detected cancers. METHODS AND RESULTS: Data were analysed from a comprehensive polyp-level pathology database representing all endoscopy specimens from programme inception in 2010 until 2021. A total of 9800 individuals underwent 13 472 endoscopy procedures, yielding 25 967 pathology specimens and 32 119 diagnoses. Index specimen diagnoses (4.1%) and index colonoscopies (10.4%) yielded a diagnosis of colorectal cancer, representing 1045 cancers from 1020 individuals (25 with synchronous cancers). A further 13 index cancers were identified via computed tomography colonography; 65.3% of cancer diagnoses were in males; 41.7% were stage I, 23.1% stage II, 25.8% stage III and 1.8% stage IV (7.6% unstaged). Of 233 pT1 cancers diagnosed within local excision specimens, 79 (33.9%) had completion surgery. Ten-year trends showed a steady decline in the proportion of index colonoscopies that yielded a diagnosis of cancer (14.7% in year 1; 4.8% in year 11) or advanced colorectal polyp. There was a strong upward trend in diagnoses of sessile serrated lesions, which overtook hyperplastic polyps in proportions of total index diagnoses by the end of the study time-frame (8.7% compared to 8.5%). CONCLUSIONS: Over the first 10 years of a population colorectal cancer screening programme, 'real world' pathology data demonstrate success in the form of reduced diagnoses of cancer and advanced colorectal polyp with passage of successive screening rounds. Interesting trends with respect to serrated polyp diagnoses are also evident, probably related to pathologist and endoscopist behaviour.

Preventing Postoperative Opioid-Induced Respiratory Depression Through Implementation of an Enhanced Monitoring Program.

BACKGROUND: Opioid-induced respiratory depression (OIRD) is a serious complication that can lead to negative outcomes. There are known risk factors for OIRD; however, a lack of national guidelines for the prevention and early detection of OIRD exists. METHODS: An evidence-based practice study was conducted to create an enhanced monitoring (EM) program. The EM program consisted of risk stratification of surgical spine patients, including the use of STOP-BANG screening for obstructive sleep apnea, capnography monitoring, use of home positive airway pressure therapy, capnography alarm optimization, hospitalist consultation, nursing education, and patient education. RESULTS: Approximately 17% (N = 937/5,462) of surgical spine patients were enrolled in the EM program. Fifty-six percent of EM patients were monitored with capnography and had out of range end-tidal carbon dioxide levels 17% of the time. The rate of transfers to the intensive care unit (ICU) for OIRD decreased, though not statistically significant (p = .151). CONCLUSIONS: The EM program with risk stratification was found to reduce transfers to the ICU for OIRD. Although not statistically significant, the decreased number of transfers was clinically significant. Engagement of the interprofessional team and capnography alarm parameter optimization helped to reduce nonactionable alarms.

A comparison of endoscopy versus pathology sizing of colorectal adenomas and potential implications for surveillance colonoscopy.

BACKGROUND AND AIMS: The aim of this study was to compare endoscopy and pathology sizing in a large population-based series of colorectal adenomas and to evaluate the implications for patient stratification into surveillance colonoscopy. METHODS: Endoscopy and pathology sizes available from intact adenomas removed at colonoscopies performed as part of the Northern Ireland Bowel Cancer Screening Programme, from 2010 to 2015, were included in this study. Chi-squared tests were applied to compare size categories in relation to clinicopathologic parameters and colonoscopy surveillance strata according to current American Gastroenterology Association and British Society of Gastroenterology guidelines. RESULTS: A total of 2521 adenomas from 1467 individuals were included. There was a trend toward larger endoscopy than pathology sizing in 4 of the 5 study centers, but overall sizing concordance was good. Significantly greater clustering with sizing to the nearest 5 mm was evident in endoscopy versus pathology sizing (30% vs 19%, P < .001), which may result in lower accuracy. Applying a 10-mm cut-off relevant to guidelines on risk stratification, 7.3% of all adenomas and 28.3% of those 8 to 12 mm in size had discordant endoscopy and pathology size categorization. Depending on which guidelines are applied, 4.8% to 9.1% of individuals had differing risk stratification for surveillance recommendations, with the use of pathology sizing resulting in marginally fewer recommended surveillance colonoscopies. CONCLUSIONS: Choice of pathology or endoscopy approaches to determine adenoma size will potentially influence surveillance colonoscopy follow-up in 4.8% to 9.1% of individuals. Pathology sizing appears more accurate than endoscopy sizing, and preferential use of pathology size would result in a small, but clinically important, decreased burden on surveillance colonoscopy demand. Careful endoscopy sizing is required for adenomas removed piecemeal.

B-vitamin status in relation to bone mineral density in treated celiac disease patients.

OBJECTIVES: Patients with celiac disease (CD) are at increased risk of osteoporosis and compromised B-vitamin status. Emerging evidence supports a beneficial role of folate and the metabolically related B-vitamins in bone health in generally healthy adults, but no previous study has investigated this in CD patients. The aim of the current study was to examine the relationship of folate, vitamins B12, B6 and B2 (riboflavin), and the related metabolite homocysteine, with bone mineral density (BMD) in CD patients. MATERIALS AND METHODS: Of the 400 treated adult CD patients invited to participate, 110 responded and met the eligibility criteria for study participation. BMD was measured using dual energy X-ray absorptiometry scanning at the lumbar spine (L1-L4), femoral neck, and total hip sites. Biomarker status of the relevant B-vitamins and homocysteine, and dietary B-vitamin intakes, were measured. RESULTS: The significant predictors of low BMD were increasing age (B = 0.080, p < 0.001) and decreasing weight (B = 0.072, p = 0.004), whereas no significant relationship with serum 25-hydroxyvitamin D (B = 0.093, p = 0.928) was observed. Following adjustment for these predictors, serum vitamin B12 (but no other B-vitamin biomarker) was found to be a significant determinant of BMD at the femoral neck (ß = 0.416, p = 0.011) and total hip (ß = 0.327, p = 0.049) in men only. No significant relationships were found between any of the B-vitamin biomarkers investigated and BMD (at any measured site) in women. CONCLUSION: These findings add to current evidence suggesting a potential role of vitamin B12 in BMD, particularly in men, and show such a relationship for the first time in CD patients.

Joint BAPEN and British Society of Gastroenterology Symposium on 'Coeliac disease: basics and controversies'. Coeliac disease in the twenty-first century.

Coeliac disease (CD), traditionally perceived as a rare childhood condition presenting with malabsorption, is instead an autoimmune multisystem disorder usually presenting in adulthood, affecting > or = 1% of the population and linked to the genetic expression of human leucocyte antigens (HLA) DQ2 and DQ8. Presentation occurs most often in the 40-60 years age-group, but potentially at any age. Symptoms attributable to the gut or to malabsorption may be mild, non-specific or absent; under one-third of patients have diarrhoea and almost half are overweight. Histological diagnosis no longer requires small intestine villous atrophy. The Marsh classification recognizes increased intraepithelial lymphocytes and crypt hyperplasia with intact villi as part of the gluten enteropathy spectrum, while some individuals have more subtle abnormalities identified only on electron microscopy. Serological testing for CD autoantibodies (to endomysium and tissue transglutaminase) has revolutionized diagnosis, shifting the process towards primary care. However, a substantial number of patients with CD are seronegative, particularly those without villous atrophy. The autoantibody to endomysium may be produced before histological change. The immune response to transglutaminase is crucial to the disease process. An exciting new development is the link between antibodies to organ-specific transglutaminases and clinical presentation; transglutaminases 2 (gut), 3 (skin) and 6 (nervous system). Negative testing for CD does not preclude its development later and HLA testing may allow 'once and for all' exclusion. In conclusion, an increasing proportion of patients with CD do not meet the 'classic' picture of malabsorption, positive serological testing and villous atrophy. Insisting on all these criteria for diagnosis will result in under diagnosis.

Diagnostic immunology in celiac disease.

Serum autoantibodies to transglutaminase and endomysium are found in the majority of patients with celiac disease, an autoimmune multisystem disorder affecting approximately 1% of Western and Middle-Eastern populations. Detection of these antibodies plays a crucial role in the diagnosis of celiac disease. The aim of this review is to summarize recent publications in this field, with particular focus on the applications and limitations of celiac autoantibody testing in routine clinical practice.

Homocysteine and related B-vitamin status in coeliac disease: Effects of gluten exclusion and histological recovery.

OBJECTIVE: Hyperhomocysteinaemia is considered to be a risk factor for cardiovascular disease (particularly stroke) and has been implicated in recurrent miscarriage and osteoporotic fracture, recognized manifestations of coeliac disease (CD). The objective of this study was to compare plasma homocysteine levels and biomarker status of metabolically related B vitamins (folate, vitamin B(12), B(6) and riboflavin) in treated and untreated CD patients and healthy controls. MATERIAL AND METHODS: CD patients attending a clinic for either initial or follow-up biopsy (at least 12 months after commencing a gluten-free diet) were categorized into three groups: 1) newly diagnosed (untreated; n=35); 2) persistent villous atrophy (VA) at follow-up (n=24) or 3) recovered VA at follow-up (n=41). Blood samples were analysed for plasma homocysteine, serum and red cell folate and serum vitamin B(12) levels, and for plasma pyridoxal 5-phosphate (PLP, vitamin B(6)) and riboflavin (vitamin B(2)) status. RESULTS: Homocysteine concentrations were significantly higher (p=0.05) and red cell and serum folate significantly lower (p<0.001) in untreated patients compared with controls, while all three reached normal levels in recovered VA patients. Although untreated and persistent VA patients tended to have lower B(12) levels, these did not reach significance. There was no evidence of compromised B(6) or riboflavin status, even in untreated CD patients. Homocysteine concentrations were inversely associated with both serum (r=-0.421; p<0.001) and red cell (r=-0.459; p<0.001) folate and with serum vitamin B(12) (r=-0.353; p=0.001). CONCLUSIONS: Gluten exclusion in CD improves folate status and normalizes homocysteine concentrations. Reducing the risk of homocysteine-related disease may be another reason for aggressive diagnosis and treatment of CD.

Making oats safer for patients with coeliac disease.

(Table is included in full-text article). Studies suggest that oats can be tolerated in the gluten-free diet by a majority of patients with coeliac disease. Concerns remain, however, about the possibility of contamination of commercially available oat products by wheat, barley and rye. The R5 ELISA allows the identification and quantification of wheat, barley and rye prolamins, and has demonstrated significant contamination in a range of products. If patients with coeliac disease are to take oats, it is important that those consumed are free of contamination. This assay should allow the identification of safe oat products.

West Nile viremic blood donors and risk factors for subsequent West Nile fever.

BACKGROUND: While increasing age is a known risk factor for neuroinvasive West Nile virus (WNV) disease, little is known about risk factors for West Nile fever (WNF). In 2003, United States blood centers identified WN (West Nile) viremic donors using nucleic acid-amplification tests (NATs), making it possible to prospectively determine risk factors for WNF. We report the characteristics of WN viremia among donors at Colorado's largest blood center and risk factors for WNF in viremic donors. METHODS: Prospective public health surveillance was conducted in WN viremic donors. NAT-reactive donors who developed WNV-specific IgM antibody were considered viremic donors. Demographic data were abstracted from blood center records for all viremic donors aged>or=18 years. Standardized telephone questionnaires were administered a median of 39 days following donation. Donors reporting fever and headache within seven days following donation were considered West Nile fever (WNF) cases. RESULTS: Of 66,771 donations screened from July 1-October 31, 146 (0.22%) were from viremic donors (1:457 donations). Of 135 surveyed donors, 81 (60%) were male. The median age was 49 years (range: 18-78). Forty-one (30%) donors developed WNF; of these, 12 (29%) visited a physician. Other reported symptoms included body aches (98%), eye pain (63%), and skin rash (61%). The risk of WNF was inversely correlated with age (odds ratio: 0.95 for every 1-year increase in age; 95% CI 0.91, 0.99; p=0.008). CONCLUSIONS: WN viremia was frequently identified in Colorado blood donors during the 2003 WNV epidemic. The high frequency of WNF and subsequent physician visits among healthy blood donors suggest substantial morbidity from WNF in the general population. The inverse correlation between age and WNF is a new finding and its pathophysiology is unknown.

A case of sequential development of celiac disease and ulcerative colitis.

BACKGROUND: A 65-year-old white female who presented with flatulence and weight loss was investigated by celiac antibody testing, esophagogastroduodenoscopy, duodenal biopsy and colonoscopy. There were no positive findings, except for diverticulosis. Almost 5 years later repeat investigations performed in response to the patient's anemia confirmed the development of celiac disease. After 18 months of symptom improvement as a result of gluten exclusion the patient developed diarrhea, and colonoscopy revealed ulcerative colitis. INVESTIGATIONS: Physical examination; analysis of full blood count; measurement of serum ferritin, vitamin B(12), folate and C-reactive protein levels; thyroid and autoantibody profiling (including analysis of endomysial and tissue transglutaminase antibodies); CT scanning of the chest, abdomen and pelvis; and performance of esophagogastroduodenoscopy, push enteroscopy, colonoscopy and wireless capsule endoscopy. DIAGNOSIS: Celiac disease and ulcerative colitis. MANAGEMENT: Gluten-free diet, mesalazine and prednisolone.

Overweight in celiac disease: prevalence, clinical characteristics, and effect of a gluten-free diet.

BACKGROUND: It is well established that a minority of celiac patients present with "classic" symptoms due to malabsorption. However, few studies have focussed on the distribution of body mass index (BMI) in celiac populations and its relationship to clinical characteristics, or on its response to treatment. METHODS: We reviewed BMI measurements and other clinical and pathological characteristics from a database of 371 celiac patients diagnosed over a 10-yr period and seen by a single gastroenterologist. To assess response to gluten exclusion, we compared BMI at diagnosis and after 2 yr treatment in patients with serological support for dietary compliance. RESULTS: Mean BMI was 24.6 kg/m2 (range 16.3-43.5). Seventeen patients (5%) were underweight (BMI < 18.5), 211 (57%) were normal, and 143 (39%) were overweight (BMI > or = 25), including 48 (13% of all patients) in the obese range (BMI > or = 30.0). There was a significant association between low BMI and female gender, history of diarrhea, reduced hemoglobin concentration, reduced bone mineral density (BMD), osteoporosis, and higher grades (subtotal/total) of villous atrophy. Of patients compliant with a gluten-free diet, 81% had gained weight after 2 yr, including 82% of initially overweight patients. CONCLUSIONS: Few celiac patients are underweight at diagnosis and a large minority is overweight; these are less likely to present with classical features of diarrhea and reduced hemoglobin. Failed or delayed diagnosis of celiac disease may reflect lack of awareness of this large subgroup. The increase in weight of already overweight patients after dietary gluten exclusion is a potential cause of morbidity, and the gluten-free diet as conventionally prescribed needs to be modified accordingly.

Endoscopic markers for celiac disease.

Celiac disease is common and can present with nonspecific upper gastrointestinal symptoms. Patients may therefore undergo esophagogastroduodenoscopy as their initial investigation. Markers of villous atrophy, which can be seen in the duodenum during endoscopy, are well described. They have limited sensitivity for patients with mild enteropathy and duodenal biopsies should be performed if there is strong suspicion of celiac disease irrespective of endoscopic appearance. Endoscopic markers do, however, allow the selection of patients with nonspecific symptoms for duodenal biopsy, and these markers should, therefore, be looked for routinely during esophagogastroduodenoscopy.

Evaluation of a new blood glucose monitoring system with auto-calibration for home and hospital bedside use.

A new self-calibrating blood glucose monitoring system (BGMS) was evaluated in a series of clinical studies with both ambulatory subjects and with hospitalized patients. The new BGMS requires a 0.6microL sample volume, provides results in 15s, and uses a glucose dehydrogenase chemistry that is oxygen independent. In the first study, Ascensia Contour meters calibrated to whole blood were tested by health care professionals (HCP) and lay users at two clinical sites. Both HCPs and lay users obtained results that fulfilled the ISO 15197:2003 criteria that 95% of self-monitoring blood glucose (SMBG) measurements should fall within +/-20% (for blood glucose (BG) concentrations> or =4.2mmol/L or +/-0.83mmol/L for BG concentrations<4.2mmol/L) of the laboratory value. Lay users and HCPs obtained 97.2 and 96.7% of glucose results within ISO criteria, respectively. In a second study, HCPs assayed blood samples from patients at the hospital bedside using meters calibrated to give whole blood glucose and meters calibrated to give plasma glucose results. Overall, 94.7% of the measurements met the ISO 15197:2003 criteria. Most lay subjects rated the BGMS as either excellent or very good in a questionnaire, and were able to use it properly without training. These findings indicate that this new BGMS is a convenient and accurate instrument system suitable for both hospital bedside use by HCPs and for SMBG by people who routinely monitor their blood glucose.

Parallel cannulation technique at ERCP rendezvous.

BACKGROUND: Biliary access at ERCP rendezvous is usually achieved by withdrawing a wire passed antegrade via the accessory channel of the duodenoscope, which is then used for over-the-wire cannulation. The wire is time consuming to maneuver and may be damaged during withdrawal. OBJECTIVE: Description of a simple technique for cannulation at rendezvous that overcomes these problems. DESIGN: Observational study. SETTING: Gastroenterology department of a teaching district general hospital. PATIENTS: Fourteen consecutive patients undergoing rendezvous after percutaneous transhepatic cholangiography (PTC). INTERVENTION: A transpapillary drain was placed at PTC in 13 patients. At rendezvous, cannulation alongside the drain was attempted with a sphincterotome cannula. After successful cannulation, the drain was progressively withdrawn, allowing retrograde therapeutic intervention. RESULTS: In all 13 patients, parallel cannulation was successful, allowing stone removal or biliary stent placement, with cannulation alongside a guidewire in the fourteenth patient. There were no complications except right hypochondrial pain after drain removal. CONCLUSIONS: Parallel cannulation is straightforward and effective, avoiding the need for guidewire manipulation.

Surveillance for Barrett's oesophagus: results from a programme in Northern Ireland.

BACKGROUND: The reported incidence of adenocarcinoma in patients with Barrett's oesophagus in surveillance programmes varies widely. Great Britain has one of the highest incidence rates of this cancer in the world, but there are no data from Ireland reporting its incidence in patients with Barrett's oesophagus undergoing surveillance. We carried out a study of all such patients at a large District General Hospital in Northern Ireland. METHODS: A retrospective review of all patients with Barrett's oesophagus from January 1986 to March 2004 at Altnagelvin Area Hospital, Derry, Northern Ireland was performed. Barrett's oesophagus was defined as specialized intestinal metaplasia present in the tubular oesophagus. RESULTS: A total of 277 patients had Barrett's oesophagus. Twenty-one patients had adenocarcinoma and two patients had high-grade dysplasia at initial endoscopy and were excluded. Of the remaining 254 patients, 178 were entered into the surveillance programme (127 men, 51 women). The average follow-up period was 3.4 years, resulting in 613 patient-years of follow-up. Three patients developed adenocarcinoma, an incidence of 1/204 patient-years of follow-up. Two of the three patients had early-stage (T1 or T2) cancers detected and are alive and well. A total of 429 surveillance endoscopies were performed, and a marked year-on-year increase in the workload generated as a result of the surveillance programme was observed. CONCLUSIONS: The incidence of adenocarcinoma in patients in Northern Ireland was similar to the incidence reported by other large institutions. Clinical benefit is suggested but is not certain from these data, because of biases that affect surveillance programmes. Large multicentre studies are required to determine whether surveillance is beneficial.