'Missed' oesophageal adenocarcinoma and high-grade dysplasia in Barrett's oesophagus patients: A large population-based study.

BACKGROUND: A systematic review suggests that 25% of oesophageal adenocarcinomas (OAC) are 'missed' at index endoscopy for Barrett's oesophagus (BO); however, this included few population-based studies and may be an overestimate. OBJECTIVE: The objective of this article is to quantify the 'missed' rates of high-grade dysplasia (HGD) and OAC at index BO endoscopy. METHODS: Patients from the Northern Ireland BO register diagnosed between 1993 and 2010 (n = 13,159) were linked to the Northern Ireland Cancer Registry to identify patients who developed OAC or HGD. Logistic regression analysis compared characteristics of 'missed' vs 'incident' HGD/OAC, defined as diagnoses within 3-12 months vs >1 year after incident BO, respectively. RESULTS: A total of 267 patients were diagnosed with HGD/OAC ≥3 months after BO diagnosis, of whom 34 (12.7%) were potentially 'missed'. The proportion of 'missed' HGD/OAC was 25% among BO patients with low-grade dysplasia (LGD) and 9% among non-dysplastic BO patients. Older age and BO-LGD carried a higher risk of 'missed' HGD/OAC. Non-dysplastic BO patients were more often diagnosed with a 'missed' OAC (rather than HGD; 89%), compared with BO-LGD patients (40%). CONCLUSIONS: Approximately one in 10 HGD/OAC cases are 'missed' at incident BO diagnosis, which is significant but lower than previous reports. However, 'missed' HGD/OAC cases represent only 0.26% of all BO patients.

Colorectal Cancer Risk Following Adenoma Removal: A Large Prospective Population-Based Cohort Study.

BACKGROUND: Randomized controlled trials have demonstrated significant reductions in colorectal cancer incidence and mortality associated with polypectomy. However, little is known about whether polypectomy is effective at reducing colorectal cancer risk in routine clinical practice. The aim of this investigation was to quantify colorectal cancer risk following polypectomy in a large prospective population-based cohort study. METHODS: Patients with incident colorectal polyps between 2000 and 2005 in Northern Ireland were identified via electronic pathology reports received to the Northern Ireland Cancer Registry. Patients were matched to the Northern Ireland Cancer Registry to detect colorectal cancer and deaths up to December 31, 2010. Colorectal cancer standardized incidence ratios (SIR) were calculated and Cox proportional hazards modeling applied to determine colorectal cancer risk. RESULTS: During 44,724 person-years of follow-up, 193 colorectal cancer cases were diagnosed among 6,972 adenoma patients, representing an annual progression rate of 0.43%. Colorectal cancer risk was significantly elevated in patients who had an adenoma removed (SIR, 2.85; 95% CI, 2.61-3.25) compared with the general population. Male sex, older age, rectal site, and villous architecture were associated with an increased colorectal cancer risk in adenoma patients. Further analysis suggested that not having a full colonoscopy performed at, or following, incident polypectomy contributed to the excess colorectal cancer risk. CONCLUSIONS: Colorectal cancer risk was elevated in individuals following polypectomy for adenoma, outside of screening programs. IMPACT: This finding emphasizes the need for full colonoscopy and adenoma clearance, and appropriate surveillance, after endoscopic diagnosis of adenoma.

Oesophageal adenocarcinoma and prior diagnosis of Barrett's oesophagus: a population-based study.

OBJECTIVE: Endoscopic surveillance of Barrett's oesophagus (BO) provides an opportunity to detect early stage oesophageal adenocarcinoma (OAC). We sought to determine the proportion of OAC patients with a prior diagnosis of BO on a population basis and to evaluate the influence of a prior diagnosis of BO on survival, taking into account lead and length time biases. DESIGN: A retrospective population-based study of all OAC patients in Northern Ireland between 2003 and 2008. A prior BO diagnosis was determined by linkage to the Northern Ireland BO register. Stage distribution at diagnosis and histological grade were compared between patients with and without a prior BO diagnosis. Overall survival, using Cox models, was compared between patients with and without a prior BO diagnosis. The effect of adjusting the survival differences for histological grade and estimates of lead and length time bias was assessed. RESULTS: There were 716 OAC cases, 52 (7.3%) of whom had a prior BO diagnosis. Patients with a prior BO diagnosis had significantly lower tumour stage (44.2% vs. 11.1% had stage 1 or 2 disease; p<0.001), a higher rate of surgical resection (50.0% vs. 25.5%; p<0.001) and had a higher proportion of low/intermediate grade tumours (46.2% vs. 26.5%; p=0.011). A prior BO diagnosis was associated with significantly better survival (HR for death 0.39; 95% CI 0.27 to 0.58), which was minimally influenced by adjustment for age, sex and tumour grade (adjusted HR 0.44; 95% CI 0.30 to 0.64). Correction for lead time bias attenuated but did not abolish the survival benefit (HR 0.65; 95% CI 0.45 to 0.95) and further adjustment for length time bias had little effect. CONCLUSIONS: The proportion of OAC patients with a prior diagnosis of BO is low; however, prior identification of BO is associated with an improvement in survival in OAC patients.

Symptoms and endoscopic features at barrett's esophagus diagnosis: implications for neoplastic progression risk.

OBJECTIVES: Risk stratification of Barrett's esophagus (BE) patients based on clinical and endoscopic features may help to optimize surveillance practice for esophageal adenocarcinoma (EAC) development. The aim of this study was to investigate patient symptoms and endoscopic features at index endoscopy and risk of neoplastic progression in a large population-based cohort of BE patients. METHODS: A retrospective review of hospital records relating to incident BE diagnosis was conducted in a subset of patients with specialized intestinal metaplasia from the Northern Ireland BE register. Patients were matched to the Northern Ireland Cancer Registry to identify progressors to EAC or esophageal high-grade dysplasia (HGD). Cox proportional hazards models were applied to evaluate the association between endoscopic features, symptoms, and neoplastic progression risk. RESULTS: During 27,997 person-years of follow-up, 128 of 3,148 BE patients progressed to develop HGD/EAC. Ulceration within the Barrett's segment, but not elsewhere in the esophagus, was associated with an increased risk of progression (hazard ratio (HR) 1.72; 95% confidence interval (CI): 1.08-2.76). Long-segment BE carried a significant sevenfold increased risk of progression compared with short-segment BE; none of the latter group developed EAC during the study period. Conversely, the absence of reflux symptoms was associated with an increased risk of cancer progression (HR 1.61; 95% CI: 1.05-2.46). CONCLUSIONS: BE patients presenting with a long-segment BE or Barrett's ulcer have an increased risk of progressing to HGD/EAC and should be considered for more intense surveillance. The absence of reflux symptoms at BE diagnosis is not associated with a reduced risk of malignant progression, and may carry an increased risk of progression.

Dietary fiber and the risk of precancerous lesions and cancer of the esophagus: a systematic review and meta-analysis.

Dietary fiber has several anticarcinogenic effects and is thought to be protective against esophageal cancer. The aim of this systematic review was to quantify the association between dietary fiber and the risk of esophageal cancer by investigating histological subtypes of esophageal cancer and the stage at which fiber may influence the carcinogenic pathway. Systematic search strategies were used to identify relevant studies, and adjusted odds ratios (ORs) were combined using random-effects meta-analyses to assess the risk of cancer when comparing extreme categories of fiber intake. Ten relevant case-control studies were identified within the timeframe searched. Pooled estimates from eight studies of esophageal adenocarcinoma revealed a significant inverse association with the highest fiber intakes (OR 0.66; 95% confidence interval [CI] 0.44-0.98). Two studies also identified protective effects of dietary fiber against Barrett's esophagus. Similar, though nonsignificant, associations were observed when results from five studies of fiber intake and risk of squamous cell carcinoma were combined (OR 0.61; 95%CI 0.31-1.20). Dietary fiber is associated with protective effects against esophageal carcinogenesis, most notably esophageal adenocarcinoma. Potential methods of action include modification of gastroesophageal reflux and/or weight control.

Tobacco smoking increases the risk of high-grade dysplasia and cancer among patients with Barrett's esophagus.

BACKGROUND & AIMS: Esophageal adenocarcinoma arises from Barrett's esophagus (BE); patients with this cancer have a poor prognosis. Identification of modifiable lifestyle factors that affect the risk of progression from BE to esophageal adenocarcinoma might prevent its development. We investigated associations among body size, smoking, and alcohol use with progression of BE to neoplasia. METHODS: We analyzed data from patients with BE identified from the population-based Northern Ireland BE register, diagnosed between 1993 and 2005 with specialized intestinal metaplasia (n = 3167). Data on clinical, demographic, and lifestyle factors related to diagnosis of BE were collected from hospital case notes. We used the Northern Ireland Cancer Registry to identify which of these patients later developed esophageal adenocarcinoma, adenocarcinomas of the gastric cardia, or esophageal high-grade dysplasia. Cox proportional hazards models were used to associate lifestyle factors with risk of progression. RESULTS: By December 31, 2008, 117 of the patients with BE developed esophageal high-grade dysplasia or adenocarcinomas of the esophagus or gastric cardia. Current tobacco smoking was significantly associated with an increased risk of progression (hazard ratio = 2.03; 95% confidence interval, 1.29-3.17) compared with never smoking, and across all strata of smoking intensity. Alcohol consumption was not related to risk of progression. Measures of body size were infrequently reported in endoscopy reports, and body size was not associated with risk of progression. CONCLUSIONS: Smoking tobacco increases the risk of progression to cancer or high-grade dysplasia 2-fold among patients with BE, compared with patients with BE that have never smoked. Smoking cessation strategies should be considered for patients with BE.

Risk of malignant progression in Barrett's esophagus patients: results from a large population-based study.

BACKGROUND: Barrett's esophagus (BE) is a premalignant lesion that predisposes to esophageal adenocarcinoma. However, the reported incidence of esophageal adenocarcinoma in patients with BE varies widely. We examined the risk of malignant progression in patients with BE using data from the Northern Ireland Barrett's esophagus Register (NIBR), one of the largest population-based registries of BE worldwide, which includes every adult diagnosed with BE in Northern Ireland between 1993 and 2005. SUBJECTS AND METHODS: We followed 8522 patients with BE, defined as columnar lined epithelium of the esophagus with or without specialized intestinal metaplasia (SIM), until the end of 2008. Patients with incident adenocarcinomas of the esophagus or gastric cardia or with high-grade dysplasia of the esophagus were identified by matching the NIBR with the Northern Ireland Cancer Registry, and deaths were identified by matching with records from the Registrar General's Office. Incidence of cancer outcomes or high-grade dysplasia was calculated as events per 100 person-years (% per year) of follow-up, and Cox proportional hazard models were used to determine incidence by age, sex, length of BE segment, presence of SIM, macroscopic BE, or low-grade dysplasia. All P values were from two-sided tests. RESULTS: After a mean of 7.0 years of follow-up, 79 patients were diagnosed with esophageal cancer, 16 with cancer of the gastric cardia, and 36 with high-grade dysplasia. In the entire cohort, incidence of esophageal or gastric cardia cancer or high-grade dysplasia combined was 0.22% per year (95% confidence interval [CI] = 0.19% to 0.26%). SIM was found in 46.0% of patients. In patients with SIM, the combined incidence was 0.38% per year (95% CI = 0.31 to 0.46%). The risk of cancer was statistically significantly elevated in patients with vs without SIM at index biopsy (0.38% per year vs 0.07% per year; hazard ratio [HR] = 3.54, 95% CI = 2.09 to 6.00, P < .001), in men compared with women (0.28% per year vs 0.13% per year; HR = 2.11, 95% CI = 1.41 to 3.16, P < .001), and in patients with low-grade dysplasia compared with no dysplasia (1.40% per year vs 0.17% per year; HR = 5.67, 95% CI = 3.77 to 8.53, P < .001). CONCLUSION: We found the risk of malignant progression among patients with BE to be lower than previously reported, suggesting that currently recommended surveillance strategies may not be cost-effective.

Increasing incidence of Barrett's oesophagus: a population-based study.

Oesophageal adenocarcinoma, a highly fatal cancer, has risen in incidence in Western societies, but it is unclear whether this is due to increasing incidence of its pre-cursor condition, Barrett's oesophagus (BO) or whether the proportion of BO patients undergoing malignant progression has increased in the face of unchanged BO incidence. Data from population-based studies of BO incidence is limited, with equivocal results to date difficult to distinguish from changes in endoscopic practices. The aim of this study was to assess population trends in Barrett's oesophagus (BO) diagnoses in relation to endoscopy and biopsy rates over a 13 year period. The Northern Ireland Barrett's oesophagus Register (NIBR) is a population-based register of all 9,329 adults diagnosed with columnar epithelium of the oesophagus in Northern Ireland between 1993 and 2005, of whom 58.3% were male. European age-standardised annual BO incidence rates were calculated per 100,000 of the population, per 100 endoscopies and per 100 endoscopies including an oesophageal biopsy. Average annual BO incidence rates rose by 159% during the study period, increasing from 23.9/100,000 during 1993-1997 to 62.0/100,000 during 2002-2005. This elevation far exceeded corresponding increases in rates of endoscopies and oesophageal biopsies being conducted. BO incidence increased most markedly in individuals aged < 60 years, and most notably amongst males aged < 40 years. This study points towards a true increase in the incidence of BO which would appear to be most marked in young males. These findings have significant implications for future rates of oesophageal adenocarcinoma and surveillance programmes.

Anatomical study of the unusual origin of a nerve to the mylohyoid muscle and its clinical relevance.

Anomalous patterns in the human body are usually seen in cadaver dissections and during investigations. We have studied 50 cadavers of southern Indian men and women to find the variable origins of the mylohyoid nerve in the infratemporal region. We discovered an unusual origin of the nerve during a routine educational dissection. Here we describe the course of the aberrant nerve and its distributing branches. Awareness of such anatomical variations could help during surgical or dental interventions.

Are accelerated infliximab infusions safe in patients with inflammatory bowel disease?

BACKGROUND: Infliximab is a monoclonal antibody used in the treatment of inflammatory bowel disease (IBD). The manufacturer-recommended administration is over 2 hours followed by 2 hours of patient observation. The data relating to adverse outcomes in patients receiving accelerated infusions for IBD are limited. METHODS: Our unit utilizes an accelerated protocol for infliximab infusion in selected patients with IBD (those with no adverse reaction in their first four standard infusions). Our aim was to assess if the accelerated infusion protocol (infusion over 1 hour or 30 minutes with 1 hour or no monitoring according to protocol) was associated with any increase in adverse outcomes. Data were collected retrospectively on protocol used and adverse outcomes for all infliximab infusions between October 2005 and June 2008. RESULTS: Out of 69 patients, 27 received the accelerated protocol (130 infusions). All patients received a total of 306 infusions on the standard protocol. No adverse reactions were reported in the accelerated protocol patients. In patients on the standard protocol, 16 adverse reactions were observed: seven were acute (occurring during infusion); nine were delayed (occurring within 1-7 days following infusion). No patient required intramuscular adrenaline or hospitalization. CONCLUSIONS: Our findings suggest that an accelerated protocol for infliximab infusion is well tolerated in selected patients. The monitoring period following infusion may not be necessary, as all acute reactions occurred within an hour of initiating infusion and did not warrant hospitalization. The accelerated infusion may allow more efficient utilization of hospital resources and reduce patient inconvenience.

A ferritin level >50 microg/L is frequently consistent with iron deficiency.

BACKGROUND: The British Society of Gastroenterology (BSG) suggests that a serum ferritin level or=2 and 17 had Index

Spontaneous bacterial peritonitis.

Since its initial description in 1964, research has transformed spontaneous bacterial peritonitis (SBP) from a feared disease (with reported mortality of 90%) to a treatable complication of decompensated cirrhosis, albeit with steady prevalence and a high recurrence rate. Bacterial translocation, the key mechanism in the pathogenesis of SBP, is only possible because of the concurrent failure of defensive mechanisms in cirrhosis. Variants of SBP should be treated. Leucocyte esterase reagent strips have managed to shorten the 'tap-to-shot' time, while future studies should look into their combined use with ascitic fluid pH. Third generation cephalosporins are the antibiotic of choice because they have a number of advantages. Renal dysfunction has been shown to be an independent predictor of mortality in patients with SBP. Albumin is felt to reduce the risk of renal impairment by improving effective intravascular volume, and by helping to bind pro-inflammatory molecules. Following a single episode of SBP, patients should have long-term antibiotic prophylaxis and be considered for liver transplantation.

Nitrofurantoin-induced lung- and hepatotoxicity.

We present the case of a patient referred to the gastroenterology service for investigation of abnormal liver function tests. She had been taking nitrofurantoin for 16 months as prophylaxis against urinary tract infections. CT scan showed evidence of lung pneumonitis and low attenuation in the liver parenchyma. Nitrofurantoin-induced pneumonitis and hepatotoxicity was diagnosed. The patient responded both clinically and biochemically to withdrawal of nitrofurantoin. This combination of adverse reaction to nitrofurantoin is rare.