Incidence, Demographics, and Clinical Characteristics of Diabetes of the Exocrine Pancreas (Type 3c): A Retrospective Cohort Study.

OBJECTIVE: This study was conducted to describe the incidence of diabetes following pancreatic disease, assess how these patients are classified by clinicians, and compare clinical characteristics with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Primary care records in England (n = 2,360,631) were searched for incident cases of adult-onset diabetes between 1 January 2005 and 31 March 2016. We examined demographics, diabetes classification, glycemic control, and insulin use in those with and without pancreatic disease (subcategorized into acute pancreatitis or chronic pancreatic disease) before diabetes diagnosis. Regression analysis was used to control for baseline potential risk factors for poor glycemic control (HbA1c ≥7% [53 mmol/mol]) and insulin requirement. RESULTS: We identified 31,789 new diagnoses of adult-onset diabetes. Diabetes following pancreatic disease (2.59 [95% CI 2.38-2.81] per 100,000 person-years) was more common than type 1 diabetes (1.64 [1.47-1.82]; P < 0.001). The 559 cases of diabetes following pancreatic disease were mostly classified by clinicians as type 2 diabetes (87.8%) and uncommonly as diabetes of the exocrine pancreas (2.7%). Diabetes following pancreatic disease was diagnosed at a median age of 59 years and BMI of 29.2 kg/m2. Diabetes following pancreatic disease was associated with poor glycemic control (adjusted odds ratio, 1.7 [1.3-2.2]; P < 0.001) compared with type 2 diabetes. Insulin use within 5 years was 4.1% (3.8-4.4) with type 2 diabetes, 20.9% (14.6-28.9) with diabetes following acute pancreatitis, and 45.8% (34.2-57.9) with diabetes following chronic pancreatic disease. CONCLUSIONS: Diabetes of the exocrine pancreas is frequently labeled type 2 diabetes but has worse glycemic control and a markedly greater requirement for insulin.

Toward More Efficient Surveillance of Barrett's Esophagus: Identification and Exclusion of Patients at Low Risk of Cancer.

BACKGROUND: Endoscopic surveillance of Barrett's esophagus (BE) is probably not cost-effective. A sub-population with BE at increased risk of high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) who could be targeted for cost-effective surveillance was sought. METHODS: The outcome for BE surveillance from 2003 to 2012 in a structured program was reviewed. Incidence rates and incidence rate ratios for developing HGD or EAC were calculated. Risk stratification identified individuals who could be considered for exclusion from surveillance. A health-state transition Markov cohort model evaluated the cost-effectiveness of focusing on higher-risk individuals. RESULTS: During 2067 person-years of follow-up of 640 patients, 17 individuals progressed to HGD or EAC (annual IR 0.8%). Individuals with columnar-lined esophagus (CLE) ≥2 cm had an annual IR of 1.2% and >8-fold increased relative risk of HGD or EAC, compared to CLE <2 cm [IR-0.14% (IRR 8.6, 95% CIs 4.5-12.8)]. Limiting the surveillance cohort after the first endoscopy to individuals with CLE ≥2 cm, or dysplasia, followed by a further restriction after the second endoscopy-exclusion of patients without intestinal metaplasia-removed 296 (46%) patients, and 767 (37%) person-years from surveillance. Limiting surveillance to the remaining individuals reduced the incremental cost-effectiveness ratio from US$60,858 to US$33,807 per quality-adjusted life year (QALY). Further restrictions were tested but failed to improve cost-effectiveness. CONCLUSIONS: Based on stratification of risk, the number of patients requiring surveillance can be reduced by at least a third. At a willingness-to-pay threshold of US$50,000 per QALY, surveillance of higher-risk individuals becomes cost-effective.

The socioeconomic profile of a Barrett's oesophagus cohort assessed by the 2010 Index of Multiple Deprivation.

BACKGROUND: Several reports have described the relationship between socioeconomic status and oesophageal adenocarcinoma but only one with its precursor condition, Barrett's oesophagus. We therefore investigated such an association. PATIENTS: The majority (88%) of patients diagnosed with Barrett's at Rotherham District General Hospital between 28 April 1978 and 31 August 2012 consented to inclusion in the UK Barrett's Oesophagus Registry. Those residing within Rotherham form the basis of this study. METHODS: We assessed socioeconomic status using the Index of Multiple Deprivation 2010 scores which can be assigned to every English postcode. The scores for the whole of England were divided into five equal groups; those of the 6257 postcodes within Rotherham (including those of Barrett's patients) were compared against the national quintile relevant to their score. We examined the ratio of observed against expected numbers of Barrett's in each quintile before and since 2001, the median year of diagnosis. RESULTS: The study group comprised 1076 patients with Barrett's oesophagus. Before 2001 their distribution across the deprivation quintiles was similar to that expected. Since then it has changed significantly, with 37% more Barrett's patients than expected among the two least deprived quintiles, but 11% fewer than expected in the larger population comprising the two most deprived quintiles (P=0.0001). There was no significant difference in the distribution of sex (P=0.27), nor the mean age at diagnosis between the two time periods (P=0.92). CONCLUSION: Since 2001, there has been a major change in the distribution of Barrett's in relation to socioeconomic status, measured by the Index of Multiple Deprivation.

Comparative genomic analysis of esophageal cancers.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on comparative genomic analysis of esophageal cancers: genomic polymorphisms, the genetic and epigenetic drivers in esophageal cancers, and the collection of data in the UK Barrett's Oesophagus Registry.

Surgical treatments for esophageal cancers.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the role of the nurse in preparation of esophageal resection (ER); the management of patients who develop high-grade dysplasia after having undergone Nissen fundoplication; the trajectory of care for the patient with esophageal cancer; the influence of the site of tumor in the choice of treatment; the best location for esophagogastrostomy; management of chylous leak after esophagectomy; the optimal approach to manage thoracic esophageal leak after esophagectomy; the choice for operational approach in surgery of cardioesophageal crossing; the advantages of robot esophagectomy; the place of open esophagectomy; the advantages of esophagectomy compared to definitive chemoradiotherapy; the pathologist report in the resected specimen; the best way to manage patients with unsuspected positive microscopic margin after ER; enhanced recovery after surgery for ER: expedited care protocols; and long-term quality of life in patients following esophagectomy.

Anterior 180° partial fundoplication--how I do it.

Laparoscopic Nissen fundoplication is the standard operation for the surgical control of gastro-oesophageal reflux in many centres. However, in some patients, it can be followed by troublesome side effects, and to minimise the risk of these, partial fundoplications have been recommended. One approach is to construct an anterior 180° partial fundoplication. Randomised trials and a large outcome study have confirmed that in most patients, this approach achieves effective reflux control, as well as a reduced incidence of side effects. In this paper, we describe our approach to this procedure. The procedure entails full dissection of the oesophageal hiatus, hiatal repair with posteriorly placed sutures and then construction of an anterior 180° partial fundoplication using three sutures to attach the anterior gastric fundus to the oesophagus and right hiatal pillar, and two further sutures between the fundus and the apex of the hiatus.

The relationship between smoking and severe dysplastic disease in patients with Barrett's columnar-lined oesophagus.

The aim of this study was to examine the relationship between smoking and oesophageal high-grade dysplasia (HGD) or adenocarcinoma (AC) in a large cohort of patients with Barrett's columnar-lined oesophagus (CLO). A total of 1280 patients diagnosed with CLO and registered with the UK National Barrett's Oesophagus Registry were included. Data, including smoking habits, were collected from the patient's notes and development of HGD or AC noted. Analysis was performed with SPSS using logistic regression for calculation of odds ratios (ORs) for development of HGD/AC. Data on smoking habits were available in 956 (74.6%) patients. There was no significant difference between smokers and nonsmokers in mean age (P=0.877) or length of follow-up (P=0.359). There was a significant risk of HGD/AC in patients with any history of smoking compared with those who had never smoked (P<0.001, OR 2.81). Ex-smokers of 10 years or more remained at a significantly higher risk of HGD/AC compared with those who had never smoked (P=0.001, OR 3.37). Current smokers were not at a significantly higher risk of HGD/AC compared with ex-smokers (P=0.857) nor were those who smoked at least 20 a day compared with those who smoked fewer than 20 a day (P=0.632). In patients with CLO, smoking appears to be a significant risk factor for the development of severe dysplastic disease; however, we did not observe a dose-dependent effect of smoking on progression of disease.

Barrett's esophagus registries.

The following on Barrett's esophagus registries contains commentaries on the data sets to be included, organizational issues, and the demographic, lifestyle, and diagnostic differences between the United States and Europe. The importance of collaborative studies is also discussed.

Barrett's, blood groups and progression to oesophageal cancer: is nitric oxide the link?

INTRODUCTION: Incidence of oesophageal adenocarcinoma (OAC) is increasing rapidly. OAC arises in columnar-lined oesophagus (CLO), a metaplastic change affecting some patients with gastro-oesophageal reflux disease (GORD). As yet there is no reliable method of identifying those at highest risk. Our earlier observation of an association between OAC and blood group O Rhesus negative, if confirmed, may help identify those at greatest risk. AIM AND METHODS: To assess the distribution of blood group and Rhesus D (RhD) factor in patients with GORD compared with the blood donating general population. GORD was categorized as nonerosive reflux (NER), erosive oesophagitis, CLO and OAC. The Rotherham Hospital database holds details of all GORD, CLO and OAC patients seen in the Gastroenterology Unit. Blood group information for patients with GORD was obtained from patients' records and the hospital's blood transfusion service. The blood group distribution in the general population was obtained from the National Blood Transfusion Service. The number of expected to observed patients in each blood group for each subtype was compared. RESULTS: Two thousand six hundred and ten NER, 2813 erosive oesophagitis, 568 CLO and 73 OAC patients had a recorded blood group. For RhD positive patients observed proportions in each blood group were similar to expected. The most striking difference was the marked excess of OAC in blood group O, Rhesus negative (P=0.002). CONCLUSION: CLO patients with blood group O, RhD negative carry a disproportionately higher risk of developing OAC. The mechanism is unknown but the finding has practical application in guiding risk stratification and intensity of surveillance.

Splenectomy for non-haematological metastatic malignant disease.

PURPOSE: Multiple cases and small series of patients who have undergone splenectomy for metastatic malignant disease have been reported. This study examines the outcome of patients with metastatic malignant disease to the spleen treated by splenectomy at a tertiary oncology centre and a review of cases published in the last 10 years. METHODS: The hospital histopathology database was searched over a 25-year period up to 2004 for patients who had undergone splenectomy for non-haematological malignancy. Medical records of these patients were reviewed and clinical course was examined. The literature review was undertaken using a search of PubMed for the terms "splenectomy" and "metastasis" from 2000 to 2010. RESULTS: Twenty-one cases at our institution were identified. The most common primary site of malignancy was ovary (nine cases), followed by malignant melanoma (three) and pancreas (three). There were two cases of metastatic disease from colonic primary and one each from renal, breast, nasopharyngeal and unknown primary disease. There were two cases of long-term disease-free survival (both primary ovarian tumours) and four cases of patients who survived more than 4 years but had disease recurrence (ovarian and colonic primaries). The literature review provided a further 115 cases. CONCLUSIONS: More favorable outcomes were seen in patients with metachronous disease. There was a trend to improved outcome in ovarian and colorectal primaries over malignant melanoma. It is postulated that improved outcome may be seen in patients for whom there were effective adjuvant chemotherapeutic options, low probability of other metastatic disease and less aggressive tumour biology. However, frequently the presentation is indicative of aggressive widespread disease with a poor prognosis.

Modelling the carbon footprint of reflux control.

BACKGROUND: The NHS is responsible for approximately 30% of all public sector carbon emissions. The Climate Change Act 2008 introduced legally binding targets to cut emissions of greenhouse gases (GHGs) by at least 80% of the 1990 baseline by 2050. This paper seeks to examine two different strategies for the treatment of gastro-oesophageal reflux disease and their modelled costs and carbon emissions. METHODS: This study uses data from the costs of care of patients in the REFLUX study and NHS England Carbon Emissions Carbon Footprinting Report to model the carbon emissions associated with medical and surgical treatment of gastro-oesophageal reflux disease. The main outcome measures are modelled financial costs and carbon emissions for medical and surgical treatment pathways. RESULTS: There is a high initial cost (financially and carbon emissions) for surgery, however subsequent year-on-year financial spend and carbon emissions are lower in patients who have had surgical treatment such that the total modelled financial cost of surgery is lower in the 14th year and carbon emissions are lower in the 9th year. The model is sensitive to changes in the efficiency of pharmaceutical procurement and surgical failure rate. CONCLUSIONS: The model has demonstrated that in cases of equivalent clinical benefit one pathway may be preferred on the basis of other factors including carbon emissions.

Aspirin is not chemoprotective for Barrett's adenocarcinoma of the oesophagus in multicentre cohort.

Barrett's columnar-lined oesophagus is the precursor lesion for oesophageal adenocarcinoma. The overall rate of progression to adenocarcinoma is 0.59% per annum. A large prospective multicentre trial is recruiting to assess the role of aspirin as a chemoprotective agent in prevention of development of cancer as well as cardiovascular protection in patients with Barrett's oesophagus. This retrospective analysis of the large UK National Barrett's Oesophagus Registry database seeks to analyse this question from within its large natural history study cohort. Multicentre UK retrospective cohort compared patients known to have been taking aspirin with those who did not take aspirin during the course of surveillance for columnar-lined oesophagus. End point was development of dysplasia or oesophageal adenocarcinoma. Analysis was undertaken using Cox's proportional hazard ratio. Total follow-up was 3683 patient-years. Eighty-six patients were taking aspirin, 650 were not taking aspirin (reference group). Numbers of patients developing all grades of dysplasia and adenocarcinoma were: 13 aspirin (15.1%) and 97 no aspirin (14.9%) (hazard ratio 0.723, 95% confidence interval 0.410-1.310, P = 0.294), high-grade dysplasia and adenocarcinoma: five aspirin (5.8%) and 25 no aspirin (3.8%) (hazard ratio 0.898, 95% confidence interval 0.340-2.368, P = 0.827) and adenocarcinoma: four aspirin (4.7%) and 16 no aspirin (2.5%) (hazard ratio 1.092, 95% confidence interval 0.358-3.335, P = 0.877). No significant difference was observed in hazard of developing dysplasia or adenocarcinoma between patients taking aspirin and those not taking aspirin during the course of follow-up of surveillance for columnar-lined oesophagus. In conclusion, no difference in risk of development of dysplasia or adenocarcinoma was observed between patients taking aspirin and those not taking aspirin in this large cohort.

Are newly diagnosed columnar-lined oesophagus patients getting younger?

OBJECTIVES: The prevalence of columnar-lined oesophagus seems to have increased steadily in the past three decades in Europe and North America. Although the vast majority of columnar-lined oesophagus will not progress to malignancy, it is nevertheless important to identify the risk factors associated with this condition. This study investigates whether there has been a change, at diagnosis, in age of columnar-lined oesophagus patients between 1990 and 2005, or an increase in the number of patients aged less than 50 years. METHODS: Data on age of diagnosis were abstracted from medical records of 7220 patients from 19 centres registered with UK National Barrett's Oesophagus Registry, between the years 1990 and 2005. Linear regression analysis was carried out to assess any trends in the mean age of diagnosis. RESULTS: Overall there was a mean decrease in age at diagnosis for each 1-year increase in time. This equated to a mean decrease of 3 years over the study period, 1990-2005 with the greatest difference being seen in female patients. About 18% of patients in the study were aged less than 50 years at the time of diagnosis. With this group also, the trend was similar, with an increase in the number of patients aged less than 50 years, at the time of diagnosis, with increasing years. CONCLUSION: The mean age of diagnosis of columnar-lined oesophagus has decreased between the years 1990 and 2005 in both men and women, more so in women. This is also reflected in an increase in newly diagnosed columnar-lined oesophagus patients below the age of 50 years.

Surveillance of Barrett's columnar-lined oesophagus in the UK: endoscopic intervals and frequency of detection of dysplasia.

OBJECTIVES: Endoscopic surveillance of patients with columnar-lined oesophagus (CLO) may identify those with early adenocarcinoma (AC). The benefits of surveillance are unproven and there is little evidence to support recommendations for precise endoscopic intervals. We sought to examine surveillance practice for CLO in the UK and the impact of endoscopic intervals on detection of dysplastic disease. METHODS: Eight hundred and seventeen patients with CLO, registered with the UK National Barrett's Oesophagus registry and undergoing surveillance were studied. Endoscopic intervals were calculated and frequency of detection of dysplastic disease analysed using chi2 test of association. Factors affecting surveillance intervals were analysed using multiple linear regression. RESULTS: 94.7% of patients with low-grade dysplasia (LGD), 95.0% with high-grade dysplasia (HGD) and 71.4% with AC were diagnosed on surveillance endoscopies. Mean endoscopic surveillance intervals varied between the centres from 1.07 to 1.63 years for nondysplastic CLO; 0.69-1.19 years for LGD, and 0.35-1.17 years for HGD; with overall mean surveillance intervals of 1.29, 1.01 and 0.44 years, respectively. When LGD was surveyed, significantly higher proportions of HGD/AC were detected at intervals of 3 months or less (P=0.013). Shorter endoscopic intervals were significantly associated with the presence of oesophageal strictures (P=0.002), ulcers (P=0.046), increasing patient age (P<0.001) and higher grade of dysplasia surveyed (P<0.001). CONCLUSION: A variation in surveillance practice for CLO was observed throughout the UK. A large proportion of dysplastic disease is detected on specific surveillance endoscopies. Shorter endoscopic intervals for surveillance of LGD are associated with an increased detection of HGD/AC.

Treatment modality and risk of development of dysplasia and adenocarcinoma in columnar-lined esophagus.

Columnar metaplasia is the precursor lesion for esophageal adenocarcinoma, resulting from prolonged gastroesophageal reflux. The influence of the efficacy of reflux control on the development of neoplastic change in columnar-lined esophagus is not established. This study compares the rate of development of dysplasia and adenocarcinoma in patients with columnar metaplasia of the esophagus between patients treated pharmacologically and those treated with antireflux surgery. This study is a retrospective review of a cohort of patients enrolled in a multicenter national registry involving 738 patients from seven UK centers. Forty-one were treated with antireflux surgery, 42 with H2 receptor antagonist, 532 with proton pump inhibitor, and 114 with a combination of these medications. Nine had none of these medications or surgery. Total follow-up was 3697 years. Mean age and follow-up for patients treated medically were 61.6 and 4.96 years and surgically were 50.5 and 6.19 years, respectively. No patient in the surgical group developed high-grade dysplasia (HGD) or adenocarcinoma. Twenty patients treated medically developed adenocarcinoma and 10 developed HGD. Hazards ratio comparing pharmacological to surgical therapy for development of all grades of dysplasia and adenocarcinoma 1.77 (P = 0.272). Log rank test comparing antireflux surgery to pharmacological therapy for development of HGD or adenocarcinoma P = 0.1287 and for adenocarcinoma P = 0.2125. Although there was a trend towards greater efficacy of antireflux surgery over pharmacological therapy in reducing the development of dysplasia and adenocarcinoma, this did not reach statistical significance.

Current United Kingdom practice in the diagnosis and management of columnar-lined oesophagus: results of the United Kingdom National Barrett's Oesophagus Registry endoscopist questionnaire.

The management of the columnar-lined oesophagus (CLO) has remained controversial for the last 10 years, with practices varying between individual physicians and centres throughout the United Kingdom. Various guidelines exist, although international consensus over issues such as the recognition of short-segment disease and surveillance policies for uncomplicated and dysplastic disease is lacking. Questionnaires examining the practice of diagnosis and surveillance of CLO were sent to 41 centres spread throughout the United Kingdom. Thirty (73%) centres replied. Twelve (40%) had a specific written policy for the management of CLO. Twenty-five (83%) centres made a diagnosis of CLO in the presence of any length of columnarization. Twenty-seven (90%) centres surveyed CLO with 81% of them undertaking a selective surveillance policy. Endoscopic surveillance intervals were fairly consistent for uncomplicated CLO and high-grade dysplasia, but were less consistent for low-grade dysplasia. Results confirmed that even amongst centres with a specialist interest in the management of CLO, marked variations exist in diagnosis and surveillance practice.

Oral potassium supplementation in surgical patients.

Hospital inpatients are frequently hypokalaemic. Low plasma potassium levels may cause life threatening complications, such as cardiac arrhythmias. Potassium supplementation may be administered parenterally or enterally. Oral potassium supplements have been associated with oesophageal ulceration, strictures and gastritis. An alternative to potassium salt tablets or solution is dietary modification with potassium rich food stuffs, which has been proven to be a safe and effective method for potassium supplementation. The potassium content of one medium banana is equivalent to a 12 mmol potassium salt tablet. Potassium supplementation by dietary modification has been shown to be equally efficacious to oral potassium salt supplementation and is preferred by the majority of patients. Subsequently, it is our practice to replace potassium using dietary modification, particularly in surgical patients having undergone oesophagogastrectomy or in those with peptic ulcer disease.

Relevance of the detection of intestinal metaplasia in non-dysplastic columnar-lined oesophagus.

OBJECTIVE: In the USA, detection of intestinal metaplasia is a requirement for enrollment in surveillance programmes for dysplasia or adenocarcinoma in columnar-lined oesophagus. In the UK, it is believed that failure to detect intestinal metaplasia at index endoscopy does not imply its absence within the columnarized segment or that the tissue is not at risk of neoplastic transformation. The aim of this study was to investigate the factors predicting the probability of detection of intestinal metaplasia in the columnarized segment. MATERIAL AND METHODS: Demonstration of intestinal metaplasia was analysed in 3568 biopsies of non-dysplastic columnar-lined oesophagus from 1751 patients from 7 centres in the UK. Development of dysplasia and adenocarcinoma was analysed in 322 patients without intestinal metaplasia and compared with that in 612 patients with intestinal metaplasia. RESULTS: Intestinal metaplasia was more commonly detected in males than in females (odds ratio 1.244), longer segment length (10.3% increase per centimetre) and increasing number of biopsies taken (24% increase per unit increase). After 5 years of follow-up, 54.8% of patients without intestinal metaplasia at index endoscopy demonstrated intestinal metaplasia, and 90.8% after 10 years. There was no significant difference in the rate of development of dysplasia or adenocarcinoma between patients with or without intestinal metaplasia detection at index endoscopy. CONCLUSIONS: Detection of intestinal metaplasia is subject to significant sampling error. It increases with segment length and number of biopsies taken. In the majority of patients, if sufficient biopsies are taken over time, intestinal metaplasia will be demonstrated. The decision to offer surveillance should not be based upon the presence or absence of intestinal metaplasia at index endoscopy as the risk of dysplasia and adenocarcinoma is similar in both groups.

Short segment columnar-lined oesophagus: an underestimated cancer risk? A large cohort study of the relationship between Barrett's columnar-lined oesophagus segment length and adenocarcinoma risk.

OBJECTIVE: Longer columnar-lined oesophagus (CLO) segments have been associated with higher cancer risk, but few studies have demonstrated a significant difference in neoplastic risk stratified by CLO segment length. This study establishes adenocarcinoma risk in CLO by segment length. METHODS: This is a multicentre retrospective observational study. Medical records of 1000 patients registered from six centres were examined and data extracted on demographic factors, endoscopic features and histopathology of oesophageal biopsies. Adenocarcinoma incidence was evaluated for patients stratified by their diagnostic segment length. RESULTS: Seven hundred and eighty-one patients had biopsy-proven CLO and a segment length recorded. Four hundred and ninety patients had at least 1 year of follow-up, providing 2620 patient-years of follow-up for incidence analysis. The overall annual adenocarcinoma incidence was 0.62%/year (95% confidence interval: 0.36-1.01). The annual incidence in the segment length groups was 0.59% (0.19-1.37) in short segment (3 6 9 cm; P=0.004. CONCLUSION: This study demonstrates that the neoplastic risk of CLO varies according to segment length, and that overall, the risk of adenocarcinoma development is similar in short-segment and long-segment (>3 cm) CLO. The highest adenocarcinoma risk was found in the longest CLO segments and lowest risk in segments >3