Retrospective cohort study of an enhanced recovery programme in oesophageal and gastric cancer surgery.

Introduction Enhanced recovery programmes have been established in some areas of elective surgery. This study applied enhanced recovery principles to elective oesophageal and gastric cancer surgery. Methods An enhanced recovery programme for patients undergoing open oesophagogastrectomy, total and subtotal gastrectomy for oesophageal and gastric malignancy was designed. A retrospective cohort study compared length of stay on the critical care unit (CCU), total length of inpatient stay, rates of complications and in-hospital mortality prior to (35 patients) and following (27 patients) implementation. Results In the cohort study, the median total length of stay was reduced by 3 days following oesophagogastrectomy and total gastrectomy. The median length of stay on the CCU remained the same for all patients. The rates of complications and mortality were the same. Conclusions The standardised protocol reduced the median overall length of stay but did not reduce CCU stay. Enhanced recovery principles can be applied to patients undergoing major oesophagogastrectomy and total gastrectomy as long as they have minimal or reversible co-morbidity.

Mortality in Barrett's esophagus: three decades of experience at a single center.

BACKGROUND AND STUDY AIMS: There is a view that the majority of deaths in patients with Barrett's esophagus are from causes other than esophageal adenocarcinoma (EAC). The aim of this analysis was to establish the pattern of mortality for a number of causes in patients with Barrett's esophagus. PATIENTS AND METHODS: This was a single-center prospective cohort study of patients from Rotherham District General Hospital, which is a secondary referral center. The cohort consisted of 1239 patients who were diagnosed with Barrett's esophagus between April 1978 and March 2009.  Follow-up for mortality was undertaken by "flagging" the patients with the NHS Information Center. Causes of death were compared with UK Office of National Statistics age- and sex-specific mortality data for 1999, the median year of diagnosis. Analysis was by a "person - years at risk" calculation from date of diagnosis. RESULTS: The ratio of observed deaths from EAC compared with those expected in this cohort was 25.02 - a very large excess. There was no difference in mortality from colorectal cancer or circulatory disease and there were fewer deaths from cancers other than esophageal adenocarcinoma and colon cancer compared with national statistics. There was a small statistically significant difference in mortality from all causes but this disappeared completely when deaths from esophageal adenocarcinoma were excluded. CONCLUSIONS: Overall, mortality in Barrett's esophagus is increased significantly but only as a result of the large excess of deaths from EAC. This strengthens the case for endoscopic surveillance if successful interventions can be undertaken in patients with Barrett's esophagus to prevent development of esophageal adenocarcinoma.

Anti-neutrophil cytoplasmic antibody-associated systemic vasculitis: nature or nurture?

This review examines the environmental and genetic contributions to the anti-neutrophil cytoplasmic antibody-associated systemic vasculitides. The dominant environmental risk factors appear to be silica exposure for all three syndromes, and vitamin D deficiency is strongly suggested by the latitude and ultraviolet radiation gradient observed for Wegener's granulomatosis and Churg-Strauss syndrome. Genetic factors are generally not very strong, consistent with the rarity of these conditions in children. However, multiple genetic factors, each with a relatively small effect, may combine to create a state of susceptibility towards autoimmunity. With infection as a triggering agent, it is possible to synthesise a pathogenetic hypothesis that accounts for both environmental and genetic effects in regard to both necrotising vasculitis and granuloma formation.

Antireflux surgery.

Gastro-oesophageal reflux disease is extremely common throughout Europe and the United States. This review on antireflux surgery examines the best evidence for surgical treatment of gastro-esophageal reflux disease. Comparison is made with medical antireflux therapy including histamine H2 receptor antagonist and proton pump inhibitor therapy. The randomized trials and systematic reviews available on gastro-esophageal reflux disease are reviewed and where data are scarce, the largest cohort studies available are discussed. Overall, laparoscopic antireflux surgery is safe and has a similar efficacy to open antireflux surgery and best medical therapy with proton pump inhibitors. There is a failure rate, which in some series is greater than 50% at 5 years. Due to the cost of a proportion of patients still taking antireflux medications, it cannot be recommended on cost-effectiveness grounds over best medical therapy. The choice of procedure lies between complete wrap with Nissen's fundoplication and partial fundoplication (most frequently Toupet). Division of the short gastric vessels is not usually necessary and is associated with increased wind-related complications. Total fundoplication tends to produce superior reflux control, but at the cost of increased risk of dysphagia. There is a trend for antireflux surgery to be superior to best medical therapy in cancer prevention in Barrett's oesophagus, but this has not reached statistical significance.

The influence of symptom type and duration on the fate of the metaplastic columnar-lined Barrett's oesophagus.

BACKGROUND: Prolonged gastro-oesophageal reflux resulting in columnar metaplasia of the oesophagus is the main risk factor for oesophageal adenocarcinoma. AIM: To examine the duration of symptoms and associations of different symptoms with the development of columnar-lined oesophagus, dysplasia and adenocarcinoma. METHODS: UK multicentre cohort study of patients with columnar-lined oesophagus whose date of symptom onset (1082 patients) and/or types of symptoms reported (1681 patients) were documented. Follow-up was examined by analysis of histological reports from the registering centers. RESULTS: Symptoms of dysphagia/odynophagia and nausea/vomiting were associated with development of dysplasia. High-grade dysplasia and adenocarcinoma were associated with dysphagia/odynophagia and weight loss. Median duration from symptom onset to detection of columnar-lined oesophagus without intestinal metaplasia: 2.6 years, columnar-lined oesophagus with intestinal metaplasia: 5.0 years, indefinite changes for dysplasia: 19.3 years and low-grade dysplasia: 30.0 years. One tenth of patients had developed high-grade dysplasia at 9.6 years and one tenth had developed adenocarcinoma at 13.8 years from symptom onset. CONCLUSIONS: In patients with columnar-lined oesophagus, symptoms of dysphagia/odynophagia and nausea/vomiting were associated with a higher risk of development of dysplasia and adenocarcinoma. There is a trend for longer duration of symptoms to the detection of dysplasia.

Barrett's columnar-lined oesophagus: demographic and lifestyle associations and adenocarcinoma risk.

OBJECTIVES: Lifestyle and demographic risk factors for the development of oesophageal adenocarcinoma developing from columnar-lined oesophagus are not well defined. METHODS: Demographic and lifestyle factors, endoscopy and histology reports were extracted from 1,761 subjects from seven UK centres. The associations of columnar-lined oesophagus with demographic and lifestyle factors and the development of adenocarcinoma were examined. RESULTS: 5.5% of patients had prevalent adenocarcinoma (more common in males, older patients, patients diagnosed earlier in the cohort and current or recent smokers). Adenocarcinoma incidence was 23 patients in 3,912 years or 0.59% per annum. Only increased age at diagnosis correlated with an increased risk of incident adenocarcinoma. There was no association with obesity or alcohol history. CONCLUSIONS: Oesophageal adenocarcinoma occurs more commonly in older patients and is more frequent in males than females. Once columnar-lined oesophagus had been diagnosed, there were no other demographic or lifestyle factors which were predictive of the development of incident adenocarcinoma in this cohort.

Does the length of the columnar-lined esophagus change with time?

A number of previous studies have reported patients with Barrett's columnar metaplasia who have an increase or decrease in segment length over time. It is not clear whether patients who have an apparent shortening of the metaplastic segment are subsequently at a lower neoplastic risk and those whose segment length appears to increase are at a higher risk of adenocarcinoma development. The aim of this study was to investigate these issues by studying a large cohort of patients from the UK National Barrett's Oesophagus Registry. Medical records of 1533 patients registered with the UK National Barrett's Oesophagus Registry were examined from seven UK centers. Data were extracted on metaplastic segment length at surveillance endoscopies and histological findings on biopsy. Overall changes in segment length, variability in measurement and probability of the development of dysplasia and neoplasia over time were examined. At least two segment lengths were measured in 763 patients. The median change from measured diagnostic length to most outlying measured segment length was 3.0 cm, but overall there was no tendency for segment length to increase or decrease in the majority of patients with a follow up of up to 20 years. Most patients were treated with proton pump inhibitors. One hundred and eighty-six patients had three or more segment lengths over the first 10 years of follow up. No change in risk was demonstrated in these patients where length appeared to consistently increase with time or when it appeared to decrease. Overall, metaplastic columnar-lined esophagus segment length does not change over time, and when an apparent change is observed, this does not influence a risk of dysplasia or adenocarcinoma.

Carbon monoxide wash-in method to determine gas transfer in vascular beds: application to rat hindlimb.

The vascular barrier to gas transfer is an important physiological parameter; however, no readily applicable technique exists to quantitate the process. A simple technique to measure the permeability-surface area (PS) product for gas transfer in vascular beds is proposed using wash in of carbon monoxide (CO) and Crone-Renkin analysis. Wash-in experiments were performed on the perfused hindlimbs of male Wistar rats (n = 15) by using CO as a surrogate marker for oxygen and technetium-99m-labeled albumin as the vascular marker. The use of CO and erythrocyte-free perfusate and the collection of outflow samples into tubes preloaded with erythrocytes obviated the need for an anaerobic collection device or consideration of Hb binding in the analysis. The PS product for CO was determined from the early extraction as 0.013 +/- 0.006 ml. s(-1). g(-1). Compartmental analysis revealed that the fractional recovery of CO was 0.45 +/- 0.14 and the volume of distribution was 2.31 +/- 0.76 ml/g. This technique detected a small measurable barrier to the transfer of CO across the hindlimb vasculature and is potentially applicable to other vascular beds in health and disease.

Lepidopterism: two cases of systemic reactions to the cocoon of a common moth, Chelepteryx collesi.

Lepidopterism is a general term for the ill-effects to humans from contact with moths and butterflies. We describe two cases of systemic reactions after contact with the cocoon of the Australian species Chelepteryx collesi, or white-stemmed gum moth--irritant and toxic effects in one and a systemic allergic reaction in the other. Early removal of urticating hairs from the skin in such cases may be advisable.

Neurological and obstetric manifestations of the antiphospholipid syndrome.

The experience of a single centre with the neurological and obstetric complications of the antiphospholipid syndrome is presented and reviewed briefly with the general world literature. Both the neurologic and the obstetric manifestations exemplify the need for a greater understanding of underlying pathogenetic mechanisms and a more rigorous approach to therapy.

Creation of an academic medical centre: management and service delivery at the Canberra Clinical School.

The Canberra Clinical School is attached to Woden Valley Hospital, the principal hospital in the Australian Capital Territory. The clinical school arose out of a memorandum of understanding signed between the University of Sydney and the ACT Department of Health (as it then was) in March 1993. One of the aspirations of those who negotiated the memorandum of understanding was that the creation of the clinical school would lead to a cultural shift in attitudes towards change within the health care system. This paper looks at the management structure of Woden Valley Hospital and at what the development of a clinical school in Canberra can achieve, particularly in relation to hospital and health service management.

The bcl-2 proto-oncogene is overexpressed in systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) is a disease in which lymphoid hyper-reactivity occurs. Whether this is primary or secondary is not always clear. SLE occurs on a well defined genetic background including genes associated with the major histocompatibility complex (MHC) although family studies demonstrate that other genes must be involved as well. Other potential genes include those involved in intrinsic lymphoid hyper-reactivity, for example by preventing programmed cell death. Such examples exist in murine models of SLE, and in this study we provide evidence that one such controlling protein, bcl-2, is expressed in an increased proportion of both B and T cells in SLE patients. The increased expression was not readily related to disease activity measured by the SIS, nor by routine serological markers. This raises the possibility that the increased expression of bcl-2 seen in lymphoid cells from SLE patients may be of intrinsic genetic origin rather than being secondary to the auto-reactive process. Such increased expression could be expected to interfere with programmed cell death, to produce lymphoid hyper-reactivity and to contribute to the induction and maintenance of this prototypic systemic autoimmune disease.

Restricted junctional diversity of T cell receptor delta gene rearrangements expressed in systemic lupus erythematosus (SLE) patients.

SLE is an autoimmune connective tissue disorder affecting multiple organs, in which T cells may play a central role. This study investigated T cell receptor (TCR) gamma/delta repertoire expression in peripheral blood mononuclear cells (PBMC) of SLE patients and healthy individuals using variable (V) gene family-specific polymerase chain reaction (PCR) amplification of TCR cDNA. The expressed V gamma repertoires were diverse in SLE and control PBMC, although V gamma IV gene rearrangements were barely detectable or not expressed in some patients. In contrast, delta chain expression was limited in all SLE patients, with delta transcripts rearranged primarily to the V delta 1 and V delta 2 genes, as opposed to control PBMC, in which all six V delta genes were detected. To assess the clonality of TCR populations, cDNA clones containing rearranged V delta 1, V delta 2 and V gamma 9 transcripts were sequenced from PBMC of both patients and controls. For controls, delta chain junctional region sequences showed extensive molecular heterogeneity, since virtually all 34 V delta 1 and 32 V delta 2 cDNA clones analysed were unique. A few V gamma 9 cDNA clones (3/21) had the same junctional region sequence motif (EVQEL) encoded largely by the V gamma 9 and joining (J) gamma P gene segments. Identical V gamma 9 junctional sequences were found in SLE patients that did not contain the EVQEL motif present in normal peripheral blood gamma/delta lymphocytes. Moreover, the predominant V delta 1-J delta -constant (C) delta and V delta 2-J delta-C delta gene rearrangements expressed in SLE PBMC showed restricted junctional diversity, but the oligoclonal delta transcripts were different in each patient. These findings suggest in vivo oligoclonal expansion of gamma/delta T cells in the periphery of SLE patients in response to a limited number of nominal ligands. Whether gamma/delta T cells contribute to the development of systemic autoimmunity remains to be investigated.

A cluster of mutations within a short triplet repeat in the C1 inhibitor gene.

Mutations in the C1 inhibitor gene that result in low functional levels of C1 inhibitor protein cause hereditary angioneurotic edema. This disease is characterized by episodic edema leading to considerable morbidity and death. Among 60 unreported kindred with the disease, four patients were discovered to have mutations clustered within a 12-bp segment of exon 5 from nucleotide 8449 to nucleotide 8460. This short segment of DNA contains three direct repeats of the triplet CAA and is immediately preceded by a similar adenosine-rich sequence (CAAGAACAC). These triplet repeats make this region susceptible to mutation by a slipped mispairing mechanism. There are two other short triplet repeat elements in the coding region for this gene, but they have not become mutated in any kindred examined. This suggests that the apparent enhanced mutation rate in this region of exon 5 may be influenced by DNA structural characteristics.