Population-based cohort study of the management and survival of patients with early-stage oesophageal adenocarcinoma in England.

BACKGROUND: Until recently, oesophagectomy was the treatment of choice for early oesophageal cancer. Endoscopic treatment has been introduced relatively recently. This observational national database study aimed to describe how endoscopic therapy has been introduced in England and to examine the safety of this approach. METHODS: A population-based cohort study was undertaken of patients diagnosed with oesophageal adenocarcinoma between October 2007 and June 2009 using three linked national databases. Patients with early-stage disease (T1 tumours with no evidence of spread) were identified, along with the primary treatment modality where treatment intent was curative. Short-term outcomes after treatment and 5-year survival were evaluated. RESULTS: Of 5192 patients diagnosed with oesophageal adenocarcinoma, 306 (5·9 per cent) were considered to have early-stage disease before any treatment, of whom 239 (79·9 per cent of 299 patients with data on treatment intent) were managed with curative intent. Of 175 patients who had an oesophagectomy, 114 (65·1 (95 per cent c.i. 57·6 to 72·7) per cent) survived for 5 years. Among these, 47 (30·3 per cent of 155 patients with tissue results available) had their disease upstaged after pathological staging; this occurred more often in patients who did not have staging endoscopic ultrasonography before surgery. Of 41 patients who had an endoscopic resection, 27 (66 (95 per cent c.i. 49 to 80) per cent) survived for 5 years. Repeat endoscopic therapy was required by 23 (56 per cent) of these 41 patients. CONCLUSION: Between 2007 and 2009, oesophagectomy remained the initial treatment of choice (73·2 per cent) among patients with early-stage oesophageal cancer treated with curative intent; one in five patients were managed endoscopically, and this treatment was more common in elderly patients. Although the groups had different patient characteristics, 5-year survival rates were similar.

Influence of surgical rate on patients' reported clinical need and outcomes in English NHS.

BACKGROUND: To determine if higher rates of surgery are associated with lower levels of need (patients' pre-operative reports of their symptoms, functional status and quality of life) and with less benefit (patients' post-operative reports). METHODS: Patient-reported outcome measures (PROMs) collected before and after joint replacement, hernia repair or varicose vein (VV) surgery in National Health Service (NHS)-funded patients (2009/11). Regression analysis for associations between 10% increase in rates and mean PROM score for Primary Care Trust (PCT) populations. RESULTS: National rate for hip and knee replacement increased by 6%, unchanged for hernia repair and decreased by 26% for VV surgery. Changes in PCT rates varied but had little or no association with the mean level of need of patients: 10% increase in the rate was associated with only 0.3% decline in the pre-operative PROM score for knee replacement (P < 0.05) and VV surgery (P < 0.001) and no significant change for other procedures. There was no significant association between a 10% change in the rate and the amount of benefit from surgery apart from a slight reduction (0.46%; P < 0.001) in the disease-specific PROM score for VV surgery. CONCLUSION: Policies by commissioners to reduce surgical rates in the English NHS cannot be justified on the grounds of avoiding inappropriate operations or increasing cost-utility.

Brachytherapy in the Palliation of Oesophageal Cancer: Effective but Impractical?

Dysphagia in people with advanced oesophageal cancer can be treated by oesophageal stents, external beam radiotherapy (EBRT) and intraluminal brachytherapy. Despite guidelines recommending brachytherapy for patients with a predicted life expectancy exceeding 3 months, its uptake in the UK has been limited. Here we examine the strength of the evidence supporting the use of brachytherapy compared with oesophageal stents and EBRT and possible reasons for its limited uptake. Trials and observational studies suggest brachytherapy alone confers a benefit to patients, but its impact is less immediate than oesophageal stents; the evidence on effectiveness and value-for-money is limited. Moreover, stronger evidence will probably be insufficient to increase uptake, due to the extra complexity of delivery compared with stents and EBRT and a lack of experience among specialists.

Changes in volume, clinical practice and outcome after reorganisation of oesophago-gastric cancer care in England: A longitudinal observational study.

AIM: The centralisation of oesophago-gastric (O-G) cancer services in England was recommended in 2001, partly because of evidence for a volume-outcome effect for patients having surgery. This study investigated the changes in surgical services for O-G cancer and postoperative mortality since centralisation. METHODS: Patients with O-G cancer who had an oesophageal or gastric resection between April 2003 and March 2014 were identified in the national Hospital Episodes Statistics database. We derived information on the number of NHS trusts performing surgery, their surgical volume, and the number of consultants operating. Postoperative mortality was measured at 30 days, 90 days and 1 year. Logistic regression was used to examine how surgical outcomes were related to patient characteristics and organisational variables. RESULTS: During this period, 29 205 patients underwent an oesophagectomy or gastrectomy. The number of NHS trusts performing surgery decreased from 113 in 2003-04 to 43 in 2013-14, and the median annual surgical volume in NHS trusts rose from 21 to 55 patients. The annual 30 day, 90 day and 1 year mortality decreased from 7.4%, 11.3% and 29.7% in 2003-04 to 2.5%, 4.6% and 19.8% in 2013-14, respectively. There was no evidence that high-risk patients were not undergoing surgery. Changes in NHS trust volume explained only a small proportion of the observed fall in mortality. CONCLUSION: Centralisation of surgical services for O-G cancer in England has resulted in lower postoperative mortality. This cannot be explained by increased volume alone.

Pooled human IGG (PHIG) inhibits the binding of anti-myeloperoxidase antibodies to myeloperoxidase.

This study demonstrates that pooled human immunoglobulin (PHIG) contains anti-idiotypes to anti-myeloperoxidase (MPO) antibodies and can inhibit the binding of anti-MPO to MPO. The variability seen in the inhibitory effect of different PHIG preparations in the same and also in different patient sera suggests heterogeneity in the idiotypic repertoire of anti-MPO antibodies.

Little evidence for anti-endothelial-cell antibodies in microscopic polyarteritis and Wegener's granulomatosis.

Sera from patients with a vasculitis and controls were investigated for the presence of anti-endothelial cell antibodies(AECA), anti- neutrophil cytoplasmic antibodies(ANCA) and anti-myeloperoxidase (MPO) antibodies. Only 19% of patients with Wegener's granulomatosis and 2% of patients with microscopic polyarteritis had AECA. Our data suggests that AECA are a minor antibody system in vasculitis.

Cytokines in haemolytic uraemic syndrome associated with verocytotoxin-producing Escherichia coli infection.

The proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) interleukin (IL)-1 beta, IL-6, and IL-8 were measured in plasma and urine samples from 19 children with verocytotoxin-producing Escherichia coli (VTEC) induced haemolytic uraemic syndrome (HUS) and 30 controls. TNF-alpha was detected in the plasma of two cases and one control; IL-6 in the plasma of one, and the urine of two cases, and in the plasma of one control. IL-1 beta and IL-8 were each identified in eight of the 19 cases and in one and two controls respectively. Urinary IL-8 was found in seven cases, four of whom had plasma concentrations below the limit of detection suggesting renal secretion of this cytokine. Cytokine concentrations did not correlate with peripheral blood neutrophil count at onset of disease. These data confirm the systemic release of cytokines responsible for the coordination of acute inflammatory processes in some children with VTEC induced HUS.

Little evidence for anti-endothelial cell antibodies in microscopic polyarteritis and Wegener's granulomatosis.

We studied sera from patients with vasculitis and controls for the presence of anti-endothelial cell antibodies (AECA) and correlated these with disease type, anti-neutrophil cytoplasmic antibodies (ANCA) and anti-myeloperoxidase (MPO) antibodies. AECA were detected by a cellular ELISA on cultured human umbilical vein endothelium. AECA were found in the sera of one of 43 patients with microscopic polyarteritis (2%), five of 27 patients with Wegener's granulomatosis (19%), three of 23 patients with an idiopathic glomerulonephritis (13%), none of eight patients with rheumatoid arthritis and three of 12 patients with rheumatoid vasculitis (25%). In patients with a vasculitis AECA titres were higher in sera with a positive ANCA as compared with ANCA negative sera although the difference was not significant (P = 0.0702) and there was no correlation between AECA and anti-MPO titres (r = 0.1171 P = 0.114). AECA binding was not enhanced following upregulation of endothelial ICAM-1 and ELAM-1 by TNF alpha. This study shows that AECA occur infrequently in microscopic polyarteritis and Wegener's granulomatosis, and are not a major antibody system in these vasculitides.

Anti-idiotypic activity against anti-myeloperoxidase antibodies in pooled human immunoglobulin.

We investigated the ability of six different pooled human immunoglobulin (PHIG) preparations to inhibit the binding of anti-myeloperoxidase (MPO) antibodies to MPO. All six PHIG preparations inhibited the binding of anti-MPO antibodies from six sera to MPO in a concentration-dependent manner in the concentration range 0.016-10 mg/ml. There was considerable variation in the ability of each PHIG preparation to inhibit the binding of anti-MPO antibody in a given serum. Further differences were seen in the ability of a given PHIG to inhibit anti-MPO binding in different sera. F(ab')2 fragments from two PHIG preparations also inhibited in a concentration-dependent manner anti-MPO binding to MPO in all six sera in the concentration range 0.002-2.65 mg/ml, with a maximum inhibition of 42%. Little inhibition was seen with F(ab')2 of normal human IgG from individual donors (1.8-12.2% at the maximum concentration of 2 mg/ml). F(ab')2 fragments from three anti-MPO containing sera and two affinity-purified anti-MPO antibodies were eluted by affinity chromatography from Sepharose-bound PHIG F(ab')2 and showed anti-MPO antibody activity. We have shown that PHIG and F(ab')2 fragments of PHIG inhibit anti-MPO binding to MPO, and further that F(ab')2 fragments of PHIG bind to F(ab')2 fragments of anti-MPO antibodies. These observations indicate binding between the variable regions of PHIG and the antigen binding site of anti-MPO antibodies, and are consistent with an anti-idiotypic reaction. The variability seen in the inhibitory effect of the different PHIG preparations in anti-MPO-positive sera implies differences in their anti-idiotype content, while the variability of the inhibitory effect of a particular PHIG preparation between different sera suggests heterogeneity in the idiotypic repertoire of anti-MPO antibodies. Such variations in the inhibitory effect of different PHIG preparations on antibody binding may be an important determinant of their therapeutic effect.