Pilot study of cytological testing for oesophageal squamous cell dysplasia in a high-risk area in Northern Iran.

BACKGROUND: Oesophageal squamous cell carcinoma (ESCC) is a fatal disease with 5-year survival rates of <5% in Northern Iran. Oesophageal squamous dysplasia (ESD) is the precursor histologic lesion of ESCC. This pilot study was conducted to assess the feasibility, safety, and acceptability of non-endoscopic cytological examination of the oesophagus and to provide initial data on the accuracy of cytological atypia for identifying patients with ESD in this very-high-risk area. METHODS: Randomly selected asymptomatic participants of the Golestan Cohort Study were recruited. A cytological specimen was taken using a capsule sponge device and evaluated for atypical cells. Sections of the cytological specimen were also stained for p53 protein. Patient acceptability was assessed using a visual analogue scale. The cytological diagnosis was compared with a chromoendoscopic examination using Lugol's solution. RESULTS: Three hundred and forty-four subjects (43% male, mean (s.d.) age 55.6 (7.9) years) were referred to the study clinic. Three hundred and twelve met eligibility criteria and consented, of which 301 subjects (96.5%) completed both cytological and endoscopic examinations. There were no complications. Most of the participants (279; 92.7%) were satisfied with the examination. The sensitivity and specificity of the cytological examination for identifying subjects with high-grade ESD were 100 and 97%, respectively. We found an accuracy of 100% (95% CI=99-100%) for a combination of cytological examination and p53 staining to detect high-grade ESD. CONCLUSIONS: The capsule sponge methodology seems to be a feasible, safe, and acceptable method for diagnosing precancerous lesions of the oesophagus in this population, with promising initial accuracy data for the detection of high-grade ESD.

Fracture incidence after liver transplantation: results of a 10-year audit.

BACKGROUND: High rates of fracture following liver transplantation were reported in earlier years, but the impact of subsequent changes in immune suppression and the introduction of bone-protective therapy on fracture rate have not been reported. AIM: The aim of this study was to document clinical fracture incidence during the period 1998-2008 in a single transplant centre, following the introduction of a bone management protocol. DESIGN: It was designed as a retrospective cohort. METHODS: Records were retrieved from 531 of 592 eligible patients in an audit of all patients undergoing a first liver transplant during the 10-year period. All fractures were verified radiologically. RESULTS: The mean follow-up period was 61.4 months. Prior to transplantation 5.6% of patients had a history of fracture. Incident clinical fractures following transplantation were recorded in just 15 (3.5%) patients. The most common fracture site was the spine and the median time from transplant to fracture was 26 months (range 2-83 months). CONCLUSION: There was a low fracture rate in patients undergoing liver transplantation in this centre over the past 10 years. This rate is lower than that in previous reports, which is likely to reflect the use of lower doses of prednisolone for immune suppression and the administration of bone-protective therapy to high-risk patients.

Non-endoscopic screening biomarkers for Barrett's oesophagus: from microarray analysis to the clinic.

BACKGROUND AND AIMS: Barrett's oesophagus predisposes to oesophageal adenocarcinoma but the majority of patients are undiagnosed. A novel non-endoscopic cytological screening device, called a capsule sponge, makes population-based screening for the disease a feasible option. However, due to the mixed cell population retrieved by the capsule sponge, biomarkers specific for Barrett's oesophagus are required. METHODS: Three publically available microarray datasets were used to identify putative biomarkers present in Barrett's oesophagus but absent from normal oesophagus and gastric mucosa. Validation was performed by qPCR (n = 10 each of normal oesophagus, Barrett's oesophagus, gastric mucosa) and immunohistochemistry (normal oesophagus, n = 20; Barrett's oesophagus, n = 21; gastric mucosa, n = 24; duodenum, n = 18). The biomarker was then prospectively evaluated on capsule sponge specimens from 47 patients with Barrett's oesophagus and 99 healthy controls. RESULTS: 2/14 genes identified, dopa decarboxylase (DDC) and Trefoil factor 3 (TFF3), were confirmed by qPCR to be upregulated in Barrett's oesophagus compared to normal oesophagus (p<0.01) and gastric mucosa (p<0.01 and p<0.05, respectively). Immunohistochemistry confirmed that DDC protein expression was restricted to Barrett's oesophagus but was confined to <1% of the cells within the crypt compartment. TFF3 protein was expressed to high levels at the luminal surface of Barrett's oesophagus compared to absent expression in normal oesophagus and gastric mucosa (p<0.001). Using the capsule sponge 36/46 patients with Barrett's oesophagus (one inadequate sample) and 6/96 controls were positive for TFF3 giving a sensitivity of 78% and a specificity of 94%. CONCLUSIONS: TFF3 is a promising marker for Barrett's oesophagus screening since it is expressed at the luminal surface of Barrett's oesophagus but not in adjacent tissue types and may be applied to a non-endoscopic screening device.

Changes in bone mineral density, body composition and biochemical markers of bone turnover during weight gain in adolescents with severe anorexia nervosa: a 1-year prospective study.

Osteoporosis is a serious complication of anorexia nervosa and in affected adolescents may result in a permanent deficit in bone mass. The pathophysiology of this bone disease has not been clearly defined. In this prospective study of 26 young women with anorexia nervosa aged 13-20 years (mean 16.5) we have measured changes in bone mineral density, total body composition and biochemical indices of bone turnover over 1 year. Over this period there was a mean weight gain of 10 kg and significant height gain with baseline and final values for body mass index of 14.2+/-1.7 and 17.6+/-2.3 kg/m2 (P<0.001). However, no significant changes were seen in bone mineral density in the spine or proximal femur during the study; total body bone mineral content was significantly higher than baseline at 3 months and 12 months (P=0.001 and P<0.0001), but total body bone mineral density at 3 months was significantly lower than baseline (P=0.003). Serum osteocalcin and bone-specific alkaline phosphatase values increased significantly and remained higher than baseline at all time points whereas urinary NTX/creatinine excretion showed a non-significant increase over the first 6 months of the study, but at 12 months, the mean value was significantly lower than baseline. Mean serum 25-hydroxyvitamin D levels showed a significant decrease at 6 months (P<0.05), but returned towards baseline thereafter. There was a significant increase in serum parathyroid hormone levels at all time points compared to baseline, these occurring within the normal range. These results indicate that although weight gain in young anorexics is associated with linear growth, bone mineral density does not increase. Whether this deficit can be corrected subsequently requires longer-term prospective studies.

A prospective study of discordance in diagnosis of osteoporosis using spine and proximal femur bone densitometry.

The T-score definition of osteoporosis, originally intended for epidemiologic research in this condition, is frequently used in making treatment decisions for individual patients. Discordance in classification depending on the site and type of measurement has been reported in retrospective and cross-sectional studies, but the impact of such discordance on clinical practice is unknown. This is potentially important in view of a recent proposal to confine osteoporosis diagnosis to densitometry at the hip. Having excluded those with degenerative changes in the lumbar spine, we compared the T-score classification of a prospective cohort of patients referred for their first dual-energy X-ray absorptiometry (DXA) scan, analyzing data for men and women in 10-year age groups. Total hip and neck of femur DXA identified significantly fewer osteoporotic patients than spine DXA, and this reduced sensitivity could not be improved by adjusting the T-score threshold without an unacceptable increase in non-osteoporotic cases. The majority of patients undetected by proximal femur DXA were at significantly increased risk of vertebral fracture. DXA at the lumbar spine had only moderate sensitivity and specificity for osteoporosis redefined by total hip densitometry, indicating differential rates of bone loss at the proximal femur and spine. We conclude that, as the most usual indication for bone densitometry is to aid the determination of an individual's fracture risk, both proximal femur and lumbar spine should continue to be assessed.