Controversies of the cardiac mucosa and Barrett's oesophagus

Confusion regarding the diagnosis of Barrett's oesophagus exists because of a false dogma that cardiac mucosa is normally present in the gastro-oesophageal junctional region. Recent data indicate that the only normal epithelia in the oesophagus and proximal stomach are squamous epithelium and gastric oxyntic mucosa. When this fact is recognized, it becomes easy to develop precise histological definitions for the normal state (presence of only squamous and oxyntic mucosa), metaplastic oesophageal columnar epithelium (cardiac mucosa with and without intestinal metaplasia, and oxynto-cardiac mucosa), the gastro-oesophageal junction (the proximal limit of gastric oxyntic mucosa), the oesophagus (that part of the foregut lined by squamous and metaplastic columnar epithelium), reflux disease (the presence of metaplastic columnar epithelium), and Barrett's oesophagus (cardiac mucosa with intestinal metaplasia). It is also possible to assess accurately the severity of reflux which is directly proportional to the amount of metaplastic columnar epithelium, and the risk of adenocarcinoma which is related to the amount of dysplasia in intestinal metaplastic epithelium present within the columnar lined segment of the oesophagus. Histopathological precision cannot be matched by any other modality and can convert the confusion that exists regarding diagnosis of Barrett's oesophagus to complete lucidity in a manner that is simple, accurate, and reproducible.     

Distribution of laminins in the basement membranes of the upper gastrointestinal tract and Barrett's oesophagus

Barrett's oesophagus predisposes to oesophageal adenocarcinoma. In vitro, laminin, a component of the epithelial basement membrane (BM), is important in regulation of cell differentiation. There is limited information on the distribution of laminin chains in the upper gastrointestinal tract (GIT) and none in Barrett's oesophagus. This study aimed to investigate qualitatively the distribution of laminins in the normal upper GIT mucosa and Barrett's oesophagus in order to understand the role of laminins in metaplasia. Immunoperoxidase staining for laminin chains alpha1, alpha2, alpha3, alpha5, beta1, beta2, beta3, gamma1, and gamma2 was performed on frozen endoscopic squamous and Barrett's oesophageal biopsies and surgical resection specimens from squamous oesophagus (in resection specimens for oesophageal cancer), and in oesophageal and gastric biopsies from control subjects. alpha1 laminin was expressed in the BM of submucosal glands and ducts in squamous oesophagus and Brunner's glands in the duodenum, but not in Barrett's oesophagus or elsewhere in the upper GIT. alpha2 laminin chain was expressed in a granular distribution in the BM of squamous epithelium. In columnar epithelium, including Barrett's oesophagus, alpha2 laminin chain was expressed continuously in the BM of glands and deeper pits, but expression was reduced and granular in the surface epithelial BM. beta2 laminin was continuous in squamous epithelial BM, but in Barrett's and cardia, gastric body, and duodenum, it was expressed faintly in the surface but continuously in the BM of glands and deeper pits. The constituents of laminin-5 were continuously expressed in the BM of squamous epithelium, but in the cardia, gastric body, duodenum, and Barrett's, they were expressed only in the BM of surface epithelium, with a sharp decline in the glandular and deeper pit BM. Site-specific distribution of the alpha2 and beta2 laminin chains may therefore have an important role in Barrett's metaplasia. However, the absence of alpha1 laminin in Barrett's mucosa suggests that this is unlikely to play an important role in columnar metaplasia.     

Ablation treatment for Barrett oesophagus: what depth of tissue destruction is needed?

AIM: To establish the depth of Barrett's columnar epithelium and normal squamous oesophageal epithelium, in order to determine the depth of destruction required in ablation treatment for Barrett oesophagus. METHODS: Histological specimens from 100 cases of Barrett oesophagus and 100 samples of normal squamous oesophageal epithelium were studied. Using a system of multiple measurements until the change in cumulative mean values varied by less than 5%, the overall mean and normal range of depth was calculated for each type of epithelium. RESULTS: Barrett columnar epithelium is minimally thicker (mean (SEM) 0.50 (0.004) mm; range 0.39 to 0.59 mm) than normal squamous epithelium (0.49 (0.003) mm; 0.42 to 0.58 mm), although this difference is probably too small to be of clinical relevance. CONCLUSIONS: Although there are numerous clinical reports of various methods of ablation treatment for Barrett oesophagus, little attention has been paid to the depth of tissue destruction required. This is the first study to look specifically at this issue, and it provides information on the necessary depth of epithelial ablation.     

Submucosal glands in the columnar-lined oesophagus: evidence of an association with metaplasia and neosquamous epithelium

Lörinc E & Öberg S
(2012) Histopathology  61, 53–58 Submucosal glands in the columnar‐lined oesophagus: evidence of an association with metaplasia and neosquamous epithelium Aim: A multipotential stem cell, possibly located in the submucosal gland ducts, has been suggested as the origin of metaplastic mucosa in the oesophagus. The topographic distribution of these glands and their excretory ducts (SMG) within the columnar lined oesophagus (CLO) is largely unknown. The aim of this study was to examine the distribution of SMG in relation to the type of overlying epithelium in patients with CLO. Methods and results: Seven oesophageal resection specimens were examined histologically in toto. The median frequency of SMG was similar in the metaplastic segments (0.12 SMG/mm) and the normal squamous segments (0.10 SMG/mm). Within the metaplastic segments, the median frequency of SMG beneath the squamous islands was significantly higher than that observed under the columnar lined parts (0.22 versus 0.08 SMG/mm, P = 0.046), There was a strong accumulation of SMG at the squamo‐columnar transition zones (0.53 SMG/mm), which was significantly greater than that found in the columnar and squamous parts (P = 0.001 and 0.002, respectively). Conclusions: The relative accumulation of SMG beneath squamous islands and the squamo‐columnar junctions within the metaplastic segment supports the hypothesis that both metaplastic columnar mucosa and neosquamous epithelium originate from a progenitor in the SMG.     

Morphological characteristics of the columnar epithelium lining the lower oesophagus in patients with Barrett's syndrome

Summary Biopsies of five patients with Barrett's syndrome were examined by light microscopic, cytochemical and electron microscopic techniques. It was shown that the mucosa in the lower oesophagus lined by columnar epithelium was very similar to the mucosa lining the cardia of the stomach. It is supposed that such esophageal epithelium represents an upgrowth of cardia mucosa as a response to injury of the squamous epithelium of the oesophagus caused by chronic reflux of gastric contents. The occurrence of goblet cells and patches of villous columnar cells was interpreted as intestinal metaplasia.     

Loss of human leucocyte antigen class I and gain of class II expression are early events in carcinogenesis: clues from a study of Barrett's oesophagus

BACKGROUND: Human leucocyte antigen (HLA) expression is altered in oesophageal carcinomas compared with normal tissue. It is unclear, however, whether this phenotype precedes malignant transformation or results as a consequence of it. AIM: To investigate HLA class I and II expression in Barrett's oesophagus and normal squamous oesophageal tissue. METHODS: Asian patients with Barrett's oesophagus (n = 64) and a control group (n = 60) with a normal oesophagus but without reflux symptoms were recruited using endoscopic and histopathological criteria. Tissue samples were stained with monoclonal antibodies specific for HLA-ABC, HLA-DR alpha chain or HLA-DP/DQ/DR, and scored semiquantitatively. The results of immunohistochemical staining were correlated with clinical and histopathological characteristics of patients. RESULTS: Marked expression of HLA-ABC was observed in 50% of Barrett's oesophagus sections as compared with 68.3% of controls (p = 0.038). HLA-DR staining was seen in 51.6% of Barrett's oesophagus samples versus 11.7% of controls (p<0.001). Expression of HLA-DP/DQ/DR was evident in 73.4% of oesophageal intestinal metaplasia tissue as opposed to 18.3% of controls (p<0.001). Importantly, a total loss of HLA-ABC and a concomitant gain of HLA-DP/DQ/DR expression were seen in 37.5% of patients with Barrett's oesophagus but in none of the controls (p<0.001). Interestingly, this phenotype was associated positively with dysplasia (adjusted p, p* = 0.031) but negatively with non-steroidal anti-inflammatory drug use (p* = 0.004). CONCLUSIONS: HLA class I expression is down regulated and class II expression is up regulated in Barrett's oesophagus. As these changes predate malignant transformation, altered major histocompatibility complex expression may be a key event in disease progression, possibly in facilitating evasion from immune surveillance.     

In vitro validation of a right ventricular thermodilution ejection fraction system

Right ventricular ejection fraction (RVEF) is used clinically as an index of right ventricular (RV) pump function. Clinical measurements of RVEF are complicated by the need for complex imaging equipment to compute RV volumes. Recently, the use of thermodilution (TD) methods have been suggested as a simplified means to measure RVEF (RVEF_TD) in patients using rapid response thermistors. Validation, however, by comparison of RVEF_TD and other methodsin vivo, is difficult. Accordingly, thermodilution derived EF measurements (EF_TD) were compared to known values using anin vitro system, with known ejection fractions (EF) set from 17–78% and stroke rates varying independently from 50–100 strokes/min. EF_TD was computed by fitting the downslope of the TD curve to a monoexponential function and computing the time constant of thermal decay. A significant correlation existed between EF_TD and actual EF over the entire study (r=0.96, p<0.001). Bias analysis showed that the points were within a 95% confidence interval of ±12%. Multivariate analysis showed that stroke rate did not significantly affect TD measurements (r=0.03, p>0.7). This study demonstrates that TD accurately predicts EF using anin vitro system and appears to be independent of stroke rate. Thus, TD methods may provide an accurate, simple and reliable means to serially measure RVEF in the clinical setting. This work was supported in part by a Grant-in-Aid from the American Heart Association, and the Bioengineering Alliance of South Carolina.     

On the histogenesis of Barrett's oesophagus and its associated squamous islands: a three-dimensional study of their morphological relationship with native oesophageal gland ducts

Current hypotheses concerning the histogenesis and regression of Barrett's oesophagus are based predominantly on animal models. Our study was formulated to assess, in human tissue, the morphological relationship between oesophageal gland ducts and both Barrett's oesophagus and their associated squamous islands. Serial sections were cut through a total of 46 blocks of archived oesophageal resection tissue containing oesophageal gland ducts underlying Barrett's epithelium. Serial sections were also taken through 15 squamous islands, taken from the same archived tissue, to assess their underlying histology: 21 of the ducts opened onto overlying Barrett's epithelium; in 17 there was a relatively sharp distinction between the two cell types, at the junction, whereas in four there was continuity and a gradual morphological change between the cells of the oesophageal gland ducts and the Barrett's epithelium. All 15 squamous islands sectioned were found to be continuous with an underlying gland duct. This study suggests an interrelationship between Barrett's epithelium and oesophageal gland ducts. More definitively we confirm that squamous islands are universally associated with oesophageal gland duct epithelium. These findings are of fundamental importance for the development of more targeted management strategies for Barrett's oesophagus.     

Early Barrett's carcinoma: the depth of infiltration of the tumour correlates with the degree of differentiation, the incidence of lymphatic vessel and venous invasion

The incidence of regional lymph node metastasis in early Barrett's carcinoma is determined by the depth of infiltration of the tumour. The present study investigated the possible relationship between the depth of infiltration of the tumour, its degree of differentiation and the incidence of lymphatic vessel and venous invasion in early Barrett's carcinoma. To this end, a total of 805 endoscopically resected specimens obtained from 472 patients with early Barrett's carcinomas were analysed. The results of this analysis revealed that increasing depth of tumour infiltration is associated with an increase in the incidence of poorly differentiated carcinomas—from 0.8% for lesions limited to the mucosa (m1) to 41.4% when the depth of infiltration extended to the lower third of the submucosa (sm3). A similar correlation was also found for the incidence of lymphatic vessel invasion (m1, 0.6%; sm3, 44.8%) and for venous invasion (m1, 0%; sm3, 13.8%). All of these observations proved to be statistically highly significant (p < 0.001). In conclusion, the results show that the degree of differentiation, as well as the incidence of lymphatic vessel and venous invasion, correlates with the depth of infiltration of the early carcinoma in Barrett's oesophagus.     

Proliferating activity in columnar cell lesions of the breast

With the introduction of mammographic screening, columnar cell lesions (CCLs) are observed more and more frequently because they are often associated with microcalcifications. Until now, the proliferative activity of these lesions has not been previously evaluated. Ki67 index was performed by immunohistochemistry in CCLs without atypia [columnar cell change (CCC) n = 20 and columnar cell hyperplasia without atypia (CCH without atypia) n = 20], flat epithelial atypia (FEA DIN1A n = 20), low-grade intraductal carcinoma (DIN1C n = 20), high-grade intraductal carcinoma (DIN 2–3 n = 20). Adjacent terminal duct-lobular unit (TDLU) of normal breast tissue served as control. Ki-67 index is extremely low and close in CCLs without atypia (CCC mean 0.1% and CCH mean 0.76%) and paradoxically is lower than in normal TDLU (mean 2.4%) (p < 0.001). In the FEA, in comparison with normal TDLU and CCLs without atypia, the Ki67 is higher (mean 8.2%) (p < 0.001) but extremely close to those of DIN1C (mean 8.9%) (p = 0.6 NS). Lastly, the Ki67 index is higher in DIN 2–3 (mean 25.4%) than in CCLs without atypia and FEA (p < 0.001). CCLs are disparate lesions having in common cells with columnar configuration but different proliferative characteristics. These data represent findings of biological interest which could help us to better understand these controversial lesions.     

Estimation of habituation and signal-to-noise ratio of cortical evoked potentials to oesophageal electrical and mechanical stimulation

Electrical and mechanical stimulation of the oesophagus has been recently proposed to examine the physiological effects of autonomic stimulation in humans. Cortical evoked potentials (EPs) to oesophageal stimulation provide an assessment of afferent fibres and central processing. However, habituation takes place during averaging of cortical EPs and reduces the signal-to-noise ratio (SNR) as the number of stimuli increases. The SNR of cortical EPs to oesophageal stimulation is computed for 15 normal subjects. Habituation is characterised by the Euclidean distance between the EEG response to single stimuli and the averaged EP, to serve as an objective measure of similarity between the averaged EP and the single-stimulus EEG. With electrical stimulation, the SNR is highest (0.41±0.21) for 1–12 stimuli and then significantly decreases to 0.2±0.08 for 13–24 stimuli (p<0.001). With balloon distension (BD), the SNR is highest (0.22±0.16) for 1–12 stimuli and lowest (0.12±0.14) for 13–24 stimuli, but these SNRs are not significantly different from each other. Both electrical and mechanical stimulation of the oesophagus produce rapidly adapting EPs. The SNR of the EPs is higher with electrical stimulation than with BD. The EPs response to BD has a higher variability and is more noisy. Consequently, these results suggest that the overall cortical EP response to electrical stimulation of the oesophagus is more reproducible than that due to balloon distension.     

Human papillomavirus infection in Barrett's oesophagus in the UK: An infrequent event

BACKGROUND: Human papillomavirus (HPV) infection has been reported in squamous cell carcinomas of the oesophagus and has been recently described in Barrett's oesophagus, a premalignant condition which may give rise to oesophageal adenocarcinoma. OBJECTIVES: To investigate HPV infection in Barrett's oesophagus in a UK population. STUDY DESIGN: DNA was extracted from 73 Barrett's oesophagus biopsies and examined for the presence of DNA for 14 high risk (HR) and 6 low risk (LR) HPV types. RESULTS: HPV DNA was present in only 1 of 73 samples; genotyping indicated this was a high risk type 51 infection. CONCLUSIONS: HPV infection appears unlikely to be a significant factor in the aetiology of Barrett's oesophagus in the UK.     

Barrett's adenocarcinomas resemble adenocarcinomas of the gastric cardia in terms of chromosomal copy number changes,but relate to squamous cell carcinomas of the distal oesophagus with respect to the presence of high-level amplifications

Three different cancers predominantly occur at the gastro-oesophageal junction: squamous cell carcinomas of the distal oesophagus, adenocarcinomas of the distal oesophagus (Barrett's carcinomas), and adenocarcinomas of the gastric cardia. The aim of the present study was to investigate how, and to what extent, Barrett's carcinoma differs from adenocarcinoma of the gastric cardia on the one hand and squamous cell carcinoma of the distal oesophagus on the other, with respect to chromosomal aberrations and related gene expression. The present study analysed 14 squamous cell carcinomas, 24 Barrett's carcinomas, and 16 carcinomas of the gastric cardia. Comparative genomic hybridization revealed chromosomal abnormalities in all cases. Typical chromosomal aberrations for the squamous cell carcinoma type were gains at 3q and 11q13, and losses at 3p, 4q, 9p, 11q, and 13q. In contrast, typical copy number changes for both cardiac and Barrett's adenocarcinomas were gains at 2q, 7p, and 13q, and losses at 17p. High-level amplification occurred in all three groups, but its frequency in the cardiac carcinomas was lower than in the other two groups. In conclusion, squamous cell carcinomas are characterized by chromosomal aberrations which are distinct from those seen in carcinomas of the gastric cardia and in Barrett's adenocarcinomas. With respect to Barrett's cancer, the chromosomal aberrations more closely reflect the adenocarcinoma phenotype than the squamous origin of the epithelium.     

Evaluation of applanation resonator sensors for intra-ocular pressure measurement: Results from clinical and<Emphasis Type="Italic">in vitro</Emphasis> studies

Glaucoma is an eye disease that, in its most common form, is characterised by high intra-ocular pressure (IOP), reduced visual field and optic nerve damage. For diagnostic purposes and for follow-up after treatment, it is important to have simple and reliable methods for measuring IOP. Recently, an applanation resonator sensor (ARS) for measuring IOP was introduced and evaluated using anin vitro pig-eye model. In the present study, the first clinical evaluation of the same probe has been carried out, with experimentsin vivo on human eyes. There was a low but significant correlation between IOP_ARS and the IOP measured with a Goldmann applanation tonometer (r=0.40, p=0.001, n=72). However, off-centre positioning of the sensor against the cornea caused a non-negligible source of error. The sensor probe was redesigned to have a spherical, instead of flat, contact surface against the eye and was evaluated in thein vitro model. The new probe showed reduced sensitivity to off-centre positioning, with a decrease in relative deviation from 89% to 11% (1 mm radius). For normalised data, linear regression between IOP_ARS and direct IOP measurement in the vitreous chamber showed a correlation of r=0.97 (p<0.001, n=108) and a standard deviation for the residuals of SD≦2.18 mm Hg (n=108). It was concluded that a spherical contact surface should be preferred and that further development towards a clinical instrument should focus on probe design and signal analysis.     

Skin blood flow in the human hand in relation to applied pressure

Our aim was to study the relationship between external pressure and skin blood flow (BF) in the area of the palm (P) of the human hand and the relationship between BF and pressure pain thresholds. A special probe was designed for measuring simultaneously the skin BF using a laser Doppler flowmeter and the pressure using an algometer. The normal BF in the distal phalanx of the index finger and in the middle of the thenar musculature was higher than in the middle phalanx of the middle finger and the middle of P. A pressure of 15–33 kPa was required to reduce BF by 50% and 30–52 kPa to reduce by 85% except in P where the pressure had to be much higher; for 50% of the subjects the reduction in BF did not reach 85% even at 100 kPa. After the removal of the pressure the BF was 170%–230% of the normal readings. The BF did not correlate with the pressure pain thresholds. These results indicate that continuously applied pressure in the hand should not be above 50 kPa to avoid tissue damage due to the cessation of BF in the skin. Electronic Publication     

Influence of peripheral chemodenervation on the complexity of respiratory patterns during early maturation

Previous studies in humans have revealed that, during development, the fetus/neonate may be susceptible to environmental perturbations such as overheating, smoking, hypercapnia and hypoxia (Lewis andBosque, 1995;Maskery, 1995). In particular, alterations in behavioural states during early development can result in permanent alterations in their organisational states and subsequent abnormalities in the regulation of the cardiovascular and respiratory systems. The influence of the peripheral chemoreceptor afferent input on the approximate entropy (complexity) of the phrenic neurogram in the piglet was investigated in three different age groups: 3–7 days (n-7), 10–16 days (n=6) and 25–31 days (n=4). The phrenic neurogram was recorded from piglets during control (40% O₂) and severe hypoxia (gasping) (5–10% O₂), before and after peripheral chemodenervation, and was analysed using the approximate entropy (ApEn) method. The results show that the complexity values of the phrenic neurogram during eupnea and gasping did not change significantly before and after chemodenervation, regardless of postnatal age. The complexity values during gasping were not significantly influenced by the carotid chemodenervation for the 3–7 day-old group, but they were significantly decreased by the carotid chemodenervation for the 10–16 day-old age group (p<0.01) and the 25–31 day-old age group (p<0.05). However, the complexity values significantly decreased when the O₂ concentration was shifted from eupnea to gasping (p<0.001), both before and after the chemodenervation (p<0.001), regardless of the postnatal age. These results suggest that the peripheral chemodenervation reduces the complexity of the phrenic neurograms during gasping only for the 10–16 day-old and 25–31 day-old age groups, and it has no significant influence on the 3–7 day-old age group. Therefore it is speculated that the peripheral chemoreceptors may be inactive for the first seven days of postnatal life and become more active after seven days.     

Characteristics of the respiratory mechanical and muscle function of competitive breath-hold divers

Competitive breath-hold divers (BHD) employ glossopharyngeal insufflation (GI) to increase intrapulmonary oxygen stores and prevent the lungs from dangerous compressions at great depths. Glossopharyngeal insufflation is associated with inflation of the lungs beyond total lung capacity (TLC). It is currently unknown whether GI transiently over-distends the lungs or adversely affects lung elastic properties in the long-term. Resting lung function, ventilatory drive, muscle strength, and lung compliance were measured in eight BHD who performed GI since 5.5 (range 2–6) years on average, eight scuba divers, and eight control subjects. In five BHD subsequent measures of static lung compliance (Cstat) were obtained after 1 and 3 min following GI. Breath-hold divers had higher than predicted ventilatory flows and volumes and did not differ from control groups with regard to gas transfer, inspiratory muscle strength, and lung compliance. A blunted response to CO₂ was obtained in BHD as compared to control groups. Upon GI there was an increase in mean vital capacity (VC_GI) by 1.75 ± 0.85 (SD) L compared to baseline (p < 0.001). In five BHD Cstat raised from 3.7 (range 2.9–6.8) L/kPa at baseline to 8.1 (range 3.4–21.2) L/kPa after maximal GI and thereafter gradually decreased to 5.6 (range 3.3–8.1) L/kPa after 1 min and 4.2 (range 2.7–6.6) L/kPa after 3 min (p < 0.01). We conclude that in experienced BHD there is a transient alteration in lung elastic recoil. Resting lung function did not reveal a pattern indicative of altered lung ventilatory or muscle function.     

The limited difference between keratin patterns of squamous cell carcinomas and adenocarcinomas is explicable by both cell lineage and state of differentiation of tumour cells.

AIM: To study the differentiation of epithelial tissues within their histological context, and to identify hypothetically, on the basis of keratin pattern, the putative tissue origin of a (metastatic) carcinoma. METHODS: Using well characterised monoclonal antibodies against individual keratins 7, 8, 18, and 19, which are predominantly found in columnar epithelia, and keratins 4, 10, 13, and 14, predominantly expressed in (non)-keratinising squamous epithelia, the keratin patterns for a series of 45 squamous cell carcinomas and 44 adenocarcinomas originating from various epithelial tissues were characterised. RESULTS: The predominant keratins in all adenocarcinomas proved to be 8, 18, and 19. In addition, these keratins were also abundantly present in squamous cell carcinomas of the lung, cervix, and rectum and, to a lesser extent, of the larynx, oesophagus, and tongue, but not in those of the vulva and skin. Keratins 4, 10, 13, and 14 were present in almost all squamous cell carcinomas, but also focally in some of the adenocarcinomas studied. CONCLUSIONS: There is a limited differential expression of distinctive keratin filaments between squamous cell carcinomas and adenocarcinomas. Apparently, squamous cell carcinomas that originate from columnar epithelium by squamous metaplasia gain the keratins of squamous cells but retain the keratins of columnar epithelial cells. However, the simultaneous expression of two of three squamous keratins (4, 10, and 13) identifies a squamous cell carcinoma, and thus might be useful in solving differential diagnostic problems.     

Association of COX-2 expression with corresponding active and chronic inflammatory reactions in Barrett's metaplasia and progression to cancer

AIMS: Risk reduction for Barrett's cancer in individuals taking non-steroidal anti-inflammatory drugs has been reported. Cyclooxygenase (COX)-2, one of the inhibited enzymes, is putatively involved in Barrett's cancer pathogenesis. The aim of this study was to examine a possible association between COX-2 protein expression and the development and progression of the Barrett's metaplasia-dysplasia-carcinoma sequence and the type and degree of associated inflammatory reaction. METHODS AND RESULTS: Squamous epithelium, metaplastic, low-grade, high-grade dysplastic lesions and tumour tissue of 49 resection specimens from patients with Barrett's adenocarcinoma were immunohistochemically analysed. Active and chronic inflammatory reactions were classified according to the Updated Sydney System. Within the Barrett's sequence, a significant progressive increase in COX-2 expression was identified (P < 0.0001). The most significant differences were detected between squamous epithelium and Barrett's metaplasia (P < 0.001) and from low- to high-grade dysplasia (P < 0.0001). Active and chronic inflammation were significantly different between squamous epithelium and Barrett's metaplasia (P < 0.0001), but not during further progression in the sequence. CONCLUSIONS: Increasing COX-2 expression in Barrett's metaplasia is significantly associated with a change in the local inflammatory reaction, but not during further progression through dysplasia to cancer. This supports the potential of a chemoprevention strategy using COX-2 inhibitors independent of the extent and type of the inflammatory reaction in Barrett's oesophagus.     

Mechanics of porcine coronary arteriesex vivo employing impedance planimetry: A new intravascular technique

Our objective was to evaluate methodological aspects of impedance planimetry, a new balloon catheter-based technique, for the investigation of coronary artery mechanical wall properties. We used a four ring-electrode electrical impedance measuring system that was located inside a balloon. Two of the electrodes were used for excitation and connected to a generator producing a constant alternating current of 250 mA at 5 kHz. The other two electrodes for detection were placed midway between the excitation electrodes. The balloon was distended with electrically conducting fluid through an infusion channel. The vessel cross-sectional area (CSA) was measured according to the field gradient principle by measuring the impedance of the fluid inside the balloon. Impedance planimetry was applied in the three major branches of the coronary arteries of seven extracted porcine hearts to assess luminal CSAs in response to internal pressurization. The biomechanical wall properties were evaluated by computing the strain [(r−r ₀)·r ₀ ⁻¹, wherer is the vessels inner radius computed as (CSA · π⁻¹)^? andr ₀ is the radius of the vessel at a minimal distension pressure], the tension [(r·dP), wheredP is the transmural pressure difference], and the pressure elastic modulus (ΔP·r·Δr ⁻¹). We found thatin vitro testing demonstrated that impedance planimetry was accurate and reproducible. The technique has controllable sources of crror. Measurements were performed with consecutively increasing pressures in the range 1–25 kPa (8–188 mmHg, 0.01–0.25 atm). The CSAs increased nonlinearly and were significantly larger in the left anterior descendent coronary artery (LAD) (1 kPa, mean 5.0 mm²; 25 kPa, mean 21.8 mm²) than in both the left circumflex (Cx) (4.5–16.0 mm²) and the right coronary artery (RCA) (2.8–15.6 mm²) (analysis of variance,P<0.001 for both). The circumferential wall tension-strain relation showed exponential behavior. For a given strain, tension values for LAD were significantly lower than those of Cx (P<0.01). The pressure elastic modulus-strain relation also was exponential, and values for Cx were significantly lower than values for LAD (P<0.001) and RCA (P<0.05). Impedance planimetry was applied to the study of coronary artery biomechanicsex vivo. The LAD had the largest CSA, and the Cx was the least compliant. Methodological aspects of anin vivo introduction of the method require additional evaluation.