Histological assessment of oesophageal columnar mucosa

This review presents the pathological features of Barrett's oesophagus, with an emphasis on the role of pathologists in the diagnosis, surveillance and treatment of the disease. The diagnosis of Barrett's oesophagus is based both on endoscopy and histology. The surveillance of patients relies on systematic biopsy sampling, looking for dysplasia - intraepithelial neoplasia. Well established classifications of dysplasia are now used by pathologists, but there remain problems with this marker. Therefore, many alternative biomarkers have been proposed, that remain of limited interest in daily practice, including DNA-ploidy, proliferation markers, and p53 abnormalities. Endoscopic improvements already allow a better selection of biopsies, and it may be that new technologies will allow 'virtual biopsies'. The role of pathologists is now extended to the evaluation of new therapeutic modalities of early neoplastic lesions in Barrett's oesophagus, especially endoscopic mucosal resection.     

Barrett's oesophagus: from metaplasia to dysplasia and cancer

Barrett's oesophagus is a premalignant condition that predisposes to the development of oesophageal adenocarcinoma. It is detected on endoscopy and confirmed histologically by the presence in the lower oesophagus of a metaplastic mucosa, the so-called specialised epithelium, which resembles incomplete intestinal metaplasia in the stomach. These similarities with incomplete intestinal metaplasia are present on histology, mucin histochemistry, and immunohistochemistry with various differentiation markers (cytokeratins and MUC antigens). On morphology, the carcinogenetic process of Barrett's mucosa progresses through increasing grades of epithelial dysplasia. Dysplasia, a synonym of intraepithelial neoplasia, is the only marker that can be used at the present time to delineate a population of patients at high risk of cancer. Among the numerous molecular events that have been shown to play a role in the neoplastic transformation of Barrett's mucosa, only changes in DNA ploidy, increased proliferation, and alterations of the p53 gene have been suggested to be of potential help in the surveillance of patients.     

Comparison of methylene blue-directed biopsies and four-quadrant biopsies in the detection of high-grade intraepithelial neoplasia and early cancer in Barrett''s oesophagus

BACKGROUND: Barrett's oesophagus embodies the risk of malignant transformation. High-grade intraepithelial neoplasia and early cancer in Barrett's oesophagus are often discrete or macroscopically occult lesions and show a patchy distribution and therefore, directed biopsies in combination with four-quadrant random biopsies are the gold standard for surveillance. AIMS: The aim of this prospective study was to compare methylene blue staining and random biopsies in patients with early Barrett's neoplasia. PATIENTS AND METHODS: Eighty-six patients (mean age 65+/-8 years) with histologically proven but macroscopically in evident high-grade intraepithelial neoplasia (n=17) or early cancer in Barrett's oesophagus (n=69) on HR-endoscopy with all together 98 lesions, were included. In the first step, four-quadrant random biopsies were taken during routine endoscopy (group I). In a second step, staining was performed with a 0.5% solution of methylene blue with a spray catheter. Biopsies of focal areas with decreased stain, heterogeneity of stain or absence stain were taken (group II). RESULTS: In 75/86 patients, high-grade intraepithelial neoplasia or early cancer in Barrett's oesophagus could be diagnosed in the methylene blue group while 56 patients were determined in the random biopsies group (P=0.053). High-grade intraepithelial neoplasia or early cancer was diagnosed in significantly more methylene blue-directed biopsies (80.9% versus 26.4%, P<0.005) and also significantly more lesions could be identified in the methylene blue group (96/98; 98%) while in the random biopsies group only 58/98 lesions (59%) could be localised (P<0.05). When methylene blue was used (1217 versus 562, P<0.0001), the average number of specimens taken with methylene blue per patient was about half of that with random biopsy (6.5 versus 14.1, P<0.0001). CONCLUSIONS: Chromoendoscopy with methylene blue diagnosed significantly more patients and lesions with intraepithelial neoplasia or early cancer in Barrett's oesophagus compared to random biopsies. In addition, significantly less biopsies were needed with methylene blue compared to random biopsies. The use of methylene blue-directed biopsies appears to improve the detection of intraepithelial neoplasia and early cancer in Barrett's oesophagus.     

The Vienna classification of gastrointestinal epithelial neoplasia

BACKGROUND: Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. AIM: To develop common worldwide terminology for gastrointestinal epithelial neoplasia. METHODS: Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. RESULTS: The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). CONCLUSION: The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.     

Squamous intraepithelial neoplasia of the esophagus: past, present, and future

With regard to the esophagus, the term “squamous dysplasia” has been used in European countries, the United States, and China, while its use is controversial in Japan. Recently, “low-grade intraepithelial neoplasia” and “high-grade intraepithelial neoplasia” have been used as inclusive terms for dysplasia and carcinoma in situ in the World Health Organization classification. Endoscopically, it is often difficult to identify squamous intraepithelial neoplasia by conventional endoscopy, but application of iodine is useful for the diagnosis of such a lesion. In addition, new types of endoscopic techniques, including magnifying endoscopy, narrow-band imaging (NBI), and endocytoscopy are helpful to detect squamous intraepithelial neoplasia. NBI is very useful for identifying the intrapapillary capillary loop pattern. Regarding the pathological criteria of squamous dysplasia and squamous cell carcinoma, the views of Japanese and Western pathologists have differed significantly. Before the term “intraepithelial neoplasia” was introduced, severe dysplasia as diagnosed by Western pathologists was in fact the same as squamous cell carcinoma in situ or noninvasive carcinoma as diagnosed by Japanese pathologists. This problem has been solved by the introduction of the Vienna classification; however, there are still some issues that need to be resolved. One of them is the presence of basal layer type squamous cell carcinoma in situ, which is often underdiagnosed as lowgrade intraepithelial neoplasia by Western pathologists. Endoscopic treatments such as endoscopic mucosal resection and endoscopic submucosal dissection have recently become possible choices for squamous intraepithelial neoplasia; however, these techniques are not in widespread use in the West. We believe that a consensus meeting between Japanese and Western pathologists as well as endoscopists should be held promptly to reach a common ground for the nomenclature.     

Barrett''s mucosa, Barrett''s dysplasia and Barrett''s carcinoma: diagnostic endoscopy without biopsy-taking does not suffice

Many gastroenterologists are of the opinion that endoscopic diagnosis of gastro-oesophageal reflux disease (GORD) suffices and that additional biopsies are not necessary. The data obtained from 1068 consecutive patients with histologically confirmed Barrett's oesophagus were analysed retrospectively. In 37.9% of the patients, the histological diagnosis of Barrett's oesophagus was an incidental finding, whereas 32.7% of Barrett's carcinomas were diagnosed only at histology but not during endoscopy. Of the Patients with dysplasia, 92.4% were diagnosed only by the pathologist. Our analysis shows that an endoscopic diagnosis suspicious for Barrett's mucosa is made in 62.1% of the cases, carcinoma in 70%, and dysplasia in only 7.6% of the cases. Also, because neoplasia is detected for the most part at the invasive carcinoma state, but not in the dysplasia stage, the diagnosis of Barrett's oesophagus, with and without dysplasia, needs to be improved by additional biopsies for histopathological investigation.     

Management of pre-malignant and malignant lesions by endoscopic resection

Endoscopic resection (ER) has gained more and more importance in the treatment of early gastrointestinal neoplasia over the last few years. The choice of the different available techniques depends on the site, the macroscopic type of the tumour and the personal experience of the endoscopist. The 'suck-and-cut' technique with ligation device or cap should be favoured to normal strip biopsy in the oesophagus because of the size of the resected specimen and its technical feasibility. A recently described method of ER in the stomach is the circumferential mucosal incision with a type of needle-knife and subsequent en-bloc resection following prior injection under the lesions. ER of high-grade intraepithelial neoplasia and mucosal adenocarcinoma in Barrett's oesophagus should be considered as the treatment of choice. First mid-term results of endoscopic therapy of early squamous-cell neoplasia in the oesophagus show promising results; however, long-term results are awaited. Studies with large numbers of patients in Japan proved the efficiency and safety of ER in low-risk early gastric carcinoma. Duodenal lesions and adenomas of the major duodenal papilla were also proved to be treated successfully by ER. In the colon, ER is used successfully for resection of adenomas and small well-differentiated or moderately differentiated carcinomas that are restricted to the mucosa. ER of gastrointestinal lesions is a safe and effective method but should be performed only by experienced endoscopists.     

Magnification endoscopy,high resolution endoscopy,and chromoscopy; towards a better optical diagnosis

In the past few years, optical magnification endoscopy and chromoscopy have gained renewed interest in the West as a means for the early detection of minute lesions in patients with Barrett's oesophagus and in patients referred for colonic cancer screening. In Barrett's oesophagus, the vast majority of data on the use of chromoscopy deals with the application of methylene blue. Conventional videoendoscopy in combination with methylene blue staining improves the detection of Barrett's mucosa. A correlation has been shown between variation and intensity of staining and histologically verified stages of dysplasia or cancer. Magnification endoscopy and chromoscopy improve the detection of colonic non-polypoid lesions associated with neoplasia and carcinoma. Pitt pattern analysis enables the distinction of non-neoplastic non-polypoid lesions (type I and II) from neoplastic type non-polypoid lesions (type III-V) with great accuracy. It is certain that "old fashioned" chromoscopy combined with advanced endoscopic technology carry a great diagnostic potential and should be further put to the test for use in daily clinical practice.     

Endoscopic removal or ablation of oesophageal and gastric superficial tumours

Endoscopic mucosal resection was developed in Eastern countries as a curative treatment for superficial carcinomas in the stomach and oesophagus. Experience in Western countries is more recent and limited due to less frequent diagnosis of early gastric cancers compared to the Japanese and Korean populations and to more frequent use of ablation techniques such as argon plasma coagulation and photodynamic therapy in pre-neoplastic lesions and superficial tumours. This review summarizes the respective indications, advantages, disadvantages, limitations and complications of the different ablative and resection techniques in the upper gastrointestinal tract. Several methods are described such as electrocoagulation, argon plasma coagulation, photodynamic therapy, lift and cut resection, cap assisted aspiration and band ligation mucosectomy, and endoscopic submucosal dissection. Local results in more than 170 patients managed with endoscopic resection of oesophageal high grade dysplasia or squamous cell carcinoma and gastric or Barrett's epithelium high grade dysplasia or adenocarcinoma furthermore demonstrate the safety and effectiveness of endoscopic resection practiced in experienced centres.     

The importance of the concept and histological criteria of “intraepithelial squamous cell carcinoma” of the esophagus: in comparison between Western and Japanese criteria

Background

There are differences in the histological diagnostic criteria for early stage gastrointestinal carcinoma between Western and Japanese pathologists. Western histological criteria of carcinoma are “presence of stromal invasion of neoplastic cells”, while Japanese criteria are “the degree of cytological and structural abnormality of neoplastic cells, regardless of stromal invasion”. The aim of the present study is to clarify and review the present status of the Western and Japanese histological criteria of early stage esophageal squamous cell carcinoma (SCC) and also to clarify their significance and accuracy.

Methods

Twenty-nine Polish, German, and Japanese pathologists participated in this study. A total of 18 histological slides of biopsy, endoscopic submucosal dissection (ESD), and surgical resection of esophageal squamous lesions were diagnosed using a virtual slide system.

Results

Most of noninvasive (intraepithelial) carcinomas diagnosed by Japanese pathologists were diagnosed as high- or low-grade dysplasia (intraepithelial neoplasia) or reactive atypia by the majority of Polish and German pathologists. Diagnoses of not only high-grade dysplasia but also low-grade dysplasia or reactive lesion by Western criteria were given for many biopsy specimens of cases in which the corresponding ESD or surgical specimens showed definite stromal invasion.

Conclusion

There still exist differences in the histological diagnostic criteria for early stage esophageal carcinoma between Western and Japanese pathologists. The Japanese diagnostic criteria could improve agreement of diagnoses between biopsy and resected specimens of esophageal SCC. Moreover, diagnostic approaches using Western criteria may cause delay in the early diagnosis and treatment of esophageal SCC.

     

K-ras codon 12 mutations in Barrett's oesophagus and adenocarcinomas of the oesophagus and oesophagogastric junction

BACKGROUND: Activation of the ras oncogene is commonly found in gastrointestinal tract cancers, but the role of ras in the development and progression of Barrett's oesophagus and associated cancers is uncertain. METHODS: The frequency of K-ras codon 12 point mutations was assessed in 52 paraffin-embedded tissues from 44 patients with oesophageal pathology. The specimens were classified pathologically as follows: adenocarcinoma of the oesophagus or oesophagogastric junction (n = 23), Barrett's high-grade dysplasia (n = 5), low-grade dysplasia (n = 14), intestinal metaplasia (n = 4), normal oesophagus (n = 5) or normal stomach (n = 1). DNA was extracted from three consecutive sections of each paraffin block and mutations at bases 1 and 2 of K-ras codon 12 were identified using a novel restriction endonuclease-mediated selective polymerase chain reaction method. RESULTS: Mutations were found in 7 of 23 (30.4%) adenocarcinomas and in 2 of 5 (40%) high-grade dysplasia specimens. No mutations were found in specimens of low-grade dysplasia, intestinal metaplasia without dysplasia, or normal oesophagus and stomach. There were no significant associations between the presence of mutations and clinicopathologic features in the patients with cancer. One patient who progressed from low-grade to high-grade dysplasia was found to have developed mutant K-ras in the course of this transformation. CONCLUSION: These results suggest that K-ras codon 12 mutations may occur frequently in patients with Barrett's oesophagus with high-grade dysplasia or adenocarcinoma of the oesophagus or oesophagogastric junction. K-ras mutation may be a late event in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence.     

Time gated fluorescence spectroscopy in Barrett's oesophagus

BACKGROUND AND AIMS: Specialised intestinal metaplasia and its dysplastic transformation, which precedes cancer in Barrett's oesophagus cannot be differentiated in standard gastroscopy. The aim of this study was to investigate whether laser induced protoporphyrin IX fluorescence permits the detection of specialised intestinal metaplasia and dysplasia during endoscopy and to take biopsy specimens in a guided rather than random manner. METHODS: In 53 patients with Barrett's oesophagus 5-aminolaevulinic acid was sprayed on the mucosa. Approximately 60 to 120 minutes later, biopsy specimens were taken based on point-like measurements of delayed fluorescence intensity ratios of protoporphyrin IX in vivo. Two independent pathologists examined the 596 biopsy specimens taken, 168 of which were selected to be investigated by a third pathologist. Among these specimens only those (n=141) with a consensus diagnosis by at least two pathologists and p53 expression as additional marker were included in the analysis. RESULTS: The median of normalised fluorescence intensity (ratio of delayed PpIX fluorescence intensity to immediate autofluorescence intensity) in non-dysplastic specialised intestinal metaplasia (0.51, 68% CI 0.09 to 1.92) and low grade dysplasia (1.89, 68% CI 0.55 to 3.92) differed significantly (p<0.005). Dysplasia was detected at a rate 2.8-fold higher compared with screening endoscopy despite taking fewer specimens. In addition, three early cancers were detected for the first time. Moreover, this method permitted differentiation of specialised intestinal metaplasia from junctional or gastric-fundic type epithelium (p<0.013). CONCLUSIONS: For the first time it was possible to differentiate low grade dysplasia from non-dysplastic Barrett's mucosa during endoscopy based on delayed laser induced fluorescence endoscopy of PpIX. Furthermore, the method helps to detect specialised intestinal metaplasia in short Barrett's oesophagus.     

Helicobacter pylori infection: protection against Barrett's mucosa and neoplasia?

BACKGROUND: Since Helicobacter pylori (Hp) infection provokes intestinal and gastric metaplasia, the question arises whether the specialized metaplasia (Barrett's mucosa (BM)) and dysplasia or carcinoma in Barrett's epithelium seen in gastro-oesophageal reflux disease (GORD) might not also be correlated with Hp infection, or whether the latter offers protection against Barrett's oesophagus and Barrett's adenocarcinoma. PATIENTS: Gastric and oesophageal biopsies obtained from a total of 2,201 patients were analysed retrospectively. 297 of these patients had GORD (age 53.5 +/- 13.4 years; m:f ratio 2.1:1), 1,192 patients had BM (age 62.8 +/- 14.6 years; m:f 2.3:1) with or without neoplasia. 1,054 of these patients were diagnosed as having BM alone, 138 patients having BM neoplasia (high-grade dysplasia or adenocarcinoma). Patients with BM and low-grade dysplasia were excluded from this study because of the uncertainty in differentiating low-grade dysplasia from regenerative epithelium. A total of 712 patients with non-ulcer dyspepsia (NUD; average age 40.0 +/- 16.1 years; m:f 0.3:1) served as a control group. RESULTS: The percentage of Hp infection did not differ between patients with GORD with (53.3%)/without BM (51.4%) and neoplasia (47.8%), but is statistically significantly lower than in patients with NUD (65.7%). CONCLUSION: Our analysis shows that patients with GORD and Hp infection have no increased risk for the development of BM or neoplasia in BM. Since Hp infection is significantly less frequent in GORD than in NUD patients, a protective effect of the Hp infection is a possibility worth discussing.     

Barrett's oesophagus: Current controversies

Oesophageal adenocarcinoma is rapidly increasing in Western countries. This tumour frequently presents late in its course with metastatic disease and has a very poor prognosis. Barrett's oesophagus is an acquired condition whereby the native squamous mucosa of the lower oesophagus is replaced by columnar epithelium following prolonged gastro-oesophageal reflux and is the recognised precursor lesion for oesophageal adenocarcinoma. There are multiple national and society guidelines regarding screening,surveillance and management of Barrett's oesophagus,however all are limited regarding a clear evidence base for a well-demonstrated benefit and cost-effectiveness of surveillance,and robust risk stratification for patients to best use resources. Currently the accepted risk factors upon which surveillance intervals and interventions are based are Barrett's segment length and histological interpretation of the systematic biopsies. Further patient risk factors including other demographic features,smoking,gender,obesity,ethnicity,patient age,biomarkers and endoscopic adjuncts remain under consideration and are discussed in full. Recent evidence has been published to support earlier endoscopic intervention by means of ablation of the metaplastic Barrett's segment when the earliest signs of dysplasia are detected. Further work should concentrate on establishing better risk stratification and primary and secondary preventative strategies to reduce the risk of adenocarcinoma of the oesophagus.     

Magnification chromoendoscopy for the detection of intestinal metaplasia and dysplasia in Barrett's oesophagus

BACKGROUND: The presence of intestinal metaplasia (IM) in the columnar lined distal oesophagus defines Barrett's oesophagus with the risk of future malignant transformation. The distribution of both IM and dysplasia (low grade (LGD) and high grade (HGD)) within the columnar lined oesophagus is patchy and mosaic requiring random biopsies. Techniques that could help target areas of high yield within Barrett's mucosa would be helpful. AIM: To study the utility of high magnification chromoendoscopy (MCE) in the detection of IM, LGD, and HGD in patients with Barrett's oesophagus. METHODS: Consecutive patients detected with columnar mucosa in the distal oesophagus were studied using an Olympus magnification endoscope (GIF-Q16OZ, 115x). The distal oesophagus was sprayed with indigo carmine solution and the oesophageal columnar mucosa patterns were noted under high magnification and targeted for biopsy. All biopsies were read by pathologists blinded to the endoscopic findings. RESULTS: Eighty patients with suspected Barrett's oesophagus (that is, columnar lined distal oesophagus) were studied: mean age 62.7 years (range 35-81). Mean length of columnar mucosa was 3.7 cm (range 0.5-17). Three types of mucosal patterns were noted within the columnar mucosa after spraying indigo carmine and using MCE: ridged/villous pattern, circular pattern, and irregular/distorted pattern. The yield of IM on target biopsies according to the patterns was: ridged/villous 57/62 (97%) and circular 2/12 (17%). Six patients had an irregular/distorted pattern and all had HGD on biopsy (6/6 (100%)). Eighteen patients had LGD on target biopsies; all had the ridged/villous pattern. All patients with long segment Barrett's were identified using MCE whereas 23/28 patients (82%) with short segment Barrett's had the ridged/villous pattern. CONCLUSIONS: MCE helps visually identify areas with IM and HGD having specific patterns but not patients with LGD (appear similar to IM). MCE may be a useful clinical tool for the increased detection of patients with IM as well as for surveillance of patients for the detection of HGD. If these preliminary results are validated, MCE would help identify high yield areas, potentially eliminating the need for random biopsies.     

Endoscopic mucosal resection in the upper gastrointestinal tract

Endoscopic mucosal resection （EMR） is a technique used to locally excise lesions confined to the mucosa. Its main role is the treatment of advanced dysplasia and early gastrointestinal cancers. EMR was originally described as a therapy for early gastric cancer. Recently its use has expanded as a therapeutic option for ampullary masses, colorectal cancer, and large colorectal polyps. In the Western world, the predominant indication for EMR in the upper gastrointestinal tract is the staging and treatment of advance dysplasia and early neoplasia in Barrett＇s esophagus. This review will describe the basis, indications, techniques, and complications of EMR, and its role in the management of Barrett＇s esophagus.     

A surveillance programme for Barrett's oesophagus in a UK general hospital

BACKGROUND: Surveillance programmes for oesophageal cancer in patients with Barrett's columnar-lined oesophagus have reported varying efficacies. AIM: To review the effectiveness of an endoscopic surveillance programme for patients with Barrett's oesophagus in a UK general hospital. METHODS: Patients with Barrett's oesophagus (> or =3 cm histologically proven columnar-lined oesophagus) were identified from endoscopic and histological records and outcomes recorded when surveillance was performed with 2-yearly endoscopies and quadrantic biopsies at 3 cm intervals. RESULTS: One hundred and twenty-one patients (24%) entered the surveillance programme (mean age 60.2 years, 69.5% men, mean length of Barrett's mucosa 7.5 cm) of 505 patients identified with Barrett's oesophagus. Two hundred and five endoscopies were performed over a mean follow-up of 3.5 years. Five cases of high-grade dysplasia and two cases of adenocarcinoma were detected during the surveillance. One patient with high-grade dysplasia refused surgery and died of oesophageal carcinoma. The other six patients underwent oesophagectomy and five of the six resected specimens showed early (Tis to T2, N0) adenocarcinoma. All six patients remained well and tumour free at 24 months. No interval oesophageal cancers occurred. CONCLUSION: This surveillance programme for classical Barrett's oesophagus was effective with six cancers being detected early and treated. The detection rate was 1/71 patient-years of surveillance. Endoscopic workload was not excessive and no interval cancers occurred.     

Expression of the p53 homologue p63alpha and DeltaNp63alpha in the neoplastic sequence of Barrett's oesophagus: correlation with morphology and p53 protein

BACKGROUND: While loss of p53 function is a key oncogenic step in human tumorigenesis, mutations of p53 are generally viewed as late events in the metaplasia-dysplasia-adenocarcinoma sequence of Barrett's oesophagus. Recent reports of a series of genes (p63, p73, and others) exhibiting close homology to p53 raise the possibility that abnormalities of these p53 family members may exert their influence earlier in the sequence. AIM: Following recent characterisation of expression of p63 and a major isoform DeltaNp63 by generation of an antiserum that recognises p63 isoforms, but not p53, our aim was a comparative study of expression of p63 protein and p53 protein in a morphologically well defined biopsy series representative of all stages of the metaplasia-dysplasia-carcinoma sequence in Barrett's oesophagus. METHODS: A series of 60 biopsy cases representing normal oesophagus through to invasive adenocarcinoma were stained, using immunohistochemistry, with antibodies to p63 and p53. All biopsies derived from patients with endoscopic and histopathological substantiation of a diagnosis of traditional/classical Barrett's oesophagus. RESULTS: There was exact concordance in p53 and p63 expression in more advanced forms of neoplasia, high grade dysplasia, and invasive adenocarcinoma, while p63, but not p53, was detected in the proliferative compartment of some non-neoplastic oesophageal tissue, in both squamous mucosa and in the non-neoplastic metaplastic glandular epithelium. CONCLUSIONS: In neoplastic Barrett's oesophagus there is upregulation of both p63 and p53 while p63 isoforms may well have an important role in epithelial biology in both non-metaplastic and metaplastic mucosa of the oesophagus. While abnormalities of p53 function represent an indisputable and critical element of neoplastic transformation, other closely linked genes and their proteins have a role in both the physiology and pathophysiology of the oesophageal mucosa.     

Elastic scattering spectroscopy accurately detects high grade dysplasia and cancer in Barrett's oesophagus

BACKGROUND AND AIMS: Endoscopic surveillance of Barrett's oesophagus currently relies on multiple random biopsies. This approach is time consuming, has a poor diagnostic yield, and significant interobserver variability. Elastic scattering spectroscopy is a real time in vivo optical technique which detects changes in the physical properties of cells. The aim of this study was to assess the potential for elastic scattering to detect high grade dysplasia or cancer within Barrett's oesophagus. METHODS: Elastic scattering spectroscopy measurements collected in vivo were matched with histological specimens taken from identical sites within Barrett's oesophagus. All biopsies were reviewed by three gastrointestinal pathologists and defined as either "low risk" (non-dysplastic or low grade dysplasia) or "high risk" (high grade dysplasia or cancer). Two different statistical approaches (leave one out and block validation) were used to validate the model. RESULTS: A total of 181 matched biopsy sites from 81 patients, where histopathological consensus was reached, were analysed. There was good pathologist agreement in differentiating high grade dysplasia and cancer from other pathology (kappa = 0.72). Elastic scattering spectroscopy detected high risk sites with 92% sensitivity and 60% specificity and differentiated high risk sites from inflammation with a sensitivity and specificity of 79%. If used to target biopsies during endoscopy, the number of low risk biopsies taken would decrease by 60% with minimal loss of accuracy. A negative spectroscopy result would exclude high grade dysplasia or cancer with an accuracy of >99.5%. CONCLUSIONS: These preliminary results show that elastic scattering spectroscopy has the potential to target conventional biopsies in Barrett's surveillance saving significant endoscopist and pathologist time with consequent financial savings. This technique now requires validation in prospective studies.     

Evaluation of dysplasia in gastrointestinal diseases

Dysplasia, or intraepithelial neoplasia, consists of noninvasive neoplastic cellular proliferation that may precede or accompany invasive neoplasia. Diagnosis is mainly based on histological criteria, which include cytological and structural alterations, since macroscopically identifiable lesions often do not occur. In all current classifications, dysplasia is divided in two categories, low- and high-grade, with the aim of attempting to evaluate risk and guide the therapeutic approach. The classification of the Vienna consensus aims to unity criteria and decrease interobserver variability in diagnosis. In the digestive tract, evaluation of epithelial dysplasia is especially important in four entities: Barrett's esophagus, chronic gastritis, inflammatory bowel disease, and colorectal adenomas. The criteria for diagnosis and dysplasia staging are the same in all these entities, but the therapeutic approach may vary according to the affected organ and the clinico-pathological context.