David Poller

Consensus Statements for Management of Barrett's Dysplasia and Early-Stage Esophageal Adenocarcinoma, Based on a Delphi Process

BACKGROUND & AIMS Esophageal adenocarcinoma (EA) is increasingly common among patients with Barretts esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. METHODS We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. RESULTS Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. CONCLUSIONS We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies.

Individual crypt genetic heterogeneity and the origin of metaplastic glandular epithelium in human Barrett's oesophagus

Objectives: Current models of clonal expansion in human Barrett’s oesophagus are based upon heterogenous, flow-purified biopsy analysis taken at multiple segment levels. Detection of identical mutation fingerprints from these biopsy samples led to the proposal that a mutated clone with a selective advantage can clonally expand to fill an entire Barrett’s segment at the expense of competing clones (selective sweep to fixation model). We aimed to assess clonality at a much higher resolution by microdissecting and genetically analysing individual crypts. The histogenesis of Barrett’s metaplasia and neo-squamous islands has never been demonstrated. We investigated the oesophageal gland squamous ducts as the source of both epithelial sub-types. Methods: Individual crypts across Barrett’s biopsy and oesophagectomy blocks were dissected. Determination of tumour suppressor gene loss of heterozygosity patterns, p16 and p53 point mutations were carried out on a crypt-by-crypt basis. Cases of contiguous neo-squamous islands and columnar metaplasia with oesophageal squamous ducts were identified. Tissues were isolated by laser capture microdissection and genetically analysed. Results: Individual crypt dissection revealed mutation patterns that were masked in whole biopsy analysis. Dissection across oesophagectomy specimens demonstrated marked clonal heterogeneity, with multiple independent clones present. We identified a p16 point mutation arising in the squamous epithelium of the oesophageal gland duct, which was also present in a contiguous metaplastic crypt, whereas neo-squamous islands arising from squamous ducts were wild-type with respect to surrounding Barrett’s dysplasia. Conclusions: By studying clonality at the crypt level we demonstrate that Barrett’s heterogeneity arises from multiple independent clones, in contrast to the selective sweep to fixation model of clonal expansion previously described. We suggest that the squamous gland ducts situated throughout the oesophagus are the source of a progenitor cell that may be susceptible to gene mutation resulting in conversion to Barrett’s metaplastic epithelium. Additionally, these data suggest that wild-type ducts may be the source of neo-squamous islands.

Fine-needle aspiration of the thyroid.

Although fine‐needle aspiration (FNA) of the thyroid is the key preoperative investigation of thyroid lesions, there are overlaps in the criteria for diagnosis of certain lesions, particularly important among which are those for follicular neoplasms. A proposal for a 5‐category working system for thyroid FNA diagnosis is presented, devised using clearly defined diagnostic guidelines with a prospective 2‐year evaluation in 1 center.

The Interobserver Reproducibility of Thyroid Fine-Needle Aspiration Using the UK Royal College of Pathologists’ Classification System

The overall interobserver reproducibility of thyroid fine-needle aspiration (FNA) has not been comprehensively assessed. A blinded 6-rater interobserver reproducibility study was conducted of 200 thyroid FNA cases using the UK System, which is similar to The Bethesda System for Reporting Thyroid Cytology: Thy1, nondiagnostic; Thy2, nonneoplastic; Thy3a, atypia, probably benign; Thy3f, follicular lesion; Thy4, suspicious of malignancy; and Thy5, malignant. There was good interobserver agreement for the Thy1 (κ = 0.69) and Thy5 (κ = 0.61), moderate agreement for Thy2 (κ = 0.55) and Thy3f (κ = 0.51), and poor agreement for Thy3a (κ = 0.11) and Thy4 (κ = 0.17) categories. Combining categories implying surgical management (Thy3f, Thy4, and Thy5) achieved good agreement (κ = 0.72), as did combining categories implying medical management (Thy1, Thy2, and Thy3a; κ = 0.72). The UK thyroid FNA terminology is a reproducible and clinically relevant system for thyroid FNA reporting. This study demonstrates that international efforts to harmonize and refine thyroid cytology classification systems can improve consistency in the clinical management of thyroid nodules.

Acetic Acid Spray Is an Effective Tool for the Endoscopic Detection of Neoplasia in Patients With Barrett's Esophagus

BACKGROUND & AIMS Diagnosis of Barretts neoplasia requires collection of large numbers of random biopsy samples; the process is time consuming and can miss early-stage cancers. We evaluated the role of acetic acid chromoendoscopy in identifying Barretts neoplasia. METHODS Data were collected from patients with Barretts esophagus examined at a tertiary referral center, between July 2005 and November 2008 using Fujinon gastroscopes and EPX 4400 processor (n = 190). All procedures were performed by a single experienced endoscopist. Patients were examined with white light gastroscopy and visible abnormalities were identified. Acetic acid (2.5%) dye spray was used to identify potentially neoplastic areas and biopsy samples were collected from these, followed by quadrantic biopsies at 2 cm intervals of the remaining Barretts mucosa. The chromoendoscopic diagnosis was compared with the ultimate histological diagnosis to evaluate the sensitivity of acetic acid chromoendoscopy. RESULTS Acetic acid chromoendoscopy had a sensitivity of 95.5% and specificity of 80% for the detection of neoplasia. There was a correlation between lesions predicted to be neoplasias by acetic acid and those diagnosed by histological analysis (r = 0.98). There was a significant improvement in the detection of neoplasia using acetic acid compared with white light endoscopy (P = .001). CONCLUSIONS Analysis of this large series showed that acetic acid-assisted evaluation of Barretts esophagus detects neoplasia better than white light endoscopy, with sensitivity and specificity equal to that of histological analysis.

The importance of skip lesions in temporal arteritis

Aim—To determine the frequency of skip lesions in an unselected series of temporal artery biopsies and compare the results with other series. Methods—The study was a retrospective review of 102 consecutive temporal artery biopsies taken in a five year period (1992–1997) in one large hospital. Results—35 cases (34.3%) showed evidence of active cranial vasculitis with pathological evidence of inflammation of the intima or media, with or without giant cells. Three of these cases (8.5%) showed apparent skip lesions: normal intima, media, and adventitia in one segment while in other segments there was clear evidence of active vasculitis. Immunocytochemical stains for leucocyte common antigen (LCA) and CD15 were helpful in identifying the absence of intimal or medial inflammatory cell infiltrates within skip lesions. Skip lesions have been described in up to 28.3% of cases in some series, while others have not found evidence of skip lesions or have identified them in a much smaller percentage of cases. Conclusions—In this series skip lesions were relatively rare, accounting for 8.5% of cases of active vasculitis. The degree of inflammation in temporal arteritis is discontinuous. Immunostaining for inflammatory cells, for example LCA and CD15, may be helpful in identifying the presence of an inflammatory cell infiltrate in skip lesion segments of the temporal artery.

Fine needle aspiration cytology (FNAC) of salivary gland tumours: repeat aspiration provides further information in cases with an unclear initial cytological diagnosis.

INTRODUCTION Fine needle aspiration cytology (FNAC) for salivary gland tumours requires expertise in interpretation. When a diagnosis is not clear (despite a cellular aspirate), published work is lacking on the value of repeating the test. METHODS A retrospective study of 135 patients who had FNAC followed by definitive excision for a suspected salivary gland tumour. Accuracy was compared among those requiring repeat FNAC on one more occasion because of a non-diagnostic initial cytology report. RESULTS 33 patients (24% of study group) had repeat FNAC. A definite cytological diagnosis was subsequently made in 27/33 patients (82%). The sensitivity (84%) and specificity (93%) of repeat FNAC in distinguishing benign from malignant tumours was similar to initial FNAC (70% and 95%, respectively). CONCLUSIONS Repeat FNAC may provide a cytological diagnosis in cases where the initial diagnosis is not clear, although cytology should be used in conjunction with other investigations of salivary tumours, including image-guided biopsy examination where appropriate. Ideally salivary gland FNAC should be interpreted by a specialist pathologist.

Diagnostic terminology for reporting thyroid fine needle aspiration cytology: European Federation of Cytology Societies thyroid working party symposium, Lisbon 2009

G. Kocjan, B. Cochand‐Priollet, P. P. de Agustin, C. Bourgain, A. Chandra, Y. Daneshbod, A. Deery, J. Duskova, C. Ersoz, G. Fadda, A. Fassina, P. Firat, B. Jimenez‐Ayala, P. Karakitsos, O. Koperek, N. Matesa, D. Poller, L. Thienpont, A. Ryska, U. Schenck, T. Sauer, F. Schmitt, E. Tani, T. Toivonen, M. Tötsch, G. Troncone, L. Vass and P. Vielh
Diagnostic terminology for reporting thyroid fine needle aspiration cytology: European Federation of Cytology Societies thyroid working party symposium, Lisbon 2009

Thyroid FNAC cytology: can we do it better?

This article reviews recent developments in thyroid fine needle aspiration cytology (FNAC). While thyroid nodules are common, carcinoma is comparatively rare. Although histological assessment is used in most studies as the benchmark, the differential diagnosis on cytology or histology is not always reproducible. The literature shows wide variations in criteria for inadequate thyroid FNAC and study inclusion or exclusion criteria. In‐clinic assessment of specimen adequacy and in‐clinic reporting of thyroid FNAC has become popular although the costs and resource implications of in‐clinic thyroid FNAC assessment and reporting are substantial. Many centres continue to use conventional techniques although liquid‐based cytology and ultrasound‐guided FNAC are gaining in popularity. Standardized categorical systems for FNAC reporting can make results easier to understand for clinicians and give clear indications for therapeutic action. Multidisciplinary case review is also essential, especially when there is diagnostic uncertainty. While currently of limited use, molecular pathology testing holds out some promise for the future.

INDUCIBLE NITRIC OXIDE SYNTHASE : CORRELATION WITH EXTRACAPSULAR SPREAD AND ENHANCEMENT OF TUMOR CELL INVASION IN HEAD AND NECK SQUAMOUS CELL CARCINOMA

Extracapsular nodal spread is a major prognostic indicator in head and neck cancer. Nitric oxide (NO), primarily produced by the enzyme inducible NO synthase (iNOS), has a large number of actions in cancer biology, but no studies have investigated its possible role in extracapsular spread or tumor invasion.