Search

Background/objectives: To determine the incidence, proportion and location of periocular tumours in an English county over a five year period, and compare to other studies in the UK and worldwide., Subjects/methods: A retrospective review of histopathology reports was performed for all periocular excision biopsies of malignancies from the county's three main hospitals over a 5-year period. These hospitals cover a population of just over one million. Tumours were classified according to type and location., Results: 1220 lesions were included in this study. Right-sided lesions were more common than left. The incidence of basal cell carcinoma was 22 per 100,000 and squamous cell carcinoma 1.3 per 100,000, which were found most commonly on the lower eyelid and eyebrow respectively. The incidences of all other types of lesions were less than 0.5 per 100,000 per year., Conclusions: The incidence of periocular basal cell carcinomas in the predominantly elderly Caucasian population was at least three times the published national average. The high incidence of periocular tumours in this North East Anglian county is set to increase further as the proportion of over 65 year olds in the population is predicted to nearly double within two decades., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

A 59-year-old woman with schizoaffective disorder presented with an itchy, blistering generalised rash. One month prior, she had started empagliflozin, a sodium glucose transporter-2 (SGLT-2) inhibitor, used in type-2-diabetes. She was already established on paliperidone, an atypical antipsychotic, for 1 year. Serology at presentation was positive for anti-pemphigoid antibodies. Histology demonstrated subepidermal blistering, perivascular inflammation and eosinophils. Direct immunofluorescence was characteristic of bullous pemphigoid (BP), with linear IgG and C3 at the basement membrane. Both empagliflozin and paliperidone were discontinued. However, the blisters persisted. Treatment included: topical Dermovate and Eumovate ointment for the body and face respectively, alongside oral doxycycline 200 mg and prednisolone 40 mg for a week (reducing by 5 mg/week over 8 weeks). Nevertheless, new blisters continued developing, hence dapsone 50 mg was introduced, with significant improvement. Increasingly, several neurological and psychiatric disorders have been linked with BP, complicating aetiology and management. The underlying mechanism for these associations is not fully understood. Bullous pemphigoid autoantigens BP180 and BP230 are expressed in the central nervous system and it is thought that neurodegeneration may expose antigens to the immune system, generating a cross-reactive immune response. However, there also appears to be bidirectional causality between BP and neuropsychological conditions. Furthermore, as there was an association of empagliflozin initiation and BP onset, this further complicates the aetiology and presents a potential novel drug cause of BP. This case emphasises the neuropsychological issues associated with managing complex BP cases, a possible novel cause of drug-induced BP and highlights the likelihood of these issues becoming increasingly prevalent for the future., Competing Interests: Dr George W. M. Millington is the Editor in Chief of Skin Health and Disease. Dr Sarah M. Dyson is an Associate Editor of Skin Health and Disease., (© 2022 The Authors. Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Aims: To evaluate primary periocular basal cell carcinomas (BCCs) in depth including comparing histological margins with subtype, location and surgical specialty after wide local excision., Methods: A retrospective review was performed for all BCCs excised from three hospitals over 5 years, covering a population of just over 1 million. Tumours were classified according to histological subtype location. Incomplete excision rates and margins were analysed in detail and comparisons made., Results: The most common subtype found was nodular followed by infiltrative. Lesions were most commonly located at the lower lid. Infiltrative BCCs were associated with perineural invasion and incomplete excision despite the largest peripheral margins. Superficial BCCs had the smallest mean peripheral margin but the largest mean deep margin. 2 mm histological margins gave an 83.7% complete excision rate, 6.4% incomplete excision rate and 7.1% where the clearance margin was 0.3 mm or less., Conclusion: Distribution of eyelid BCCs based on subtype and periocular location mirrored the general consensus. Infiltrative BCCs should be excised with wider margins or referred for Mohs surgery, especially if the medial canthus is involved. Superficial BCCs should be excised with wider but shallower surgical margins. Ophthalmologists were more likely than dermatologists or plastic surgeons to incompletely excise a periocular BCC, which is reflective of their more difficult case mix.

Background: Merkel Cell Carcinoma (MCC) is an infrequent but highly aggressive skin cancer. Five-year survival rates are poor, as there are high rates of metastases at primary diagnoses. Recurrences are also common. There is controversy about actual incidence rates which vary considerably between developed countries with majority populations of fair skin types., Objectives: We report the age-standardized incidence rates of MCC for both males and females from the East of England, and use linear regression analyses to estimate numbers of cases for 2020 and 2025 to aid healthcare planning and allocation of resources., Methods: All cases of MCC diagnosed histopathologically between 1 st January 2004 and 31 st December 2013 were extracted from the databases of the Eastern Office, National Cancer Registration Service, Public Health England, and the Pathology department of the Norfolk and Norwich University Hospital, which serves as the tertiary referral centre for the region. Age-standardization incidence rate calculations (ASIs) and linear regression analyses were performed., Results: The ASIs for males and females were 0.70 and 1.08 per 100 000 person-years respectively. The total age-adjusted incidence rate was therefore 1.78 per 100 000 person-years. The ratio of female: male disease was 3:2. The total number of cases for this region over the time period studied was 73. There has been a threefold increase over this period. Estimated cases for this region are 17 in 2020, and 22 in 2025. Estimated UK cases for 2020 are 920, and 1134 in 2025., Conclusions: MCC is increasing steadily in the East of England, and has risen threefold over the last 10 years and is similar to the highest reported rates from Western Australia. These data are 12-fold higher than previous UK estimates, and suggest that the incidence rate is also rising in other regions of the UK., (© 2016 European Academy of Dermatology and Venereology.)

Although the role of the skin in the development and propagation of Dupuytren disease remains unclear, dermofasciectomy and full-thickness skin grafting (FTSG) appears to delay recurrence. In 2011, a 71-year-old, left-handed man presented with recurrent Dupuytren disease in the dominant hand. In 1991, he originally underwent a primary dermofasciectomy and FTSG for Dupuytren disease involving the palmar skin. Twenty years later, the left middle finger was drawn into flexion by a recurrent cord, and the old graft and adjacent palmar skin were clinically involved by fibromatosis. We performed a revision dermofasciectomy and FTSG. Microscopic analysis of the excised graft demonstrated dense infiltration of the entire skin graft by Dupuytren disease, with areas of active and burnt-out fibromatosis distinct from hypertrophic scarring. This report of Dupuytren fibromatosis infiltrating a skin graft raises questions about the pathophysiology of Dupuytren disease., (Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: Determining the BRAF mutation status of patients with advanced metastatic melanoma is essential in order to assess patients' eligibility for targeted BRAF inhibitor therapy. The aim of this study was to validate the utility of immunohistochemistry (IHC) to rapidly obtain the BRAF status in the UK cancer centre setting., Methods: All samples sent for molecular testing for detection of the BRAF mutation over a 26-month period were prospectively tested using the VE1 monoclonal antibody IHC stain., Results: Two-hundred and nineteen samples from 214 patients were identified. All patients were AJCC stage III/IV, except one. There was an overall 95.0% (208/219) concordance rate, with a sensitivity of 94.4% (84/89) and a specificity of 95.4% (124/130) when using genomic assays as the gold standard. Discordance resulted from the inability of the molecular technique to detect the V600E2 mutation and an inability of the IHC staining technique to detect non-V600E mutations. Molecular testing on smaller tumour deposits was also unreliable., Conclusions: IHC staining has good sensitivity and excellent specificity for BRAF V600E mutations. BRAF IHC can be incorporated into a BRAF mutation testing algorithm for UK cancer centres to as a feasible first-line assay and identify a subset of cases that require subsequent genomic testing. It has the additional major advantages of reduced cost and rapid turnaround time.

Unlabelled: Whether the palmar skin has a role in the development, propagation or recurrence of Dupuytren's disease remains unclear. Clinical assessment for skin involvement is difficult and its correlation with histology uncertain. We prospectively biopsied the palmar skin of consecutive patients undergoing single digit fasciectomy (for primary Dupuytren's disease without clinically involved skin) and dermofasciectomy (for clinically involved skin or recurrence) in order to investigate this relationship. We found dermal fibromatosis in 22 of 44 patients (50%) undergoing fasciectomy and 41 of 59 patients (70%) undergoing dermofasciectomy. Dermal fibromatosis appeared to be associated with greater preoperative angular deformity, presence of palmar nodules and occupations involving manual labour. Dermal fibromatosis exists in the absence of clinical features of skin involvement and we hypothesize that the skin may have a greater role in the development and propagation of Dupuytren's disease than previously thought., Level of Evidence: III., (© The Author(s) 2015.)

Background: Complete excision of high-risk extensive non-melanoma skin cancers in the head and neck is paramount to achieving loco-regional control. However, achieving clear margins still remains a significant challenge. Mohs' micrographic surgery (MMS) provides the most accurate method of intraoperative mapping and histological assessment of tumour margins. We have developed a technique combining MMS with reconstruction as a single-stage procedure performed under general anaesthetic. We present our experience and results., Materials and Methods: Following regional skin cancer multidisciplinary team (MDT) discussion, patients considered appropriate for management as a single-stage combined procedure were referred for assessment. At surgery, a two-team approach was employed consisting of an MMS resection team and a reconstructive team, allowing simultaneous resection and elevation of any free tissue required for reconstruction. Outcome data were retrieved from a prospectively collated MMS database., Results: Twenty-six cases were performed between January 2010 and January 2013. Fifty-eight percent of cases were basal cell carcinomas. Clear margins were achieved in 50% of cases following the first Mohs' layer. Free tissue reconstruction was required in 13 cases. Mean anaesthetic time was 445 min. Loco-regional control was achieved in 96% of patients, at a mean follow-up period of 29 months (range 11-50 months)., Conclusions: This study shows that the combined single-stage MMS and reconstruction surgical model is safe, results in a low recurrence rate and improved patient care. It is a model that can be replicated in other tertiary skin cancer units., (Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: Intraoperative frozen section analysis (IFSA) is traditionally performed for complex and high-risk non-melanoma skin cancer (NMSC) resections, particularly when surgery under a general anaesthetic and a complex reconstruction is required, and where Mohs micrographic surgery (MMS) is not available., Methods: A retrospective audit of 253 cases between 1999 and 2009 was undertaken, investigating the accuracy and efficacy of IFSA for the treatment of NMSC in our tertiary skin tumour unit based in a university hospital setting., Results: The combined incomplete and very narrow (<1 mm) excision margin rates were 28.7% and 27.5% for basal cell and squamous cell carcinoma, respectively. Unrepresentative sampling of the excision margins intraoperatively was the overwhelming cause of error (94%)., Conclusion: After a thorough audit of our data, IFSA has been abandoned for the treatment of NMSC in our unit. MMS is practised intraoperatively, even in advanced cases. We believe that IFSA no longer has any role in our complex, multidisciplinary skin cancer practice., (© 2015 British Association of Dermatologists.)

A 72-year-old woman with a 14-year history of urticarial vasculitis (UV) and a 13-year history of bullous pemphigoid (BP) presented with associated progressive chronic lymphocytic leukaemia (CLL). Both skin conditions responded poorly to treatment, until chemotherapy for CLL was commenced. The skin features showed a clear paraneoplastic course, resolving with chemotherapy and recurring when the CLL relapsed and the lymphocyte count rose above 5 × 10(9)/L. No case of UV secondary to CLL, and very few cases of BP related to CLL have been reported, and no paraneoplastic rash of any type lasting 14 years has been reported previously., (© 2014 British Association of Dermatologists, North American Clinical Dermatologic Society and St Johns Dermatological Society.)

Background: The timing of the risk factors cigarette smoking, alcohol and obesity in the development of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) is unclear., Aims: To investigate these exposures in the aetiology of BE and EAC in the same population., Methods: The cohort included 24,068 men and women, aged 39-79 years, recruited between 1993 and 1997 into the prospective EPIC-Norfolk Study who provided information on anthropometry, smoking and alcohol intake. The cohort was monitored until December 2008 and incident cases identified., Results: One hundred and four participants were diagnosed with BE and 66 with EAC. A body mass index (BMI) above 23 kg/m(2) was associated with a greater risk of BE [BMI ≥23 vs. 18.5 to <23, hazard ratio (HR) 3.73, 95 % CI 1.37-10.16], and within a normal BMI, the risk was greater in the higher category (HR 3.76, 95 % CI 1.30-10.85, BMI 23-25 vs. 18.5 to >23 kg/m(2)). Neither smoking nor alcohol intake were associated with risk for BE. For EAC, all BMI categories were associated with risk, although statistically significant for only the highest (BMI >35 vs. BMI 18.5 to <23, HR 4.95, 95 % CI 1.11-22.17). The risk was greater in the higher category of a normal BMI (HR 2.73, 95 % CI 0.93-8.00, p = 0.07, BMI 23-25 vs. 18.5 to >23 kg/m(2)). There was an inverse association with ≥7 units alcohol/week (HR 0.51, 95 % CI 0.29-0.88) and with wine (HR 0.49, 95 % CI 0.23-1.04, p = 0.06, drinkers vs. non-drinkers)., Conclusions: Obesity may be involved early in carcinogenesis and the association with EAC and wine should be explored. The data have implications for aetiological investigations and prevention strategies.

Background/aims: Gastrointestinal stromal tumours are the most frequently occurring sarcoma of the gastrointestinal tract. Current treatment involves complete resection although the surgical or pathological margin required remains unclear. In this study we aimed to examine the risk of local and distant recurrence following laparoscopic resection., Methods: From a prospective tumour database, we identified and risk stratified primary non-metastatic tumours treated by laparoscopic resection from 2002-2012. Local technique involves allowing a 1 cm margin for resection. We then identified all cases of tumour recurrence and tumour related death in order to calculate overall survival, freedom from GIST recurrence and disease-specific survival respectively., Results: 90 patients were identified with a median follow-up of 3.9 years (range 1 week to 12.3 years). Five-year freedom from GIST recurrence and disease-specific survival rates in the high-risk group stood at 0.63 and 0.90. In the moderate-risk group these figures stood at 0.61 and 0.80 respectively. The low- and very-low-risk groups had a 10-year recurrence-free survival of 100% with no incidences of tumour-related recurrence. There were no local recurrences seen in any group at up to 10 years., Conclusion: The low recurrence rate suggests that these tumours can safely be treated laparoscopically with an R0 resection using a macroscopic surgical margin of 10 mm. Disease-specific survival was high. This may reflect earlier detection and the use of adjuvant imatinib.

We report a case of dermatitis herpetiformis co-localised with segmental vitiligo in a 37-year-old woman with a background history of autoimmune polyglandular syndrome type 2. We propose genetic mosaicism as a possible mechanism. There has only been one previous case report in which dermatitis hepetiformis co-localised in close proximity but not exclusively within vilitigo in a patient with autoimmune thyroiditis. To our knowledge, this is the first case report of dermatitis herpetiformis co-localised exclusively to segmental vitiligo in the presence of autoimmune polyglandular syndrome.

Background: UK Cancer registries have difficulties in recording the incidence of basal cell carcinoma (BCC)., Aim: To estimate the total numbers of BCCs in the UK requiring surgical treatment., Methods: The histopathology records of each year from 1999 to 2010 were examined to estimate the total annual numbers of BCCs and of people with BCC in the East Norfolk and Waveney area of the UK., Results: Over this period, the numbers of patients with surgically treated BCCs increased by 81%, and the numbers of BCCs by 70%. The ratio of BCCs recorded by the cancer registry was 2-2.2 times lower than that recorded in the histopathology data. Extrapolating the data to the UK population suggests that in 2010, approximately 200,000 patients had 247,000 BCCs treated surgically (this estimate does not include those treated by other means such as cryotherapy, topical chemotherapy, photodynamic therapy or radiotherapy, without histology). In 2008, 114,000 nonmelanoma skin cancers were registered in England and Wales and 309,000 total cancers (excluding nonmelanoma skin cancers) were registered in the UK., Conclusions: These data indicate that in the UK, BCC is nearly as common as all other cancers in all other body sites combined., (© The Author(s) CED © 2013 British Association of Dermatologists.)

Background: Several experimental studies have suggested potential anticarcinogenic effects of flavonoids, although epidemiologic evidence for the impact of dietary flavonoids on risk of gastric cancer (GC) is limited., Objective: We investigated the association between intake of dietary flavonoids and lignans and incident GC., Design: The study followed 477,312 subjects (29.8% men) aged 35-70 y from 10 European countries who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Validated dietary questionnaires and lifestyle information were collected at baseline. A food-composition database on flavonoids and lignans was compiled by using data from USDA and Phenol-Explorer databases., Results: During an average follow-up of 11 y, 683 incident GC cases (57.8% men) were mostly validated by a panel of pathologists and used in this analysis. We observed a significant inverse association between total flavonoid intake and GC risk in women (HR: 0.81; 95% CI: 0.70, 0.94; for the continuous variable after log₂ transformation) but not in men (HR: 0.97; 95% CI: 0.85, 1.09). In women, significant inverse associations with GC risk were also observed for intakes of some flavonoid subgroups (anthocyanidins, flavonols, flavones, and flavanols), particularly with intestinal type tumors for total flavonoid and flavanol intakes (P-heterogeneity < 0.1). After stratification by smoking status and sex, there was no significant heterogeneity in these associations between ever- and never-smokers., Conclusion: Total dietary flavonoid intake is associated with a significant reduction in the risk of GC in women.

Even though recent studies suggest that a high intake of heme iron is associated with several types of cancer, epidemiological studies in relation to gastric cancer (GC) are lacking. Our previous results show a positive association between red and processed meat and non cardia gastric cancer, especially in Helicobacter pylori infected subjects. The aim of the study is to investigate the association between heme iron intake and GC risk in the European prospective investigation into cancer and nutrition (EURGAST-EPIC). Dietary intake was assessed by validated center-specific questionnaires. Heme iron was calculated as a type-specific percentage of the total iron content in meat intake, derived from the literature. Antibodies of H. pylori infection and vitamin C levels were measured in a sub-sample of cases and matched controls included in a nested case-control study within the cohort. The study included 481,419 individuals and 444 incident cases of GC that occurred during an average of 8.7 years of followup. We observed a statistically significant association between heme iron intake and GC risk (HR 1.13 95% CI: 1.01-1.26 for a doubling of intake) adjusted by sex, age, BMI, education level, tobacco smoking and energy intake. The positive association between heme iron and the risk of GC was statistically significant in subjects with plasma vitamin C <39 mmol/l only (log2 HR 1.54 95% CI (1.01-2.35). We found a positive association between heme iron intake and gastric cancer risk., (Copyright © 2011 UICC.)

Sentinel lymph node biopsy provides prognostic information for melanoma patients, and the Department of Health states that it should be available across the country by 2012. We review the setting up of a melanoma sentinel lymph node biopsy service with specific consideration to resources, service implications and patient outcomes. In total, 164 patients underwent sentinel lymph node biopsy for melanoma from August 2008 until March 2010. The median time for sentinel lymph node excision was 26 min. The median total operative time, which includes melanoma excision and sentinel node biopsy was 65 min, compared with 22 min for excision of the melanoma performed during the previous 19 months. The complication rate was 8.5%, with only 1.2% requiring operative treatment. After the initial outlay for two gamma probes, it was possible to deliver a cost neutral service within the National Tariff. Despite a significant increase in demand for the service in the second half of the study period, and 106% increase in the number of regional lymphadenectomies, only 1 patient (0.6%) breached the 'Going Further on Cancer Waits' target. In conclusion, a sentinel lymph node biopsy service for malignant melanoma can be effectively delivered within the majority of UK plastic surgery departments., (Copyright © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Granulomatous inflammations, characterized by the presence of activated macrophages (MAs) forming epithelioid cell (EPC) clusters, are usually easy to recognize. However, in ambiguous cases the use of a MA marker that expresses selectively in EPCs may be needed. Here, we report that carboxypeptidase-M (CPM), a MA-differentiation marker, is preferentially induced in EPCs of all granuloma types studied, but not in resting MAs. As CPM is not expressed constitutively in MAs, this allows utilization of CPM-immunohistochemistry in diagnostics of minute granuloma detection when dense non-granulomatous MAs are also present. Despite this rule, hardly any detectable CPM was found in advanced/active tubercle caseous disease, albeit in early tuberculosis granuloma, MAs still expressed CPM. Indeed, in vitro both the CPM-protein and -mRNA became downregulated when MAs were infected with live mycobacteria. In vitro, MA-CPM transcript is neither induced remarkably by interferon-γ, known to cause classical MA activation, nor by IL-4, an alternative MA activator. Instead, CPM is selectively expressed in lipid-laden MAs, including the foam cells of atherosclerotic plaques, xanthomatous lesions and lipid pneumonias. By using serum, rich in lipids, and low-density lipoprotein (LDL) or VLDL, CPM upregulation could be reproduced in vitro in monocyte-derived MAs both at transcriptional and protein levels, and the increase is repressed under lipid-depleted conditions. The microarray analyses support the notion that CPM induction correlates with a robust progressive increase in CPM gene expression during monocyte to MA maturation and dendritic cell (DC) differentiation mediated by granulocyte-MA-colony-stimulating factor+IL-4. M-CSF alone also induced CPM. These results collectively indicate that CPM upregulation in MAs is preferentially associated with increased lipid uptake, and exposure to CSF, features of EPCs, also. Therefore, CPM-immunohistochemistry is useful for granuloma and foam MA detections in tissue sections. Furthermore, the present data offer CPM for the first time to be a novel marker and cellular player in lipid uptake and/or metabolism of MAs by promoting foam cell formation.

Lymph node yield is a key factor in enabling the accurate determination of prognosis in colorectal cancer patients. The Royal College of Pathologists guidelines state a "minimum" recommended mean number of 12 lymph nodes. In this study of 391 patients, the authors aim to determine the optimal node counts in patients with colorectal cancer, examine for correlations between maximum tumor diameter and lymph node yield, and examine for correlations between lymph node yield and involved node numbers. Furthermore, the authors aim to examine the impact of specimen type on the harvested node numbers and assess whether the personal differences between surgeons and pathologists have significant influence on node yield. A moderate positive correlation between maximum tumor diameter and final lymph node yield was noted (Spearman's correlation coefficient = .328, P = .0001). There was significant variation shown by pathologists (Kruskal-Wallis test P = .001) and by differing specimen type (Kruskal-Wallis test P = .029) on the lymph node yield.

The NHS has introduced the two week wait scheme to detect upper gastrointestinal cancers at an early stage and improve survival rates The aim of this study was to assess the impact of this scheme and changes in endoscopy waiting times on tumour stage and resection rates over a four year period. Data were analysed prospectively for all patients diagnosed with oesophagogastric cancer between September 1998 and September 2002 and from those referred under the two week wait scheme since its introduction in 2000. Of those tumours diagnosed by this scheme (15%) only 5% were early disease (stage 1 or 2). Patients with early cancer, mainly diagnosed by routine gastroscopy, do not present with symptoms meeting the two week wait criteria. An increase in the resection rates for early disease will most probably be seen with a reduction in routine endoscopy waiting times.

Background: Hürthle cell carcinoma is a variant of follicular cell carcinoma of thyroid. It may present as a low-grade tumour or as a more aggressive type. Prognosis depends upon the age of the patient, tumour size, extent of invasion and initial nodal or distant metastasis., Patient and Methods: The case of Hürthle cell carcinoma is reported in a 79-year-old man who presented with a rapidly increasing lump on the left side of his neck, having had a right hemithyroidectomy for colloid goitre 24-years-ago. Fine needle aspiration cytology confirmed the presence of Hürthle cells, raising the possibility of a Hürthle cell neoplasm. The patient underwent staging and surgery. Histology showed Hürthle cell carcinoma and the patient underwent adjuvant therapy. The literature on Hürthle cell neoplasms is reviewed., Conclusions: Fine needle aspiration cytology may recognise Hürthle cell lesion but final diagnosis of carcinoma depends upon histological confirmation of vascular or capsular invasion. Staging and surgery in Hürthle cell carcinoma are similar to follicular carcinoma of thyroid with favourable outcome despite the controversy regarding the histological classification and adjuvant therapy. Elderly patients with Hürthle cell carcinoma need to be made aware of their poorer prognosis and should be offered more radical treatment.

Background: The incidence of Barrett's oesophageal adenocarcinoma is increasing more rapidly than any other malignancy in industrialized countries. Cyclo-oxygenase-2 appears to play an important role in gastrointestinal carcinogenesis. Previous studies on cyclo-oxygenase-2 expression in Barrett's oesophageal carcinogenesis have utilized tissue samples obtained from different patients. We sought a definitive comparison of cyclo-oxygenase-2 expression in the sequence of Barrett's metaplasia-dysplasia-adenocarcinoma within the same patients., Methods: Paraffin-embedded oesophago-gastrectomy specimens from 20 patients, containing successive stages of Barrett's metaplasia, high-grade dysplasia and adenocarcinoma, were analysed for cyclo-oxygenase-2 expression by immunohistochemistry., Results: Cyclo-oxygenase-2 was constitutively expressed in the basal layers of cells in the adjacent normal squamous oesophageal epithelium, but a higher cyclo-oxygenase-2 expression was observed in Barrett's metaplasia. A further increase in cyclo-oxygenase-2 expression was detected in high-grade dysplasia, but cyclo-oxygenase-2 was decreased in adenocarcinoma tissue, regardless of its stage or level of differentiation., Conclusions: Cyclo-oxygenase-2 expression is progressively increased when squamous oesophageal epithelium develops into Barrett's metaplastic epithelium and then into high-grade dysplasia, but appears to decrease when adenocarcinoma develops. These findings may be significant for an effective chemo-prevention strategy with selective cyclo-oxygenase-2 inhibitors.