The object of this article is to assess current staging accuracies for individual modalities and to investigate the influence of the multidisciplinary team (MDT) on clinical staging accuracies and treatment selection for patients with gastro-esophageal cancer. Patients newly diagnosed with gastric or esophageal cancer and who were deemed suitable for surgical resection by the MDT were studied. Patients were staged with a combination of computerized tomography (CT), endoscopic ultrasound (EUS) and laparoscopic ultrasound (LUS). Additionally, the MDT determined an overall clinical stage for each patient after discussion at the MDT meeting. Treatments were selected according to this final clinical stage. Final histopathological staging (pTNM) was available for all patients and was used as the gold standard for determining staging accuracy. Suitability of treatment selection was assessed once final pTNM was available. One hundred and eighteen patients were studied. Endoscopic ultrasound was the most accurate individual staging modality for the loco-regional assessment of esophageal tumors (T stage accuracy 78%, N stage accuracy 70%). Laparoscopic ultrasound was the most accurate modality in T staging of gastric cancers (91%). The MDT stage was more accurate than each individual staging modality for T and N staging for both gastric and esophageal cancers (accuracy range: 88-89%) and was better for the assessment of nodal disease than each individual modality (CT P < 0.001, EUS P < 0.01, LUS P < 0.01). Overall staging accuracy as determined at the MDT meeting was increased and resulted in only 2/118 (2%) patients being under-treated. The MDT significantly improves staging accuracy for gastro-esophageal cancer and ensures that correct management decisions are made for the highest number of individual patients.
Six histopathologists allocated 100 sections from patients with long-standing ulcerative colitis into four diagnostic categories, regular hyperplasia, reactive atypia, low-grade and high-grade dysplasia. Their allocations were analysed using kappa statistics, including Fleiss's multiple kappa for groups of observers, and agreement on specific diagnoses was explored by constructing a conditional probability matrix. The nature of their disagreements was investigated using coefficients for systematic and haphazard errors. Over the four diagnostic categories there was a wide range of pairwise agreement from a low of 49% up to 72% and kappa values were only 'fair' or 'moderate'. As expected, agreement over the two categories 'dysplasia' vs 'no dysplasia' was better, ranging from 68% to 84%, and for 'atypia present' (reactive atypia, low- and high-grade dysplasia) vs "no atypia' two pairings achieved over 90% and 11 pairings over 80% agreement. In view of its clinical importance, conditional agreement on high-grade dysplasia, pairwise agreement on this diagnosis ranged from 100% down to as low as 33%. However, most of these disagreements fell into the low-grade dysplasia category so that closer follow-up and further biopsies would still have been indicated. It is a truism that the basis for safe management is careful co-operation between clinicians and pathologists who have all the relevant facts and who know and trust one another's judgement. Thus, several aspects of the ideal diagnostic process cannot be evaluated in inter-observer studies and the element of artificiality should be borne in mind when applying the findings to diagnostic practice. Nevertheless, the low level of agreement on the diagnosis of high-grade dysplasia achieved by certain pairings of specialist pathologists is a disturbing outcome of this study. Inaccuracies should be minimized by a concensus approach and we therefore recommend referral of putative cases of dysplasia to interested pathologists for further opinions. We would also advocate that pathologists faced with appearances which are indefinite between reactive atypia and dysplasia, would do better to describe them in terms of "atypia, significance uncertain', so that closer surveillance is undertaken, rather than force them into more precise diagnostic categories which may be incorrect.
Systemic inflammation is associated with adverse prognosis cancer but its aetiology remains unclear. We investigated the expression of proinflammatory cytokines within normal mucosa from healthy controls and tumour tissue in cancer patients and related these levels with markers of systemic inflammation and with the presence of a tumour inflammatory infiltrate. Tissue was collected from 56 patients with gastro-oesophageal cancer and from 12 healthy controls. Tissue cytokine mRNA concentrations were measured by real-time PCR and tissue protein concentrations by cytometric bead array. The degree of chronic inflammatory cell infiltrate was recorded. Serum cytokine and acute phase protein concentrations (including C-reactive protein (CRP)) were measured by enzymelinked immunosorbent assay. Proinflammatory cytokines were significantly overexpressed (interleukin (IL)-1b, IL-6, IL-8 and tumour necrosis factor-a) both at mRNA and protein levels in the cancer specimens compared with mucosa from controls. Interleukin-1b was expressed in greatest (10 -100-fold) concentration and protein levels correlated significantly with systemic inflammation (CRP) (P ¼ 0.05, r ¼ 0.31). A chronic inflammatory infiltrate was observed in 75% of the cancer specimens and was associated with systemic inflammation (CRP: P ¼ 0.01). However, the presence of chronic inflammation per se was not associated with altered cytokine expression within the tumour. Both a chronic inflammatory infiltrate and systemic inflammation (CRP) were associated with reduced survival (P ¼ 0.05 and P ¼ 0.03, respectively). Tumour chronic inflammatory infiltrate and tumour tissue IL-1b overexpression are potential independent factors influencing systemic inflammation in oesophagogastric cancer patients.
SUMMARY We describe a long term study of 76 patients with dermatitis herpetiformis. Unlike patients with coeliac disease, where the peak incidence was during the first and fourth decades, no dermatitis herpetiformis patients presented in the first decade; also, there was a male preponderance in dermatitis herpetiformis which contrasts with the excess of females in coeliac disease. The apparent prevalence of dermatitis herpetiformis was 11 per 100 000 in our population; approximately one fifth of that of coeliac disease. Jejunal villous atrophy was present in 78% of our dermatitis herpetiformis patients, and a single jejunal biopsy was as effective at detecting this as the multiple biopsy technique. A majority of patients were able to stop, or radically reduce their dapsone or sulphapyridine treatment after the institution of a gluten free diet. Spontaneous remission of the skin lesion occurred in only two patients not receiving a gluten free diet. Gastric parietal or thyroid antibodies were detected in 38% of patients, and three cases of thyroid disease and two cases of pernicious anaemia were detected. Lymphoma developed in two patients, one being intestinal in origin. We conclude that a gluten free diet is of therapeutic benefit in dermatitis herpetiformis and that spontaneous remission is uncommon in those not on a diet. Despite patchiness of the enteropathy, a single jejunal biopsy is quite adequate to diagnose the presence of upper intestinal villous atrophy.Since the first report of the association of dermatitis herpetiformis with coeliac disease in 1966,1 evidence of close links between the two disorders has accumulated. Well documented points of similarity include the response of the enteropathy to a gluten free diet,23 the high prevalence of HLA B8 and DR3 phenotypes, the occurrence of hyposplenism78 and a predisposition to the development of lymphoma.9 10 While these associations are not in dispute, controversy has arisen in relation to the major differences between the two disorders. By definition, the appearance of the skin lesions characterises dermatitis herpetiformis, but, while some authors believe that exclusion of gluten from the diet leads to remission of the skin disease 11-14 others disagree.5 16 Similarly, there is disagreement about the frequency with which intestinal villous
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