Prediction of a positive circumferential resection margin at surgery following neoadjuvant chemotherapy for adenocarcinoma of the oesophagus.

Background: A positive circumferential resection margin (CRM) has been associated with higher rates of locoregional recurrence and worse survival in oesophageal cancer. The aim of this study was to establish if clinicopathological and radiological variables might predict CRM positivity in patients who received neoadjuvant chemotherapy before surgery for oesophageal adenocarcinoma. Methods: Multivariable analysis of clinicopathological and CT imaging characteristics considered potentially predictive of CRM was performed at initial staging and following neoadjuvant chemotherapy. Prediction models were constructed. The area under the curve (AUC) with 95% confidence intervals (c.i.) from 1000 bootstrapping was assessed. Results: A total of 223 patients were included in the study. Poor differentiation (odds ratio (OR) 2·84, 95 per cent c.i. 1·39 to 6·01) and advanced clinical tumour status (T3-4) (OR 2·93, 1·03 to 9·48) were independently associated with an increased CRM risk at diagnosis. CT-assessed lack of response (stable or progressive disease) following chemotherapy independently corresponded with an increased risk of CRM positivity (OR 3·38, 1·43 to 8·50). Additional CT evidence of local invasion and higher CT tumour volume (14 cm3) improved the performance of a prediction model, including all the above parameters, with an AUC (c-index) of 0·76 (0·67 to 0·83). Variables associated with significantly higher rates of locoregional recurrence were pN status (P = 0·020), lymphovascular invasion (P = 0·007) and poor response to chemotherapy (Mandard score 4-5) (P = 0·006). CRM positivity was associated with a higher locoregional recurrence rate, but this was not statistically significant (P = 0·092). Conclusion: The presence of advanced cT status, poor tumour differentiation, and CT-assessed lack of response to chemotherapy, higher tumour volume and local invasion can be used to identify patients at risk of a positive CRM following neoadjuvant chemotherapy.

Antecedentes: Un margen de resección circunferencial (circumferential resection margin, CRM) positivo se ha asociado con tasas más elevadas de recidiva locorregional y peor supervivencia en el cáncer de esófago. El objetivo de este estudio fue establecer si las variables clínico­patológicas y radiológicas podrían predecir la positividad del CRM en el adenocarcinoma de esófago tras quimioterapia neoadyuvante antes de la cirugía. Métodos: Se realizó un análisis multivariable de las características clínico­patológicas y de la tomografía computarizada (computed tomography, CT) que se consideraron potencialmente predictivas de CRM en la estadificación inicial y tras la quimioterapia neoadyuvante. Se construyeron modelos de predicción. Se evaluó el área bajo la curva (area under curve, AUC) con el i.c. del 95% a partir de 1.000 muestras bootstrap. Resultados: Se incluyeron 223 pacientes en el estudio. Una pobre diferenciación (razón de oportunidades, odds ratio, OR 2,84, i.c. del 95% 1,39­6,01) y un estadio clínico T avanzado (T3­4) (OR 2,93, i.c. del 95% 1,03­9,48) se asociaron de forma independiente con un riesgo aumentado de CRM en el diagnóstico. La falta de respuesta en la CT (estable o enfermedad en progresión) tras la quimioterapia se correspondía de forma independiente con un riesgo aumentado de CRM positivo (OR 3,38, i.c. del 95% 1,43­8,50). Además, la evidencia por CT de invasión local y un mayor volumen del tumor en CT (14 cm3) mejoraron el funcionamiento del modelo predictivo, incluyendo todos los parámetros previamente señalados; con AUC (índice c) de 0,76 (0,68­0,83). Las variables asociadas de forma significativa con tasas más elevadas de recidiva locorregional fueron el estado de los ganglios linfáticos patológicos (P = 0,002), la invasión linfovascular (P = 0,007) y la respuesta pobre a la quimioterapia (Mandard 4 y 5 (P = 0,006)). La positividad del CRM se asoció con una tasa de recidiva locorregional más elevada pero sin alcanzar significación estadística (P = 0,09). Conclusión: La presencia de un estadio clínico T avanzado, tumor pobremente diferenciado, falta de respuesta a la quimioterapia en la TC, mayor volumen del tumor en la TC e invasión local pueden ser utilizados para identificar pacientes en riesgo de un CRM positivo tras quimioterapia neoadyuvante.

Total adventitial resection of the cardia: 'optimal local resection' for tumours of the oesophagogastric junction.

INTRODUCTION: Little is published about the local resection of oesophageal cancers. We adopted the principles of rectal cancer surgery, ie standard surgical dissection techniques as well as standard pathological processing and reporting, and assessed the feasibility of applying them to oesophagogastric junction (OGJ) cancer. METHODS: Over a two-year period consecutive patients with invasive cancers of the OGJ were studied. Following staging and neoadjuvant chemotherapy (NAC), a standard dissection defined as a total adventitial resection of the cardia (TARC) was performed. Standard histopathological processing involved external inking, photographing, transverse slicing and mounting of cut samples on megablocks. Hospital morbidity and mortality as well as survival at five years' follow-up were assessed. RESULTS: Forty consecutive patients had a TARC for OGJ carcinoma. Of these, 32 were offered NAC. Introducing TARC did not result in increased morbidity or mortality. Twenty-seven patients (68%) had an R0 resection that was directly related to the tumour stage and significantly related to a response to chemotherapy. Sixteen patients (42%) were alive five years after their TARC operation. CONCLUSIONS: Although the adventitia of the OGJ is not as well developed as that of the rectum, TARC can be performed safely as a standardised resection for OGJ cancers. Whereas the R0 rate for early stage tumours is very high, it remains disappointingly low for T3N1 tumours despite NAC. Improved long-term survival for these advanced tumours will only be achieved with better neoadjuvant and adjuvant therapies.

Phenotype of exogenous microparticle-containing pigment cells of the human Peyer's patch in inflamed and normal ileum.

OBJECTIVES: Pigmented cells, that contain inert, submicron-sized dietary particles, are a consistent feature of the base of human Peyer's patches (PP). We aimed (i) to phenotype these intestinal pigment cells (PC) in archival tissue specimens and (ii) to establish whether PC phenotype is altered in inflammatory conditions, especially Crohn's disease (CD). METHODS: PCs contained within PP were identified by routine haematoxylin and eosin (H&E) staining and dark field microscopy of archival ileal sections for: adenocarcinoma (n=16), colonic CD (n=23), non-CD colitis (n=10). Paraffin-embedded serial sections were graded for microscopic inflammation and then investigated immunohistochemically with antibodies against CD68, MAC387, CD14, CD11b, CD15, CD1a, S100, HLA-DR, CD86 and Cathepsin D. Analyses were by light and confocal microscopies. RESULTS: The majority of PCs were CD68 positive (circa 80%) with a minority (circa 20%) staining for MAC387. Microparticles were mainly identified within cathepsin D negative lysosomal compartments. Histological inflammatory grade and disease type had no influence on cell phenotype. CONCLUSIONS: The microparticle-containing PCs of the PP base are mainly mature macrophages (CD68) of low metabolic and immunological activity. There is no evidence of differential PC phenotype or activation in differing disease states, including CD.

Diagnostic role of upper gastrointestinal endoscopy in pediatric inflammatory bowel disease.

BACKGROUND: Discrimination between ulcerative colitis (UC) and Crohn disease (CD) may be difficult on ileo-colonoscopy alone because of a lack of definitive lesions. Retrospective studies show upper gastrointestinal endoscopy may be helpful in confirming diagnosis in such cases. AIMS: To prospectively determine importance of upper gastrointestinal endoscopy in diagnosis of inflammatory bowel disease (IBD) and assess factors predictive of upper gastrointestinal involvement in IBD. METHODS: All pediatric patients were enrolled prospectively and consecutively over a 2-year period and investigated with an ileo-colonoscopy and barium meal follow-through. Children with procto-sigmoiditis, later confirmed histologically to be typical of UC, were excluded from the study. The remainder underwent upper gastrointestinal endoscopy. The protocol and methodology were determined a priori. RESULTS: 65 children suspected of IBD underwent colonoscopy. Of the total, 11 had recto-sigmoiditis with typical macroscopic appearances of UC; once this was confirmed on histology these patients were excluded from the study. Of the 54 children (males, 31; median age, 11.1 years) remaining, 23 were initially diagnosed with CD on ileo-colonoscopy and 18 (33%) were diagnosed with UC. The diagnosis remained ambiguous in 13 (six colonic, four ileo-colonic, three normal colon) on clinical, radiologic and histologic grounds. Upper GI endoscopy helped to confirm CD in a further 11 (20.4%). Two patients were diagnosed with indeterminate colitis. Upper gastrointestinal inflammation was seen in 29 of 54 (22 CD; 7 UC ). Epigastric and abdominal pain, nausea and vomiting, weight loss and pan-ileocolitis were predictive of upper gastrointestinal involvement (P < 0.05). However, 9 children with upper gastrointestinal involvement were asymptomatic at presentation (31%). Overall upper gastrointestinal tract inflammation was most common in the stomach (67%), followed by the esophagus (54%) and duodenum (22%). CONCLUSIONS: Upper gastrointestinal tract endoscopy should be part of the first-line investigation in all new cases suspected of IBD. Absence of specific upper gastrointestinal symptoms do not preclude presence of upper gastrointestinal inflammation.

Epithelial-myoepithelial carcinoma of the parotid gland: a case report and review of the cytological and histological features.

Epithelial-myoepithelial carcinoma (EMC) is a rare biphasic tumour of the salivary glands typically arising in the parotid. Fine needle aspiration cytology is widely used in the initial investigation of salivary gland swellings and whilst the cytological features of this tumour have been described they are not well recognized. This report describes the clinicopathological features of a case of epithelial-myoepithelial carcinoma of the parotid gland and highlights the importance of awareness of this tumour in the differential diagnosis of biphasic tumours on fine needle aspiration cytology.