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.

Reversible khat-induced hepatitis: two case reports and review of the literature.

Recreational chewing of Catha edulis (khat) leaves is part of the ethnic culture of Somali, Yemeni and other East African societies for its stimulant properties. With increasing emigration, khat use has become common in these ethnic groups once they move to other areas such as Europe and the USA; one-third of the UK Somali population report khat use within the last month. Cathinone, the active component of the khat leaves, is controlled under the UK Misuse of Drugs Act, but the use of the khat plant and its leaves remains not subject to control in the UK. There have been several previous reports of acute hepatitis related to chronic use of khat leading to acute liver failure, and resulting in transplantation or death. We report two cases with severe acute khat-related hepatitis that resolved on cessation of khat use initially, but relapsed with further use, reinforcing the importance of permanent khat cessation to prevent progression to liver failure. With reference to the current literature, we also consider the difficult diagnosis of this disorder, then go on to consider the pathophysiology, mechanisms of liver injury and potential future areas of research.

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.

Granulomatous ulcerative colitis: a re-appraisal of the mucosal granuloma in the distinction of Crohn's disease from ulcerative colitis.

AIMS: To determine whether the presence and location of giant cells or granulomas in relation to crypts distinguishes between ulcerative colitis and Crohn's disease. METHODS AND RESULTS: Twenty-nine large bowel mucosal biopsy specimens showing giant cells and/or granulomas in a background more typical of ulcerative colitis than Crohn's disease were collected between 1986 and 1996. Each was subject to detailed independent analysis by three histopathologists. Follow-up of the cases was by examination of all previous and subsequent gastrointestinal surgical or biopsy material and by scrutiny of the clinical notes by a gastroenterologist. On the basis of the accumulated histological data 10 of these 29 cases were accorded the diagnosis of ulcerative colitis. In nine of these 10 cases the clinical diagnosis, where known, was in keeping with this and all nine contained only crypt-associated giant cells and/or granulomas. The tenth case contained a solitary free-standing granuloma and clinically the patient had perianal disease, suggesting that the true diagnosis was Crohn's disease. CONCLUSIONS: Isolated giant cells and well-defined epithelioid granulomas distant from crypts do not, as a rule, occur in ulcerative colitis, and hence their presence in a colonoscopic biopsy showing features of chronic inflammatory bowel disease is a strong pointer towards the diagnosis of Crohn's disease. Crypt-associated giant cells and granulomas can occur in ulcerative colitis and in themselves are unreliable features for the discrimination between Crohn's disease and ulcerative colitis.

Haemophagocytic syndrome and histiocytic necrotising lymphadenitis (Kikuchi's disease).

A young boy presented with a rash, fever, and cervical lymphadenopathy, originally thought to be caused by tuberculosis. A lymph node biopsy showed the features of Kikuchi's disease, with necrosis and histiocytic infiltration without neutrophils. No evidence of tuberculosis was found on staining, culture, or the polymerase chain reaction. Bone marrow biopsy revealed prominent haemophagocytosis, and a diagnosis of haemophagocytic syndrome was reached. The aetiology of haemophagocytic syndrome, and its association with Kikuchi's lymphadenitis, is discussed.

Fatal phenytoin hypersensitivity syndrome.

The phenytoin (hydantoin) hypersensitivity syndrome is rare but potentially fatal. Often, as in this case, it presents with non-specific symptoms and signs, requiring a high degree of clinical suspicion for diagnosis.

Invasive candidiasis of a late presentation laryngeal chondroradionecrosis.

Laryngeal chondroradionecrosis is an unusual condition which may present many years after the initial radiotherapy. We present a case of late onset chondroradionecrosis which was complicated by invasive candidiasis of the arytenoid cartilages which had themselves been extruded through the laryngeal mucosa.

The cardiac form of the tissue-specific SmN protein is identical to the brain and embryonic forms of the protein.

The SmN protein is a component of small nuclear ribonucleoprotein particles and closely related to the ubiquitously expressed SmB and B' splicing proteins. However, SmN is only expressed in a limited range of tissues and cell types such as brain, heart and early embryonic cells. The isolation of cDNA clones derived from the mRNA encoding SmN in different cell types has indicated that the brain and embryonic forms of the protein are identical and are encoded by a distinct gene to that encoding SmB and B'. It has been suggested however, that the cardiac form of SmN is encoded by a distinct mRNA which is derived from a different gene from that encoding the brain and embryonic forms of SmN. By using the polymerase chain reaction as well as cDNA cloning we have shown that this is not the case and that the cardiac, brain and embryonic forms of the protein are identical and are translated from the same mRNA encoded by a single gene. The significance of this finding is discussed in terms of the complex expression pattern of this gene and the possible functional role of SmN.