Authors writing an oesophageal cancer include adenocarcinoma to a variable extent--between 1 and 75 per cent--but the true incidence of this histological type is about 1 per cent. Most adenocarcinomas are gastric in origin, involving the lower oesophagus, have a lower operative mortality than in the middle or upper one-third of the oesophagus and poorer prognosis than squamous cell carcinoma, but there is no alternative treatment to surgery. Squamous cell carcinoma of the oesophagus, separated incompletely but as far as possible, has been analysed by reviewing data on 83 783 patients in 122 paERS. After trying to standardize the data, it appears that of 100 patients with the condition, 58 will be explored and 39 have the tumour resected, of whom 13 will die in hospital. Of the 26 patients leaving hospital with the tumour excised, 18 will survive for 1 year, 9 for 2 years and 4 for 5 years. Oesophageal resection for squamous cell carcinoma has the highest operative mortality of any routinely performed surgical procedure today.

IL-33 is associated with atopic and autoimmune diseases and, as reported here, it interacts synergistically with Ag to markedly enhance production of inflammatory cytokines in rodent mast cells even in the absence of degranulation. Investigation of the underlying mechanisms revealed that synergy in signaling occurred at the level of TGFβ-activated kinase1 which was then transmitted downstream through JNK, p38 MAP kinase, and AP1. Stimulation of the Ca2+/calcineurin/NFAT pathway by Ag, which IL-33 did not, was critical for the synergy between Ag and IL-33. For example, selective stimulation of the NFAT pathway by thapsigargin also markedly enhanced responses to IL-33 in a calcineurin-dependent manner. As indicated by luciferase-reporter assays, IL-33 failed to stimulate the transcriptional activities of NFAT and AP1 but augmented the activation of these transcription factors by Ag or thapsigargin. Robust stimulation of NFκB transcriptional activity by IL-33 was also essential for synergy. These and pharmacologic data suggested that the enhanced production of cytokines resulted in part from amplification of the activation of AP1 and NFAT as well as co-operative interactions among transcription factors. IL-33 may retune mast cell responses to Ag towards enhanced cytokine production and thus determine the symptoms and severity of Ag-dependent allergic and autoimmune diseases.

There has been no controlled trial of radiotherapy versus surgery for squamous cell carcinoma of the oesophagus. Radiotherapy is generally used for those patients with extensive disease or those who are unfit for surgery. In spite of this, the 1-year survival of 18 per cent is similar to that for surgically treated patients and there is no equivalent operative mortality. The 5-year survival is 6 per cent compared with that for surgery of 4 per cent. There are no results available to suggest what would happen if a patient with a localized tumour, technically suitable for surgical resection, were treated instead by radiotherapy.

The role of different cytokines in the peripheral blood mononuclear cell (PBMC) proliferative response and in in vitro granuloma formation was evaluated in a cross-sectional study with patients with the different clinical forms and phases of Schistosoma mansoni infection, as well as a group of individuals naturally resistant to infection named normal endemic (NE). The blockage of IL-4 and IL-5 using anti-IL-4 and anti-IL-5 antibodies significantly reduced the PBMC proliferative response to soluble egg (SEA) and adult worm (SWAP) antigens in acute (ACT), chronic intestinal (INT) and hepatosplenic (HS) patients. Similar results were obtained in the in vitro granuloma formation. Blockage of IL-10 had no significant effect on either assay using PBMC from ACT or HS. In contrast, the addition of anti-IL-10 antibodies to PBMC cultures from INT patients significantly increased the proliferative response to SEA and SWAP as well as the in vitro granuloma formation. Interestingly, association of anti-IL-4 and anti-IL-10 antibodies did not increase the PBMC proliferative response of these patients, suggesting that IL-10 may act by modulating IL-4 and IL-5 secretion. Addition of recombinant IL-10 decreased the proliferative response to undetectable levels when PBMC from patients with the different clinical forms were used. Analysis of IFN-γ in the supernatants showed that PBMC from INT patients secreted low levels of IFN-γ upon antigenic stimulation. In contrast, PBMC from NE secreted high levels of IFN-γ. These data suggest that IL-10 is an important cytokine in regulating the immune response and possibly controlling morbidity in human schistosomiasis mansoni, and that the production of IFN-γ may be associated with resistance to infection.

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