Laparoscopic repair of perforated peptic ulcer proves to be technically feasable and carries an acceptable morbidity and mortality rate, compared with conventional surgery.

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Baume, Nicholls and Baxter report the potent effect of lipopolysaccharide on gastric secretion as if this were a uew observation 1 • But, the effect was clearly described in 1950 (ref. 2). We have made similar experiments in conscious dogs with vagally denervated pouches of the body of the stomach. Gastric secretion was stimulated by a low dose of histamine given by constant intravenous infusion (100 [Lg/h of histamine base).Gastric acid secretion was abolished by doses of IO [Lg/kg of Pseudomonas polysaccharide pyrogen ('Piromen', Flint Laboratories Inc.) given intravenously over a period of about :lO min during stimulation with histamine. Secretion failed progressively over 2-3 h during which time tho dogs developed pyrexia as indicated by a thermistor in the rectum (Fig. 1). In control experiments in which saline was given in place of 'Piromen' secretion was maintained.When gastric acid secretion is stimulated in conscious dogs by feeding, by intravenous 2-deoxy-n-glucose, or by gastrin infusion, atropine sulphate (0•1 mg/kg intravenously) practically abolishes the secretion.Under similar conditions secretion stimulated by histamine is ,•irtually unaffected 3 • Also, secretion stimulated by histamine is much more resistant to depression caused by devation of the plasma calcium concentration than is Hccretion stimulated by gastrin•. From this we deduce that histamine acts, as is generally supposed, directly on the secreting cells. The potent action of lipopolysaccharide against secretion stimulated by histamine is therefore likely to reflect an effect on the secretory mechanism and not on intrinsic or extrinsic nerves. We agree with Baume et aU that alterations in gastric blood flow could be responsible for the effect.The slow development of inhibition of secretion in our ex:periments~it seemed to run parallel with rise in body temperaturc~suggcsts that inhibition of secretion, like pyrexia, depends on development of a mediator such as leucocyte bacterial pyrogen•. It should, however, be mentioned that it has been claimed that in rats lipopoly-879 saccharide has gastric secretory inhibitory activity unrelated to its pyrexic effect•.The significance of these observations is two-fold: first, the potency of bacterial lipopolysaccharide in inhibiting gastric secretion merits further investigation: and second, gastric secretory inhibition by biological extracts and other substances should always be accompanied by temperature recordings over several hours.

The aim of this prospective study is to report our experience in the multimodal management of locally advanced esophageal squamous cell carcinoma (LAESC; stage III cTNM), focusing on the results of chemoradiotherapy followed by surgery. These findings were compared to the results of a standard group of patients with locally advanced esophageal carcinoma (LAEC; stage III pTNM) treated in our center with surgery alone. Sixty-one patients with LAESC underwent preoperative chemoradiotherapy (5-fluorouracil + cisplatin) with concomitant 45 Gray radiotherapy in a 5-week course. Transthoracic esophagectomy was performed 4 to 5 weeks after the end of the neoadjuvant therapy. Thirty-eight patients underwent surgery, and 37 of them had resections (resectability: 97% in the multimodal group; 84% in the standard surgical series; p = 0.07). The R0 (complete) resection rate was 78% compared to 56% in the standard surgical group (p <0.03). Eleven patients had no residual tumor in the resected specimen (pathologic complete response: pCR: 30%). The operative mortality rate was 19% compared with 8.8% in the standard series. The overall median survival of the resected patients was 21 months, with a 5-year survival rate of 11% (14% in the surgical group; NS). The 3-year and 5-year survival rates were 34% for the pCR group and respectively 5% and 0% for the group with pathologic incomplete response (pIR; p <0.05). The median survival was 28 months for the pCR patients and 19 months for the pIR group. In this non-randomized trial, preoperative chemoradiotherapy in LAESC seems to increase the resectability and R0 resection rates, to allow a higher pCR rate and a longer survival only in the pCR group, at the expense of an inadequate increase in operative mortality. This multimodal treatment cannot be proposed as a standard procedure unless less toxic regimens are developed, increasing the benefits with better local and distant failure control and decreasing operative mortality.

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