One hundred patients with hepatic metastases from colorectal cancer underwent 'radical' liver resection from 1980 to 1989. At least 1 cm of normal parenchyma surrounded the tumour and no microscopic invasion of resection margins was evident. The disease was staged according to our own staging system. Lobectomy was performed in 50 patients and non-anatomical resection in the remainder. The postoperative mortality rate was 5 per cent and the major morbidity rate was 11 per cent. The actuarial 5-year survival rate for patients in stages I, II and III was 42 per cent, 34 per cent and 15 per cent respectively (P less than 0.001). The overall actuarial 5-year survival rate was 30 per cent. The prognostic importance of various patient and tumour variables was evaluated by univariate analysis and then by multivariate analysis. Age of patient, site of primary, disease-free interval between treatment of primary and of hepatic metastases, preoperative carcinoembryonic antigen levels, and number of metastases, did not relate to prognosis, while sex (P = 0.024), stage of primary (P = 0.026), extent of liver involvement (P less than 0.001), distribution of metastases (P = 0.01) and type of surgery (P = 0.028) significantly affected prognosis as single factors. Multivariate analysis revealed that only the extent of liver involvement and stage of the primary tumour were independent predictors of survival. We conclude that liver resection is effective in selected patients with hepatic metastases from colorectal cancer. In resectable patients it is not yet possible to formulate a clear prognosis based on clinical factors. The extent of liver involvement and the staging system used may be significant, although not absolute, indicators of outcome.

Thirty-three chordomas were observed at the Istituto Nazionale Tumori of Milan from 1933 to 1983: 27 sacrococcygeal, 3 spheno-occipital, and 3 vertebral. The male:female ratio was 2.7, and the median age was 63 yr for patients with sacrococcygeal and 35.2 yr for those with nonsacral chordomas. After pathologic reassessment, distinct cytologic patterns were found: physaliphorous, syncytial, and mixed subtypes, with variable degrees of cytologic atypia. However, no evident difference in survival was documented in relation to these cytohistologic features. Four cases had a prior traumatic fracture, and the pathogenetic role of trauma is stressed. Eight cases were operated with adequate surgery and only three recurred, whereas of 11 inadequate operations, 10 developed local relapse. However, follow-up for recent adequate operations is short. Radiation therapy seemed to be effective with adjuvant or palliative aims. No chemotherapeutic regimen achieved any result; one case had a short complete remission after cis-dichlorodiammineplatinum + vinblastine + bleomycin (PVB). This analysis confirms the possibility of achieving radicality with high resection of the sacrum for lesions confined below the second sacral vertebra. Nonsacral chordomas were all unresectable. The best treatment for unresectable lesions seems to be palliative surgery plus radiotherapy.

A review was carried out of morbidity and mortality after hepatic resection for metastatic colorectal cancer in 208 consecutive patients who underwent this procedure between 1980 and 1992. Overall postoperative morbidity and mortality rates were 35 and 2.4 per cent respectively. The major morbidity rate was 18 per cent, the main complications being intra-abdominal sepsis, biliary fistula and haemorrhage. Of the different factors examined, morbidity was significantly related to the extent of liver resection (53 versus 21 per cent after major and minor resections respectively), amount of blood transfused (18 versus 52 per cent for no transfusion and more than 300 ml transfused respectively) and the date of the operation (53 versus 24 per cent before and after 1986 respectively). Multivariate analysis showed that only the extent of hepatic resection and the period at which surgery was performed retained their statistical significance. These data support the opinion that surgical treatment of hepatic metastases from colorectal cancer is an effective procedure with acceptable mortality and morbidity rates. An extensive experience of hepatic surgery is, however, necessary to optimize results.

The cell types of the gut expressing Toll-like receptor 4, which recognizes specifically bacterial lipopolysaccharides, as well as the functionality of this receptor, have remained controversial. We aimed to clarify these issues. Mouse and human intestinal specimens were stained immunohistochemically to detect Toll-like receptor 4 expression. Smooth muscle and myenteric plexus cells but not enterocytes revealed receptor expression. Murine intestinal smooth muscle and myenteric plexus cells but not enterocytes showed nuclear translocation of nuclear factor-kappaB after in vivo stimulation with lipopolysaccharide. Moreover, lipopolysaccharide added to human jejunum biopsies free of epithelial cells induced release of interleukin-8 (IL-8). We can conclude that Toll-like receptor 4 is not expressed in epithelial layer, but rather on smooth muscle and myenteric plexus cells and that expression is functional. The expression of Toll-like receptor 4 on smooth muscle and myenteric plexus cells is consistent with the possibility that these cells are involved in intestinal immune defense; the low or absent expression of Toll-like receptor 4 on enterocytes might explain the intestinal epithelium hyporesponsiveness to the abundance of LPS in the intestinal lumen.

A total of 45 patients, after surgical resection of colorectal liver cancer metastases, were retrospectively analyzed to define areas of failure, to identify some possible prognostic factors (site of primary, stage, site, number of metastases, preoperative carcinoembryonic antigen, differentiation of the primary, type of surgery), and to seek a new rationale for a multimodal approach. The median postoperative follow-up was 18 months (range: 4-45 months). Survival rate was calculated by the arial method, and statistical signUicance was tested by the Mantel-Haenszel test. Twenty-eight patients had a relapse. These recurrences were hepatic in 11 patients, extrahepatic (intra-and extra-abdominal) in 12 patients, and intra-and extrahepatic in five patients: The stage (classification of the Istituto Nazionale Tumori of Milan) was the most important parameter related to the overall recurrence rate (47% in stage I, 62% in stage II, and 81% in stage III) and to the overall and disease-free survival. Stage was significantly related to hepatic relapse but not to extrahepatic relapse. In stage I the failure rate of 18 months was similar in hepatic and extrahepatic relapses (one third to one fourth of the patients), in stages II and Ill the hepatic failure rate was always higher than the extrahepatic rate. These data indicate that surgery alone is an inadequate form of therapy in cases of colorectal cancer metastases of the liver, and an adjuvant therapy, incluig altermate regimens of intraperitoneal and systemic chemotherapy, should be considered.A LTHOUGH SURGICAL RESECTION of hepatic metastases from colorectal cancer has gained worldwide acceptance as a therapeutic approach in selected cases, and several reports deal with more than 20 cases from individual institutions,'-5 there is little information available"' 3'16'18 on the natural history of the resected cases and the areas of failure after hepatic resec- We thus evaluated the recurrence rate and the areas of failure after curative liver resection for metastatic colorectal cancer in a series of 45 consecutive patients.