The role of the liver in the response to LPS: experimental and clinical findings.

The liver plays an important physiological role in lipopolysaccharide (LPS) detoxification and, in particular, hepatocytes are involved in the clearance of endotoxin of intestinal derivation. In experimental shock models, tumor necrosis factor (TNF)-alpha induces hepatocyte apoptosis and lethal effects are due to secreted TNF-alpha and not to cell-associated TNF-alpha. An exaggerated production of TNF-alpha has been reported in murine viral infections, in which mice become sensitized to low amounts of LPS and both interferon (IFN)-gamma and IFN-alpha/beta are involved in the macrophage-induced release of TNF-alpha. The prominent role of LPS and TNF-alpha in liver injury is also supported by studies of ethanol-induced hepatic damage. In humans, evidence of LPS-induced hepatic injury has been reported in cirrhosis, autoimmune hepatitis, and primary biliary cirrhosis and a decreased phagocytic activity of the reticulo-endothelial system has been found in these diseases. The origin of endotoxemia in hepatitis C virus (HCV) infected patients seems to be multifactorial and LPS may be of exogenous or endogenous derivation. In endotoxemic HCV-positive patients responsive to a combined treatment with IFN-alpha/ribavirin (RIB), endotoxemia was no longer detected at the end of the therapeutic regimen. By contrast, 48% of the non-responders to this treatment were still endotoxemic and their monocytes displayed higher intracellular TNF-alpha and interleukin (IL)-1beta levels than responders. Moreover, in responders, an equilibrium between IFN-gamma and IL-10 serum levels was attained. In the non-responders, serum levels of IL-10 did not increase following treatment. This may imply that an imbalance between T helper (Th)1 and Th2 derived cytokines could be envisaged in the non-responders.

Malignant peritoneal mesothelioma. A clinical and laparoscopic study of ten cases.

A retrospective study of 10 cases of malignant peritoneal mesothelioma from two centers is reported. All cases were initially diagnosed between 1967 and 1986 utilizing laparoscopy and the histologic interpretation of laparoscopic biopsy samples. Subsequently, the original diagnosis was confirmed by two independent pathologists employing both histological and histochemical techniques. In five cases immunohistochemical studies were also performed. The clinical findings and course of the disease were similar to other reported series. Laparoscopic findings of mesothelioma were indistinguishable from metastatic peritoneal neoplasms. However, the presence of homogeneous spreading of nodules, plaques, or fleshy masses on both parietal and visceral peritoneum; the absence of direct or indirect signs of other abdominal neoplasms; and the absence of hepatic metastases or the possible presence of nodules or plaques on Glisson's capsule without any parenchymal involvement, when observed, allowed the laparoscopist to suspect the disease in four of 10 cases. Laparoscopy may be useful in detecting mesothelioma. The diagnosis is mainly morphological, but even morphology has its inherent limitations. Further studies are necessary to improve the diagnostic accuracy of this tumor.

Laparoscopy in staging, follow-up, and restaging of ovarian carcinoma.

Laparoscopy was systematically employed for the study of 143 cases of primary ovarian tumor in the various phases of staging, treatment, follow-up, and restaging. We found that laparoscopy allowed a more precise staging if used before laparotomy. Verification of response at any time in the course of therapy was readily achieved by laparoscopy.

Primary and metastatic tumors of the liver associated with cirrhosis. A study based on laparoscopy and autopsy.

In a series of 2,538 cases of cirrhosis seen at laparoscopy there were 140 primary liver carcinomas and 19 cases of metastases to a cirrhotic liver out of a total of 167 extrahepatic neoplasms associated with cirrhosis. In an autopsy series of 1,073 cases of cirrhosis there were 190 primary liver carcinomas and 22 cases of metastases to a cirrhotic liver out of a total of 98 extrahepatic neoplasms. In another autopsy series of 498 cases of cirrhosis there were 71 primary liver carcinomas and 18 cases of metastases to a cirrhotic liver out of a total of 58 extrahepatic neoplasms. The laparoscopy series showed a predominance (31.8%) of esophageal tumors associated with cirrhosis, but these tumors rarely gave rise to liver metastases (3.7%); in the autopsy series there was a predominance (35.3%) of tumors of the portal territory, giving rise to metastases in cirrhotic livers in 35.2% of cases.