Patients at risk for peritoneal surface malignancy of colorectal cancer origin: the role of second look laparotomy.

Peritoneal surface malignancy (PSM) is a frequent occurrence in the natural history of colorectal cancer (CRC). Although significant advances have been made in screening of CRC, similar progress has yet to be made in the early detection of PSM of colorectal cancer origin. The fact that advanced CRC can be confined to the peritoneal surface without distant dissemination forms the basis for aggressive multi-modality therapy consisting of cytoreductive surgery (CRS) plus hyperthermic intra-peritoneal chemotherapy (HIPEC), and neoadjuvant and/or adjuvant systemic therapy. Reported overall survival with complete CRS+HIPEC exceeds that of systemic therapy alone for the treatment of PSM from CRC, underscoring the advantage of this multi-modality therapeutic approach. Patients with limited peritoneal disease from CRC can undergo complete cytoreduction, which is associated with the best reported outcomes. As early or limited peritoneal carcinomatosis is undetectable by conventional imaging modalities, second look laparotomy is an important means to identify disease in high-risk patients at a stage most amenable to complete cytoreduction. This review focuses on the identification of patients at risk for PSM from CRC and discusses the role of second look laparotomy.

Amino-terminal region of the beta-amyloid precursor protein activates mitogen-activated protein kinase.

The secreted form of the beta-amyloid precursor protein (beta-APP) has previously been shown to stimulate mitogen-activated protein (MAP) kinases in PC-12 pheochromocytoma cells. The amino-terminal half of secreted beta-APP contains a region rich in cysteine residues reminiscent of cysteine-rich binding regions in other families of extracellular proteins. We found that reductive alkylation of disulfide linkages eliminated the ability of secreted beta-APP to activate MAP kinase. To confirm the role of the cysteine-rich amino-terminal region, fragments representing the amino- and carboxyl-terminal halves of secreted beta-APP were expressed in bacteria as fusion proteins and purified. Ten-minute treatment with the amino-terminal segment of beta-APP activated MAP kinase approximately 15-fold, while the carboxyl segment had no effect. The amino-terminal fragment, like intact secreted beta-APP, was substantially inactivated by reduction of sulfhydryl groups. These results suggest that the amino-terminal region of beta-APP is responsible for activation of MAP kinase and that it requires structural loops created by disulfide linkages for activity.

Gallstones and diet in Tel Aviv and Gaza.

To study the possible association between diet and gallstones we investigated these two variables in two populations in Tel Aviv and Gaza with presumed differences in both. Gallstones were more frequent in Jews in Tel Aviv than in Arabs in Gaza, 12.1% versus 3.8% (p less than 0.001). This difference was fully accounted for by the 60+ age groups in both populations. There were no significant differences in the frequency of gallstones among the 20-39 and 40-59 age groups. Numerous and marked differences in diet composition were found between both populations. Energy, carbohydrate and fiber intake was higher in Gaza. The consumption of unsaturated fats was greater in Gazans and their P/S ratio was higher, 0.92 versus 0.70 in Tel Aviv. Beef and fish were usually eaten in Gaza while poultry was more frequently consumed in Tel Aviv. There were also differences in vitamin and mineral consumption. It cannot be determined which, if any, of these dietary differences is related to the lower frequency of gallstones in the older population of Gaza. Alternatively it could be the diet eaten in Gaza many decades ago, presumably poorer in protein and fat, which is responsible for these differences.