Loss of epithelial p53 and αv integrin cooperate through Akt to induce squamous cell carcinoma yet prevent remodeling of the tumor microenvironment.

Most of the squamous cell carcinomas (SCCs) of the skin and head and neck contain p53 mutations. The presence of p53 mutations in premalignant lesions suggests that they represent early events during tumor progression and additional alterations may be required for SCC development. Here we show that codeletion of the p53 and αv integrin genes in mouse stratified epithelia induced SCCs in 100% of the mice, more frequently and with much shorter latency than deletion of either gene alone. The SCCs that lacked p53 and αv in the epithelial tumor cells exhibited high Akt activity, lacked multiple types of infiltrating immune cells, contained a defective vasculature and grew slower than tumors that expressed p53 or αv. These results reveal that loss of αv in epithelial cells that lack p53 promotes SCC development, but also prevents remodeling of the tumor microenvironment and delays tumor growth. We observed that Akt inactivation in SCC cells that lack p53 and αv promoted anoikis. Thus, tumors may arise in these mice as a result of the increased cell survival induced by Akt activation triggered by loss of αv and p53, and by the defective recruitment of immune cells to these tumors, which may allow immune evasion. However, the defective vasculature and lack of a supportive stroma create a restrictive microenvironment in these SCCs that slows their growth. These mechanisms may underlie the rapid onset and slow growth of SCCs that lack p53 and αv.

Perforated appendicitis is not a contraindication to laparoscopy.

Recent studies have reported an increased risk of intra-abdominal abscess formation following laparoscopic operation for perforated appendicitis. We undertook this study to compare laparoscopic versus open appendectomy in the treatment of perforated appendicitis. Records of all patients undergoing an appendectomy between January 1994 and June 1997 were reviewed, classifying appendicitis as acute, gangrenous, or perforated based on the intraoperative findings. Operative procedures were categorized as open, laparoscopic converted to open, or laparoscopic. The study group included 690 patients; four hundred fourteen (60%) were acute, 77 (11%) were gangrenous, and 199 (29%) were perforated. Although mean length of stay was shorter for all patients undergoing laparoscopic appendectomy, patients with perforated appendicitis had similar length of stay between treatment groups. Mean operative time for open appendectomy was significantly shorter than for converted or laparoscopic appendectomy regardless of diagnosis (P<0.01). Ten patients (1.4%) developed an intra-abdominal abscess: six after open appendectomy (1.7%), one after converted appendectomy (3.7%), and three after laparoscopic appendectomy (1%). There was no significant difference in rate of abscess formation in patients with perforated appendicitis undergoing open, converted, or laparoscopic appendectomy. We conclude that laparoscopic appendectomy for perforated appendicitis is not associated with an increased rate of intra-abdominal abscess formation.