Microbial pathogens within the peritoneal cavity are thought to encounter three categories of host defense mechanisms: (i) removal mechanisms, which occur via diaphragmatic lymphatic absorption; (ii) killing mechanisms, in which host phagocytes act as effector cells; and (iii) sequestration mechanisms due to fibrin trapping and the formation of adhesions between visceral surfaces. We sought to define and quantitate the relative role of the first two components in an experimental rat model of Escherichia coli peritonitis in which fibrinous adhesions do not form. Intraperitoneal challenge with -2 x 108 CFU of viable E. coli led to an initial decline in bacterial numbers followed by ongoing proliferation and >50% mortality. With inocula of c5 x 107 CFU, elimination of bacteria occurred after moderate initial proliferation, and no mortality ensued. Nonviable, radiolabeled E. coli organisms were utilized to examine bacterial clearance via translymphatic absorption and phagocytosis. Both processes were extremely rapid, serving to eliminate free bacteria rapidly within the peritoneal cavity. Although macrophages and polymorphonuclear leukocytes within the peritoneal cavity demonstrated similar phagocytic capacities, the predominance of macrophages at the time of the initial bacterial insult led to the conclusion that these cells, in addition to translymphatic absorption, represent the first line of host defenses, acting to eliminate bacteria in the incipient stages of infection.
In a prospective randomized trial, 700 patients with a confirmed histological diagnosis of adenocarcinoma of the rectum or rectosigmoid were randomized to receive radiotherapy prior to operation (2000 to 2500 rads in two weeks) or surgery alone. Five year observed survival in the 453 patients on whom "curative" resection was possible was 48.5% in the X-ray treated group compared with 38.8% in controls, while in the 305 having low lying lesions requiring abdominoperineal resection, survival in the treated group was 46.9% compared with 34.3% in controls. Although suggestive of a treatment benefit, neither is considered statistically significant. Histologically positive lymph nodes were found in 41.2% of the control group and in only 27.8% of the patients receiving radiotherapy. Reveiw of all patients who died during the study shows a consistently lower death rate from cancer in the radiotherapy group. Although this study suggests a treatment benefit from preoperative radiotherapy, further studies now in progress by this group and others are necessary to determine the optimal dose regimen.
In a prospective randomized trial, 361 male patients with histologically proven adenocarcinoma of the rectum, judged preoperatively to require abdominoperineal resection (APR), were treated by surgery alone or were given 3,150 rads of preoperative radiotherapy. Surgical resection was done on 320 patients, 262 having "curative" APR. Only moderate symptoms from radiotherapy were noted and postoperative complications and 30-day mortality were similar in both groups. Five-year survival for curative APR was the same in both groups (50% for both treated and control patients). The incidence of positive lymph nodes in the resected specimens was 35% in treated and 41% in controls. In the first preoperative radiotherapy trial conducted by the group, 5-year survival in patients undergoing "curative" APR was 47% in treated versus 34% in control groups. Additionally, the difference in positive lymph nodes in the resected specimens was substantially greater in the first trial (26% in treated versus 44% in controls).
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