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Bacteria possess a remarkable number of ways to become resistant to antibiotics. Antibiotic resistance has become a major problem in the treatment of Gram-positive infections. Resistance to methicillin and vancomycin in staphylococci and enterococci has resulted in organisms that are resistant to all known antibiotics. Although it is important to continue to search for newer and more effective antibiotics, it is imperative that we develop a surgical mindset of appropriate antibiotic stewardship. The use of single-dose prophylactic regimens, using narrow-spectrum agents when possible for therapeutic indications, limiting the duration of therapeutic agents appropriately, avoiding the use of vancomycin except when necessary, and adhering to strict infection control measures are all steps that will limit the spread and development of resistant organisms.

Postoperative infections remain common after high-risk gastrointestinal procedures. PGG-glucan (Betafectin; Alpha Beta Technology Inc, Worcester, Mass), derived from yeast cell walls, promotes phagocytosis and intracellular killing of bacterial pathogens by leukocytes, prevents infection in an animal model of wound infection, and acts synergistically with antibiotics to reduce mortality in rat peritonitis.We hypothesized that infectious complications in these patients might be reduced by the administration of a nonspecific immune-enhancing agent.Multicenter, prospective, randomized, double-blind, placebo-controlled trial of 1249 patients prospectively stratified into colorectal or noncolorectal strata.Thirty-nine medical centers throughout the United States.Aged 18 years or older, scheduled for gastrointestinal procedure lasting 2 to 8 hours, with 2 or more defined risk factors.PGG-glucan, 0.5 mg/kg or 1.0 mg/kg, or placebo once preoperatively and 3 times postoperatively. All patients received standardized antibiotic prophylaxis.Serious infection or death within 30 days.All randomized patients revealed no difference in serious infections and deaths in the treated groups compared with placebo groups (15% vs 14%, P.90). In the prospectively defined noncolorectal stratum (n = 391), PGG-glucan administration was associated with a statistically significant relative reduction (39%) in serious infections and death (placebo, 46 [36%] of 129 vs either PGG-glucan group, 29 [21%] of 132 and 28 [22%] of 130, P.02). PGG-glucan reduced postoperative infection or death in malnourished patients having noncolorectal procedures (31 [44%] of 70, placebo group; 16 [24%] of 68, 0.5-mg/kg PGG-glucan group; 12 [17%] of 72, 1.0-mg/kg PGG-glucan group; P.001). Study drug was stopped owing to adverse effects more frequently for patients receiving PGG-glucan than placebo (2%, 4%, and 7% for the placebo group, 0.5-mg/kg PGG-glucan group, and 1.0-mg/kg PGG-glucan group, respectively, P.003).Perioperative administration of PGG-glucan reduced serious postoperative infections or death by 39% after high-risk noncolorectal operations.

Barrett esophagus predisposes individuals to esophageal carcinoma, which develops from intermediate stages of tissue dysplasia primarily in the vicinity of the gastroesophageal junction. Understanding the cellular and molecular events in the progression of Barrett esophagus to adenocarcinoma may contribute to its early diagnosis and treatment. Mutation and overexpression of the tumor suppressor p53 have previously been observed in Barrett high grade dysplasia and adenocarcinoma. The expression of the cyclin-dependent kinase (CdK) inhibitor p21 can be up-regulated by p53, resulting in the down-regulation of cell division at the G(1)/S-phase transition. The current study examined the correlation between the expression of p21 and p53 by quantifying their levels during the progression of dysplasia and adenocarcinoma in Barrett esophageal tissues.Barrett esophageal tissue samples that were negative or indefinite for dysplasia, contained dysplasia, and contained adenocarcinoma were examined by immunohistochemistry. Paraffin embedded sections of lining and glandular epithelia were adsorbed with primary murine antibodies against human p21 or p53 followed by horseradish peroxidase secondary antibody. An immunoreactivity score for each primary antibody and section was obtained by multiplying a staining intensity factor by the percent of positively stained cells.Nuclear p21 expression was detectable immunohistochemically in Barrett esophagus that was negative for dysplasia, but it was significantly elevated (P/= 0.05) in tissues scored as indefinite for dysplasia, positive for low grade or high grade dysplasia, and positive for adenocarcinoma. Importantly, p53 expression did not parallel p21 expression. p53 levels were low in the early stages of Barrett dysplasia and were increased in high grade dysplasia and adenocarcinoma. There were no differences in p21 or p53 levels between glandular and lining epithelia in Barrett tissue throughout the histologic stages of neoplastic progression evaluated in this study.p21 expression in Barrett tissue scored as indefinite for dysplasia or low grade dysplasia was significantly elevated relative to p53 expression. Elevated levels of p21 were also observed in high grade dysplasia and adenocarcinoma, in which they do not appear to be effective in down-regulating cell division. Analysis of p21 and p53 expression may aid in the evaluation of tissue abnormalities in Barrett esophagus.

Colorectal cancer is a common disease in the Western world. Most, if not all, colorectal cancers develop from previously benign adenomas. There are a number of genetic abnormalities including mutations in oncogenes and tumor suppressor genes which either present as a germline, or acquired defects lead to the development of colorectal cancer. Two well-defined hereditary colorectal cancer syndromes exist, hereditary nonpolyposis colorectal cancer syndrome and familial adenomatous polyposis coli, for which genetic testing is possible and advised. Guidelines for screening for colorectal cancer in average, moderate, and high risk patients are available from the American Cancer Society and were updated in 1997. The American Society of Clinical Oncology has published guidelines for genetic testing in a variety of cancers including colorectal cancer.

Adenocarcinoma of the pancreas is becoming an increasingly common disease. The differential diagnosis of pancreatic adenocarcinoma is that of obstructive jaundice. Suspicious findings on history and physical examination can be confirmed with appropriate laboratory and radiologic testing. Approximately 20% of patients with small lesions and no metastatic disease may be cured with resection. The operative mortality and morbidity for major pancreatic resections is now sufficiently low to warrant a more aggressive approach to these patients.

During a 30-month period 73 patients underwent operation for choledocholithiasis. Thirty-three of these patients (45%) had cholangitis preoperatively. When compared to patients with common duct stones who had no preoperative cholangitis, patients with cholangitis were older (P less than 0.001), more likely to present with jaundice (P less than 0.01) and leukocytosis (P less than 0.01), and more likely to have retained or primary common duct stones (P less than 0.01). Cholangitis patients were also more likely to have bactibilia (P less than 0.025), and anaerobes were isolated from the bile of 27% of these patients (P less than 0.01). Twenty-nine of 33 cholangitis patients (88%) received a minimum of 4 days of broad-spectrum antibiotics including an aminoglycoside prior to operation (P less than 0.01). Despite these clear differences, patients with preoperative cholangitis were not more likely to develop infective sequelae or biliary complications. However, cholangitis patients were much more likely (P less than 0.001) to develop an increase in serum creatinine (33% versus 3%) which, in turn, contributed to a longer (P less than 0.01) postoperative hospitalization. Since therapy with aminoglycosides may have contributed to postoperative morbidity and prolonged hospital stay, aminoglycosides should be reserved only for patients with the most severe cholangitis and should be used with great caution.

Controlled studies have demonstrated that systemic prophylactic antibiotics significantly reduce the sepsis rate after biliary tract surgery. Other studies have documented the efficacy of topical antibiotic irrigation in decreasing the incidence of wound infection after a wide variety of procedures. Whether systemic antibiotics or the combination of systemic and topical antibiotics provide any advantage over topical antibiotics alone, however, has not been determined. Therefore, a prospective, randomized study was carried out comparing topical intra-abdominal and wound antibiotic irrigation (neomycin and polymyxin) with topical antibiotic irrigation plus parenteral antibiotics (gentamicin and penicillin) in 54 patients undergoing "high-risk" biliary surgery. All patients underwent either an elective common bile duct exploration or a biliary-enteric anastomosis for obstructive jaundice. Twenty-five patients were randomized to the group receiving only topical antibiotics, and 29 received topical plus systemic antibiotics. The two groups were similar with respect to age, sex, presence of common duct stones, incidence of jaundice, positive bile cultures at surgery, and type of surgery performed. There were three wound infections in each group, and no patient developed an intra-abdominal abscess. Other infectious complications occurred with similar frequency in the two study groups. This study suggests that topical antibiotics provide effective prophylaxis in biliary tract surgery and that broad-spectrum systemic antibiotic therapy is of no additional benefit. Topical antibiotics provide an alternative means of prophylaxis for patients discovered intraoperatively to be at "high risk" for infection.