Systemic bone loss and induction of coronary vessel disease in a rat model of chronic inflammation.

Clinically, osteopenia or low bone mass has been observed in a variety of chronic inflammatory diseases, and elevated proinflammatory mediators have implicated this process. The purpose of this study was to develop an in vivo model of bone loss induced by chronic systemic inflammation. Time-release pellets designed to deliver one of three doses of LPS: Low (3.3 microg/day), High (33.3 microg/day), or Placebo over 90 days, were implanted subcutaneously in 3-month-old male Sprague-Dawley rats (n = 8/group). Neutrophil counts, indicative of ongoing inflammation, were elevated (P < 0.05) in both LPS groups at 30 days post-implant and remained significantly elevated in the High dose throughout the 90-day study period. At the end of the study, bone loss occurred in the femur as indicated by decreased bone mineral density (BMD) in both LPS-treated groups, but vertebral BMD was reduced in the High dose animals only. Microcomputed tomography revealed that trabecular bone volume (BV/TV) of the proximal tibial metaphysis tended to be reduced in the High dose LPS group. Deleterious effects on trabecular number (TbN) and trabecular separation (TbSp) were observed in both LPS-treated groups, but only the High dose group reached statistical significance. These alterations in trabecular microarchitecture resulted in compromised biomechanical properties. No changes in cortical thickness, porosity, or area of the tibia midshaft were evident at either dose of LPS. Up-regulation of the proinflammatory mediators, cyclooxygenase (COX)-2, interleukin (IL)-1, and tumor necrosis factor (TNF)-alpha was demonstrated in the metaphyseal region where the deleterious effects of LPS were observed. In addition to these alterations in bone, trichrome staining indicated changes in the coronary arterioles, consistent with vascular disease. Utilization of a LPS time-release pellet appears to provide an in vivo model of chronic inflammation-induced bone loss and a potentially novel system to study concurrent development of osteopenia and vascular disease.

Equilibrium binding of Hoechst 33258 and Hoechst 33342 fluorochromes with rat colorectal cells.

We examined the biophysical characteristics of the interaction of Hoechst 33258 and 33342 dyes with normal rat colorectal cells as functions of fixation and solution composition. Classical dye-binding techniques were used to investigate the stoichiometry and binding constants with whole cells, and quantitative fluorescence image analysis was used to specifically study nuclear dye binding in intact cells. In aqueous solution, H-33258 dye bound cooperatively with intact cells, with a binding constant of between 3-4 x 10(5). In ethanolic solution, binding appeared less cooperative, although Scatchard analysis could not be used. The binding constant was slightly lower (2 x 10(5)), but the total number of cell binding sites was decreased by a factor of 5, reflecting a great decrease in cytoplasmic sites. QFIA studies identified conditions optimal for DNA quantitation under which the fluorescence signal was independent of dye or cell concentration. The proportionality between absolute nuclear fluorescence intensity and DNA content was established, and the upper limit of DNA content of normal colorectal cells was also determined.

Consequences of preoperative cholangitis and its treatment on the outcome of operation for choledocholithiasis.

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.

The role of topical antibiotics in "high-risk" biliary surgery.

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.

Repair of parastomal hernias using polypropylene mesh.

Parastomal hernias are a common complication of ostomy construction. We have developed a method of repair that uses two strips of polypropylene prosthetic mesh through a midline incision. The medical records of 19 patients who underwent parastomal hernia repair were retrospectively reviewed. All nine patients operated on for this condition by the senior author (R.G.P.) (group 1) underwent repairs with this technique. All ten patients operated on by other surgeons in our center (group 2) underwent repairs in which the stoma was moved, the fascia was directly repaired through a parastomal incision, or the fascia was repaired via a midline incision. No patients in group 1 had recurrences while five patients in group 2 had recurrences. Neither group developed strictures or stomal prolapse. Our method of repair is technically easy and has excellent results. It is especially suitable in very large hernias in which incisional hernia is likely in the original stoma site if the stoma is moved.

Biliary bacteria: significance and alterations after antibiotic therapy.

Patients undergoing urgent and complex biliary operations were studied to determine (1) whether bactibilia is associated with postoperative complications amd (2) whether antibiotic therapy influences biliary bacteriology. Aerobic and anaerobic cultures were performed on hepatic bile obtained at surgery in 134 patients. Cultures were repeated four to seven days postoperatively in 111 patients who had indwelling biliary tubes. Positive operative bile cultures were associated with an increased incidence of wound infection and postoperative renal dysfunction. Postoperative bile cultures showed a significant increase in the number of patients having bactibilia, and a significant alteration in the types of organisms isolated. Anaerobes were cultured from 15% of operative and 23% of postoperative cultures. Antibiotic therapy did not sterilize bile, but merely altered biliary bacteriology. Furthermore, prolonged aminoglycoside therapy was associated with a high incidence of renal dysfunction, especially in elderly patients.

Effect of PGG-glucan on the rate of serious postoperative infection or death observed after high-risk gastrointestinal operations. Betafectin Gastrointestinal Study Group.

BACKGROUND: 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. HYPOTHESIS: We hypothesized that infectious complications in these patients might be reduced by the administration of a nonspecific immune-enhancing agent. DESIGN: Multicenter, prospective, randomized, double-blind, placebo-controlled trial of 1249 patients prospectively stratified into colorectal or noncolorectal strata. SETTING: Thirty-nine medical centers throughout the United States. PATIENTS: Aged 18 years or older, scheduled for gastrointestinal procedure lasting 2 to 8 hours, with 2 or more defined risk factors. INTERVENTIONS: 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. MAIN OUTCOME MEASURES: Serious infection or death within 30 days. RESULTS: 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). CONCLUSION: Perioperative administration of PGG-glucan reduced serious postoperative infections or death by 39% after high-risk noncolorectal operations.

Past, present, and future of pancreatic surgery.

The advances in the surgical treatment of pancreatic disease in the 20th century were built on careful anatomic and physiologic studies dating to the early 1800s. Operations for neoplastic diseases developed in the 1930s by Whipple, Trimble, and others allowed pancreatic malignancies to be removed with ever increasing safety. Endocrine tumors of the pancreas were described and treated surgically. Patients with pancreatitis now have a number of surgical alternatives available for their individual circumstances. The future of surgery for pancreatic disease lies in the results of the human genome project and the fields of genomics and proteomics that resulted. The rapidity with which knowledge of gene expression is advancing owing to new technologies such as the microarray biochip is amazing. The future of pancreatic surgery is bright.

Adenocarcinoma of the colon in adolescents.

A retrospective study was carried out in nine children between the ages of 10 and 20 years with adenocarcinoma of the colon. No family history, significant medical history, or predisposing factors were identified, except for Turcot's syndrome in one child. Common presenting signs and symptoms were vague abdominal pain, nausea and vomiting, weight loss, change in bowel habits, and guaiac-positive stools. Five of the patients' diagnoses were delayed for an average of 11.6 months, the majority of whom had Dukes' D disease. Their median survival was 4 months compared with 24 months in the four patients diagnosed early. As with adults, the mainstay of therapy is operation. Our data indicate that an increased awareness and consideration of colon cancer in children will result in earlier diagnosis, a more favorable disease stage, and prolonged survival.

Pancreatic pseudocysts: cause, therapy, and results.

Sixty-nine patients with pancreatic pseudocysts were reviewed. Chronic alcohol abuse was associated with pancreatitis in 78 percent of the patients. Presenting signs and symptoms were nonspecific. Ultrasonographic and computerized axial tomographic scans were most commonly used to established the diagnosis. Twenty patients were managed conservatively and resolution occurred in 11 of these patients. Forty-nine patients underwent operation. Internal drainage was performed on 31 occasions in 29 patients, and external drainage was performed in 11. In addition, pancreatic resection was carried out in 8 patients, and needle aspiration in 2 patients. Infected pseudocysts were present in 11 patients. Complications occurred in 18 patients in the operated group and 2 patients died (4 percent). There was recurrence of pseudocysts in 10 patients. Our results suggest that pseudocysts remain a common complication of pancreatitis, and infected pseudocysts are the major cause of postoperative morbidity. Computerized axial tomography and ultrasonography are the mainstays of diagnosis. Surgical therapy is safe, but continues to be associated with significant rates of morbidity and recurrence. When pseudocysts recur, they are generally anatomically distant from the original lesion and probably represent new disruptions of the pancreatic duct.

Treatment of esophageal cancer: the continued need for surgical resection.

We conclude that preoperative radiotherapy and chemotherapy is very likely to improve the length of survival in patients with squamous cell carcinoma undergoing surgical resection and decreases the incidence of symptomatic local recurrence requiring additional palliative treatment. A favorable tumor response to adjuvant therapy, however, did not significantly improve the survival curves in our study, does not guarantee complete tumor regression, and should not be cited as a basis for elimination of esophagectomy in treatment protocols. Adenocarcinoma treated with surgical resection has a better prognosis than similarly treated squamous cell carcinoma, but has a poorer prognosis than squamous cell carcinoma treated with preoperative adjuvant therapy and surgical resection.

Comparison of postoperative outcomes in ulcerative colitis and familial polyposis patients after ileoanal pouch operations.

BACKGROUND: Pouchitis is a poorly understood inflammatory condition that occurs in the ileal pouches of patients who have undergone the ileal-pouch anal anastomosis after restorative proctocolectomy. This postoperative condition is much more common in patients with ulcerative colitis (UC) than familial adenomatous polyposis (FAP) colitis. It has been suggested that, owing to pouchitis, UC patients do not attain the same quality of life that FAP patients do after the ileal-pouch anal anastomosis operation. We hypothesized that health-related quality of life does not differ between FAP and UC patients. METHODS: We analyzed the postoperative morbidity and gastrointestinal function in 110 consecutive patients having undergone the ileal-pouch anal anastomosis for either UC or FAP at OU Medical Center from 1983 to 2000 by retrospective record review. Health-related quality of life was assessed in 83 patients using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and the Medical Outcome Study Short-Form 36 (SF-36) questionnaire. RESULTS: With the exception of pouchitis, there was no difference in perioperative outcome, morbidity, or functional status between UC and FAP patients. The SIBDQ and SF-36 revealed no statistically significant difference between FAP and UC patients. CONCLUSIONS: As expected, UC patients are more likely to develop pouchitis. Despite this, our data reveal that both patient groups enjoy a similarly good functional status and quality of life.

Five year experience with pancreatic pseudocysts.

Twenty-six patients with pancreatic pseudocysts underwent surgical intervention from 1975 through 1979. Chronic alcohol use was associated with pancreatic disease in 84.6 percent of these patients. The clinical findings are not specific, and ultrasonographic examination of the abdomen and computed tomographic scanning have been the most reliable diagnostic tests. External drainage is performed for infected or thin-walled cysts, and carries a complication rate of 72.7 percent in this series. Internal drainage was complicated 31 percent of the time. There were no deaths in this series.

Factors predicting failure of medical therapy for gastric ulcers.

We reviewed the charts of all patients admitted with a diagnosis of gastric ulcer from January 1970 to December 1980. Multiple risk factors were recorded in patients receiving medical treatment and compared in those patients successfully treated medically versus those requiring operation after a failed course of medical treatment. One hundred patients were treated medically without surgical intervention, and 34 patients underwent operation after medical therapy failed. Significant risk factors in patients requiring operative therapy included smoking (p = 0.03), multiple trauma and sepsis (p = 0.02), large ulcers (p = 0.03), and multiple ulcers (p = 0.02). We have identified a set of factors associated with a high risk of failure of medical therapy. Patients with any of these risk factors may be treated most effectively by a limited trial of medical therapy with close follow-up. If their ulcer disease does not respond readily to standard medical therapy, they should be considered for early elective surgery.

Factors affecting mortality in biliary tract surgery.

Fifteen clinical and laboratory parameters in 155 consecutive patients having bile duct surgery over a 3 year period were analyzed in an effort to define the factors associated with a poor outcome and to define the subpopulation of patients at greatest risk. Ten of the 15 parameters evaluated were found to correlate significantly (p < 0.05) with hospital mortality. Five or more risk factors correlated significantly with mortality (p < 0.0001) and with postoperative renal failure, bacteremia and upper gastrointestinal hemorrhage (p < 0.005). This risk-factor analysis has the advantages of providing information rapidly and employing only clinical observations and readily available laboratory tests. Patients with five or more risk factors should be considered for preoperative percutaneous transhepatic decompression.

Early detection of colorectal cancer by quantitative fluorescence image analysis of exfoliated cells.

Early-stage colorectal cancer is potentially curable. In the present study, we applied quantitative fluorescence image analysis (QFIA) cytology to the detection of experimental colorectal cancer in a rodent model. QFIA cytology combines visual cytologic examination with quantitation of DNA content in single exfoliated cells. Cancer was induced by treating 110 rats with subcutaneous 1,2-dimethylhydrazine. Sequential colon washes were obtained weekly from each animal for 20 weeks. Control animals were treated identically except for the administration of carcinogen. Cells that were cytologically abnormal or had increased DNA content were found starting in the second week. By the eighth week, roughly 50 percent of animals had positive results, and this level remained approximately constant for the duration of the study. Tissue pathologic results were normal during weeks 1 to 7. Dysplasias became common during weeks 8 to 15 whereas most cancers appeared during weeks 16 to 21. These results indicate that QFIA cytology is a highly sensitive method for detecting even preneoplastic changes resulting from carcinogen administration and may prove useful in detecting human colorectal cancer.

Antibiotic-resistant organism infection.

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.

Pancreatic adenocarcinoma: a review for primary care physicians.

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.

Colorectal cancer: genetics and screening.

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.