Alistair C. J. Windsor

Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis

Background—In patients with major trauma and burns, total enteral nutrition (TEN) significantly decreases the acute phase response and incidence of septic complications when compared with total parenteral nutrition (TPN). Poor outcome in acute pancreatitis is associated with a high incidence of systemic inflammatory response syndrome (SIRS) and sepsis. Aims—To determine whether TEN can attenuate the acute phase response and improve clinical disease severity in patients with acute pancreatitis. Methods—Glasgow score, Apache II, computed tomography (CT) scan score, C reactive protein (CRP), serum IgM antiendotoxin antibodies (EndoCAb), and total antioxidant capacity (TAC) were determined on admission in 34 patients with acute pancreatitis. Patients were stratified according to disease severity and randomised to receive either TPN or TEN for seven days and then re-evaluated. Results—SIRS, sepsis, organ failure, and ITU stay, were globally improved in the enterally fed patients. The acute phase response and disease severity scores were significantly improved following enteral nutrition (CRP: 156 (117–222) to 84 (50–141), p<0.005; APACHE II scores 8 (6–10) to 6 (4–8), p<0.0001) without change in the CT scan scores. In parenterally fed patients these parameters did not change but there was an increase in EndoCAb antibody levels and a fall in TAC. Enterally fed patients showed no change in the level of EndoCAb antibodies and an increase in TAC. Conclusion—TEN moderates the acute phase response, and improves disease severity and clinical outcome despite unchanged pancreatic injury on CT scan. Reduced systemic exposure to endotoxin and reduced oxidant stress also occurred in the TEN group. Enteral feeding modulates the inflammatory and sepsis response in acute pancreatitis and is clinically beneficial.

Localization of cyclooxygenase-2 in human sporadic colorectal adenomas.

A putative target for the anti-colorectal cancer action of nonsteroidal anti-inflammatory drugs is the inducible isoform of cyclooxygenase (COX), COX-2. COX-2 is expressed within intestinal adenomas in murine polyposis models, but expression has been poorly characterized in human colorectal neoplasms. Therefore, we investigated the localization of the COX-2 protein in human sporadic colorectal adenomas. Immunohistochemistry for COX-2 and CD68 (a tissue macrophage marker) was performed on formalin-fixed, paraffin-embedded (n = 52) and frozen, acetone-fixed (n = 6) sections of human sporadic colorectal adenomas. Forty of 52 (77%) formalin-fixed adenomas expressed immunoreactive COX-2. COX-2 was localized to superficial interstitial macrophages in 39 cases (75%) and to deep interstitial macrophages in 9 cases (17%). COX-2 staining of dysplastic epithelial cells was observed in 15 cases (29%). A logistic regression analysis identified the adenoma site (P = 0.012) and histological type (P = 0.001) as independent predictors of superficial macrophage COX-2 expression. There was no relationship between the number of macrophages within an adenoma and macrophage COX-2 expression. These results indicate that COX-2 is expressed predominantly by interstitial macrophages within human sporadic colorectal adenomas. If COX-2 does indeed play a role in the early stages of colorectal carcinogenesis in man, these data suggest COX-2-mediated paracrine signaling between the macrophages and epithelial cells within adenomas.

Lack of correlation between failure of gut barrier function and septic complications after major upper gastrointestinal surgery.

OBJECTIVE To determine the influence of abnormal gut barrier function on the risk of septic complications in patients undergoing major resectional surgery for upper gastrointestinal cancer. SUMMARY BACKGROUND DATA A failure of the gut mucosal barrier to exclude bacteria and endotoxin from the portal and systemic circulation is incriminated in the development of sepsis and multiple organ failure. Although the experimental data is compelling, corroborative evidence from studies in humans is sparse. This study attempted to correlate both preoperative gut barrier dysfunction and the pattern of change after surgery with septic outcome. METHODS Sixty-eight patients undergoing curative resectional surgery for upper gastrointestinal cancer were monitored for 30-day septic morbidity (intraabdominal abscesses/empyema and pneumonia). Intestinal permeability, serum IgM and IgG anti-endotoxin antibodies (EndoCAb), and serum C-reactive protein were measured before surgery and on postoperative days 1 and 7. RESULTS Increased intestinal permeability before surgery did not predict septic outcome. Major surgery was associated with increased intestinal permeability and evidence of endotoxin exposure. Comparing sepsis and nonsepsis groups, however, there was no significant difference in intestinal permeability, endotoxin exposure, and the acute phase response after surgery. CONCLUSIONS This study demonstrates that gut barrier dysfunction occurs after surgery, but the magnitude of change does not differentiate patients in whom sepsis develops and those in whom it does not. Preoperative increased intestinal permeability had no predictive value for sepsis. This study failed to support the thesis that gut barrier dysfunction is directly linked to sepsis.

Monocyte human leukocyte antigen-DR expression correlates with intrapulmonary shunting after major trauma

BACKGROUND Severe injury is often complicated by the development of sepsis and the adult respiratory distress syndrome. Since the outcome from severe injury also correlates with changes in monocyte human leukocyte antigen (HLA)-DR expression in such patients, the present study aimed to determine whether or not there was a relationship between monocyte HLA-DR expression and indicators of early pulmonary dysfunction. METHODS Monocyte HLA-DR expression and serum interleukin (IL)-6 were measured on admission and then again on days 1, 3, 5, and 7 after major injury in 29 patients admitted for the management of trauma with an injury severity score of 9 or more. Noninvasive intrapulmonary shunt measurement was also performed in all these patients within 6 hours of emergency surgery in all patients. RESULTS Monocyte HLA-DR followed the characteristic suppression followed by recovery in those who followed an uncomplicated course but progressively declined in those who suffered septic complications. The degree of intrapulmonary shunting observed 6 hours after injury in the patients who developed sepsis was significantly higher than that in the uncomplicated group. Peak monocyte HLA-DR expression during the recovery phase correlated inversely with the degree of intrapulmonary shunting. CONCLUSIONS The degree of intrapulmonary shunting observed following severe trauma correlates with the failure of circulating monocytes to re-express HLA-DR antigen, and this may provide some insights into the early events that result in the adult respiratory distress syndrome after major injury.

Paradoxical clinical deterioration despite near-complete pathological response to neoadjuvant chemotherapy for locally advanced gastro-oesophageal adenocarcinoma

Neoadjuvant chemotherapy for proximal gastric cancer has shown promise in early clinical trials. We report on a clinical deterioration, yet near-complete pathological and radiological response to a combination of cisplatin and fluorouracil in a patient with locally-advanced gastric adenocarcinoma.