Andrew B. Connolly

Sequential changes in the metabolic response in severely septic patients during the first 23 days after the onset of peritonitis.

OBJECTIVE To quantify the sequential changes in metabolic response occurring in patients with severe sepsis after the onset of peritonitis. SUMMARY BACKGROUND DATA Understanding the changes in energy expenditure and body composition is essential for the optimal management of severely septic patients; however, they have not been quantified in the context of modern surgical care. METHODS Twelve patients with severe sepsis secondary to peritonitis (median APACHE II score = 21.5) had measurements of energy expenditure and body composition as soon as they were hemodynamically stable and 5, 10, and 21 days later. Sequential measurements of acute-phase proteins and cytokine responses were also made. RESULTS Resting energy expenditure rose to 49% above predicted and remained elevated throughout the study period. Total energy expenditure was 1.25 x resting energy expenditure. Body fat was oxidized when energy intake was insufficient to achieve energy balance. There was a positive fluid balance of 12.5 1 over the first 2 days after onset of sepsis; thereafter, body water changes closely paralleled body weight changes and were largely accounted for by changes in extracellular water. During the 21 -day study period, there was a loss of 1.21 kg (13%) of total body protein. During the first 10 days, 67% of the protein lost came from skeletal muscle, but after this time it was predominantly from viscera. Intracellular potassium levels were low but did not deteriorate further after hemodynamic stability had been reached. There was a reprioritization of hepatic protein synthesis that was obligatory and independent of changes in total body protein. The cytokine responses demonstrated the complexity, redundancy, and overlap of mediators. CONCLUSIONS The period of hypermetabolism in severely septic patients is similar to that previously described, but the fluid changes are larger and the protein loss is greater. Protein loss early on is predominantly from muscle, thereafter from viscera. Fat loss can be prevented and cell function preserved once hemodynamic stability is achieved.

Lymph Node Evaluation and Long-Term Survival in Stage II and Stage III Colon Cancer: A National Study

The most important prognostic factor in colonic cancer is the presence or absence of regional lymph nodes metastases. The aim of this study was to evaluate the relationship between 5-year mortality in the New Zealand population, and the number of nodes examined in Stage II and III colon cancers. New Zealand Cancer Registry data were retrieved for patients with colonic cancer from January 1995 to July 2003. Patients with incomplete entries, Stage I tumors, and distant metastases were excluded from analysis. Univariate and Cox regression models were used with 5-year mortality as the primary endpoint. The study identified 4309 patients. Younger age, female gender, Pacific Island descent, and right-sided tumors were associated with significantly higher lymph node retrieval. Cox regression analysis showed that the number of nodes examined was a significant predictor of 5-year mortality when age, sex, ethnicity, and site were controlled for. Five-year survival consistently improved between nodal strata until the 16-node mark, above which survival advantage was minimal. For Stage III cancers, a higher lymph node ratio was associated with a significant increase in mortality. Increased rates of nodal examination are associated with a significantly lower 5-year mortality for Stage II and III colonic cancer, but this survival advantage appears to be minimal after the 16-node mark. The lymph node ratio has been validated as a powerful predictor of survival in Stage III cancer. Our results support the current practice of harvesting and examining as many nodes as possible during attempted curative resection.BackgroundThe most important prognostic factor in colonic cancer is the presence or absence of regional lymph nodes metastases. The aim of this study was to evaluate the relationship between 5-year mortality in the New Zealand population, and the number of nodes examined in Stage II and III colon cancers.MethodsNew Zealand Cancer Registry data were retrieved for patients with colonic cancer from January 1995 to July 2003. Patients with incomplete entries, Stage I tumors, and distant metastases were excluded from analysis. Univariate and Cox regression models were used with 5-year mortality as the primary endpoint.ResultsThe study identified 4309 patients. Younger age, female gender, Pacific Island descent, and right-sided tumors were associated with significantly higher lymph node retrieval. Cox regression analysis showed that the number of nodes examined was a significant predictor of 5-year mortality when age, sex, ethnicity, and site were controlled for. Five-year survival consistently improved between nodal strata until the 16-node mark, above which survival advantage was minimal. For Stage III cancers, a higher lymph node ratio was associated with a significant increase in mortality.ConclusionsIncreased rates of nodal examination are associated with a significantly lower 5-year mortality for Stage II and III colonic cancer, but this survival advantage appears to be minimal after the 16-node mark. The lymph node ratio has been validated as a powerful predictor of survival in Stage III cancer. Our results support the current practice of harvesting and examining as many nodes as possible during attempted curative resection.

Effect of a chimeric antibody to tumor necrosis factor-alpha on cytokine and physiologic responses in patients with severe sepsis-a randomized, clinical trial

OBJECTIVES Tumor necrosis factor (TNF)-alpha appears central to the pathogenesis of severe sepsis, but aspects of the cytokine cascade and the link to physiologic responses are poorly defined. We hypothesized that a monoclonal antibody to TNF-alpha given early in the course of severe sepsis would modify the pattern of systemic cytokine release and, as a consequence, resuscitation fluid requirements, net proteolysis, and hypermetabolism would be reduced. DESIGN Randomized, double-blind, placebo-controlled trial. SETTING Critical Care Unit and University Department of Surgery in a single tertiary care center. PATIENTS Fifty-six patients (from 92 eligible patients) with severe sepsis. Twenty-eight patients were randomized to treatment, and were comparable with the placebo group for age, gender, race, Acute Physiology and Chronic Health Evaluation II score, and site and type of infection. INTERVENTIONS A 300-mg single dose of cA2 (a chimeric neutralizing antibody to TNF-alpha) was given intravenously within 12 hrs of the onset of severe sepsis. Standard surgical and intensive care therapy was otherwise delivered. MEASUREMENTS AND MAIN RESULTS Plasma concentrations of TNF-alpha, interleukin (IL)-1beta IL-6, IL-8, IL-10, soluble 75-kilodalton TNF-alpha receptor (sTNFR-75), and IL-1beta receptor antagonist (IL-1ra) were measured by sandwich enzyme-linked immunosorbent assay before cA2 infusion, 8 hrs later, and then daily for a minimum of 4 days. Sequential changes in total body protein, body water spaces, and resting energy expenditure over 21 days were measured, as soon as patients achieved hemodynamic stability, by in vivo neutron activation analysis, tritium and bromide dilution, and indirect calorimetry, respectively. Twenty-one patients died, ten having received cA2. Suppression of measurable TNF-alpha was observed at 8 hrs with subsequent rebound by 24 hrs after cA2 treatment. The concentrations of other cytokines were high, were not reduced by intervention, and decreased logarithmically over 5 days. Both groups reached hemodynamic stability at similar times (57.5 +/- 11.8 hrs in controls vs. 58.6 +/- 9.2 hrs in the cA2 group) and following similar volumes of infused fluids (29.1 +/- 3.4 L vs. 28.9 +/- 4.4 L). No differences in net proteolysis, resolution of body water expansion, or alteration in resting energy expenditure were demonstrated. CONCLUSION A single dose of cA2 did not alter the overall pattern of cytokine activation or the profound derangements in physiologic function that accompany severe sepsis.

Systematic review and meta-analysis of use of serum C-reactive protein levels to predict anastomotic leak after colorectal surgery.

Several recent studies have investigated the role of C‐reactive protein (CRP) as an early marker of anastomotic leakage following colorectal surgery. The aim of this systematic review and meta‐analysis was to evaluate the predictive value of CRP in this setting.

Randomized clinical trial of the effect of glucocorticoids on peritoneal inflammation and postoperative recovery after colectomy.

Recent data have suggested a relationship between postoperative fatigue and the peritoneal cytokine response after surgery. The aim of this study was to test the hypothesis that preoperative administration of glucocorticoids before surgery would decrease fatigue and enhance recovery, by reducing the peritoneal production of cytokines.

Chewing gum and postoperative ileus in adults: a systematic literature review and meta-analysis.

INTRODUCTION Post-operative ileus (POI) is a major problem following elective abdominal surgery. Several studies have been published investigating the use of chewing gum to reduce POI. These studies however, have produced variable results. Thus, there is currently no consensus on whether chewing gum should be widely instituted as a means to help reduce POI. METHODS We performed a systematic literature review to evaluate whether the use of chewing gum post-operatively improves POI in abdominal surgery. A comprehensive review of the literature was conducted according to the guidelines in the PRISMA statement. The following databases were searched: MEDLINE, PUBMED, EMBASE, SCOPUS, Science Direct, CINAHL and the Cochrane Central Register of Controlled Trials. Clinical outcomes were extracted and meta-analysis was performed. RESULTS There were 1019 patients from 12 randomised controlled studies included in this review. Only one study was conducted in an Enhanced Recovery after Surgery (ERAS) environment. Seven of the twelve studies concluded that chewing gum reduced post-operative ileus. The remaining five studies found no clinical improvement. Overall, there was a small benefit in reducing time to flatus, and time to bowel motion, but no difference in the length of stay or complications. CONCLUSION Chewing gum offers only a small benefit in reducing time to flatus and time to passage of bowel motion following abdominal surgery. This benefit is of limited clinical significance. Further studies should be conducted in a modern peri-operative care environment.

Quantitative lymph node evaluation as an independent marker of long-term prognosis in stage III rectal cancer.

Background:  The prognostic significance of lymph node evaluation is not well described for rectal cancer due to a lack of reproducibility in nodal counts and variable use of adjuvant and neoadjuvant therapy. The aim of this study was to examine the role of quantitative lymph node evaluation as an independent marker of prognosis in stage III rectal cancer.

MINIMAL ACCESS COLONIC SURGERY: IS IT TRULY MINIMALLY INVASIVE?

Laparoscopic colonic surgery has an established role in the management of both benign and malignant conditions. Proposed benefits from laparoscopic surgery include decreased pain, decreased metabolic disturbance to the patient and faster recovery. It is now generally accepted that pro‐inflammatory mediators, including cytokines, are to a great extent responsible for the metabolic changes associated with injury and surgery, and that these metabolic changes are related to postoperative recovery. Cytokine levels in the serum are decreased after major laparoscopic colorectal surgery compared with open surgery. However, the cytokine concentration in abdominal drain fluid is the same independent of the size of the incision and these concentrations are far higher than those found in the serum suggesting that the peritoneal would from the surgery itself is more important to metabolic events than the skin wound used to access the abdominal cavity to perform the operation. When looked at critically in programmes where patients are optimally managed perioperatively, there appears to be minimal metabolic benefit from performing a major colonic resection using minimal access surgery. Thus, it appears that the wound is critical when the operation involves only minor peritoneal disruption, such as in laparoscopic cholecystectomy, but when large peritoneal defects are created, such as in major colorectal surgery, then the skin wound becomes irrelevant to metabolism and hence recovery. Thus, minimal access does not necessarily equate to minimal invasion and the terms should not be used interchangeably in the context of laparoscopic colorectal surgery.

Ethnic disparity in colonic cancer outcomes in New Zealand – biology or an access issue?

Background  There is an ethnic variation in outcomes for colonic cancer in New Zealand. Whether this disparity is caused by cancer biology or inequitable provision of treatment services after diagnosis has not been elucidated.

Efficacy of general practitioners with specialty interests for surgical procedures

General practitioners with specialty interests (GPwSIs) have been an emerging entity in the last decade or so and aim to improve patients access to specialist level care in the primary care setting. This is achieved by them providing equivalent quality and outcomes to secondary consultant‐led services, while not necessarily providing the same breadth of clinical care as them. In this systematic review, we attempt to address their efficacy for surgical procedures and specialties.