Evan Ong

Augmented inducible nitric oxide synthase expression and increased NO production reduce sepsis-induced lung injury and mortality in myeloperoxidase-null mice

The myeloperoxidase (MPO)-hydrogen peroxide-halide system is an efficient oxygen-dependent antimicrobial component of polymorphonuclear leukocyte (PMN)-mediated host defense. However, MPO deficiency results in few clinical consequences indicating the activation of compensatory mechanisms. Here, we determined possible mechanisms protecting the host using MPO(-/-) mice challenged with live gram-negative bacterium Escherichia coli. We observed that MPO(-/-) mice unexpectedly had improved survival compared with wild-type (WT) mice within 5-12 h after intraperitoneal E. coli challenge. Lungs of MPO(-/-) mice also demonstrated lower bacterial colonization and markedly attenuated increases in microvascular permeability and edema formation after E. coli challenge compared with WT. However, PMN sequestration in lungs of both groups was similar. Basal inducible nitric oxide synthase (iNOS) expression was significantly elevated in lungs and PMNs of MPO(-/-) mice, and NO production was increased two- to sixfold compared with WT. Nitrotyrosine levels doubled in lungs of WT mice within 1 h after E. coli challenge but did not change in MPO(-/-) mice. Inhibition of iNOS in MPO(-/-) mice significantly increased lung edema and reduced their survival after E. coli challenge, but iNOS inhibitor had the opposite effect in WT mice. Thus augmented iNOS expression and NO production in MPO(-/-) mice compensate for the lack of HOCl-mediated bacterial killing, and the absence of MPO-derived oxidants mitigates E. coli sepsis-induced lung inflammation and injury.

1990–2001 U.S. general surgery chief resident gastric surgery operative experience: analysis of paradigm shift

The almost complete disappearance of benign gastric ulcer disease has led to the perception that there may be an insufficient gastric surgery experience for surgery residents. This study analyzed residentreported gastric procedure experience by chief residents from U.S. programs. The Resident Statistic Summaries (Report C) for 1990–2001 were compiled and analyzed. Results are expressed as the average number of operations performed per resident, standard deviation (SD), and the percentage (%) of total gastric operative cases. For all gastric-related surgery, the average reported cases per chief resident ranged from 9.8-12.4 with a peak in 1990 and a nadir in 1999; in 2001 the reported case average was 11.3 (SD ranged from 6–8). Over the same interval, vagotomy decreased from 24% in 1990 to 7% in 2001, whereas gastric-reduction operations increased from 5%—34%. Total gastrectomy remained a constant less than 1.0 per chief resident (range 0.6-0.8), whereas partial gastric resection (PGR) was unchanged. The percentage of all types of gastric resections slightly diminished from 34% in 1990 to 29% in 2001. U.S. surgical chief residents report a widely variable experience in gastric surgery over the period analyzed. However, their overall experience has not significantly diminished since 1990 although specific procedural volume has varied.

A Priori Dietary Ω-3 Lipid Supplementation Results in Local Pancreatic Macrophage and Pulmonary Inflammatory Response Attenuation in a Model of Experimental Acute Edematous Pancreatitis (AEP)

BACKGROUND Acute pancreatitis is often complicated by multiorgan dysfunction, which is postulated to occur in part by macrophage infiltration into the pancreas. Eicosapentaenoic acid (EPA), an ω-3 fatty acid, is the principal biologic component of fish oil and has clinically and experimentally been demonstrated to be anti-inflammatory. We hypothesized that dietary EPA supplementation before the induction of pancreatitis would attenuate both Mϕ-mediated local pancreatic and systemic pulmonary inflammatory response in an in vivo model of acute edematous pancreatitis (AEP). METHODS Male Sprague-Dawley (SD) rats were pretreated 2 times per day with oral gavage with EPA (ω-3 fatty acid; 5 mg/kg/dose) or ω-6 fatty acid control (5 mg/kg/dose) or saline (equal volume) for 2 weeks. AEP was induced in ω-3, ω-6, and saline pretreated rats by 5 hourly subcutaneous (SC) injections of cerulein. Pancreas, lung, and serum were harvested 3 hours after the last cerulein injection. Severity of pancreatitis was confirmed by serum amylase and by histopathologic score. Pancreatic macrophage infiltration was assessed by confocal fluorescent microscopy, and pulmonary leukocyte respiratory burst (LRB) analysis was performed on mononuclear cells obtained from bronchioalveolar lavage (BAL). RESULTS All animals demonstrated acute pancreatitis through hyperamylasemia and histopathologic examination. Confocal analysis demonstrated significantly lower macrophage infiltration, and BAL analysis by flow cytometry demonstrated significantly lower ( p < .05) LRB in the ω-3-treated group compared with theω -6 and the saline pancreatitis group. CONCLUSIONS Attenuation of both pancreatic MΦ inflammatory response and pulmonary leukocyte respiratory burst in AEP by EPA supports further investigation into the potential role for EPA dietary supplementation in the progression of pancreatitis-associated sequelae.

Hepatic Intra-Arterial Chemotherapy

The potential value of hepatic intra-arterial chemotherapy (HIAC) can be considered from several different perspectives. A fundamental assumption for this discourse requires that, in this evaluation, HIAC is being provided with the intent of providing regional hepatic therapy for metastatic hepatic disease. With the exception of colorectal cancer (CRC), there are only limited published data for HIAC evaluation for noncolorectal metastases, and, as such, the terms cancer and hepatic metastasis are specific to CRC in this discussion. It is the aim of this review to summarize the HIAC literature in terms of (1) hepatic drug/agent delivery, (2) clinical applicability and potential outcome benefits/consequences, and (3) novel applications of the HIAC concept as a neoadjuvant/prophylactic approach for the prevention of CRC hepatic metastases. Despite advances in CRC screening, surgical techniques, and several novel adjuvant agents, CRC continues to be a significant medical challenge. In the United States, approximately 130,000 cases of colon cancer are diagnosed annually. Of these patients, approximately 60% will ultimately develop metastatic disease, and <30% of the initial patient population will have disease confined to the liver. Hepatic resection for CRC metastasis with the potential for cure is achievable in approximately 30% of patients. However, for diverse reasons, many patients are not candidates for hepatic resection. Whether resected or not, ultimately the liver is the most common site of subsequent disease progression or recurrence. Historically, with 5-fluorouracil (5-FU)–based systemic chemotherapy, the 5-year survival rate for patients with hepatic CRC metastasis is not greater than 3% with a median survival of approximately 23 to 25 months. Conceptually, regional hepatic chemotherapy by means of intra-arterial drug delivery was developed to potentially improve outcomes for these patients. Although we are presently in the era of oxaliplatin-based systemic regimens and monoclonal antibody therapies, we lack long-term data for these new therapeutic regimens to supplant the historical experience described previously. It is the aim of this article to consider the value of HIAC, and this can be accomplished only with the data set already completed. Discussion of the potential effects of these novel regimens and the long-term outcomes, which are pending, is outside of the scope of this article.

SURGISIS-assisted surgical site control in the delayed repair of a complex bile duct injury after laparoscopic cholecystectomy

Although laparoscopic cholecystectomy has revolutionized the surgical approach to patients with gallbladder disease, it has also brought a marked increase in the incidence of complex and serious bile duct injuries. Many of these major injuries represent a major technical challenge for even the most seasoned hepatobiliary-trained surgeon. Herein, we present a case outlining the algorithmic treatment approach for delayed-presentation complex biliary injury and report on the novel use of small intestinal submucosal biomaterial for surgical site control in the staged repair of a complex biliary injury (Strasberg E4) after laparoscopic cholecystectomy.