Shaw Somers

PURPOSE: Our aim was to test the hypothesis that laparoscopic-assisted resection for colorectal cancer has an immunologic advantage over traditional open surgery. METHODS: Sixteen patients with colorectal cancer were randomized to undergo laparoscopic-assisted resection or open surgery. Basic patient data were recorded, and serum interleukin-6 levels, relative proportions of lymphocytes, and human leukocyte antigen-DR expression on monocytes were determined at specific time intervals. RESULTS: Operating time was longer for laparoscopic-assisted resection (P=0.02), but analgesic requirements were less (P=0.04). All patients exhibited the following: interleukin-6 levels increased to a maximum at 4 hours and returned to preoperative levels within 48 hours. This response appeared greater for open resection (mean peak level, 313 vs. 173 pg/ml; P=0.25). Relative granulocytosis (P < 0.001) was seen within 48 hours, which was offset by a decrease in percentage of lymphocytes (P < 0.001). Changes in lymphocyte subfractions were most significant seven days postsurgery: natural killer cells decreased (P=0.003); T cells increased (P=0.008), with elevation in the CD4/CD8 ratio (P=0.003). B cells were largely unchanged at all time periods. Human leukocyte antigen-DR expression on monocytes was significantly less at 48 hours postsurgery (P < 0.001). All changes were reversed within three weeks of surgery. There were no differences when comparing laparoscopic-assisted resection with open surgery. CONCLUSIONS: Both laparoscopic-assisted resection and open surgery affect the immune response. It would appear that laparoscopic-assisted resection does not have an immunologic advantage over open surgery in patients with colorectal cancer.

BACKGROUND: Tumor resistance to chemotherapy may be present at the beginning of treatment, develop during treatment, or become apparent on re-treatment of the patient. The mechanisms involved are usually inferred from experiments with cell lines, as studies in tumor-derived cells are difficult. Studies of human tumors show that cells adapt to chemotherapy, but it has been largely assumed that clonal selection leads to the resistance of recurrent tumors. METHODS: Cells derived from 47 tumors of breast, ovarian, esophageal, and colorectal origin and 16 paired esophageal biopsies were exposed to anticancer agents (cisplatin; 5-fluorouracil; epirubicin; doxorubicin; paclitaxel; irinotecan and topotecan) in short-term cell culture (6 days). Real-time quantitative PCR was used to measure up- or down-regulation of 16 different resistance/target genes, and when tissue was available, immunohistochemistry was used to assess the protein levels. RESULTS: In 8/16 paired esophageal biopsies, there was an increase in the expression of multi-drug resistance gene 1 (MDR1) following epirubicin + cisplatin + 5-fluorouracil (ECF) chemotherapy and this was accompanied by increased expression of the MDR-1 encoded protein, P-gp. Following exposure to doxorubicin in vitro, 13/14 breast carcinomas and 9/12 ovarian carcinomas showed >2-fold down-regulation of topoisomerase IIalpha (TOPOIIalpha). Exposure to topotecan in vitro, resulted in >4-fold down-regulation of TOPOIIalpha in 6/7 colorectal tumors and 8/10 ovarian tumors. CONCLUSION: This study suggests that up-regulation of resistance genes or down-regulation in target genes may occur rapidly in human solid tumors, within days of the start of treatment, and that similar changes are present in pre- and post-chemotherapy biopsy material. The molecular processes used by each tumor appear to be linked to the drug used, but there is also heterogeneity between individual tumors, even those with the same histological type, in the pattern and magnitude of response to the same drugs. Adaptation to chemotherapy may explain why prediction of resistance mechanisms is difficult on the basis of tumor type alone or individual markers, and suggests that more complex predictive methods are required to improve the response rates to chemotherapy.

BACKGROUND: The prevalence of obesity is increasing worldwide and the past decade has witnessed an exponential rise in the number of bariatric operations performed. As a consequence, an increasing number of patients are presenting to non-specialist units with complications following bariatric procedures. This article outlines the management of the most common late postoperative complications that are likely to present to the general surgeon. METHODS: A search was conducted for late postoperative complications after bariatric surgery using PubMed, Embase, OVID and Google search engines, and combinations of the terms bariatric surgery, gastric bypass, gastric banding or sleeve gastrectomy, and late or delayed complications. Only studies with follow-up longer than 6 months were included. RESULTS: The most common long-term complications after gastric banding include band slippage and erosion. Deflation or removal of the band is often required. Internal hernia, adhesions and anastomotic stenosis are common causes of intestinal obstruction after gastric bypass surgery. Hepatobiliary complications pose a particular challenge because of the altered anatomy. Functional disorders such as reflux and dumping, and nutritional deficiencies are common and should be differentiated from conditions that require urgent investigations and timely surgical intervention. CONCLUSION: The immediate management of bariatric patients presenting with complications outside the immediate postoperative period requires adherence to basic surgical principles. Accurate diagnosis often relies on high-quality contrast and cross-sectional imaging, and effective surgical intervention necessitates a broad understanding of the altered anatomy, advanced surgical skills and liaison with specialists in the field when necessary.

A prospective randomized study of the immunological effects of three total parenteral nutrition (TPN) regimens in patients undergoing preoperative parenteral nutrition was conducted. In one regimen the calories were derived solely from glucose. The others were identical except that 50 per cent of the calories were provided as lipid emulsion, in one as long-chain triglycerides (LCT) only while the other contained half the fat as medium-chain triglycerides (MCT) and half as LCT (MCT/LCT). Natural killer (NK) activity and lymphokine-activated killer (LAK) activity were significantly higher after TPN with the MCT/LCT solution. A significant fall in LAK activity occurred after TPN with the LCT solution. The interleukin 2 content in supernatants from activated T lymphocytes was significantly higher after TPN with the LCT-containing solution. Solutions containing LCT and those containing MCT perturb cytokine interactions, but this is less with MCT-containing solutions, which may augment certain responses. These observations may have implications for the design of TPN regimens.

CONTEXT: Current best evidence is in favour of early institution of enteral feeding in acute severe pancreatitis with promising results from trials in immunonutrition on other patient groups. OBJECTIVE: To identify which groups of patients and products are associated with benefit, we investigated immunonutrition in patients with predicted acute severe pancreatitis. DESIGN: A randomised trial of a study feed containing glutamine, arginine, tributyrin and antioxidants versus an isocaloric isonitrogenous control feed was undertaken. PATIENTS: Thirty-one patients with a diagnosis of acute pancreatitis predicted to develop severe disease: 15 study feeds and 16 control feeds. INTERVENTIONS: Enteral feeding via nasojejunal tube for 3 days. If patients required further feeding the study was continued up to 15 days. MAIN OUTCOME MEASURES: Reduction in C-reactive protein (CRP) by 40 mg/L after 3 days of enteral feeding was the primary endpoint. Carboxypeptidase B activation peptide (CAPAP) levels were taken at regular intervals. RESULTS: After 3 days of feeding, in the study group 2/15 (13%) of patients had reduced their CRP by 40 mg/L or more. In the control group 6/16 (38%) of patients had reduced their CRP by this amount. This difference was found to be near the statistical significant limit (P=0.220). CONCLUSIONS: The cause of the unexpectedly higher CRP values in the study group is unclear. The rise in CRP was without a commensurate rise in CAPAP or outcome measures so there was no evidence that this represented pancreatic necrosis. The contrast between the CRP and CAPAP results is of interest and we believe that specific pancreatic indices such as CAPAP should be considered in larger future studies.