Biomedical subjects

A Belizon

Publications and source records attributed to A Belizon.

3 recordsLinked to original sources

PubMed2006

Major surgical trauma induces proteolysis of insulin-like growth factor binding protein-3 in transgenic mice and is associated with a rapid increase in circulating levels of matrix metalloproteinase-9.

BACKGROUND: The authors previously demonstrated a significant decrease in plasma levels of intact insulin-like growth factor binding protein-3 (IGFBP-3) after major open but not after laparoscopic-assisted surgery in humans. They postulated that this decrease may have an effect on postoperative tumor growth. It also has been shown that plasma levels of matrix metalloproteinase-9 (MMP-9), a protease capable of degrading IGFBP-3, are transiently increased after open colectomy in humans. The authors aimed to develop an animal model that would allow further study of the effect that surgical trauma has on plasma levels IGFBP-3 and MMP-9. In addition, they set out to assess the concentration of MMP-9 in circulating monocytes before and after surgery. METHODS: The 30 mice included in this study were divided into three groups: sham laparotomy, carbon dioxide (CO2) pneumoperitoneum, and anesthesia control. All mice were IGFBP-3 transgenics (overexpressing human IGFBP-3) on a CD1 background. The mice were anesthetized using ketamine and xylazine. Blood was drawn retroorbitally 48 h before the procedure. The duration of the procedure was 30 min. The animals were killed 24 h postoperatively and blood was drawn. Intact IGFBP-3 levels were measured using a combination of Western blot analysis and enzyme-linked immunoassay (ELISA) at the two time points: before and after the operation. Plasma and peripheral blood mononuclear cell levels of MMP-9 were measured at each time point using zymography. Mononuclear cell lysates were used to determine intracellular MMP-9 levels. RESULTS: Plasma levels of intact IGFBP-3 were significantly lower than preoperative levels after sham laparotomy. A mean decrease of 76.6% was noted (p < 0.05). Zymography demonstrated significantly higher plasma MMP-9-related proteolytic activity than observed preoperatively after sham laparotomy (78.5 vs 42.3 Relative Units [RU]; p < 0.05). In the pneumoperitoneum group, no significant decrease was found between the pre- and postoperative levels of intact IGFBP-3. A nonsignificant increase in MMP-9 was noted after CO2 pneumoperitoneum (38 RU preoperatively vs. 46.4 RU postoperatively; p > 0.05). The anesthesia control group did not demonstrate a significant change in either circulating intact IGFBP-3 levels or MMP-9 levels. Mononuclear intracellular levels of MMP-9 were significantly lower after laparotomy than the preoperative levels (3 vs 37 RU). The postprocedure intracellular levels of MMP-9 were not significantly decreased in the pneumoperitoneum or anesthesia control group. CONCLUSION: Plasma levels of intact IGFBP-3, a cell growth regulating factor, were found to be decreased significantly after laparotomy. This decrease was not seen after pneumoperitoneum. Depletion of intact IGFBP-3 after laparotomy correlated with a rapid release of MMP-9 from mononuclear cells and an increase in circulating plasma MMP-9 levels. Matrix metalloproteinase-9 may play an important role in IGFBP-3 proteolysis after surgical trauma. Furthermore, circulating mononuclear cells are one source of MMP-9 after surgery. Finally, the model used reproduces events in humans after surgery, and thus should permit further study on the mechanism of IGFBP-3 proteolysis after surgical trauma.

Animals↗

PubMed2006

Converted laparoscopic colectomy: what are the consequences?

BACKGROUND: The safety and benefits of laparoscopic colon resection are well documented. However, few reports have addressed the safety and comparative outcome of laparoscopic colon operations that necessitated conversion. METHODS: All consecutive laparoscopic colon resections performed by a single surgeon from July 1996 to October 2003 were assessed. Data obtained from a prospective computerized database included demographics, diagnosis, reason and time to conversion, length of stay, morbidity, and mortality. Additionally, all laparoscopic-converted colectomies were then matched with open colectomies by diagnosis and severity of disease and analyzed with respect to morbidity, mortality, and clinical outcome. RESULTS: A total of 143 laparoscopic colon resections were analyzed, 78 of which were left colon resections and 65 were right colon resections. The overall conversion rate was 19.6% (28 patients). The disease entities of the 28 converted patients were diverticulitis (16), polyps (four), Crohn's disease (three), metastatic cancer (three), and others (two). Conversion was higher in the left-sided (24 patients, 30.8%) versus right-sided (four patients, 6.1%) procedures. There were no differences regarding age, gender, and comorbidities among the laparoscopic, open, and converted groups; the median follow-up was 39 months. The median length of stay was 6, 8, and 12 days for the laparoscopic, open, and converted groups, respectively. Right-sided conversions were due to the size of the inflammatory mass in three patients and intraoperative bleeding in one patient. Left-sided conversions were due to the inflammatory process extending beyond the sigmoid colon in 12 patients, adhesions in five, obesity in four, pericolonic abscess in two, and fixed mass in one patient. Postoperative morbidity was significantly higher for laparoscopic procedures that were converted to open procedures more than 30 min into the operation. Preoperative predictors of conversion were extent of inflammatory process beyond the sigmoid colon and obesity, whereas intraoperative predictors were adhesions and bleeding. CONCLUSIONS: Laparoscopic-converted colon resection is associated with significantly greater morbidity, particularly wound complications and greater length of hospital stay, compared to open or laparoscopic colectomies. Prompt conversion (<30 min) may reduce the overall morbidity associated with converted procedures. Furthermore, thoughtful patient selection may decrease the conversion rate and thereby prevent the inherent morbidity associated with converted procedures.

Colectomy↗

PubMed2006

Altered plasma matrix metalloproteinase-9/tissue inhibitor of matrix [corrected] metalloproteinase-1 concentration during the early postoperative period in patients with colorectal cancer.

BACKGROUND: The authors have previously demonstrated that insulin-like growth factor binding protein-3 (IGFBP-3) is depleted in plasma for 1 to 3 days after major open surgery (OS), but not after laparoscopic surgery (LS). After surgery, IGFP-3 cleavage occurs rapidly and is likely attributable to altered plasma proteolytic activity. This study aimed to assess plasma proteolysis after both open and closed colorectal resection and, if possible, to identify a protease/protease inhibitor system affected by surgery. METHODS: Plasma from 88 patients with colorectal cancer (stages I-III) who underwent resection was obtained preoperatively (pre-OP) and on postoperative days (POD) 1 to 3. Plasma proteolytic activity was assessed via zymography. On the basis of the results, specific protease and protease inhibitor concentrations were next measured via enzyme-linked immunoassay (ELISA). Statistical analysis was performed using Wilcoxon's test. RESULTS: Early after surgery, zymography showed a predominant band representing a 92-kDa gelatinase corresponding to a proform of matrix metalloproteinase-9 (MMP-9), a protease known to cleave IGFBP-3. In OS patients, the mean concentration of plasma MMP-9 was significantly higher on POD 1 than at pre-OP (p < 0.003). On POD 2 and 3, no differences were noted. In the LS group, the mean levels of MMP-9 before and after surgery were comparable. The levels of a natural MMP-9 inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), also were measured. In the OS group, the level of TIMP-1 was significantly higher on POD 1 (p < 0.0003) and POD 2 (p < 0.01) and 3 (p < 0.01) than at pre-OP. In the LS group, a smaller but significant increase in TIMP-1 levels was found between the pre-OP sample and the POD 1 (p < 0.01) and POD 2 (p < 0.01) samples. No difference was noted on POD 3 (p = 0.1). CONCLUSIONS: Open surgery, but not laparoscopic surgery, is accompanied by a short-lived significant increase in MMP-9 levels, which likely accounts for the decrease in IGFBP-3 levels observed after OS. The transitory nature of MMP-9 imbalance may be attributable to the increase in TIMP-1 levels postoperatively.

Adenocarcinoma↗