Abdominal wall dimensions and umbilical position vary widely with BMI and should be taken into account when choosing port locations.

BACKGROUND: Many surgeons rely on the umbilicus when determining the location of ports for laparoscopic procedures and falsely assume that it is located in the vertical midline. The purpose of this study was to assess the degree of variation in umbilical position and abdominal dimensions in the general population. METHODS: Torso length, abdominal girth, weight, and height were recorded for 259 patients over a 9-month period. Body mass index (BMI) was calculated and used to classify patients into four groups: underweight, normal, overweight, and obese. RESULTS: Average umbilical position for all BMI groups was below the true vertical midpoint and dropped further caudally as BMI increased. In addition, average abdominal dimensions increased with increasing BMI. There was no statistical difference between males and females in each BMI group regarding umbilical position or abdominal dimensions. CONCLUSION: There is a clear relationship between increasing BMI and a drop in umbilical position as well as an increase in abdominal dimensions. We recommend determining umbilical position and abdominal dimensions prior to placing ports and shifting port positions toward target quadrants.

Perioperative GMCSF limits the proangiogenic plasma protein changes associated with colorectal cancer resection.

AIMS: Colorectal resection (CR) increases plasma VEGF levels which may promote residual tumor growth. This study assessed the effect of perioperative GMCSF on plasma levels of sVEGFR1, Ang-1 and Ang-2 and also the impact of post-GMCSF plasma on in vitro endothelial cell (EC) growth and invasion. Ang-2 increases while sVEGFR1 and Ang-1 impede angiogenesis. METHODS: Fifty-nine CR cancer patients were randomized to 7 perioperative doses of GMCSF or saline for 3days prior and 4days after CR. Blood samples were taken pre-drug (PreRx) and on several postoperative days (POD). Protein levels were assessed and PreRx and POD 5 plasma added to EC cultures after which branch point formation (ECBPF) and invasion (ECI) were measured. RESULTS: sVEGFR1 levels were significantly higher on POD 1 and POD 5 in both groups but the GMCSF POD 5 level was twice the control value (p=0.002). Ang-2 levels were higher on PODs 1 and 5 in both groups (p<0.05) but the control POD 5 value (vs. GMCSF) was greater (p=0.03). Ang-1 decreases were noted in all (p=not significant, ns). The control group POD 5 ECBPF was 35.8% greater than Pre Rx (p=0.001) while the GMCSF result was 18.0% lower (p=ns); the control POD 5 median percent change from baseline was greater than the GMCSF result(p=0.008). The POD 5 ECI was +12.2% for the control group vs. baseline (p=ns) and -17.2% for the GMCSF group (p=ns): the control median percent change was greater than in the GMCSF group(p=0.045). CONCLUSION: CR-related plasma changes are proangiogenic (>Ang-2) and anti-angiogenic (>sVEGFR1); the net effect is promotion of in vitro ECBPF. GMCSF limits the proangiogenic changes (higher POD 5 sVEGFR1 levels and lower Ang-2 elevations, lower POD 5 ECBPF and ECI). The clinical import of these effects is unclear; perioperative GMCSF has anti-angiogenic plasma effects that may limit tumor growth. Further investigation is warranted.

Persistent elevation of plasma vascular endothelial growth factor levels during the first month after minimally invasive colorectal resection.

BACKGROUND: Elevations of plasma vascular endothelial growth factor (VEGF) have been noted early after colorectal resection. The duration of this increase is unknown. Because VEGF is a potent promoter of angiogenesis, which is critical to tumor growth, a sustained increase in blood VEGF levels after surgery may stimulate the growth of residual metastases early after surgery. This preliminary study aimed to determine VEGF levels during the first month after colorectal resection. METHODS: Patients from three prospective studies that had late postoperative blood samples available comprised the study population. Demographic, perioperative, pathologic, and complication data were collected. Plasma samples were obtained preoperatively for all patients: on postoperative day (POD) 1 for most patients and at varying time points thereafter during the first month after surgery and beyond. Levels of VEGF were determined via enzyme-linked immunoassay (ELISA) and compared using Wilcoxon's matched pairs test. Because the numbers of specimens beyond POD 5 were limited, samples from 7-day time blocks were bundled and averaged to permit statistical analysis. RESULTS: A total of 49 patients with cancer and 30 patients with benign indications, all of whom underwent minimally invasive colorectal resection, were assessed separately. With regard to the patients with cancer, the median preoperative plasma value was 150 pg/ml, and the peak postoperative median value for the POD 14 to 20 time block was 611.1 pg/ml. Furthermore, compared with the preoperative results, significant VEGF elevations were noted on POD 3 as well as during week 2 (POD 7-13), week 3 (POD 14-20), and week 4 (POD 21-27) (p < 0.05 for each). With regard to the benign patients, the median preoperative VEGF level was 112 pg/ml, and the peak postoperative value, 286 pg/ml, was noted during postoperative week 2. Significant elevations were noted on POD 3, and for weeks 2 and 3 as well as for POD 28 and later. Between 63% and 89% of the patients at each time point beyond POD 5 had elevated VEGF levels. CONCLUSION: This preliminary study demonstrates that after minimally invasive colorectal resection for cancer, median VEGF levels are significantly elevated on POD 3 and remain increased for as long as 4 weeks. Significant elevations in a similar pattern also were noted for the benign patients. However, the baseline and postoperative median values were lower. The clinical impact from increased blood levels of VEGF is uncertain. It is possible that the growth of residual tumor deposits may be stimulated early after surgery. These results warrant a larger study as well as endothelial cell in vitro assays to determine whether postoperative plasma stimulates proliferation and invasion.

Perioperative sargramostim (recombinant human GM-CSF) induces an increase in the level of soluble VEGFR1 in colon cancer patients undergoing minimally invasive surgery.

INTRODUCTION: Experimentally, laparotomy is associated with increased tumor growth. In humans, abdominal surgery is associated with immunosuppression and elevated plasma VEGF levels that might stimulate tumor growth early after surgery. Avoidance of these surgery-related changes and their consequences may be advantageous. Granulocyte-macrophage colony stimulating factor (GMCSF) is a non-specific immune system up-regulator that has also been associated, experimentally, with increased release of soluble VEGF Receptor 1 (sVEGFR1) which is an endogenous inhibitor of VEGF. This study's purpose was to determine the impact of perioperatively administered recombinant human GMCSF (rhu-GMCSF) on both immune function and plasma sVEGFR1 levels in colorectal cancer patients. METHODS: This randomized placebo-controlled study included 36 colorectal cancer patients who underwent minimally invasive resection (17 GMCSF, 19 Placebo). Patients received 7 subcutaneous injections of either rhu-GMCSF, 125 microg/m2, or saline on preoperative days 3, 2 and 1 and on postoperative days (POD) 1, 2, 3 and 4. A number of immune parameters were followed and plasma levels of soluble VEGF Receptor 1 (sVEGFR1) and VEGF were determined. RESULTS: The total WBC, neutrophil, eosinophil, and monocyte counts were significantly higher after surgery in the GMCSF group; no differences were noted for the other immune parameters. In the GMCSF group, median plasma sVEGFR1 levels were significantly elevated on POD 1 (188.1 pg/ml), and on POD 5 (142.8 pg/ml) when compared to pre-GMCSF levels (0 pg/ml) (p-value<0.05 for all comparisons). In the placebo group, the POD5 median sVEGFR1 level (116.3 pg/ml) was elevated and of borderline significance (p=0.05) vs the pre-treatment result (0 pg/ml). Of note, both groups had significantly elevated median plasma VEGF levels on POD 5 (Control 435.7 pg/ml; GMCSF 385.3 pg/ml) when compared to their preoperative results (Control 183.3 pg/ml, p=0.0013; GMCSF 171.5 pg/ml, p=0.0055). CONCLUSIONS: Perioperative GMCSF was not associated with an immune function benefit in this study, however, such treatment leads to increased plasma sVEGFR1 levels. Colorectal resection, with or without GMCSF, was also associated with increased VEGF levels postoperatively. Increased plasma levels of sVEGFR1 after surgery might limit the pro-angiogenic tumor stimulatory effects of VEGF. Further study of GMCSF's impact on angiogenesis appears warranted.

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.

Open surgery induces a dramatic decrease in circulating intact IGFBP-3 in patients with colorectal cancer not seen with laparoscopic surgery.

BACKGROUND: As shown earlier by the authors via Western blot analysis, open (OS) but not laparoscopic surgery (LS) induces a qualitative decrease in plasma insulin-like growth factor-binding protein 3 (IGFBP-3) levels on postoperative day 1 (POD 1). Intact IGFBP-3 has tumor suppressive effects, but its degradation products do not. Enzyme linked immunoassay (ELISA) inevitably measures both. In this study, using a novel combined Western blot and ELISA analysis method, precise plasma levels of intact IGFBP-3 on POD2 after open and closed colorectal cancer resection (stage I-III) were determined. METHODS: This study included 15 OS patients with a mean incision length of 26.7 +/- 15.5 cm and 16 LS patients with a mean incision length of 5.3 +/- 3.1 cm. Intact IGFBP-3 levels were determined via ELISA and Western blot analysis in plasma collected preoperatively and postoperatively. RESULTS: In the OS patients, the mean preoperative concentration of intact 43-45 kDa IGFBP-3 protein was 1920 +/- 1430 ng/ml. It decreased dramatically on POD2 to 355 +/- 545 ng/ml (p < 0.005). In the LS group, no significant difference was noted between the preoperative level (1305 +/- 807 ng/ml) and the POD2 level (922 + 714 ng/ml). CONCLUSIONS: Open cancer resection, unlike its minimally invasive alternative, induces a dramatic decrease in concentration of intact IGFBP-3, which may have important implications with regard to colon cancer recurrence.

The percentage of CD31+ T cells decreases after open but not laparoscopic surgery.

BACKGROUND: Efficient killing of tumor cells depends on T cells that migrate from the circulation to the peripheral tissues; these cells express CD31. This study was undertaken to determine the impact of open (OS) and laparoscopic (LS) colorectal surgery on the percentage of circulating CD3+CD31+ cells. METHODS: Peripheral blood was collected from 27 OS and 24 LS colon cancer patients preoperatively (preOP) and on postoperative days 1 (POD1) and 3 (POD3). CD31+ T cells were assessed by flow cytometry using monoclonal antibodies. RESULTS: In the OS group, the percentage of CD3+CD31+ cells was significantly lower in POD1 and POD3 samples compared to the preOP results. LS surgery did not result in a significant change in the percentage of these T cells. A significant correlation was found between the decrease in the percentage of CD3+CD31+ cells and the length of incision in OS patients. CONCLUSIONS: The percentage of CD3+CD31+ cells decreases following OS but not LS and may be related to incision length. This may compromise T cell function in the peripheral tissues in the postoperative period.