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Background: Robotically assisted surgery offers the advantages of improved dexterity and elimination of tremor over conventional laparoscopic surgery. There have been few studies to date, however, examining the role of robotics in intestinal surgery. This study was undertaken to determine the feasibility and safety of using a robotic surgical system in the performance of intracorporeal small bowel strictureplasties in dogs.Methods: Using a robotic surgical system, a total of 16 strictureplasties were performed in the small bowel of eight dogs (two strictureplasties per dog). Using only intracorporeal robotic surgery, a 2.5 cm enterotomy was made longitudinally in the small bowel, and then closed in a Heineke-Mikulicz configuration with a one-layer running 3-0 braided absorbable suture (strictureplasty). All animals were allowed to survive for 7 days with prospective monitoring of bowel movements, level of activity, oral intake, and abdominal examination. After 7 days, necropsy was performed, examining all strictureplasty sites for signs of sepsis. The endpoints of the study were recovery of normal intestinal function (bowel movements), intraoperative and postoperative complications, and the appearance of the anastomoses at necropsy.Results: There was no intraoperative morbidity or mortality. All eight dogs survived 7 days and recovered well. All dogs had a bowel movement on the first postoperative day, and appeared healthy throughout the study period. Necropsy revealed that all 16 strictureplasty sites were healing without signs of sepsis. The median time per strictureplasty was 65 min (range, 45-110 min). One dog developed a superficial wound infection at a trocar site.Conclusions: A robotic surgical system can successfully be employed in the performance of intestinal strictureplasties in dogs. This study supports further investigation into the role of robotics in intestinal surgery in humans. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Plasma VEGF levels increase after minimally invasive colorectal resection (MICR) and remain elevated for 2–4 weeks. VEGF induces physiologic and pathologic angiogenesis by binding to endothelial cell (EC) bound VEGF-Receptor-1 (VEGFR1) and VEGFR2. Soluble forms of these receptors sequester plasma VEGF, decreasing the amount available to bind to EC-bound receptors. Ramifications of surgery-related plasma VEGF changes partially depend on plasma levels of sVEGFR1 and sVEGFR2. This study assessed perioperative sVEGFR1 and sVEGFR2 levels after MICR in patients with colorectal cancer. Forty-five patients were studied; blood samples were taken from all patients preoperatively (preop) and on postoperative days (POD) 1 and 3; in most a fourth sample was drawn between POD 7–30. Late samples were bundled into two time points: POD 7–13 and POD 14–30. sVEGFR1 and sVEGFR2 levels were measured via ELISA. sVEGFR2 data are reported as mean ± SD and were assessed with the paired samples t test. sVEGFR1 data were not normally distributed. They are reported as median and 95% confidence interval (CI) and were assessed with the Wilcoxon signed-Rank test ( p < 0.05). Preoperatively, the mean plasma sVEGFR2 level (7583.9 pg/ml) was greater than the sVEGFR1 result (98.3 pg/ml). Compared with preop levels, sVEGFR2 levels were significantly lower on POD 1 (6068.2 pg/ml, ±2034.5) and POD 3 (6227.6 pg/ml, ±2007.0), whereas sVEGFR1 levels were significantly greater on POD 1 (237.5 pg/ml; 95% CI, 89.6–103.5), POD 3 (200.2 pg/ml; 95% CI, 159–253), and POD 7−13 (102.9 pg/ml; 95% CI, 189.7–253). No differences were found on POD 7–13 for sVEGFR2 or POD 14–30 for either protein. sVEGFR2 values decreased and sVEGFR1 levels increased early after MICR; sVEGFR2 changes dominate due to their much larger magnitude. The net result is less plasma VEGF bound by soluble receptors and more plasma VEGF available to bind to ECs early after surgery. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Plasma vascular endothelial growth factor (VEGF) levels are elevated for 2–4 weeks after minimally invasive colorectal resection (MICR). VEGF induces wound and tumor angiogenesis by binding to endothelial cell (EC)-bound VEGF-receptor 1 (VEGFR1) and VEGFR2. Soluble receptors (sVEGFR1, sVEGFR2) sequester VEGF in the blood and decrease VEGF’s proangiogenic effect. The importance of the MICR-related VEGF changes depends on the effect of surgical procedures on sVEGFR1 and sVEGFR2; this study assessed levels of these proteins after MICR for benign indications. Blood samples were taken ( n = 39) preoperatively (preop) and on postoperative days (POD) 1 and 3; in most cases a fourth sample was drawn between POD 7 and 30. sVEGFR1 and sVEGFR2 levels were measured via enzyme-linked immunosorbent assay (ELISA), which detects free and VEGF bound soluble receptor. Late samples were bundled into POD 7–13 and POD 14–30 time points. Results are reported as mean and standard deviation. The data was assessed with paired-samples t-test. Preop, mean plasma sVEGFR2 level (9,203.7 ± 1,934.3 pg/ml) was significantly higher than the sVEGFR1 value (132.5 ± 126.2 pg/ml). sVEGFR2 levels were significantly lower on POD 1 (6,957.8 ± 1,947.7 pg/ml,) and POD 3 (7,085.6 ± 2,000.2 pg/ml), whereas sVEGFR1 levels were significantly higher on POD 1 (220.0 ± 132.8 pg/ml) and POD 3 (182.7 ± 102.1 pg/ml) versus preop results. No differences were found on POD 7–13 or 14–30. sVEGFR2 values decreased and sVEGFR1 levels increased early after MICR; due to its much higher baseline, the sVEGFR2 changes dominate. The net result is less VEGF bound to soluble receptor and more free plasma VEGF. [ABSTRACT FROM AUTHOR]

Plasma vascular endothelial growth factor (VEGF) levels are increased after surgery and may stimulate tumor growth after cancer resection. Angiopoietin 1 (Ang 1) and Ang 2 are proteins that impact VEGF-related angiogenesis (VRA). Ang 1 stabilizes mature vessels and inhibits VRA, whereas Ang 2 destabilizes vessels and promotes VRA. The ratio of Ang 1 to Ang 2 reflects the net effect; a low ratio promotes VRA. This study’s purpose was to determine the impact of open and minimally invasive (MIS) colorectal resection (CR) for benign indications on plasma Ang 1 and 2 levels. A total of 30 patients operated by MIS and 26 operated by open procedure were studied. Plasma was obtained preoperatively (PO) and on postoperative days (POD) 1 and 3. Plasma Ang 1 and Ang 2 levels were assessed via enzyme-linked immunosorbent assay (ELISA) in duplicate. Data were compared using Wilcoxon’s matched-pair test and the Mann–Whitney U-test (significance p < 0.05). Indications, types of resection, and morbidity for the groups were similar. The mean MIS incision length was 4.7 ± 1.6 cm while it was 16.8 ± 7.1 cm for the open group ( p = 0.0001). For both groups Ang 2 levels were significantly higher and the Ang 1 to Ang 2 ratio was significantly lower on POD 1 and 3 compared with preoperative results. Ang 1 levels were significantly decreased on POD 1 and 3 in the MIS group but only on POD 1 in the open group. For unclear reasons, preoperative Ang 1 levels and Ang 1 to Ang 2 ratios were significantly different between the groups, which precludes comparison of the postoperative results between groups. CR for benign pathology results in higher Ang 2 levels, lower Ang 1 levels, and lower Ang 1 to Ang 2 ratios early after surgery. These alterations are proangiogenic. These results, plus the already noted VEGF increases, suggest that surgery results in proangiogenic plasma protein changes that may stimulate tumor growth early after surgery. The duration of the Ang 1 and 2 changes needs to be determined. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Although magnetic endoscope imaging of the colonoscope via the Endoscope Positioning Detecting Unit (EPDU) has been studied to some extent in Europe, its application in the United States has been limited. The purposes of this study were to determine whether the technique enabled for accurate localization of the lesion and to determine if and how the device facilitated scope insertion and completion of the colonoscopic exam.Methods: Outpatient colonoscopies using the EPDU were performed by three experienced surgical endoscopists over a 5-month period. A specialized scope with electromagnetic coils or a regular scope with a magnetic probe insert in the instrument channel was used for the duration of the examination to identify loops and localize pathology.Results: A total of 80 colonoscopies were performed with the device. In two patients, the probe insert was removed prior to completion of the procedure; thus, the total number of examinations included in the study was 78. The EPDU was used in conjunction with transillumination to estimate the location of polyps or cancers in the 33 patients (42%) in whom such lesions were found. In the four patients who subsequently underwent operation, the lesion's location as estimated by EPDU was verified. In regard to the usefulness of the device during insertion, the EPDU led to the discovery of loops and to the application of pressure that resulted in prompt completion of the examination in 28% of cases (deemed most useful). In 33% of cases, the device identified loops and led to the application of abdominal wall pressure and early position changes, thus facilitating the examination; however it did not lead to its immediate or rapid completion. In 39% of cases, the device was not required or used for insertion due to the simple nature of the examination.Conclusions: The EPDU was accurate in estimating lesion location. The device also holds promise as an aid in the completion of difficult exams (about 30% of cases in this study). [ABSTRACT FROM AUTHOR]

Background: It has been well established that open abdominal surgery results in systemic immunosuppression postoperatively; in contrast, laparoscopic surgery is associated with significantly better preserved systemic immune function. However, when intraperitoneal (local) immune function is considered, laparoscopic procedures done under a CO2 pneumoperitoneum (pneumo) have been shown to result in greater immunosuppression compared to that of open surgery. Few studies have simultaneously assessed systemic and local immune function. The purpose of this study was to assess peripheral blood mononuclear cell (PBMC) and peritoneal macrophage tumor necrosis factor-α (TNF-α) levels, H2O2 production, and MHC class II antigen expression after open and laparoscopically assisted cecectomy in a rat model. Methods: A total of 75 Sprague Dawley rats were used for three separate experiments. For each study, rats were randomly divided into three groups: anesthesia alone (AC), laparoscopic-assisted cecectomy (LC), and open cecectomy via full laparotomy (OP). A CO2 pneumo was used for laparoscopic operations. On postoperative day 1 the animals were sacrificed, macrophages were harvested via intraperitoneal lavage, and PBMCs were isolated from whole blood obtained by cardiac puncture. In experiment 1, macrophages and PBMC from each animal were stimulated with lipopolysaccharide, after which TNF-α levels of the supernatant were determined. In experiment 2, after stimulation with PMA, H2O2 release was assessed by measuring fluorescence. In experiment 3, via flow cytometry, the number of cells with surface MHC class II proteins were determined. Data from the three groups in each experiment were compared using analysis of variance Tukey-Kramer tests. Results: Macrophages and PBMC from mice in the OP group released significantly more TNF-α than cells from mice in the LC (p < 0.05) or AC (p < 0.05) groups. Macrophages from mice in the OP group released significantly less H2O2 than cells from the AC (p < 0.01) and LC (p < 0.05) groups. There was no difference between the AC and LC results. No significant differences in PBMC H2O2 release were noted among any of the groups. OP group macrophages expressed significantly less MHC class II antigen than did AC group macrophages (p < 0.05). No differences were noted among the LC results and either the OP or AC group’s outcomes. No differences were noted in PBMC MHC class II expression among any of the groups. Conclusions: In all instances, the LC group’s macrophage results were similar to the AC group’s results. OC group macrophages produced significantly more TNF-α and less H2O2 than both the AC and LC groups. MHC class II protein expression was less for the OC group than for the AC group. OC group PBMCs produced more TNF-α. No differences in PBMC H2O2 release or MHC class II expression were noted. Laparoscopic methods better preserves the baseline values of the parameters studied. [ABSTRACT FROM AUTHOR]

Background: We have previously shown that preoperative vaccination with the GA733 protein does not inhibit tumor growth in mice undergoing open surgery or carbon dioxide insufflation. In this study we assessed the antitumor effect of a combined GA733 and interleukin-12 (IL-12) vaccine.Methods: For this study, BALB/c mice were immunized with GA733, IL-12, or GA733 and IL-12, or they received no vaccine. Immediately after surgery (laparotomy or insufflation), GA733-transfected CT26 cells (C26-GA733) were injected subcutaneously into all mice. After 5 weeks, the mice were sacrificed, their tumors measured, GA733-specific antibodies determined by enzyme-linked immunoassay, and GA-733-specific cytotoxicity tested by flow cytometry using labeled C26-GA733 cells.Results: Tumors were significantly (p < 0.05) smaller in both the insufflation and open groups that received combined GA733 and IL-12 than in their respective control subjects. Vaccination also induced a significant increase in the antibody and cell-mediated tumor-specific immunity.Conclusion: A preoperative vaccine consisting of GA733 and IL-12 inhibited postoperative tumor growth after open and closed surgery and allowed the mice to overcome the immunosuppressive effects of surgery. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Surgical trauma inhibits immune function. Our goal was to study the effect of surgical intervention on the development of the immune response to epithelial cell adhesion molecule (EpCAM [GA-733]), a tumor-associated protein used for vaccination in colon cancer. Methods: Recombinant GA-733 and monophosphoryl-lipid A (MPLA) were incorporated into biodegradable beads and implanted in the following groups of mice: control, insufflation, and laparotomy. After surgery, the mice were inoculated with GA-733-transfected C26 cells (C26-EpCAM). Plasma anti-GA733 IgG antibodies were detected in enzyme-linked immunoassay (ELISA). Killing specific to GA-733 was assayed by C26-EpCAM-killing assay. Results: The difference in tumor size between immunized and nonimmunized animals was statistically significant only in control mice (p < 0.05). Greater cytotoxic response to C26-GA733 developed in all immunized mice groups than in their respective controls. However, anti-GA733 IgG increased significantly in the control and insufflation groups, but not in the laparotomy group. Conclusions: Combined GA-733 vaccine allows reduction of tumor growth in control but not in surgically managed animals. This vaccine can induce a specific-cell and antibody-mediated immune response. Open surgery leads to a decreased antibody response to the GA-733 tumor vaccine. [ABSTRACT FROM AUTHOR]

The article focuses on a study conducted to analyze the impact of surgical trauma on colorectal liver metastasis. It was found through murine model used in this study that minimally invasive techniques can reduce colorectal liver metastasis. The long-term onset of metastasis are investigated by randomized studies after laparoscopic and open colon resection to decide whether laparoscopic colon resection offers any advantage.

A correction to the article "Altered plasma matrix metalloproteinase-9/tissue inhibitor of matrix metalloproteinase-1 concentration during the early postoperative period in patients with colorectal cancer," by I. Kirman, S. Jain, V. Cekic, A. Belizon, E. Balik, P. Sylla, T. Arnell, K.A. Forde and R.L. Whelan that was previously published in the journal is presented.