A colonoscopic overtube system that creates a 'therapeutic zone' and permits retraction facilitates endoscopic submucosal dissection, was associated with fewer deep bowel wall injuries and instrument exchanges, and required less lifting solution vs classic endoscopic submucosal dissection in an ex vivo bovine model.

INTRODUCTION: Endoscopic submucosal dissection (ESD) is the 'gold standard' for large flat polyps; nevertheless, the rate of adoption in the USA is low. In ESD, the polyp is 'surgically' detached with a needle knife after a submucosal lift; gravity and the dissection cap are used for retraction. ESD would be easier if active retraction were possible. In an ex vivo bovine colon model, this study assessed an overtube system (Boston Scientific ORISE Tissue Retraction System, TRS) that permits retraction and creates 'an operative field' for removal of rectal/sigmoid lesions. METHOD: Classic ESD (C-ESD) was compared to TRS-facilitated ESD (TRS-ESD). Cleaned/preserved bovine large bowel was used, and two 2-cm 'lesions'/colon were branded onto the mucosal surface 25 and 35 cm from the anus. Submucosal saline lifts were made using a thin catheter and a standard needle knife. We tracked case length, number of instrument exchanges (to refresh lift), the volume of lift solution, the fullness of resection, and deep muscle injuries. RESULTS: Fifty ESDs were carried out in 25 colons (25 C-ESD, 25 TRS-ESD). Complete resections were noted in all cases. The TRS method required fewer instrument exchanges (median 5) vs C-ESD (median 9, p < 0.0001) and less lift solution (median 39 ml) than the C-ESD cases (median 55 ml, p = 0.0003). TRS-ESD was associated with fewer deep muscle injuries (median 2) than C-ESD (median 3, p = 0.0191). Finally, the TRS group's median case length (34.5 min) was shorter than that of C-ESD (41 min, p = 0.0543). CONCLUSION: The TRS system provides retraction and facilitates ESD regarding the number of lift injections, the volume of lift solution needed, and avoidance of muscle injuries. Of note, there is an apparent TRS learning curve, and the device mandates a distal-to-proximal approach and initial 360 degree mucosal incision. Further study is warranted.

Sustained postoperative plasma elevations of plasminogen activator inhibitor-1 following minimally invasive colorectal cancer resection.

Plasminogen activator inhibitor-1 (PAI-1) is a serine protease inhibitor that inhibits urokinase-type plasminogen activator and tissue-type plasminogen activator. PAI-1 participates in angiogenesis, wound healing and tumor invasion, and additionally regulates endothelial cell proliferation, angiogenesis and tumor growth. The purpose of the present study was to measure plasma PAI-1 levels perioperatively in patients with colorectal cancer (CRC) undergoing minimally invasive colorectal resection (MICR). Patients with CRC who underwent elective MICR were eligible for the study. All patients were enrolled in an approved data/plasma bank. Patients with preoperative, postoperative day (POD) 1, POD 3, and at least one POD 7-34 plasma sample collection were studied. Plasma PAI-1 levels were determined in duplicate using ELISA, and the medians and 95% confidence intervals (CIs) were determined. The correlations between postoperative plasma PAI-1 levels and length of surgery were evaluated. PAI-1 levels were compared between patients who underwent laparoscopic-assisted vs. hand-assisted surgery. The preoperative PAI-1 levels of stage I, II, III and IV pathological stage subgroups were also compared. A total of 91 patients undergoing MICR for CRC were studied. The mean incision length was 8.0±3.9 cm, and the length of stay was 6.8±4.3 days. Compared with the median preoperative levels (17.30; 95% CI: 15.63-19.78 ng/ml), significantly elevated median levels were observed on POD 1 (28.86; 95% CI: 25.46-31.22 ng/ml; P<0.001), POD 3 (18.87; 95% CI: 17.05-21.78 ng/ml; P=0.0037), POD 7-13 (26.97; 95% CI: 22.81-28.74 ng/ml; P<0.001), POD 14-20 (25.92; 95% CI: 17.85-35.89 ng/ml; P=0.001) and POD 21-27 (22.63; 95% CI: 20.03-30.09 ng/ml; P<0.001). The PAI-1 levels in the hand-assisted group were higher compared with those in the laparoscopic-assisted group for 4 weeks after surgery; however, a significant difference was found only on POD 1. Therefore, plasma PIA-1 levels were found to be significantly elevated for 4 weeks after MICR, and the surgery-related acute inflammatory response may account for the early postoperative PIA-1 increase. Furthermore, PAI-1-associated VEGF-induced angiogenesis in the healing wounds may account for the late postoperative elevations, and increased PAI-1 levels may promote angiogenesis in residual tumor deposits.

Plasma Levels of Keratinocyte Growth Factor Are Significantly Elevated for 5 Weeks After Minimally Invasive Colorectal Resection Which May Promote Cancer Recurrence and Metastasis.

Background: Human Keratinocyte Growth Factor (KGF) is an FGF family protein produced by mesenchymal cells. KGF promotes epithelial cell proliferation, plays a role in wound healing and may also support tumor growth. It is expressed by some colorectal cancers (CRC). Surgery's impact on KGF levels is unknown. This study's purpose was to assess plasma KGF levels before and after minimally invasive colorectal resection (MICR) for CRC. Aim: To determine plasma KGF levels before and after minimally invasive colorectal resection surgery for cancer pathology. Method: CRC MICR patients (pts) in an IRB approved data/plasma bank were studied. Pre-operative (pre-op) and post-operative (post-op) plasma samples were taken/stored. Late samples were bundled into 7 day blocks and considered as single time points. KGF levels (pg/ml) were measured via ELISA (mean ± SD). The Wilcoxon paired t-test was used for statistical analysis. Results: Eighty MICR CRC patients (colon 61%; rectal 39%; mean age 65.8 ± 13.3) were studied. The mean incision length was 8.37 ± 3.9 and mean LOS 6.5 ± 2.6 days. The cancer stage breakdown was; I (23), II (26), III (27), and IV (4). The median pre-op KGF level was 17.1 (95 %CI: 14.6-19.4; n = 80); significantly elevated (p < 0.05) median levels (pg/ml) were noted on post-op day (POD) 1 (23.4 pg/ml; 95% CI: 21.4-25.9; n = 80), POD 3 (22.5 pg/ml; 95% CI: 20.7-25.9; n = 76), POD 7-13 (21.8 pg/ml; 95% CI: 17.7-25.4; n = 50), POD 14-20 (20.1 pg/ml; 95% CI: 17.1-23.9; n = 33), POD 21-27 (19.6 pg/ml; 95% CI: 15.2-24.9; n = 15) and on POD 28-34 (16.7 pg/ml; 95% CI: 14.0-25.8; n = 12). Conclusion: Plasma KGF levels were significantly elevated for 5 weeks after MICR for CRC. The etiology of these changes is unclear, surgical trauma related acute inflammatory response and wound healing process may play a role. These changes, may stimulate angiogenesis in residual tumor deposits after surgery.

Splenic flexure mobilization for sigmoid and low anterior resections in the minimally invasive era: How often and at what cost?

BACKGROUND: Splenic flexure mobilization (SFM) increases left colonic reach for a better vascularized and tension-free anastomosis. Open SFM is challenging due to anatomic position. Minimally invasive SFM improves visualization and minimizes splenic traction. METHODS: We retrospectively reviewed all sigmoid and low anterior resections (LAR) by a colorectal surgical group over 10-year period. We analyzed indications, surgical methods and perioperative outcomes of open and MIS SFM cohorts. RESULTS: 793 patients were included; 122 (15.5%) open, 671 (84.5%) MIS (60% laparoscopic-assisted (LA), 40% hand-assisted (HA)). Overall, indications were cancer (56%), diverticulitis (31%), and other benign diseases (13%). Compared to MIS, open cases had more complex disease (45% vs. 18%, p < 0.01), with fewer SFM performed (40% vs. 86%, p < 0.01), required more frequent diversion (30% vs. 21%, p = 0.02) and were complicated by higher leak/abscess (7% vs. 3%, p = 0.06) and reoperation rates (10% vs. 6%, p = 0.11). 1% of SFM required conversion (LA to HA 0.5%, MIS to open 0.5%). There were no open SFM complications. There were 26 (5%) MIS SFM complications; bleeding (18; 12 splenic capsular tears (0 splenectomy/splenorraphy), 6 mesenteric) and organ injury (bowel (3), pancreatic (4), renal (1)). CONCLUSIONS: Our SFM rate was high in the MIS group, with a low overall complication rate. Of note, the anastomotic leak/abscess rate was 3%, and may be related to the high SFM rate. It is the authors' opinion that a major advantage of MIS is to facilitate SFM, hence SFM is more likely to be performed with these methods compared to open procedures.

Plasma levels of the proangiogenic protein CXCL16 remains elevated for 1 month after minimally invasive colorectal cancer resection.

BACKGROUND: Inflammation-induced endothelial precursor cell recruitment and angiogenesis are thought to be associated with CXCL16-CXCR6 pair activity. This study's main purpose was to determine plasma CXCL16 levels after minimally invasive colorectal resection (MICR) for colorectal cancer (CRC); an adjunct study assessed wound fluid (WF) and plasma CXCL16 levels in a separate group of CRC patients. METHODS: CRC patients who had MICR and for whom plasma was available in a tissue bank were eligible. Plasma samples were collected preoperatively from all patients. Samples were also collected on postoperative days (POD) 1 and 3 and at various late postoperative time points (POD 7-34). In a separate study, blood and intra-abdominal wound fluid (WF) samples were collected from CRC MICR patients (pts). Samples were stored at - 80 °C. CXCL16 levels were determined via ELISA. The Wilcoxon signed-rank and Mann and Whitney tests were used for analysis. RESULTS: Main study: 86 CRC pts. were included. The mean preoperative plasma CXCL16 level was 2.36 ± 0.57 ng/ml. Elevated mean plasma levels (p <  0.0001 × first 4 time points) were noted on POD 1 (2.82 ± 0.81, n = 86), POD 3 (3.12 ± 0.77, n = 82), POD 7-13 (3.28 ± 0.88, n = 64), POD 14-20 (3.03 ± 0.62, n = 24), POD 21-27 (3.06 ± 0.67, n = 20, p = 0.0003), and POD 28-34 (3.17 ± 0.43, n = 11, p = 0.001) vs. preop levels. WF study: In the adjunct study, plasma and WF CXCL16 levels were determined for 23 CRC MICR pts. WF levels at all time points were significantly elevated over plasma levels. CONCLUSION: Plasma CXCL16 levels were elevated for 4 weeks after minimally invasive colorectal resection for cancer. Also, WF CXCL16 levels were 3-10 times greater than the corresponding plasma concentrations. The source of the late plasma elevations may be the healing wound. Increased plasma CXCL16 levels may promote tumor angiogenesis in the first month after MICR.