Invasive Colorectal Cancer Resection Research Articles

Plasma levels of progranulin, a tumorigenic protein, are persistently elevated during the first month after minimally invasive colorectal cancer resection

Plasma levels of progranulin, a tumorigenic protein, are persistently elevated during the first month after minimally invasive colorectal cancer resection

Osteopontin Levels Are Persistently Elevated for 4 weeks Following Minimally Invasive Colorectal Cancer Resection.

Osteopontin (OPN) is an integrin binding phosphorylated glycoprotein secreted by macrophages and leukocytes that is found in extracellular fluids and sites of inflammation; various forms of CD44 serve as receptors. Osteopontin, expressed by numerous cancers, enhances tumor progression and angiogenesis via the PI3K/AKT and ERK mediated pathways in concert with Vascular Endothelial Growth Factor (VEGF); OPN also plays a role in wound healing. The impact of minimally invasive colorectal resection (MICR) for colorectal cancer (CRC) on plasma OPN levels is unknown. This study's goal was to assess blood levels during the first month after MICR. Patients undergoing MICR for CRC who were enrolled in an IRB approved tissue/prospective data bank for whom preoperative, postop Day (POD) 1, POD 3, and at least 1 late postop plasma sample (POD 7-34) were available were studied. Osteopontin levels were determined in duplicate via enzyme linked immunosorbent assay (ELISA) (results reported as mean ± SD). The Wilcoxon signed rank test was used for analysis (significance P < .05). A total of 101 CRC patients (63% colon and 37% rectal) met study criteria. The mean preop OPN level was 89.2 ± 36.8 (ng/ml) for the entire group. Significantly elevated (P < .001) mean plasma levels were detected, vs preop, on POD1 (198.0 ± 67.4; n = 101), POD 3 (186.0 ± 72.6, n = 101), POD 7-13 (154.1 ± 70.2, n = 70), POD14-20 (146.7 ± 53.4, n=32), and POD 21-27 (123.0 ± 56.9, n = 25). No difference was noted at the POD 27-34 timepoint (P > .05). Plasma OPN levels are significantly elevated over baseline for a month after MICR for CRC. The early rise in OPN levels may be related to the postop acute inflammatory response. The persistent elevation noted in weeks 2-4, however, may be a manifestation of wound healing in which OPN plays a role. Similar persistent plasma elevations of VEGF, angiopoietin 2 (ANG 2), and 11 other proangiogenic proteins have been noted and, collectively, may promote angiogenesis in residual tumors.

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.

Metachronous advanced neoplasia after submucosal invasive colorectal cancer resection

Little is known about the incidence of metachronous advanced neoplasia (AN) following resection of submucosal invasive colorectal cancer (SM-CRC). Here, we aimed to assess the occurrence of metachronous AN following SM-CRC resection. We retrospectively reviewed consecutive patients who underwent SM-CRC resection at an academic medical center between 2005 and 2013. Among 343 patients, 250 (72.9%) underwent surgical resection or endoscopic resection followed by surgical resection and 93 (27.1%) underwent only endoscopic resection. During a median follow-up period of 61.5 months, the overall incidence of metachronous AN was 7.6%, and the cumulative incidence at 5 years was 6.1%. The cumulative incidence was significantly higher in the endoscopic resection group than in surgical resection group, in patients with colonic disease than in those with rectal disease, and in patients with synchronous AN than in those without. Multivariate analysis revealed that synchronous AN was the only significant risk factor for metachronous AN (HR 4.35; 95% CI 1.88–10.1). These findings imply that depending on synchronous AN, a surveillance protocol following SM-CRC resection can be changed for better detection of metachronous AN.

Plasma levels of the proangiogenic protein CXCL16 remains elevated for 1\xa0month after minimally invasive colorectal cancer resection

BackgroundInflammation-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.MethodsCRC 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.ResultsMain 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.ConclusionPlasma 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.

Tu1815 Plasma Levels of Progranulin, a Tumorgenic Protein, Are Persistently Elevated During the First Month After Minimally Invasive Colorectal Cancer Resection

Tu1815 Plasma Levels of Progranulin, a Tumorgenic Protein, Are Persistently Elevated During the First Month After Minimally Invasive Colorectal Cancer Resection

Colorectal resections - clinical and immunological results

INTRODUCTION : Surgery induces a generalized state of postoperative immunosuppression responsible for a lot of complications in postoperative period. Magnitude and type of the intraoperative injury depend on the extent and duration of postoperative immune suppression. This study compared clinical outcomes and immune changes after minimally invasive and open colorectal resections in patients with colorectal cancer (CRC). MATERIAL AND METHODS : Study included 40 patients with CRC who underwent colorectal resections in our clinic last year. Twenty one of them underwent minimally invasive surgery, with a mean age of 64.8 years (49-86). The rest 19 patients underwent conventional surgery, with a mean age of 66.2 years (56-84). Blood tests were performed 24 hours prior to surgery, 24 hours and 7 days after surgery. Analysis included full blood count, total protein, albumin and markers of inflammation (CRP, ESR, fibrinogen). T- (CD3+), B- (CD19+) and NK-cell lymphocyte populations were studied by means of flow cytometry, as well as activation of leucocytes, according to the expression of HLA-DR, CD38, CD279, CD163 and some clinical parameters. All data were analyzed using SPSS version 21. RESULTS: There was no significant difference in preoperative results between minimally invasive group and conventional group. At 24 hours after surgery there were significant decrease in lymphocyte percentages and increased leucocyte count, granulocyte percentages and CRP levels in conventional group. This ratio maintained at 7 days after surgery. Activated monocyte (CD 163+), total protein and albumin, eosinophiles, percentage of monocytes, lymphocytes and NKT-cells (CD3+ CD16/CD56+) were significant decrease in conventional group compared with minimally invasive group at first postoperative day. CONCLUSION S : Minimally invasive colorectal cancer resection is a technically feasible option, with comparable results in terms of oncologic clearance, lesser degrees of tissue injury, surgical metabolic stress, and immunosuppressive response to conventional open surgery. Patients undergoing minimally invasive resections demonstrated improved clinical recovery and shorter hospital stay than patients undergoing open surgery.

Plasma chitinase 3-like 1 is persistently elevated during first month after minimally invasive colorectal cancer resection.

To assess blood chitinase 3-like 1 (CHi3L1) levels for 2 mo after minimally invasive colorectal resection (MICR) for colorectal cancer (CRC). CRC patients in an Institutional Review Board approved data/plasma bank who underwent elective MICR for whom preoperative (PreOp), early postoperative (PostOp), and 1 or more late PostOp samples [postoperative day (POD) 7-27] available were included. Plasma CHi3L1 levels (ng/mL) were determined in duplicate by enzyme linked immunosorbent assay. PreOp and PostOp plasma sample were available for 80 MICR cancer patients for the study. The median PreOp CHi3L1 level was 56.8 CI: 41.9-78.6 ng/mL (n = 80). Significantly elevated (P < 0.001) median plasma levels (ng/mL) over PreOp levels were detected on POD1 (667.7 CI: 495.7, 771.7; n = 79), POD 3 (132.6 CI: 95.5, 173.7; n = 76), POD7-13 (96.4 CI: 67.7, 136.9; n = 62), POD14-20 (101.4 CI: 80.7, 287.4; n = 22), and POD 21-27 (98.1 CI: 66.8, 137.4; n = 20, P = 0.001). No significant difference in plasma levels were noted on POD27-41. Plasma CHi3L1 levels were significantly elevated for one month after MICR. Persistently elevated plasma CHi3L1 may support the growth of residual tumor and metastasis.

Plasma monocyte chemotactic protein-1 remains elevated after minimally invasive colorectal cancer resection.

To investigate plasma Monocyte Chemotactic Protein-1 levels preoperatively in colorectal cancer (CRC) and benign patients and postoperatively after CRC resection. A plasma bank was screened for minimally invasive colorectal cancer resection (MICR) for CRC and benign disease (BEN) patients for whom preoperative, early postoperative, and 1 or more late postoperative samples (postoperative day 7-27) were available. Monocyte chemotactic protein-1 (MCP-1) levels (pg/mL) were determined via enzyme linked immuno-absorbent assay. One hundred and two CRC and 86 BEN patients were studied. The CRC patient's median preoperative MCP-1 level (283.1, CI: 256.0, 294.3) was higher than the BEN group level (227.5, CI: 200.2, 245.2; P = 0.0004). Vs CRC preoperative levels, elevated MCP-1 plasma levels were found on postoperative day 1 (446.3, CI: 418.0, 520.1), postoperative day 3 (342.7, CI: 320.4, 377.4), postoperative day 7-13 (326.5, CI: 299.4, 354.1), postoperative day 14-20 (361.6, CI: 287.8, 407.9), and postoperative day 21-27 (318.1, CI: 287.2, 371.6; P < 0.001 for all). Preoperative MCP-1 levels were higher in CRC patients (vs BEN). After MICR for CRC, MCP-1 levels were elevated for 1 mo and may promote angiogenesis, cancer recurrence and metastasis.

Minimally Invasive Surgery Improves Short-term Outcomes in Elderly Colorectal Cancer Patients

Minimally invasive surgery (MIS) for colorectal resection has been shown to improve short-term outcomes compared with open surgery in patients with colorectal cancer. Currently, there is a paucity of data demonstrating similar efficacy between MIS and open colorectal resection in the elderly population. We hypothesized that minimally invasive surgery provides improved short-term outcomes in elderly patients with colorectal cancer. A review of 242 consecutive elderly (≥ 65 y of age) patients who underwent either open or MIS colorectal resection for adenocarcinoma at one institution was conducted. Short-term and oncologic outcomes were analyzed. Continuous variables were analyzed by the Mann-Whitney U test. Categorical variables were compared by χ(2) tests. Survival was compared by the Kaplan-Meier method using the log rank test for comparison. Of the 242 elderly patients with colorectal cancer (median American Society of Anesthesiology score (ASA) scores of 3), 80% (n = 195) of patients underwent open and 20% (n = 47) had MIS colorectal cancer resections. Patients undergoing MIS had a faster return of bowel function, decreased days to nasogastric tube removal, decreased days to flatus and bowel movement, and quicker advancement to clear liquid and regular diets. The overall length of hospital stay in the MIS group was decreased by 40% as well as a trend towards a 50% decrease in SICU stay. Additionally, there was 66% decrease in cardiac complications in the MIS group. When evaluating for oncologic adequacy as measured by number of lymph nodes and surgical resection margins, MIS surgery offered equivalent results as open resection. Furthermore, there was no significant difference in overall survival for MIS versus open colorectal surgery. Minimally invasive colorectal cancer resection leads to improved short-term outcomes as demonstrated by decreased length of hospital stay and faster return of bowel function. Additionally, there appears to be no difference in oncologic outcomes in the elderly. On the basis of our data, age alone should not be a contra-indication to laparoscopic colorectal cancer resection.

Evaluation of contrast-enhanced computed tomographic colonography in detection of local recurrent colorectal cancer

To evaluate the diagnostic accuracy, sensitivity, specificity of contrast-enhanced computed tomographic colonography in detecting local recurrence of colorectal cancer. From January 2000 to December 2004, 434 patients after potentially curative resection for invasive colorectal cancer were followed up for a period ranging from 20 to 55 mo. Eighty of the four hundred and thirty-four patients showing strong clinical evidence for recurring colorectal cancer during the last follow-up were enrolled in this study. Each patient underwent contrast-enhanced computed tomographic colonography and colonoscopy on the same day. Any lesions, biopsies, identified during the colonoscopic examination, immediate complications and the duration of the procedure were recorded. The results of contrast-enhanced computed tomographic colonography were evaluated by comparing to those of colonoscopy, surgical finding, and clinical follow-up. Contrast-enhanced computed tomographic colonography had a sensitivity of 100%, a specificity of 83% and an overall accuracy of 94% in detecting local recurrent colorectal cancer. Conventional colonoscopy and contrast-enhanced tomographic colonography can complement each other in detecting local recurrence of colorectal cancer.