Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
World Journal of Surgical Oncology
Published in: World Journal of Surgical Oncology 1/2018

Open Access 01-12-2018 | Research

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

Authors: H. M. C. Shantha Kumara, Erica Pettke, Abhinit Shah, Xiaohong Yan, Vesna Cekic, Melissa Alvarez Downing, Nipa Dilip Gandhi, Richard L. Whelan

Published in: World Journal of Surgical Oncology | Issue 1/2018

Login to get access

Abstract

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.
Literature
1.
American Cancer Society. Cancer facts & figures. Atlanta: American Cancer Society; 2017. p. 1–76.
2.
Fisher B, Fisher ER. Experimental evidence in support of the dormant tumor cell. Science. 1959;130:928–9.CrossRef
3.
Lee JW, Shahzad MM, Lin YG, Armaiz-Pena G, Mangala LS, Han HD, Kim HS, Nam EJ, Jennings NB, Halder J, Nick AM, Stone RL, Lu C, Lutgendorf SK, Cole SW, Lokshin AE, Sood AK. Surgical stress promotes tumor growth in ovarian carcinoma. Clin Cancer Res. 2009;15:2695–702.CrossRefPubMedPubMedCentral
4.
Coffey JC, Wang JH, Smith MJ, Bouchier-Hayes D, Cotter TG, Redmond HP. Excisional surgery for cancer cure: therapy at a cost. Lancet Oncol. 2003;4:760–8.CrossRefPubMed
5.
Hoekstra LT, van Lienden KP, Doets A, Busch OR, Gouma DJ, van Gulik TM. Tumor progression after preoperative portal vein embolization. Ann Surg. 2012;256:812–8.CrossRefPubMed
6.
Peeters CF, Westphal JR, de Waal RM, Ruiter DJ, Wobbes T, Ruers TJ. Vascular density in colorectal liver metastases increases after removal of the primary tumor in human cancer patients. Int J Cancer. 2004;112:554–9.CrossRefPubMed
7.
Veenhof AA, Sietses C, von Blomberg BM, van Hoogstraten IM, vd Pas MH, Meijerink WJ, vd Peet DL, vd Tol MP, Bonjer HJ, Cuesta MA. The surgical stress response and postoperative immune function after laparoscopic or conventional total mesorectal excision in rectal cancer: a randomized trial. Int J Color Dis. 2011;26:53–9.CrossRef
8.
Allendorf JD, Bessler M, Kayton ML, Oesterling SD, Treat MR, Nowygrod R, Whelan RL. Increased tumor establishment and growth after laparotomy vs. laparoscopy in a murine model. Arch Surg. 1995;130:649–53.CrossRefPubMed
9.
Allendorf JD, Bessler M, Horvath KD, Marvin MR, Laird DA, Whelan RL. Increased tumor establishment and growth after open vs laparoscopic bowel resection in mice. Surg Endosc. 1998;12:1035–8.CrossRefPubMed
10.
Carter JJ, Feingold DL, Kirman I, Oh A, Wildbrett P, Asi Z, Fowler R, Huang E, Whelan RL. Laparoscopic-assisted cecectomy is associated with decreased formation of postoperative pulmonary metastases compared with open cecectomy in a murine model. Surgery. 2003;134:432–6.CrossRefPubMed
11.
Fleshman J, Sargent DJ, Green E, Anvari M, Stryker SJ, Beart RW Jr, Hellinger M, Flanagan R Jr, Peters W, Nelson H. Laparoscopic colectomy for cancer is not inferior to open surgery based on 5-year data from the COST Study Group trial. Ann Surg. 2007;246:655–62.CrossRefPubMed
12.
Ohtani H, Tamamori Y, Arimoto Y, Nishiguchi Y, Maeda K, Hirakawa K. Meta-analysis of the short- and long-term results of randomized controlled trials that compared laparoscopy-assisted and conventional open surgery for colorectal cancer. J Cancer. 2011;2:425–34.CrossRefPubMedPubMedCentral
13.
14.
Ceelen W, Pattyn P, Mareel. Surgery, wound healing, and metastasis: recent insights and clinical implications. Crit Rev Oncol Hematol. 2014;89:16–26.CrossRefPubMed
15.
16.
17.
Shantha Kumara HMC, Feingold D, Kalady M, Dujovny N, Senagore A, Hyman N, Cekic V, Whelan RL. Colorectal resection is associated with persistent proangiogenic plasma protein changes postoperative plasma stimulates in vitro endothelial cell growth, migration and invasion. Ann Surg. 2009;249:973–7.CrossRefPubMed
18.
Shantha Kumara HMC, Tohme ST, Herath SA, Yan X, Senagore AJ, Nasar A, Kalady MF, Baxter R, Whelan RL. Plasma soluble vascular adhesion molecule-1 levels are persistently elevated during the first month after colorectal cancer resection. Surg Endosc. 2012;26:1759–64.CrossRefPubMed
19.
Shantha Kumara HMC, Cabot JC, Yan X, Herath SA, Luchtefeld M, Kalady MF, Feingold DL, Baxter R, Whelan RL. Minimally invasive colon resection is associated with a persistent increase in plasma PlGF levels following cancer resection. Surg Endosc. 2011;25:2153–8.CrossRefPubMed
20.
Shantha Kumara HMC, Myers EA, Herath SA, Jang JH, Njoh L, Yan X, Kirchoff D, Cekic V, Luchtefeld M, Whelan RL. Plasma monocyte chemotactic protein-1 remains elevated after minimally invasive colorectal cancer resection. World J Gastrointest Oncol. 2014;6:413–9.CrossRefPubMed
21.
Shantha Kumara HMC, Gaita DJ, Miyagaki H, Yan X, Herath SA, Cekic V, Whelan RL. Minimally invasive colorectal resection is associated with significantly elevated levels of plasma matrix metalloproteinase 3 (MMP-3) during the first month after surgery which may promote the growth of residual metastases. Surg Endosc. 2014;28:3322–8.CrossRefPubMed
22.
Shantha Kumara HMC, Gaita D, Miyagaki H, Yan X, Hearth SA, Njoh L, Cekic V, Whelan RL. Plasma chitinase 3-like 1 is persistently elevated during first month after minimally invasive colorectal cancer resection. World J Gastrointest Oncolc. 2016;8:607–14.CrossRef
23.
Shantha Kumara HMC, Sutton E, Bellini GA, Yan X, Cekic V, Gandhi ND, Whelan RL. Plasma interleukin-8 levels are persistently elevated for 1 month after minimally invasive colorectal resection for colorectal cancer. Mol Clin Oncol. 2018;3:471–6.
24.
Shantha Kumara HMC, Kirchoff D, Naffouje S, Grieco M, Herath SA, Dujovny N, Kalady MF, Hyman N, Njoh L, Whelan RL. Plasma from the second and third weeks after open colorectal resection for cancer stimulates in vitro endothelial cell growth, migration, and invasion. Surg Endosc. 2012;26:790–5.CrossRefPubMed
25.
Shantha Kumara HMC, Myers EA, Herath SA, Njoh L, Yan X, Kirchoff D, Dujovny N, Whelan RL. Minimally invasive colorectal resection for benign pathology is associated with persistent proangiogenic plasma compositional changes. Dis Colon Rectum. 2014;57:740–6.CrossRefPubMed
26.
Karayiannakis AJ, Zbar A, Polychronidis A, Simopoulos C. Serum and drainage fluid vascular endothelial growth factor levels in early surgical wounds. Eur Surg Res. 2003;35:492–6.CrossRefPubMed
27.
Wu FP, Hoekman K, Meijer S, Cuesta MA. VEGF and endostatin levels in wound fluid and plasma after breast surgery. Angiogenesis. 2003;6:255–7.CrossRefPubMed
28.
Wu FP, Hoekman K, Sietses C, von Blomberg BM, Meijer S, Bonjer HJ, Cuesta MA. Systemic and peritoneal angiogenic response after laparoscopic or conventional colon resection in cancer patients: a prospective, randomized trial. Dis Colon Rectum. 2004;47:1670–4.CrossRefPubMed
29.
30.
Scholz F, Schulte A, Adamski F, Hundhausen C, Mittag J, Schwartz A, Kruse M, Proksch E, Ludwig A. Constitutive expression and regulated release of the transmembrane chemokine CXCL16 in human and murine skin. J Invest Dermatol. 2007;127:1444–55.CrossRefPubMed
31.
Matloubian M, David A, Engel S, Ryan JE, Cyster JG. A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Nat Immunol. 2000;1:298–304.CrossRefPubMed
32.
Wilbanks A, Zondlo SC, Murphy K, Mak S, Soler D, Langdon P, Andrew DP, Wu L, Briskin M. Expression cloning of the STRL33/BONZO/TYMSTR ligand reveals elements of CC, CXC and CX3C chemokines. J Immunol. 2001;166:5145–54.CrossRefPubMed
33.
Motsinger A, Haas DW, Stanic AK, Van Kaer L, Joyce S, Unutmaz D. CD1d-restricted human natural killer T cells are highly susceptible to human immune-deficency virus 1 infection. J Exp Med. 2002;195:869–79.CrossRefPubMedPubMedCentral
34.
Kim CH, Kunkel EJ, Boisvert J, Johnston B, Campbell JJ, Genovese MC, Greenberg HB, Butcher EC. Bonzo/CXCR6 expression defines type 1-polarized T-cell subsets with extralymphoid tissue homing potential. J Clin Invest. 2001;107:595–601.CrossRefPubMedPubMedCentral
35.
Lu Y, Wang J, Xu Y, Koch AE, Cai Z, Chen X, Galson DL, Taichman RS, Zhang J. CXCL16 functions as a novel chemotactic factor for prostate cancer cells in vitro. Mol Cancer Res. 2008;6:546–54.CrossRefPubMed
36.
Wang J, Lu Y, Wang J, Koch AE, Zhang J, Taichman RS. CXCR induces prostate cancer progression by the AKT/mammalian target of rapamycin signaling pathway. Cancer Res. 2008;68:10367–76.CrossRefPubMedPubMedCentral
37.
Gutwein P, Schramme A, Sinke N, Abdel-Bakky MS, Voss B, Obermüller N, Doberstein K, Koziolek M, Fritzsche F, Johannsen M, Jung K, Schaider H, Altevogt P, Ludwig A, Pfeilschifter J, Kristiansen G. Tumorural CXCL16 expression is a novel prognostic marker of longer survival times in renal cell cancer patients. Eur J Cancer. 2009;45:478–89.CrossRefPubMed
38.
Ou DL, Chen CL, Lin SB, Hsu CH, Lin LI. Chemokine receptor expression profiles in nasopharyngeal carcinoma and their association with metastases and radiotherapy. J Pathol. 2006;210:363–73.CrossRefPubMed
39.
Matsushita K, Toiyama Y, Tanaka K, Saigusa S, Hiro J, Uchida K, Inoue Y, Kusunoki M. Soluble CXCL16 in preoperative serum is a novel prognostic marker and predicts recurrence of liver metastases in colorectal cancer patients. Ann Surg Oncol. 2012;19(Suppl 3):S518–27.CrossRefPubMed
40.
Hojo S, Koizumi K, Tsuneyama K, Arita Y, Cui Z, Shinohara K, Minami T, Hashimoto I, Nakayama T, Sakurai H, Takano Y, Yoshie O, Tsukada K, Saiki I. High-level expression of chemokine CXCL16 by tumor cells correlates with a good prognosis and increased tumor-infiltrating lymphocytes in colorectal cancer. Cancer Res. 2007;67:4725–31.CrossRefPubMed
41.
Isozaki T, Arbab AS, Haas CS, Amin MA, Arendt MD, Koch AE, Ruth JH. Evidence that CXCL16 is a potent mediator of angiogenesis and is involved in endothelial progenitor cell chemotaxis: studies in miche with K/BxN serum-induced arthritis. Arthritis Rheum. 2013;65:1736–46.CrossRefPubMed
42.
Belizon A, Balik E, Horst P, Feingold D, Arnell T, Azarani T, Cekic V, Skitt R, Kumara S, Whelan RL. Persistent elevation of plasma vascular endothelial growth factor levels during the first month after minimally invasive colorectal resection. Surg Endosc. 2008;22:287–97.CrossRefPubMed
43.
Kaibori M, Iwamoto S, Ishizaki M, Matsui K, Saito T, Yoshioka K, Hamada Y, Kwon AH. Timing of resection for synchronous liver metastases from colorectal cancer. Dig Dis Sci. 2010;55:3262–70.CrossRefPubMed
44.
Yoshidome H, Kimura F, Shimizu H, Ohtsuka M, Kato A, Yoshitomi H, Furukawa K, Mitsuhashi N, Takeuchi D, Iida A, Miyazaki M. Interval period tumor progression: does delayed hepatectomy detect occult metastases in synchronous colorectal liver metastases? J Gastrointest Surg. 2008;12:1391–8.CrossRefPubMed
45.
Scheer MG, Stollman TH, Vogel WV, Boerman OC, Oyen WJ, Ruers TJ. Increased metabolic activity of indolent liver metastases after resection of a primary colorectal tumor. J Nucl Med. 2008;49:887–91.CrossRefPubMed
46.
Peeters CF, de Geus LF, Westphal JR, de Waal RM, Ruiter DJ, Wobbes T, Oyen WJ, Ruers TJ. Decrease in circulating anti-angiogenic factors (angiostatin and endostatin) after surgical removal of primary colorectal carcinoma coincides with increased metabolic activity of liver metastases. Surgery. 2004;137:246–9.CrossRef
47.
Shantha Kumara HMC, Shah A, Pettke E, Yan X , Cekic V, Gandhi ND, Downing ma, Whelan RL. Plasma levels of the proangiogenic protein CXCL16 are persistently elevated during the first month after minimally invasive colorectal resection for colorectal cancer. The Society of American Gastrointestinal and Endoscopic Surgery, Annual Meeting, March 22–25, Houston, TX. USA- S132. 2017.
Metadata
Title
Plasma levels of the proangiogenic protein CXCL16 remains elevated for 1 month after minimally invasive colorectal cancer resection
Authors
H. M. C. Shantha Kumara
Erica Pettke
Abhinit Shah
Xiaohong Yan
Vesna Cekic
Melissa Alvarez Downing
Nipa Dilip Gandhi
Richard L. Whelan
Publication date
01-12-2018
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2018
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/s12957-018-1418-2

Other articles of this Issue 1/2018

World Journal of Surgical Oncology 1/2018 Go to the issue

Correspondence

Pancreaticojejunostomy with or without reinforcement after pancreaticoduodenectomy: surgical technique of ligamentum teres hepatis wrap around pancreaticojejunostomy

Research

Clinical significance and prognostic value of receptor conversion in hormone receptor positive breast cancers after neoadjuvant chemotherapy

Research

Clinical significance of peripheral circulating tumor cell counts in colorectal polyps and non-metastatic colorectal cancer

Technical innovations

Frontal axial pattern flap combined with hard palate mucosa transplant in the reconstruction of midfacial defects after the excision of huge basal cell carcinoma

Review

Rising global burden of breast cancer: the case of sub-Saharan Africa (with emphasis on Nigeria) and implications for regional development: a review

Research

Combined surgical treatment of esophageal cancer and coronary heart diseases in elderly patients