Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jun 15, 2019; 11(6): 470-488
Published online Jun 15, 2019. doi: 10.4251/wjgo.v11.i6.470
Plasma and wound fluid levels of eight proangiogenic proteins are elevated after colorectal resection
HMC Shantha Kumara, Xiao-Hong Yan, Erica Pettke, Vesna Cekic, Nipa Dilip Gandhi, Geoffrey A Bellini, Richard L Whelan
HMC Shantha Kumara, Xiao-Hong Yan, Erica Pettke, Vesna Cekic, Nipa Dilip Gandhi, Geoffrey A Bellini, Richard L Whelan, Division of Colon and Rectal Surgery, Department of Surgery, Mount Sinai West Hospital, New York, NY 10019, United States
Richard L Whelan, Department of Surgery, Mount Sinai Icahn School of Medicine, New York, NY 10029, United States
Author contributions: Shantha Kumara HMC contributed to the conception, design, sample processing, statistical analysis and interpretation of data, and revision of the articles; Yan XH contributed to collection of human material clinical data, revision of the article, Pettke E, Gandhi ND, Bellini GA and Cekic V contributed to human sample collection, processing, analysis and interpretation of data; Whelan RL contributed to the conception, design, interpretation of data, critical revision of the article; all authors drafted the article and made critical revisions and approved the submitted final version of the article to be published.
Supported by a generous donation from the Thompson Family Foundation to the Division of Colon and Rectal Surgery, Department of Surgery, Mount Sinai West Hospital, New York.
Institutional review board statement: This study was reviewed and approved by Mount Sinai Hospital, New York IRB.
Conflict-of-interest statement: All authors have no conflicts of interest or financial ties to disclose.
Data sharing statement: No additional data available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Richard L Whelan, MD, Professor, Division of Colon and Rectal Surgery, Department of Surgery, Mount Sinai West Hospital, Suite 7B, 425 West, 59th Street, New York, NY 10019, United States. richard.whelan@mountsinai.org
Telephone: +1-212-5238172 Fax: +1-212-5238857
Received: October 19, 2018
Peer-review started: October 19, 2018
First decision: December 10, 2018
Revised: March 7, 2019
Accepted: March 16, 2019
Article in press: March 16, 2019
Published online: June 15, 2019
Abstract
BACKGROUND

Colorectal resection is associated with 3-5 wk long elevations in the plasma levels of at least 11 proangiogenic proteins that may stimulate tumor angiogenesis post-surgery. The increases during the first week after surgery may be related to the acute inflammatory response; the cause(s) of the week 2-5 increases is unknown. The wounds are a possible source because of the important role that angiogenesis plays in the healing process. The main hypothesis of the study is that wound fluid levels of the proteins studied will be elevated well beyond plasma levels which, in turn, are elevated from preoperative baseline levels.

AIM

To determine plasma and wound fluid levels of 8 proangiogenic proteins after colorectal resection for cancer and benign pathology.

METHODS

Blood and wound fluid samples were taken simultaneously on postoperative (postop) day 1, 3, and later time points until wound drain removal in 35 colorectal cancer patients and 31 benign disease patients undergoing colorectal resection in whom closed wound drains had been placed in either the pelvis or the subcutaneous space of the abdominal incision. Postop plasma levels were compared to preop plasma and postop wound fluid levels (separate analyses for cancer and benign groups).

RESULTS

Sixty-six colorectal disease patients were studied (35 cancer, 31 benign pathology). Most patients underwent minimally invasive surgery (open surgery in 11% of cancer and 6% of benign patients). The majority in the cancer group had rectal resections while in the benign group sigmoid or right colectomy predominated. Plasma levels of all 8 proteins were significantly elevated from baseline (P < 0.05) at all post-operative time points in the cancer group and at 90% of time points (29/32) in the benign group. Wound levels of all 8 proteins were 3-106 times higher (P < 0.05) than plasma levels at 87-90 percent of postop time points; of note, wound levels were more than 10 times higher at 47-50% of time points.

CONCLUSION

Plasma protein levels were elevated for 3 weeks after surgery; wound fluid levels were much greater than corresponding blood levels. Healing wounds may be the source of the plasma increases.

Keywords: Effects of surgery, Colorectal resection, Colorectal cancer, Plasma protein levels, Wound protein levels, Angiogenesis

Core tip: Simultaneous postoperative (postop) measurement of plasma and wound fluid levels of 8 proangiogenic proteins for 3 wk after colorectal resection was carried out in 66 patients. Wound fluid protein levels were 3-106 times greater than postop plasma levels which, in turn, were significantly greater than preoperative plasma levels. Colorectal resection is associated with persistent systemic blood protein changes that might stimulate tumor angiogenesis and, thus, tumor growth in residual tumor deposits during the first month after surgery. It is hypothesized that the healing wounds are a major source of the added protein in the blood stream.