Minimally Invasive Colorectal Resection Is Associated With a Transient Increase in Plasma Hepatocyte Growth Factor Levels Early After Surgery for Colon Cancer

Kumara, H. M. C. Shantha; Tohme, Samer; Kim, Ik Y.; Kim, Donald G.; Kalady, Matthew F.; Luchtefeld, Martin; Hoffman, K.; DiMaggio, Vincent; Whelan, Richard L.

doi:10.1177/1553350611399588

Cited by 6 publications

(3 citation statements)

References 29 publications

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“…Given these results, one would think that the other cytokines that play prominent roles in the wound healing process would also be persistently elevated after surgery. Interestingly, similar studies that measured postop plasma levels of FGF, TGF, HGF and EGF[77,78], however, have not demonstrated late elevations. However, further studies of other growth factors in this time window are warranted.…”

Section: Discussionmentioning

confidence: 88%

Plasma and wound fluid levels of eight proangiogenic proteins are elevated after colorectal resection

Kumara¹,

Yan²,

Pettke³

et al. 2019

WJGO

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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.

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Section: Discussionmentioning

confidence: 88%

Plasma and wound fluid levels of eight proangiogenic proteins are elevated after colorectal resection

Kumara¹,

Yan²,

Pettke³

et al. 2019

WJGO

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“…The majority of plasma protein changes after surgery persist hours or days (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25), however, in the last decade, increases in the blood levels of at least 12 proangiogenic proteins have been noted to persist for 3-5 weeks after resection of colorectal cancer (CRC). Included on this list are vascular endothelial growth factor (VEGF), angiopoeitin-2 (Ang-2), placental growth factor (PIGF), soluble vascular adhesion molecule-1 (sVCAM-1), Angiopoietin like 4 (ANPTL4), monocyte chemotactic protein-1 (MCP-1), human chitinase 3-like 1 (Chi3L1), matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-3 (MMP-7), Chemokine (C-X-C motif) ligand 16 (CXCL 16), and Interleukin 8 (IL-8).…”

Section: Discussionmentioning

confidence: 99%

“…The vast majority of plasma protein changes after surgery last hours or days (IL-1, TNF, IL-6, CRP, etc.) (12)(13)(14), however, in the last decade, increases in blood levels of at least 12 progangiogenic proteins have been noted to persist for 3 to 5 weeks after resection of colorectal cancer (CRC) (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). In vitro studies utilizing endothelial cells (EC's), critical to angiogenesis, suggest the net effect of plasma compositional changes is proangiogenic.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Die Geschichte der laparoskopischen kolorektalen Chirurgie in den Vereinigten Staaten von Amerika

Keßler

Connelly

2022

coloproctology

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Minimally Invasive Colorectal Resection Is Associated With a Transient Increase in Plasma Hepatocyte Growth Factor Levels Early After Surgery for Colon Cancer

Abstract: MICR for CRC is associated with a 1.9- to 2.3-fold increase in plasma HGF levels during the first 3 PODs after which levels normalize. This transient increase may briefly promote angiogenesis and the growth of residual tumor cells.

Cited by 6 publications

References 29 publications

Plasma and wound fluid levels of eight proangiogenic proteins are elevated after colorectal resection

Plasma and wound fluid levels of eight proangiogenic proteins are elevated after colorectal resection

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

Die Geschichte der laparoskopischen kolorektalen Chirurgie in den Vereinigten Staaten von Amerika

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