Plasma MMP-2 and MMP-7 levels are elevated first month after surgery and may promote growth of residual metastases

BACKGROUND MMP-2 also known as gelatinase A and MMP-7(matrilysin)are members of the zinc-dependent family of MMPs(Matrix metalloproteinase).MMP-2 and MMP-7 are remodeling enzymes that digest extracellular matrix;MMP-2 is extensively expressed during development and is upregulated at sites of tissue damage,inflammation,and in stromal cells of metastatic tumors.MMP-7 is expressed in the epithelial cells and in a variety of cancers including colon tumors.Plasma MMP-2 and MMP-7 levels were assessed before and after minimally invasive colorectal resection for cancer pathology.AIM To determine plasma MMP-2 and MMP-7 levels before and after minimally invasive colorectal resection for cancer pathology.METHODS Patients enrolled in a plasma bank for whom plasma was available were eligible.Plasma obtained from preoperative(Preop)and postoperative blood samples was used.Only colorectal cancer(CRC)patients who underwent elective minimally invasive cancer resection with preop,post-operative day(POD)1,3 and at least 1 late postop sample(POD 7-34)were included.Late samples were bundled into 7 d blocks(POD 7-13,14-20,etc.)and treated as single time points.Plasma MMP-2 and MMP-7 levels were determined via enzyme-linked immunosorbent assay in duplicate.RESULTS Total 88 minimally invasive CRC resection CRC patients were studied(right colectomy,37%;sigmoid,24%;and LAR/AR 18%).Cancer stages were:1,31%;2,30%;3,34%;and 4,5%.Mean Preop MMP-2 plasma level(ng/mL)was 179.3±40.9(n=88).Elevated mean levels were noted on POD1(214.3±51.2,n=87,P<0.001),POD3(258.0±63.9,n=80,P<0.001),POD7-13(229.9±62.3,n=65,P<0.001),POD 14-20(234.9±47.5,n=25,P<0.001),POD 21-27(237.0±63.5,n=17,P<0.001,)and POD 28-34(255.4±59.7,n=15,P<0.001).Mean Preop MMP-7 level was 3.9±1.9(n=88).No significant differences were noted on POD 1 or 3,however,significantly elevated levels were noted on POD 7-13(5.7±2.5,n=65,P<0.001),POD 14-20(5.9±2.5,n=25,P<0.001),POD 21-27(6.1±3.6,n=17,P=0.002)and on POD 28-34(6.8±3.3,n=15 P<0.001,)vs preop levels.CONCLUSION MMP-2 levels are elevated for 5 wk and MMP-7 levels elevated for weeks 2-6.The etiology of these changes in unclear,trauma and wound healing likely play a role.These changes may promote residual tumor growth and metastasis.

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

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 postsurgery.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.