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.

Significance of ipsilateral breast tumor recurrence after breast conserving treatment: role of surgical removal

Objective： To analyze the pattern over time （dynamics） of further recurrence and death after ipsilateral breast tumor recurrence （IBTR） in breast cancer patients undergoing breast conserving treatment （BCT）. Methods： A total of 338 evaluable patients experiencing IBTR were extracted from a database of 3,293 patients undergoing BCT. The hazard rates for recurrence and mortality throughout 10 years of follow-up after IBTR were assessed and were compared to the analogous estimates associated to the primary treatment. Results： In a time frame with the time origin at the surgical treatment for IBTR, the hazard rate for further recurrence displays a bimodal pattern （peaks at the second and at the sixth year）. Patients receiving mastectomy for IBTR reveal recurrence and mortality dynamics similar to that of node positive （N＋） patients receiving mastectomy as primary surgery, apart from the first two-three years, when IBTR patients do worse. If the patients with time to IBTR longer than 2.5 years are considered, differences disappear. Conclusions： The recurrence and mortality dynamics following IBTR surgical removal is similar to the corresponding dynamics following primary tumor removal. In particular, patients with time to IBTR in excess of 2.5 years behave like N＋ patients following primary tumor removal. Findings may be suitably explained by assuming that the surgical manoeuvre required by IBTR treatment is able to activate a sudden growing phase for tumor foci most of which, as suggested by the systemic model of breast cancer, would have reached the clinical level according to their own dynamics.