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

World Journal of Gastrointestinal Oncology 2021年第8期13卷 879-892页

作者： hmc shantha kumara Hiromichi Miyagaki Sajith A Herath Erica Pettke Xiaohong Yan Vesna Cekic Richard L Whelan Division of Colon and Rectal Surgery Department of SurgeryLenox Hill HospitalNorthwell HealthNew YorkNY 10028United States Department of Gastroenterological Surgery Osaka UniversitySuita 565-0862OsakaJapan Analytic Department NovartisMorris PlainsNJ 07905United States Department of Surgery Swedish Medical CenterSeattleWA 98122United States Department of Surgery Donald and Barbara Zucker School of Medicine at Hofstra/NorthwellHempsteadNY 11549United States

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 ***-7 is expressed in the epithelial cells and in a variety of cancers including colon *** MMP-2 and MMP-7 levels were assessed before and after minimally invasive colorectal resection for cancer *** To determine plasma MMP-2 and MMP-7 levels before and after minimally invasive colorectal resection for cancer *** Patients enrolled in a plasma bank for whom plasma was available were *** obtained from preoperative(Preop)and postoperative blood samples was *** 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 *** samples were bundled into 7 d blocks(POD 7-13,14-20,etc.)and treated as single time *** MMP-2 and MMP-7 levels were determined via enzyme-linked immunosorbent assay in *** 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 p

关键词： Effects of surgery Colorectal resection Colorectal cancer Plasma MMP-2 and MMP-7 levels Angiogenesis

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

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World Journal of Gastrointestinal Oncology 2019年第6期11卷 470-488页

作者： 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 SurgeryMount Sinai West HospitalNew YorkNY 10019United States Department of Surgery Mount Sinai Icahn School of MedicineNew YorkNY 10029United States

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 *** 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 *** wounds are a possible source because of the important role that angiogenesis plays in the healing *** 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 *** To determine plasma and wound fluid levels of 8 proangiogenic proteins after colorectal resection for cancer and benign *** 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 *** 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 *** 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 *** 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 *** Plasma protein levels were elevat

关键词： Effects of surgery Colorectal resection Colorectal cancer Plasma protein levels Wound protein levels Angiogenesis

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Plasma chitinase 3-like 1 is persistently elevated during first month after minimally invasive colorectal cancer resection

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World Journal of Gastrointestinal Oncology 2016年第8期8卷 607-614页

作者： hmc shantha kumara David Gaita Hiromichi Miyagaki Xiaohong Yan Sonali AC Hearth Linda Njoh Vesna Cekic Richard L Whelan Division of Colon and Rectal Surgery Department of Surgery Mount Sinai West Hospital Department of Gastroenterological Surgery Osaka University

AIM: To assess blood chitinase 3-like 1(CHi3L1) levels for 2 mo after minimally invasive colorectal resection(MICR) for colorectal cancer(CRC). METHODS: CRC patients in an Institutional Review Board approved data/plasma bank who underwent elective MICR for whom preoperative(PreO p), early postoperative(PostO p), and 1 or more late PostO p samples [postoperative day(POD) 7-27] available were included. Plasma CHi3L1 levels(ng/m L) were determined in duplicate by enzyme linked immunosorbent assay. RESULTS: PreOp and PostOp plasma sample were available for 80 MICR cancer patients for the study. The median PreOp CHi3L1 level was 56.8 CI: 41.9-78.6 ng/mL(n = 80). Significantly elevated(P < 0.001) median plasma levels(ng/mL) over PreOp levels were detected on POD1(667.7 CI: 495.7, 771.7; n = 79), POD 3(132.6 CI: 95.5, 173.7; n = 76), POD7-13(96.4 CI: 67.7, 136.9; n = 62), POD14-20(101.4 CI: 80.7, 287.4; n = 22), and POD 21-27(98.1 CI: 66.8, 137.4; n = 20, P = 0.001). No significant difference in plasma levels were noted on POD27-41. CONCLUSION: Plasma CHi3L1 levels were significantly elevated for one month after MICR. Persistently elevated plasma CHi3L1 may support the growth of residual tumor and metastasis.

关键词： Colorectal cancer Recurrence Minimally inasive colorectal resection Chitinase 3-like 1 Metastasis

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Plasma monocyte chemotactic protein-1 remains elevated after minimally invasive colorectal cancer resection

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World Journal of Gastrointestinal Oncology 2014年第10期6卷 413-419页

作者： hmc shantha kumara Elizabeth A Myers Sonali AC Herath Joon Ho Jang Linda Njoh Xiaohong Yan Daniel Kirchoff Vesna Cekic Martin Luchtefeld Richard L Whelan Division of Colon and Rectal Surgery Department of Surgery Mount Sinai-Roosevelt Hospital Center New York NY 10019 United States Division of Colon and Rectal Surgery Fer-guson Clinic Grand Rapids MI 49546 United States Icahn School of Medicine at-Mount Sinai New York NY 10029 United States Surgical Oncology Department of Surgery College of Physicians and Surgeons Columbia University New York NY 10032 United States

AIM: To investigate plasma Monocyte Chemotactic Protein-1 levels preoperatively in colorectal cancer(CRC) and benign patients and postoperatively after CRC ***: A plasma bank was screened for minimally invasive colorectal cancer resection(MICR) for CRC and benign disease(BEN) patients for whom preoperative, early postoperative, and 1 or more late postoperative samples(postoperative day 7-27) were available. Monocyte chemotactic protein-1(MCP-1) levels(pg/mL) were determined via enzyme linked immuno-absorbent assay. RESULTS: One hundred and two CRC and 86 BEN patients were studied. The CRC patient's median preoperative MCP-1 level(283.1, CI: 256.0, 294.3) was higher than the BEN group level(227.5, CI: 200.2, 245.2; P = 0.0004). Vs CRC preoperative levels, elevated MCP-1 plasma levels were found on postoperative day 1(446.3, CI: 418.0, 520.1), postoperative day 3(342.7, CI: 320.4, 377.4), postoperative day 7-13(326.5, CI: 299.4, 354.1), postoperative day 14-20(361.6, CI: 287.8, 407.9), and postoperative day 21-27(318.1, CI: 287.2, 371.6; P < 0.001 for all). CONCLUSION: Preoperative MCP-1 levels were higher in CRC patients(vs BEN). After MICR for CRC, MCP-1 levels were elevated for 1 mo and may promote angiogenesis, cancer recurrence and metastasis.

关键词： Colorectal cancer Monocyte chemotactic protein-1 Minimally invasive colorectal resection angio-genesis

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