Skip to main content
Top
Published in: Diseases of the Colon & Rectum 12/2006

01-12-2006

Human Peritoneal Adhesions Show Evidence of Tissue Remodeling and Markers of Angiogenesis

Authors: Jonathan C. Epstein, M.D., M.R.C.S., Malcolm S. Wilson, M.D., F.R.C.S., Sylwia Wilkosz, Ph.D., Grenham Ireland, Ph.D., Sarah T. O’Dwyer, M.D., F.R.C.S., Sarah E. Herrick, Ph.D.

Published in: Diseases of the Colon & Rectum | Issue 12/2006

Login to get access

Purpose

This study was designed to investigate the vascular structure and angiogenic activity of human peritoneal adhesions.

Methods

Adhesions were collected from patients undergoing laparotomy (n = 32). Histologic features were documented and the distribution of mature and immature vascular markers were determined by immunolocalization and quantified by image analysis. The three-dimensional organization of blood vessels was investigated by confocal microscopy. Expression of vascular endothelial growth factor A, its receptor flk-1, and proliferating cell nuclear antigen were assessed by immunohistochemistry as indicators of angiogenic activity.

Results

Adhesions were found to be vascularized structures comprising bundles of collagen, interspersed with varying amounts of adipose tissue. Functional blood vessels expressed recognized vascular markers (vWF, CD34, α-SMA, and CD105) and formed a branching network similar to that of the peritoneum. Those adhesions expressing vascular endothelial growth factor A and its receptor showed significantly higher numbers of immature vessels as defined by expression of CD105. Omental adhesions (n = 16) contained significantly more adipose tissue (P < 0.05) and displayed a higher microvessel density (P < 0.01) but lower cellularity (P < 0.05) compared with nonomental adhesions (n = 16).

Conclusions

All adhesions contained functional blood vessels and most showed evidence of cell proliferation. The presence of vascular endothelial growth factor A and its receptor in human adhesions suggests ongoing angiogenic activity. This study demonstrates that adhesions are vascular structures with evidence of tissue remodeling and suggests potential for new prevention strategies involving antiangiogenic therapies.
Literature
1.
go back to reference Menzies, D, Ellis, H 1990Intestinal obstruction from adhesions-how big is the problemAnn R Coll Surg Engl726063PubMed Menzies, D, Ellis, H 1990Intestinal obstruction from adhesions-how big is the problemAnn R Coll Surg Engl726063PubMed
2.
go back to reference Menzies, D 1993Postoperative adhesions: their treatment and relevance in clinical practiceAnn R Coll Surg Engl75147153PubMed Menzies, D 1993Postoperative adhesions: their treatment and relevance in clinical practiceAnn R Coll Surg Engl75147153PubMed
3.
go back to reference Diamond, E 1979Lysis of postoperative pelvic adhesions in infertilityFertil Steril31287295PubMed Diamond, E 1979Lysis of postoperative pelvic adhesions in infertilityFertil Steril31287295PubMed
4.
go back to reference Krabben, AA, Dijkstra, FR, Nieuwenhuijzen, M, Reijnen, MM, Schaapveld, M, Goor, H 2000Morbidity and mortality of inadvertent enterotomy during adhesiotomyBr J Surg87467471CrossRef Krabben, AA, Dijkstra, FR, Nieuwenhuijzen, M, Reijnen, MM, Schaapveld, M, Goor, H 2000Morbidity and mortality of inadvertent enterotomy during adhesiotomyBr J Surg87467471CrossRef
5.
go back to reference Ellis, H, Moran, BJ, Thompson, JN, et al. 1999Adhesion-related hospital readmissions after abdominal and pelvic surgery: a retrospective cohort studyLancet35314761480PubMedCrossRef Ellis, H, Moran, BJ, Thompson, JN,  et al. 1999Adhesion-related hospital readmissions after abdominal and pelvic surgery: a retrospective cohort studyLancet35314761480PubMedCrossRef
6.
go back to reference Ray, NF, Denton, WG, Thamer, M, Henderson, SC, Perry, S 1998Abdominal adhesiolysis: inpatient care and expenditures in the United States in 1994J Am Coll Surg18619PubMedCrossRef Ray, NF, Denton, WG, Thamer, M, Henderson, SC, Perry, S 1998Abdominal adhesiolysis: inpatient care and expenditures in the United States in 1994J Am Coll Surg18619PubMedCrossRef
7.
go back to reference Risberg, B 1997Adhesions: preventive strategiesEur J Surg Suppl5773239PubMed Risberg, B 1997Adhesions: preventive strategiesEur J Surg Suppl5773239PubMed
8.
go back to reference Weibel, MA, Majno, G 1973Peritoneal adhesions and their relation to abdominal surgery. A postmortem studyAm J Surg126345353PubMedCrossRef Weibel, MA, Majno, G 1973Peritoneal adhesions and their relation to abdominal surgery. A postmortem studyAm J Surg126345353PubMedCrossRef
9.
go back to reference Bridges, JB, Whitting, HW 1964Parietal peritoneal healing in the ratJ Pathol Bacteriol87123130PubMedCrossRef Bridges, JB, Whitting, HW 1964Parietal peritoneal healing in the ratJ Pathol Bacteriol87123130PubMedCrossRef
10.
go back to reference Hosgood, G, Salisbury, SK, Cantwell, HD, DeNicola, DB 1989Intraperitoneal circulation and drainage in the dogVet Surg18261268PubMed Hosgood, G, Salisbury, SK, Cantwell, HD, DeNicola, DB 1989Intraperitoneal circulation and drainage in the dogVet Surg18261268PubMed
11.
go back to reference Ellis, H 1962The aetiology of post-operative abdominal adhesions. An experimental studyBr J Surg501016PubMed Ellis, H 1962The aetiology of post-operative abdominal adhesions. An experimental studyBr J Surg501016PubMed
12.
go back to reference Ellis, H 1971The cause and prevention of postoperative intraperitoneal adhesionsSurg Gynecol Obstet133497511PubMed Ellis, H 1971The cause and prevention of postoperative intraperitoneal adhesionsSurg Gynecol Obstet133497511PubMed
13.
go back to reference Myllarniemi, H, Karppinen, V 1968Vascular pattern of peritoneal adhesionsBr J Surg55605608PubMed Myllarniemi, H, Karppinen, V 1968Vascular pattern of peritoneal adhesionsBr J Surg55605608PubMed
14.
go back to reference Bigatti, G, Boeckx, W, Gruft, L, Segers, N, Brosens, I 1997Neoangiogenesis in adhesion formation and peritoneal healingTreutner, K-HSchumpelik, V eds. Peritoneal adhesionsSpringer-VerlagBerlin3748 Bigatti, G, Boeckx, W, Gruft, L, Segers, N, Brosens, I 1997Neoangiogenesis in adhesion formation and peritoneal healingTreutner, K-HSchumpelik, V eds. Peritoneal adhesionsSpringer-VerlagBerlin3748
15.
go back to reference Herrick, SE, Mutsaers, SE, Ozua, P, et al. 2000Human peritoneal adhesions are highly cellular, innervated, and vascularizedJ Pathol1926772PubMedCrossRef Herrick, SE, Mutsaers, SE, Ozua, P,  et al. 2000Human peritoneal adhesions are highly cellular, innervated, and vascularizedJ Pathol1926772PubMedCrossRef
16.
go back to reference diZerega, GS 1997Biochemical events in peritoneal tissue repairEur J Surg Suppl5771016PubMed diZerega, GS 1997Biochemical events in peritoneal tissue repairEur J Surg Suppl5771016PubMed
17.
go back to reference Ferrara, N 2004Vascular endothelial growth factor: basic science and clinical progressEndocr Rev25581611PubMedCrossRef Ferrara, N 2004Vascular endothelial growth factor: basic science and clinical progressEndocr Rev25581611PubMedCrossRef
18.
go back to reference Gille, H, Kowalski, J, Li, B, et al. 2001Analysis of biological effects and signaling properties of Flt-1 (VEGFR-1) and KDR (VEGFR-2). A reassessment using novel receptor-specific vascular endothelial growth factor mutantsJ Biol Chem27632223230PubMedCrossRef Gille, H, Kowalski, J, Li, B,  et al. 2001Analysis of biological effects and signaling properties of Flt-1 (VEGFR-1) and KDR (VEGFR-2). A reassessment using novel receptor-specific vascular endothelial growth factor mutantsJ Biol Chem27632223230PubMedCrossRef
19.
go back to reference Wiczyk, HP, Grow, DR, Adams, LA, O’Shea, DL, Reece, MT 1998Pelvic adhesions contain sex steroid receptors and produce angiogenesis growth factorsFertil Steril69511516PubMedCrossRef Wiczyk, HP, Grow, DR, Adams, LA, O’Shea, DL, Reece, MT 1998Pelvic adhesions contain sex steroid receptors and produce angiogenesis growth factorsFertil Steril69511516PubMedCrossRef
20.
go back to reference Rout, UK, Oommen, K, Diamond, MP 2000Altered expressions of VEGF mRNA splice variants during progression of uterine-peritoneal adhesions in the ratAm J Reprod Immunol43299304PubMedCrossRef Rout, UK, Oommen, K, Diamond, MP 2000Altered expressions of VEGF mRNA splice variants during progression of uterine-peritoneal adhesions in the ratAm J Reprod Immunol43299304PubMedCrossRef
21.
go back to reference Saltzman, AK, Olson, TA, Mohanraj, D, Carson, LF, Ramakrishnan, S 1996Prevention of postoperative adhesions by an antibody to vascular permeability factor/vascular endothelial growth factor in a murine modelAm J Obstet Gynecol17415021506PubMedCrossRef Saltzman, AK, Olson, TA, Mohanraj, D, Carson, LF, Ramakrishnan, S 1996Prevention of postoperative adhesions by an antibody to vascular permeability factor/vascular endothelial growth factor in a murine modelAm J Obstet Gynecol17415021506PubMedCrossRef
22.
go back to reference Molinas, CR, Campo, R, Dewerchin, M, Eriksson, U, Carmeliet, P, Koninckx, PR 2003Role of vascular endothelial growth factor and placental growth factor in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in transgenic miceFertil Steril80803811PubMedCrossRef Molinas, CR, Campo, R, Dewerchin, M, Eriksson, U, Carmeliet, P, Koninckx, PR 2003Role of vascular endothelial growth factor and placental growth factor in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in transgenic miceFertil Steril80803811PubMedCrossRef
23.
go back to reference Molinas, CR, Merces Binda, M, Carmeliet, P, Koninckx, PR 2004Role of vascular endothelial growth factor receptor 1 in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in miceFertil Steril8211491153PubMedCrossRef Molinas, CR, Merces Binda, M, Carmeliet, P, Koninckx, PR 2004Role of vascular endothelial growth factor receptor 1 in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in miceFertil Steril8211491153PubMedCrossRef
24.
go back to reference Ferrara, N, Hillan, KJ, Gerber, HP, Novotny, W 2004Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancerNat Rev Drug Discov3391400PubMedCrossRef Ferrara, N, Hillan, KJ, Gerber, HP, Novotny, W 2004Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancerNat Rev Drug Discov3391400PubMedCrossRef
25.
go back to reference Hasan, J, Byers, R, Jayson, GC 2002Intra-tumoural microvessel density in human solid tumoursBr J Cancer8615661577PubMedCrossRef Hasan, J, Byers, R, Jayson, GC 2002Intra-tumoural microvessel density in human solid tumoursBr J Cancer8615661577PubMedCrossRef
26.
go back to reference Duff, SE, Li, C, Garland, JM, Kumar, S 2003CD105 is important for angiogenesis: evidence and potential applicationsFASEB J17984992PubMedCrossRef Duff, SE, Li, C, Garland, JM, Kumar, S 2003CD105 is important for angiogenesis: evidence and potential applicationsFASEB J17984992PubMedCrossRef
27.
go back to reference Herman, IM, D’Amore, PA 1985Microvascular pericytes contain muscle and nonmuscle actinsJ Cell Biol1014352PubMedCrossRef Herman, IM, D’Amore, PA 1985Microvascular pericytes contain muscle and nonmuscle actinsJ Cell Biol1014352PubMedCrossRef
28.
go back to reference Serri, F, Montagna, W, Huber, WM 1963Studies of skin of fetus and the child. The distribution of alkaline phosphatase in the skin of the fetusArch Dermatol87234245PubMed Serri, F, Montagna, W, Huber, WM 1963Studies of skin of fetus and the child. The distribution of alkaline phosphatase in the skin of the fetusArch Dermatol87234245PubMed
29.
go back to reference Pasyk, KA, Thomas, SV, Hassett, CA, Cherry, GW, Faller, R 1989Regional differences in capillary density of the normal human dermisPlast Reconstr Surg83939945PubMedCrossRef Pasyk, KA, Thomas, SV, Hassett, CA, Cherry, GW, Faller, R 1989Regional differences in capillary density of the normal human dermisPlast Reconstr Surg83939945PubMedCrossRef
30.
go back to reference Roy, S, Clark, CJ, Mohebali, K, et al. 2004Reactive oxygen species and EGR-1 gene expression in surgical postoperative peritoneal adhesionsWorld J Surg28316320PubMedCrossRef Roy, S, Clark, CJ, Mohebali, K,  et al. 2004Reactive oxygen species and EGR-1 gene expression in surgical postoperative peritoneal adhesionsWorld J Surg28316320PubMedCrossRef
31.
go back to reference Dye, JF, Jablenska, R, Donnelly, JL, et al. 2001Phenotype of the endothelium in the human term placentaPlacenta223243PubMedCrossRef Dye, JF, Jablenska, R, Donnelly, JL,  et al. 2001Phenotype of the endothelium in the human term placentaPlacenta223243PubMedCrossRef
32.
go back to reference Fonsatti, E, Maio, M 2004Highlights on endoglin (CD105): from basic findings towards clinical applications in human cancerJ Transl Med218PubMedCrossRef Fonsatti, E, Maio, M 2004Highlights on endoglin (CD105): from basic findings towards clinical applications in human cancerJ Transl Med218PubMedCrossRef
33.
go back to reference Gu, XH, Terenghi, G, Kangesu, T, et al. 1995Regeneration pattern of blood vessels and nerves in cultured keratinocyte grafts assessed by confocal laser scanning microscopyBr J Dermatol132376383PubMedCrossRef Gu, XH, Terenghi, G, Kangesu, T,  et al. 1995Regeneration pattern of blood vessels and nerves in cultured keratinocyte grafts assessed by confocal laser scanning microscopyBr J Dermatol132376383PubMedCrossRef
34.
go back to reference Hansen-Smith, FM 2000Capillary network patterning during angiogenesisClin Exp Pharmacol Physiol278305PubMedCrossRef Hansen-Smith, FM 2000Capillary network patterning during angiogenesisClin Exp Pharmacol Physiol278305PubMedCrossRef
35.
go back to reference Bigatti, G, Boeckx, W, Gruft, L, Segers, N, Brosens, I 1995Experimental model for neoangiogenesis in adhesion formationHum Reprod1022902294PubMed Bigatti, G, Boeckx, W, Gruft, L, Segers, N, Brosens, I 1995Experimental model for neoangiogenesis in adhesion formationHum Reprod1022902294PubMed
36.
go back to reference Costa, AM, Peyrol, S, Porto, LC, Comparin, JP, Foyatier, JL, Desmouliere, A 1999Mechanical forces induce scar remodeling. Study in non-pressure-treated versus pressure-treated hypertrophic scarsAm J Pathol15516711679PubMed Costa, AM, Peyrol, S, Porto, LC, Comparin, JP, Foyatier, JL, Desmouliere, A 1999Mechanical forces induce scar remodeling. Study in non-pressure-treated versus pressure-treated hypertrophic scarsAm J Pathol15516711679PubMed
Metadata
Title
Human Peritoneal Adhesions Show Evidence of Tissue Remodeling and Markers of Angiogenesis
Authors
Jonathan C. Epstein, M.D., M.R.C.S.
Malcolm S. Wilson, M.D., F.R.C.S.
Sylwia Wilkosz, Ph.D.
Grenham Ireland, Ph.D.
Sarah T. O’Dwyer, M.D., F.R.C.S.
Sarah E. Herrick, Ph.D.
Publication date
01-12-2006
Publisher
Springer-Verlag
Published in
Diseases of the Colon & Rectum / Issue 12/2006
Print ISSN: 0012-3706
Electronic ISSN: 1530-0358
DOI
https://doi.org/10.1007/s10350-006-0747-3

Other articles of this Issue 12/2006

Diseases of the Colon & Rectum 12/2006 Go to the issue

Editorial

Signing Off

OriginalPaper

Selected Abstracts