Neoadjuvant antiangiogenic therapy with tamoxifen does not impair gastrointestinal anastomotic repair in the rat

McNamara, Deborah A.; Walsh, T. N.; Kay, Elaine W.; Bouchier‐Hayes, David

doi:10.1046/j.1463-1318.2003.00452.x

Cited by 8 publications

(6 citation statements)

References 37 publications

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“…This hypothesis was supported by the increase in adhesion formation with the duration of the pneumoperitoneum and the insufflation pressure using both CO 2 and helium pneumoperitoneum and by the decrease in adhesion formation observed after adding 2-4% of oxygen to any of the two insufflation gases [27,28]. It was also confirmed by the absence of pneumoperitoneum-enhanced adhesions in mice deficient for the genes encoding for factors regulated by hypoxia such as HIFs [54], VEGF [30] and PAI-1 [29]. The important role of hypoxia in adhesion formation was further supported by a series of in vitro studies demonstrating increased expression of many adhesiogenic factors produced by fibroblasts cultured under hypoxic conditions [62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79].…”

Section: Discussionmentioning

confidence: 87%

“…Although it was withdrawn from the market for the teratogenic side effects, the antiangiogenesis inhibitor thalidomide was shown to reduce adhesions formation after colonic anastomosis in rabbits [53]. The antiangiogenenic agent tamoxifen, however, did not show any beneficial effect for reducing adhesion formation in an ileoileal anastomosis rat model, although no adverse effects on wound or anastomotic healing were reported [54]. As mentioned before, mice data clearly demonstrate a reduction in adhesion formation after treatment with antibodies again VEGF [55], PlGF [30] or VEGFR-1 [31] opening new alternatives for adhesion prevention in humans.…”

Section: Antiangiogenic Therapy For Peritoneal Adhesion Preventionmentioning

confidence: 99%

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Angiogenic factors in peritoneal adhesion formation

Molinas¹,

Binda

Koninckx

2006

Gynecol Surg

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Abdominal surgery is considered as the leading cause of peritoneal adhesions and almost universally as adhesiogenic. Peritoneal injury at the time of surgery initiates an inflammatory reaction determining fibrin deposition on the wound surface. Depending on the balance between the different components of the plasminogen system, this fibrin can be either lysed, leading to normal peritoneal healing, or organised, serving as a scaffold for fibroblast ingrowth, extracellular matrix deposition and angiogenesis, leading to adhesion formation. The mechanism underlying the predisposition to form adhesions in some patients and in some specific anatomic sites and not in others after similar surgical procedures remains unknown. In spite of the many attempts proposed over the years for reducing the incidence of adhesion formation, peritoneal adhesions remain a major clinical problem, inducing intestinal obstruction, pelvic pain, female infertility and difficulties at the time of re-operation. The available evidence indicates that understanding the adhesion formation process at the molecular level is essential for developing successful strategies for preventing adhesions. Fortunately, the advancement in molecular biology during the last years has led to the identification of many molecules with the potential of regulating inflammatory and immune responses, tissue remodelling and angiogenesis, key events in peritoneal healing and adhesion formation. This review focuses on the role of angiogenesis and angiogenic factors in peritoneal adhesion formation.

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Section: Discussionmentioning

confidence: 87%

Section: Antiangiogenic Therapy For Peritoneal Adhesion Preventionmentioning

confidence: 99%

Angiogenic factors in peritoneal adhesion formation

Molinas¹,

Binda

Koninckx

2006

Gynecol Surg

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“…They recorded wound healing scores according to a previously reported scale from 0 to 5 as follows: 0 = complete wound dehiscence; 1 = 50–75% ulceration; 2 = 25–50% ulceration; 3 = <25% ulceration; 4 = raised skin but normal healing, and 5 = wound almost invisible [22]. A spindle-shaped incision of the abdominal wound was performed by scalpel, followed by careful inspection of the peritoneal cavity for adhesion or accumulation, and an amount of blood was withdrawn from the inferior vena cava for biochemical analyses before animal sacrifice.…”

Section: Methodsmentioning

confidence: 99%

Intraperitoneal Administration of Bevacizumab Intraoperatively Does Not Affect Abdominal Wound Healing in Rats

Pavlidis

Ballas²,

Psarras³

et al. 2011

Eur Surg Res

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Background: Bevacizumab is a monoclonal antibody targeted at vascular endothelial growth factor (VEGF) to treat advanced colorectal cancer as well as other malignancies, but the ideal time point for its administration in patients scheduled for surgery is not well defined due to serious concerns regarding possible side effects on wound healing. Therefore, we conducted an experimental study in rats to clarify this issue. Methods: Four groups of 10 Wistar rats each underwent a 4-cm midline laparotomy and closure of the wound in 2 layers. In the treatment groups (A and B), bevacizumab (Avastin®) received a single dose of 5 mg/kg i.p., and an equal amount of saline was given to the control groups (C and D). Groups A and C were sacrificed on the 7th postoperative day, and groups B and D on the 14th postoperative day. Wounds were inspected by two independent observers upon sacrifice and results were recorded; wound tissues were sent for histology to assess the degree of fibrosis and measurement of tissue hydroxyproline levels. Serum levels of endothelin-1, C-reactive protein, pro-oxidant/antioxidant balance and carbonylated proteins were also determined. For statistical analysis, the Mann-Whitney U test was used. Results: Wound healing did not differ among groups both on the 7th and the 14th postoperative days, and there was also no significant difference regarding the degree of inflammation, fibroblast proliferation and collagen synthesis, as well as hydroxyproline and biochemical marker levels among the groups. Conclusions: Intraperitoneal bevacizumab administered intraoperatively does not significantly affect abdominal wound healing in rats.

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“…Studies on animal models of wound healing concurrent with antiangiogenic therapy have been inconclusive. Results seem to be dependent on the agents used 126,127 .…”

Section: Surgery and Antiangiogenic Therapymentioning

confidence: 98%