Colonic Anastomotic Healing Research Articles

MK2 inhibitor peptide reduces adhesion formation without affecting colonic anastomotic healing

MK2 inhibitor peptide reduces adhesion formation without affecting colonic anastomotic healing

Intraperitoneally applied gentamicin increases collagen content and mechanical stability of colon anastomosis in rats

Anastomotic leakage remains a serious complication in colorectal surgery, and is being caused by a multitude of factors. Recent reports reveal changes of the extracellular matrix as risk factors as well as gentamicin as a potential agent to influence wound healing. This experimental study was initiated to investigate the influence of intraperitoneally applied gentamicin on colonic anastomotic wound healing and in particular on mechanical stability, overall collagen content and collagen type I/III ratio. Sixty Sprague Dawley rats were randomized to one of two groups. In each animal, a standard transverse colonic end-to-end anastomosis was performed. Immediately postoperative, either 5 ml gentamicin (1 ml/kg bodyweight) or NaCl 0.9% was applied intraperitoneally. On postoperative days 3, 5, and 14, ten of the animals in each group were sacrificed. Measurements of the anastomosis bursting pressure were performed on postoperative days 3 and 5. At each explantation time, the collagen per protein ratio, the collagen types I/III ratio, and both the expression of MMP-2, -9, and Ki67 were analyzed. None of the animals died. None of the rats exhibited clinical evidence of anastomotic leakage. The bursting strength in the gentamicin group was significantly elevated on postoperative day 5. Both the overall collagen content and the collagen type I/III ratio in the gentamicin group were significantly increased 3, 5, and 14 days postoperatively compared to the control group. The expression of MMP-9 was significantly elevated in the gentamicin group both 3 and 5 days postoperatively. In contrast, there were no significant differences in the expression of MMP-9 14 days postoperatively. All investigated samples demonstrated positive staining for MMP-2 and Ki67 without statistically significant differences at any term, respectively. The present data confirm that intraperitoneally applied gentamicin is able to enhance healing and stability of colonic anastomosis due to an increase of both the overall collagen content and collagen type I/III ratio.

Effects of Sildenafil Citrate on Ischemic Colonic Anastomotic Healing in Rats: Its Relationship Between Nitric Oxide and Oxidative Stress

To the Editor, We read with great interest the article by Uzun et al. [1], whose work shows that sildenafil citrate therapy might improve anastomotic healing by its effect on nitric oxide (NO) and oxidative stress metabolism. We would like to expand on this concept by introducing a major route by which sildenafil citrate could potantiate platelet inhibition and improve microcirculation. Phosphodiesterase-5 (PDE-5) inhibitors prevent the breakdown of nitric oxide–derived cGMP, primarily in vascular smooth muscle cells, and they thus cause vasodilation. Several investigators have shown that mucosal injury to the gastrointestinal system may be caused by platelet activating factor (PAF), which is known for its vasoactive properties; in the mesenteric region, PAF causes vasoconstriction and tissue hypoperfusion, which may lead to gastrointestinal mucosal ulceration [2, 3]. Platelets have also been well studied with respect to PDEs, and cGMPdependet protein kinase has been shown to play an important role in platelet inhibition by NO. Hart et al. [4] have reported that sildenafil therapy significantly improved postoperative skin flap viability by improving microcirculation and platelet inhibition. In a recent study we found that sildenafil reduced the degree of ischemic intestinal mucosal damage by its effects on the vascular smooth muscle and the microcirculatory hemodynamics related to platelet function [5]. This important mechanism should be borne in mind, as it may be of interest in examining the potential benefical effects of this drug in a model of acute mesenteric ischemia with nonocclusive vasospastic diseases.

Role of Activated Protein C on Wound Healing Process in Left Colonic Anastomoses in the Presence of Intra‐abdominal Sepsis Induced by Cecal Ligation and Puncture: An Experimental Study in the Rat

Activated protein C (APC) is a serine protease with anticoagulant and anti-inflammatory activities. The delaying effects of intra-abdominal sepsis on wound healing process in colonic anastomoses have been previously demonstrated. This study was designed to investigate the role of APC on wound healing process in left colonic anastomoses in the presence of intra-abdominal sepsis. The left colonic anastomosis was performed in 48 rats that were divided into four groups: (1) sham-operated group, laparatomy plus cecal mobilization (n = 12); (2) sham + APC group, identical to group I except for APC treatment (n = 12); (3) CLP group, cecal ligation and puncture (n = 12); 4) CLP + APC-treated group, 100 microg/kg, 15 min before the construction of colonic anastomosis (n = 12). Anastomotic bursting pressures were measured in vivo on day 7. Tissue samples were obtained for analyses of hydroxyproline (HP) contents, myeloperoxidase (MPO) acivity, malondialdehyde (MDA), and nitrate/nitrite (NO3(-) /NO2(-)) levels. The plasma levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, and D-dimer also were measured. Intra-abdominal sepsis led to significant decreases in colonic anastomotic bursting pressures and tissue HP contents, along with increases in MPO activity, MDA and NO3(-) /NO2(-) levels, and also plasma levels of TNF-alpha, IL-6, and D-dimer (P < 0.05). However, APC treatment led to significant increases in anastomotic bursting pressures and tissue HP ontents, along with decreases in MPO activity, MDA and NO3(-) /NO2(-) levels, and also plasma levels of TNF-alpha, IL-6, and D-dimer (P < 0.05). This study clearly showed that APC treatment prevented the delaying effects of intra-abdominal sepsis on colonic anastomotic wound healing process. Further clinical studies are required to determine whether APC has a useful role in the enhancement of anastomotic healing during particular surgeries in which sepsis-induced injury occurs.

The Effects of Sildenafil Citrate on Ischemic Colonic Anastomotic Healing in Rats: Its Relationship Between Nitric Oxide and Oxidative Stress

The purpose of this study was to examine the effects of sildenafil citrate on normal and ischemic colon anastomosis in the rat model by measuring the levels of blood and colonic tissues nitric oxide, thiobarbituric acid reactive substrates (as a marker of lipid peroxidation), and glutathione (as an antioxidant). Normal (group 1 and 3) and ischemic anastomosis (group 2 and 4) were performed in four equal rat groups (n = 14). Orally 10 mg/kg per day of sildenafil citrate therapy were applied in group 3 and group 4 after operation. Seven rats of the each group were killed on postoperative days 3 and 7. Sildenafil citrate therapy was resulted in elevated nitric oxide levels in both normal and ischemic anastomotic tissues (p < 0.0001 and p < 0.03) at postoperative day 3. Tissue thiobarbituric acid reactive substrate levels were elevated in rats with normal anastomosis by sildenafil therapy (p < 0.001) at postoperative days 3 and 7 (p < 0.05). Sildenafil therapy given to the normal anastomosis group has significantly higher tissue nitric oxide levels than the normal anastomosis group without therapy at postoperative day 7 (p < 0.001). On postoperative day 7, plasma nitric oxide levels were decreased by sildenafil citrate in rats with normal (p < 0.01) and ischemic anastomosis (p < 0.05). The beneficial effect of sildenafil citrate also was seen for erythrocyte glutathione levels in rats with normal anastomosis at postoperative day 7 and in rats with ischemic anastomosis at postoperative day 3. Our results suggest that sildenafil citrate may affect ischemic anastomotic healing due to its possible effects on nitric oxide metabolism and lipid peroxidation. However, functional implication of this agent further needs to be elucidated.

Activated protein C prevents deleterious effects of remote reperfusion injury caused by intestinal ischemia on wound healing in the left colonic anastomoses: an experimental study in the murine model

Background Activated protein C (APC) is a serine protease with anticoagulant and antiinflammatory activities. The delaying effects of remote reperfusion injury on the wound-healing process in colonic anastomoses have been previously shown. In this study, we aimed to investigate whether APC protects against deleterious systemic effects of intestinal ischemia/reperfusion (I/R) injury on colonic anastomotic wound healing process. Methods Male Wistar-albino rats were randomly allocated into 4 groups, and a left colonic anastomosis was performed in all animals: (1) sham-operated group, simultaneously with left colonic anastomosis, the superior mesenteric artery and collateral branches were divided from the celiac axis, and the inferior mesenteric artery were isolated but not occluded (group 1, n = 12), (2) sham + APC group, identical to group 1 except for APC treatment (100 μg/kg, intravenously, 15 minutes before construction of the colonic anastomosis), (group 2, n = 12), (3) intestinal I/R group, 60 minutes of superior mesenteric ischemia followed by reperfusion (group 3, n = 12), and (4) APC-treated group, (100 μg/kg, intravenously, 15 minutes before reperfusion) (group 4, n = 12). All animals were sacrificed, and colonic anastomotic bursting pressures were measured in vivo on day 7. Tissue samples were obtained for analysis of hydroxyproline contents, nitrate/nitrite levels, and activities of oxidative and antioxidative enzymes. The plasma levels of proinflammatory cytokines and D-dimer were also measured. Results Intestinal I/R led to significant decreases in colonic anastomotic bursting pressures, tissue hydroxyproline contents, and activities of antioxidative enzymes, along with increases in tissue nitrate/nitrite levels, activities of oxidative enzymes, and plasma levels of proinflammatory cytokines and D-dimer ( P < .05). However, APC treatment led to significant increases in colonic anastomotic bursting pressures, tissue hydroxyproline contents, and activities of antioxidative enzymes, along with decreases in tissue nitrate/nitrite levels, activities of oxidative enzymes, and plasma levels of proinflammatory cytokines and D-dimer ( P < .05). Conclusion This study clearly showed that APC treatment prevented the delaying effects of remote I/R injury on colonic anastomotic wound healing process. Further clinical studies are required to determine whether APC has a useful role in the enhancement of colonic anastomotic wound healing after particular operations in which I/R injury occurs.

The Effects of Hyperbaric Oxygen Therapy on Colonic Anastomosis in Rats With Peritonitis

The aim of this study is to investigate the healing effect of hyperbaric oxygen (HBO) on colonic anastomoses in the presence of experimentally induced peritonitis. Thirty-two rats were allocated randomly into short-term anastomosis (STA), short-term anastomosis + HBO treatment (STA+HBO), long-term anastomosis (LTA), and long-term anastomosis + HBO (LTA+HBO) treatment groups. The STA and LTA groups were administered fluid resuscitation and antibiotics for 3 and 7 days, respectively, whereas the HBO treatment groups received additional HBO therapy for 3 and 7 days, respectively. The rats were reoperated on the third and the seventh days of anostomoses for evaluation. The bursting pressures in STA+HBO and LTA+HBO therapy groups were significantly higher than those in groups with anastomoses alone (p <. 001 and p <. 01). HBO therapy did not affect the fibrotic index neither in STA nor in LTA groups (p >. 05 for both); however, it was significantly higher in LTA+HBO group than that in STA+HBO group (p <. 05). The hydroxyproline level was significantly higher in LTA group than in STA group (p <. 05), yet HBO therapy did not affect the hydroxyproline levels in STA or LTA groups (p >. 05 for both). It is concluded that hyperbaric oxygen treatment has positive effects on colonic anastomotic healing in case of peritonitis.

Colonic healing after portal ischemia and reperfusion: an experimental study with oxidative stress biomarkers

This experimental study aimed to evaluate colon healing after portal ischemia followed by reperfusion. Seventy male Wistar rats randomly distributed in four groups were used: Group 1, colonic anastomosis (n = 20); Group 2, portal ischemia-reperfusion (n = 20); Group 3, colonic anastomosis and portal ischemia-reperfusion (n = 20); and Group 4, control (n = 10). In the postoperative period, these rats were re-allocated into subgroups and lipid peroxidation and protein oxidation plasma levels were evaluated on days 1 and 5 by thiobarbituric acid reactive substances (TBARS) and slot-blotting assays, respectively. A segment of the right colon was also removed for collagen analysis. Both malondialdehyde (MDA) and protein carbonyl levels (oxidative markers of lipids and proteins) presented a significant increase after reperfusion in Group 3 on days 1 (P < 0.002) and 5 (P < 0.0001). In this same group, an extensive inflammatory process showing decreased fibroplasia was observed, with deficiency in collagen deposition on both sides of the anastomosis edges. Taken together, these results indicate that portal congestion followed by reperfusion induces an oxidative stress, which impaired the mechanism of colon anastomotic healing.

Histological evaluation of colonic anastomotic healing, during perioperative Capecitabine administration. Experimental study in rats.

Neoadjuvant chemotherapy is a highly promising treatment modality for colorectal cancer. One of the basic side effects of this method is the possible impact on anastomotic healing. Capecitabine is a tumor selective pro-drug of 5-fluorouracil, indicated for the therapy of colorectal cancer. The aim of this study is to estimate the effect of perioperative Capecitabine administration on the colonic anastomotic healing process, by evaluating histopathological findings. We studied the effect of Capecitabine on hand sutured colonic anastomosis in rats. Sixty Wistar rats were randomized in two groups. In the study group (n=30) Capecitabine was given p.o. in therapeutic dose of 359 mg/kg, (2/3 of the mean toxic dose), 1 week prior the anastomosis and throughout the study. In the control group (n=30) placebo medication was administrated. Both groups were further subdivided into 3 groups, each consisting of 10 animals. Rats of each group were sacrificed on the 3rd, 7th and 14th postoperative day, in both study and control groups. No negative impact on the healing process of colonic anastomosis was found. Histological findings indicated a more effective healing during the early postoperative days, with lesser necrosis effects on the anastomotic line for the study group, in comparison with the control group. The median bursting pressure was found to be significantly higher in the subdivision of the study group sacrificed on the 3rd day, in comparison to respective control subdivision. Perioperative administration of Capecitabine, as neoadjuvant chemotherapy, does not impair the healing of colonic anastomosis in rats.

The Effect of Remote Ischemic Preconditioning on Healing of Colonic Anastomoses

We aimed to investigate the potential protective effect of remote ischemic preconditioning (IPC) on delayed colonic anastomotic healing induced by remote ischemia and reperfusion (I/R) injury. Forty male Wistar rats were randomly assigned into four groups, each consisting of 10 rats: the control group (C), the remote I/R group [I/R, 40 min of superior mesenteric artery (SMA) occlusion], the preconditioned I/R group (IPC, two cycles of 5 min temporary occlusion of SMA before an ischemic insult of 40 min), and the preconditioned group (PC, two cycles of 5 min temporary occlusion of SMA). Colonic anastomosis was performed immediately after the ischemic insult. Anastomotic healing was assessed on postoperative day 7 by determining anastomotic bursting pressure (ABP), tissue hydroxyproline content, histopathological examination, malondialdehyde (MDA), and nitric oxide levels. Remote I/R injury resulted with significant impairment in anastomotic healing in terms of mean ABP (P = 0.004), hydroxyproline content (P = 0.002), histopathological healing score (P = 0.001), nitric oxide level (P = 0.010), and MDA levels (P = 0.0001) when compared with the control group, but remote IPC did not improve all above mentioned parameters (P = NS for all), except MDA level (P = 0.011) when compared with I/R group. PC alone impaired the ABP (P = 0.0001), but it did not significantly change the other parameters measured (P = NS). The results of this study showed that remote IPC did not prevent I/R-induced delaying in colonic anastomotic healing.

Estudo comparativo entre as técnicas de sutura total e serosubmucosa em anastomoses colônicas na presença de um protetor intraluminar em cães

OBJETIVO: Avaliar a cicatrização comparando as técnicas de sutura total e parcial em anastomoses colônicas término-terminais na presença de um protetor intraluminar confeccionado a partir de um dreno de Penrose. MÉTODOS: Foram realizadas anastomoses colônicas em 10 cães nos quais foi suturado a mucosa / submucosa um protetor intraluminar por meio da eversão do segmento intestinal proximal em 10 cm. Os animais foram distribuidos em dois grupos experimentais: Grupo 1 - sutura total e Grupo 2 - sutura serosubmucosa. Os animais foram reoperados com sete dias de pós-operatório para coleta de material e subseqüente análise histopatológica. RESULTADOS: Observamos no exame histopatológico das anastomoses realizadas com sutura serosubmucosa (Grupo 2) uma melhor cicatrização caracterizada por um menor infiltrado inflamatório e por uma maior integridade das camadas intestinais quando comparadas com o Grupo 1. CONCLUSÃO: O uso da técnica de sutura parcial mostrou-se superior a de sutura total nas anastomoses colônicas na presença de protetor intraluminar.

Effects of Aloe vera on colonic anastomoses of rats

Background: Aloe vera is a cactus‐like plant that grows in hot, dry regions. Aloe vera has been known and used in traditional medicine and also in the modern world. Aloe vera has some pharmacological actions including wound healing, anti‐inflammatory and immunostimulatory effects. We have studied the possible effects of Aloe vera gel on the healing of colonic anastomoses of rats.Material and Methods: In this study, Sprague–Dawley rats were used. Aloe vera group received 2 mL/kg per day Aloe vera, and the control group received the same amount of water. Animals underwent resection and anastomosis of the distal colon. Bursting pressures of anastomoses and hydroxyproline contents of perianastomotic region were determined on the third and seventh days. Mann–Whitney U‐test was used to compare bursting pressures and hydroxyproline levels between groups.Results: There was no difference between groups in mortality. Mean bursting pressures and mean hydroxyproline levels were lower in the control group than in the Aloe vera group both on the third and seventh days.Conclusion: Aloe vera has multiple pharmacologically active compounds. It stimulates phagocyte formation and its activity induces nitric oxide production, it has angiogenic activity, increases synthesis, maturation and cross‐linking of collagen, stimulates cell proliferation, stimulates fibroblast functions and proliferation, inhibits arachidonic acid oxidation, has anti‐inflammatory effects, reduces tumour necrosis factor‐α levels, and has antioxidant activity. Thus, according to our findings, Aloe vera has positive effects on the colonic anastomotic healing of rats.

Effects of Two Conventional Preoperative Radiation Schedules on Anastomotic Healing in the Rat Colon

Background: Preoperative radiotherapy (RT) is an increasingly popular form of adjunct therapy for rectal cancer; however, little is known about its effects on matrix metalloproteinase (MMP) expression in colonic anastomotic healing. Methods: Wistar rats were irradiated to a total dose of 25 or 40 Gy. Four days after the end of RT, an end-to-end colorectal anastomosis was performed. Animals were sacrificed at 1, 3, and 7 days after the anastomosis. A control group was studied similarly, but was not irradiated. Results: No significant differences were found in peritonitis rate and anastomotic complications. The average bursting pressure and breaking strength were only reduced significantly in the rats irradiated with 40 Gy. However, the concentration and the content of hydroxyproline in anastomotic tissues were unchanged. In irradiated rats, MMP-2 and MMP-9 were significantly increased at 40 Gy, but not at 25 Gy. On the other hand, 25-Gy irradiation induced a smaller increase in the levels of the tissue inhibitors of metalloproteinase-1 compared with the controls. Conclusion: Anastomotic strength is adversely affected by high-dose fractionated preoperative RT. In contrast, preoperative RT at 25 Gy in five fractions over 5 days is safe with regard to the maintenance of wound strength in colorectal anastomosis.

The effectiveness of a single intraperitoneal infusion of a neurokinin-1 receptor antagonist in reducing postoperative adhesion formation is time dependent

Current methods to prevent intraabdominal adhesions are not uniformly effective. We recently showed in rats that a neurokinin-1 receptor (NK-1R) antagonist is capable of reducing adhesion formation. To determine the clinical feasibility of using an NK-1R antagonist to reduce adhesions, this study examined the time dependence for the effectiveness of NK-1R antagonist administration and its effects on wound healing. Adhesions were surgically induced in rats receiving a single intraperitoneal infusion of the NK-1R antagonist, CJ-12,255, during or 1, 5, 12, or 24 hours after surgery. Adhesion formation was assessed 7 days later. In a subset of animals, tissue plasminogen activator (tPA) activity, which is a measure of peritoneal fibrinolytic activity, was determined in peritoneal fluid 24 hours after surgery (48 hours for animals infused at 24 hours). The tPA activity was also determined in nonoperated animals 24 hours after peritoneal injection of the NK-1R antagonist. Colonic burst pressures were measured 7 days after creation of anastomoses in rats that were administered the antagonist at surgery. The NK-1R antagonist significantly reduced (P=.003) intraabdominal adhesions when administered during or 1 hour after surgery, only moderately reduced (P=.08) adhesions when administered at 5 hours, and had no effect at 12 or 24 hours. Peritoneal tPA activity was significantly increased (P<.05) in peritoneal fluid 24 hours after administration of the NK-1R antagonist regardless of the surgical procedure. The NK-1R antagonist did not alter colonic anastomotic healing. These data show that some of the events critical to adhesion formation occur within the first 5 hours following an abdominal operation in this model. The fact that the NK-1R antagonist does not impair colonic anastomotic healing enhances its usefulness as a therapeutic agent to inhibit adhesion formation.

The Use of Statins in Postoperative Adhesion Prevention

The Use of Statins in Postoperative Adhesion Prevention

Does a fibrin-collagen patch support early anastomotic healing in the colon? An experimental study

The aim of this study was to evaluate the effect of absorbable fibrin-collagen patch (FCP) during early colonic anastomotic healing in rats. Prepubertal Wistar albino rats were randomly divided into 6 groups of 6 rats each. Colon was transected and then anastomosed with sutures (Group A), sutures+FCP (TachoComb; Nycomed, Austria) (Group AT) or only FCP (Group T). Rats were sacrificed either 3 or 7 days after the anastomosis. Anastomoses were evaluated for perianastomotic adhesion formation, bursting pressures and histological features. Perianastomotic adhesion formation was significant in Groups AT and T. Bursting pressures were in higher group AT than in Group A on postoperative day 3 and lower on day 7 (p < 0.05). Histological examinations revealed an increase in inflammatory cells in Group T on day 3 and decreased wound healing in Group AT when compared to Group A on day 7 (p < 0.05). In the early period of anastomotic healing, FCP supports anastomotic integrity. However, it also causes an inflammatory reaction which may increase the time necessary for healing process. Thus, the use of this biomaterial should be preferred in only selective clinical cases with a careful follow-up.

Authors' reply: selective cyclo-oxygenase 2 inhibition affects ileal but not colonic anastomotic healing in the early postoperative period (Br J Surg 2006; 93: 489–497)

Authors' reply: selective cyclo-oxygenase 2 inhibition affects ileal but not colonic anastomotic healing in the early postoperative period (<i>Br J Surg</i> 2006; 93: 489–497)

Selective cyclo-oxygenase 2 inhibition affects ileal but not colonic anastomotic healing in the early postoperative period (Br J Surg2006; 93: 489–497)

Selective cyclo-oxygenase 2 inhibition affects ileal but not colonic anastomotic healing in the early postoperative period (<i>Br J Surg</i>2006; 93: 489–497)

Selective cyclo-oxygenase 2 inhibition affects ileal but not colonic anastomotic healing in the early postoperative period

Selective cyclo-oxygenase 2 (COX-2) inhibitors are increasingly prescribed in the perioperative period. Recent recognition of a possible role for COX-2 in wound healing has raised concerns about the safety of their use in surgical practice. Therefore, the influence of celecoxib, a selective COX-2 inhibitor, on early anastomotic healing was investigated. Celecoxib, in doses of 15, 50 or 200 mg per kg per day, was given daily from the day before operation onwards to male Wistar rats that received both ileal and colonic anastomoses. Anastomotic strength was assessed by measuring the breaking strength and bursting pressure on the third day after operation. A second group received a dose of 50 mg per kg per day and a colonic anastomosis only, and healing was assessed on the third and fifth day after surgery. Expression of COX-2 protein was upregulated in the anastomotic area. Administration of celecoxib, at all doses tested, resulted in a significantly higher ileal dehiscence rate than in control rats (P = 0.002). In contrast, colonic anastomoses healed normally within the same animals. The latter was confirmed in rats with colonic anastomoses only. In this model, administration of the COX-2 inhibitor celecoxib affected ileal but not colonic anastomotic healing in the early postoperative period.

Effect of hypercholesterolemia on experimental colonic anastomotic wound healing in rats

To evaluate the mechanical and biochemical parameters of colonic anastomotic healing in hypercholesterolemic rats. Sixty rats were divided into two groups of 30 each according to their dietary regimens. The test group was fed with a high cholesterol-containing diet for two months while the control group had standard diet. These two groups were further divided into three subgroups consisting of ten rats each. After hypercholesterolemia was established, left colon resection and anastomosis were performed in both groups and samples from liver and abdominal aorta were taken to evaluate the systemic effects of hypercholesterolemia. Anastomotic wound healing, blow-out pressures and tissue hydroxyproline levels were evaluated. The test group had a significant weight gain in two months. Microscopic examination of the abdominal aorta revealed no atherosclerotic change in none of the groups, but liver tissue specimens showed significant steatosis in the test group. Tissue hydroxyproline levels and anastomotic blow-out pressures were significantly lower in the test group than in the controls. Hypercholesterolemia not only increases hydroxyproline levels and blow-out pressures but also worsens anastomotic wound healing.