Shenhuang plaster enhances intestinal anastomotic healing in rabbits through activation of the TGF-ß and Hippo/YAP signaling pathways.

Although many efforts have been made to improve management strategies and diagnostic methods in the past several decades, the prevention of anastomotic complications, such as anastomotic leaks and strictures, remain a major clinical challenge. Therefore, new molecular pathways need to be identified that regulate anastomotic healing, and to design new treatments for patients after anastomosis to reduce the occurrence of complications. Rabbits were treated with a MST1/2 inhibitor XMU-XP-1, a Chinese medicine formula Shenhuang plaster (SHP) or a control vehicle immediately after surgery. The anastomotic burst pressure, collagen deposition, and hydroxyproline concentration were evaluated at 3 and 7 days after the surgery, and qRT-PCR and western-blot analyses were used to characterize mRNA and protein expression levels. Both XMU-XP-1 and SHP significantly increased anastomotic burst pressure, collagen deposition, and the concentration of hydroxyproline in intestinal anastomotic tissue at postoperative day 7 (POD 7). Importantly, SHP could induce TGF-ß1 expression, which activated its downstream target Smad-2 to activate the TGF-ß1 signaling pathway. Moreover, SHP reduced the phosphorylation level of YAP and increased its active form, and treatment with verteporfin, a YAP-TEAD complex inhibitor, significantly suppressed the effects induced by SHP during anastomotic tissue healing. This study demonstrated that activation of the Hippo-YAP pathway enhances anastomotic healing, and that SHP enhances both the TGF-ß1/Smad and YAP signaling pathways to promote rabbit anastomotic healing after surgery. These results suggest that SHP could be used to treat patients who underwent anastomosis to prevent the occurrence of anastomotic complications.

Mesenchymal stem cell secretome-loaded fibrin glue improves the healing of intestinal anastomosis.

Anastomotic leakage is a serious complication following gastrointestinal surgery and one of the leading causes of patient mortality. Despite the significant clinical and economic burden, there are currently no reliable treatment options to improve the healing of intestinal anastomosis and subsequently prevent anastomotic leakage. Recently, the development of regenerative medicine has shown promise for improving anastomotic healing. Recent studies have illustrated that stem cell-derived secretome can enhance tissue regeneration without the safety and ethical limitations of stem cell transplantation. Herein, we developed a fibrin glue topical delivery system loaded with mesenchymal stem cells (MSCs)-derived secretome for controlled delivery of bioactive factors, and evaluated its application potential in improving the healing of intestinal anastomosis. Under in vitro conditions, the MSCs secretome significantly promoted cell proliferation viability in a dose-dependent manner and resulted in the controlled release of growth factors via fibrin glue delivery. We established a rat surgical anastomotic model and experimentally found that MSCs secretome-loaded fibrin glue enhanced anastomotic bursting pressure, increased granulation tissue formation and collagen deposition, and significantly promoted anastomotic healing. Mechanistically, fibrin glue accelerated cell proliferation, angiogenesis, and macrophage M2 polarization at the surgical anastomotic site by releasing bioactive factors in the secretome, and it also alleviated the inflammatory response and cell apoptosis at the anastomotic site. Our results demonstrated for the first time that MSCs-derived secretome could promote the healing of intestinal anastomosis. Considering the accessibility and safety of the cell-free secretome, we believed that secretome-loaded fibrin glue would be a cell-free therapy to accelerate the healing of intestinal anastomosis with great potential for clinical translation.

Crohn's Disease as a Possible Risk Factor for Failed Healing in Ileocolic Anastomoses.

Anastomotic leakage (AL) after colorectal resections is a serious complication in abdominal surgery. Especially in patients with Crohn's disease (CD), devastating courses are observed. Various risk factors for the failure of anastomotic healing have been identified; however, whether CD itself is independently associated with anastomotic complications still remains to be validated. A retrospective analysis of a single-institution inflammatory bowel disease (IBD) database was conducted. Only patients with elective surgery and ileocolic anastomoses were included. Patients with emergency surgery, more than one anastomosis, or protective ileostomies were excluded. For the investigation of the effect of CD on AL 141, patients with CD-type L1, B1-3 were compared to 141 patients with ileocolic anastomoses for other indications. Univariate statistics and multivariate analysis with logistic regression and backward stepwise elimination were performed. CD patients had a non-significant higher percentage of AL compared to non-IBD patients (12% vs. 5%, p = 0.053); although, the two samples differed in terms of age, body mass index (BMI), Charlson comorbidity index (CCI), and other clinical variables. However, Akaike information criterion (AIC)-based stepwise logistic regression identified CD as a factor for impaired anastomotic healing (final model: p = 0.027, OR: 17.043, CI: 1.703-257.992). Additionally, a CCI ≥ 2 (p = 0.010) and abscesses (p = 0.038) increased the disease risk. The alternative point estimate for CD as a risk factor for AL based on propensity score weighting also resulted in an increased risk, albeit lower (p = 0.005, OR 7.36, CI 1.82-29.71). CD might bear a disease-specific risk for the impaired healing of ileocolic anastomoses. CD patients are prone to postoperative complications, even in absence of other risk factors, and might benefit from treatment in dedicated centers.

The Impact of Phase-Specific Macrophage Depletion on Intestinal Anastomotic Healing.

Intestinal anastomotic healing (AH) is critical in colorectal surgery, since disruptive AH leads to anastomotic leakage, a feared postoperative complication. Macrophages are innate immune cells and are instrumental in orchestrating intestinal wound healing, displaying a functional dichotomy as effectors of both tissue injury and repair. The aim of this study was to investigate the phase-specific function and plasticity of macrophages during intestinal AH. Transgenic CD11b diphtheria toxin receptor (CD11b-DTR) mice were used to deplete intestinal macrophages in a temporally controlled manner. Distal colonic end-to-end anastomoses were created in CD11b-DTR, and wild-type mice and macrophages were selectively depleted during either the inflammatory (day 0-3), proliferative (day 4-10), or reparative (day 11-20) phase of intestinal AH, respectively. For each time point, histological and functional analysis as well as gene set enrichment analysis (GSEA) of RNA-sequencing data were performed. Macrophage depletion during the inflammatory phase significantly reduced the associated inflammatory state without compromising microscopic AH. When intestinal macrophages were depleted during the proliferative phase, AH was improved, despite significantly reduced perianastomotic neoangiogenesis. Lastly, macrophages were depleted during the reparative phase and GSEA revealed macrophage-dependent pathways involved in collagen remodeling, cell proliferation, and extracellular matrix composition. However, AH remained comparable at this late timepoint. These results demonstrate that during intestinal AH, macrophages elicit phase-specific effects, and that therapeutic interventions must critically balance their dual and timely defined role.

Perioperative Low-Dose Prednisolone Treatment Has Beneficial Effects on Postoperative Recovery and Anastomotic Healing in a Murine Colitis Model.

BACKGROUND AND AIMS: High-dose glucocorticoid treatment has been identified as a risk factor for anastomotic leakage in patients with inflammatory bowel disease [IBD] undergoing bowel resection surgery. By contrast, active disease during surgery is also associated with elevated morbidity. Perioperative low-dose treatment might be beneficial regarding postoperative outcomes by controlling disease activity. The present study is the first to investigate the dose-dependent effect of perioperative prednisolone therapy in a murine IBD model combining dextran sodium sulphate [DSS] colitis with intestinal anastomosis surgery. METHODS: In 84 10-week-old wild-type mice, a colorectal anastomosis was performed using a microsurgical technique. Half the animals received induction of chemical colitis with 2% DSS via drinking water prior to surgery. In both groups, one-third of the animals received daily oral administration of high-dose [0.533 mg/kg] and one-third low-dose [0.133 mg/kg] prednisolone. Evaluation was performed on postoperative days 3 and 7. RESULTS: While high-dose prednisolone treatment led to an increased anastomotic leakage rate in mice under colitis, low-dose prednisolone treatment limited preoperative disease activity and did not influence the leakage rate. Histological examination showed a beneficial effect of low-dose prednisolone treatment on microscopic abscess formation at the anastomotic site in DSS mice as well as an increased anastomotic healing score. CONCLUSIONS: We demonstrate a beneficial effect of perioperative short-term low-dose prednisolone treatment on intestinal anastomotic healing in the context of colitis. Perioperative use of short-term low-dose prednisolone treatment might be beneficial in IBD patients who need to undergo surgery during active disease.

The Science of Anastomotic Healing.

Intestinal anastomotic tissue follows a similar pattern of healing that is seen in all tissues with characteristic inflammatory, proliferative, and remodeling phases. Several aspects of intestinal healing are distinct from other tissues, however, including its time course and interaction with the environment of the gastrointestinal tract. As the anastomosis progresses through each stage, initial inflammatory cells are replaced by collagen-producing fibroblasts that generate the anastomosis' strength. A complex network of cell-to-cell signaling mediates this process through the release of cytokines and growth factors including platelet-derived growth factor (PDGF), transforming growth factor-ß (TGF-ß), and vascular endothelial growth factor (VEGF). Interventions based on these signaling pathways have been shown to improve anastomotic strength in animals, though methods for improving anastomotic healing in human patients remain unclear. Given the risks associated with anastomotic failure in patients, there is value in monitoring inflammatory markers and cytokines that can indicate the presence of a leak.

The Effect of Genistein on Anastomotic Healing in Intestinal Ischemia/Reperfusion Injury.

INTRODUCTION: Genistein is a natural isoflavonoid and has several pharmacological effects, such as antioxidant, antitumor activity, and improvement of glucose metabolism. The safety of intestinal anastomosis after ischemia-reperfusion (I/R) injury is a critical issue for surgeons. This experimental study aimed to investigate the effects of genistein on anastomotic healing after intestinal I/R injury. METHODS: A total of 36 male Wistar Albino rats were divided into four groups: control, I/R, genistein, and genistein + I/R. The control group received segmental ileal resection and ileoileal anastomosis. The I/R group received resection + anastomosis after intestinal I/R. The genistein group was administered subcutaneous injection of 1 mg/kg genistein 12 h and 1 h before the procedure and received ileal resection + anastomosis. The genistein + I/R group received I/R + ileal resection + anastomosis after genistein injection. Anastomotic bursting pressure, hydroxyproline, superoxide dismutase, and glutathione peroxidase levels and histopathological wound healing scores of all rats were measured on postoperative day 5. RESULTS: The anastomotic bursting pressure was significantly higher in the genistein and genistein + I/R groups (P < 0.001). Genistein increased the hydroxyproline concentration and the superoxide dismutase and glutathione peroxidase levels in the intestinal anastomosis (P < 0.001). In histopathological assessment, the mean wound healing score was significantly higher in the genistein group than in the other groups (P < 0.001). CONCLUSIONS: Genistein, with its anti-inflammatory and antioxidant properties, shows protective effects against increased oxidative stress after intestinal I/R injury and contributes positively to intestinal anastomotic healing.

Aspects Towards the Anastomotic Healing in Crohn's Disease: Clinical Approach and Current Gaps in Research.

Anastomotic leakage is a major complication in gastrointestinal and colorectal surgery and its occurrence increases morbidity and mortality. Its incidence is even higher in Crohn's disease surgeries. Several authors have identified factors involved in the pathophysiology of anastomotic leak in the literature, aiming to reduce its occurrence and, therefore, improve its surgical treatment. Surgical technique is the most discussed topic in studies on guiding the performance of side-to-side stapled anastomosis. Preoperative nutritional therapy also has been shown to reduce the risk of anastomotic leakage. Other factors remain controversial - immunomodulator use and biologic therapy, antibiotics, and gut microbiota - with studies showing a reduction in the risk of complication while other studies show no correlation. Although mesenteric adipose tissue has been related to disease recurrence, there is no evidence in the literature that it is related to a higher risk of anastomotic leakage. Further exploration on this topic is necessary, including prospective research, to support the development of techniques to prevent anastomotic leakage, in this way benefiting the inflammatory bowel disease patients who have to undergo a surgical procedure.

Intestinal Anastomotic Healing: What do We Know About Processes Behind Anastomotic Complications.

Colorectal surgery has developed rapidly in the recent decades. Nevertheless, colorectal anastomotic leakage continues to appear postoperatively in unpleasant rates and leads to life-threatening conditions. The development of valid complication-preventing methods is inefficient in many aspects as we are still lacking knowledge about the basics of the process of anastomotic wound healing in the gastrointestinal tract. Without the proper understanding of the crucial mechanisms, research for prevention of anastomotic leakage is predestined to be unsuccessful. This review article discusses known pathophysiological mechanisms together with the most lately found processes to be further studied. The aim of the article is to facilitate the orientation in the topic, support the better understanding of known mechanisms and suggest promising possibilities and directions for further research.

Remote ischemic postconditioning has a detrimental effect and remote ischemic preconditioning seems to have no effect on small intestinal anastomotic strength.

BACKGROUND: The effect of remote pre- and postconditioning on anastomotic healing has been sparsely studied. The aim of our study was to investigate whether remote ischemic conditioning (RIC) applied before and after the creation of a small bowel anastomosis had an effect on anastomotic healing on postoperative day five evaluated by a tensile strength test and histological analysis. MATERIALS AND METHODS: Twenty-two female piglets were randomized into two groups. The intervention group (n = 12) received RIC on the forelimbs consisting of 15 min of ischemia followed by 30 min of reperfusion before the first end-to-end ileal anastomosis was created. The RIC procedure was repeated and the second and more distal anastomosis was performed. The control group (n = 10) had two similar anastomoses with similar time intervals but without RIC. On postoperative day five, the anastomoses were subjected to macroscopic evaluation, tensile strength test and histological examination. RESULTS: Mean tensile strength when the first transmural rupture appeared (MATS-2) was significantly lower in the first anastomosis in the intervention group compared to the control group (11.4 N vs 14.7 N, p < .05). Similar result was found by the maximal strength (MATS-3) as defined by a drop in the load curve (12.3 N vs 15.9 N, p < .05). Histologically, a significantly higher necrosis score was found in the anastomosis in the intervention group (1.4 vs 0.8, p < .05). No other significant differences were found. CONCLUSIONS: In conclusion, post-anastomotic remote ischemic conditioning had a detrimental effect and pre-anastomotic conditioning seems to have no effect on small intestinal anastomotic strength.

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Despite the considerable progress in surgical level and imaging examination methods, anastomotic leakage is still the major complication after intestinal surgery with high incidence rate and mortality rate. Moreover, anastomotic leakage has become one of the serious complications threatening the postoperative life safety, prognosis and quality of life. The occurrence of anastomotic leakage involves the changes of a variety of pathophysiological factors, and is affected by intestinal microbiota, inflammation and immune system. Preoperative intestinal preparation will change the type and number of microbial population in the intestine. Intraoperative anastomotic mode and bleeding volume are also closely related to the occurrence of anastomotic leakage. In addition, the occurrence of anastomotic leakage is associated with local recurrence of colorectal cancer after surgery. Intraoperative protective stoma is confirmed to reduce the incidence of anastomotic leakage. Combined preoperative adjustment of nutritional status and inflammatory factors is important for avoiding anastomotic leakage after surgery.

Ac2-26-Nanoparticles Induce Resolution of Intestinal Inflammation and Anastomotic Healing via Inhibition of NF-κB Signaling in a Model of Perioperative Colitis.

BACKGROUND: Although in most patients with inflammatory bowel diseases, conservative therapy is successful, a significant proportion of patients still require surgery once in their lifetime. Development of a safe perioperative treatment to dampen colitis activity without disturbance of anastomotic healing is an urgent and unmet medical need. Annexin A1 (ANXA1) has been shown to be effective in reducing colitis activity. Herein, a nanoparticle-based perioperative treatment approach was used for analysis of the effects of ANXA1 on the resolution of inflammation after surgery for colitis. METHODS: Anxa1-knockout mice were used to delineate the effects of ANXA1 on anastomotic healing. A murine model of preoperative dextran sodium sulfate colitis was performed. Collagen-IV-targeted polymeric nanoparticles, loaded with the ANXA1 biomimetic peptide Ac2-26 (Ac2-26-NPs), were synthesized and administered perioperatively during colitis induction. The effects of the Ac2-26-NPs on postoperative recovery and anastomotic healing were evaluated using the disease activity index, histological healing scores, and weight monitoring. Ultimately, whole-genome RNA sequencing of the anastomotic tissue was performed to unravel underlying molecular mechanisms. RESULTS: Anxa1-knockout exacerbated the inflammatory response in the healing anastomosis. Treatment with Ac2-26-NPs improved preoperative colitis activity (P < 0.045), postoperative healing scores (P < 0.018), and weight recovery (P < 0.015). Whole-genome RNA sequencing revealed that the suppression of proinflammatory cytokine and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling was associated with the treatment effects and a phenotypic switch toward anti-inflammatory M2 macrophages. CONCLUSIONS: Proresolving therapy with Ac2-26-NPs promises to be a potent perioperative therapy because it improves colitis activity and even intestinal anastomotic healing by the suppression of proinflammatory signaling.

Innovative approaches for induction of gastrointestinal anastomotic healing: an update on experimental and clinical aspects.

PURPOSE: In most cases, traditional techniques to perform an anastomosis following gastrointestinal resections lead to successful healing. However, despite focused research in the field, in certain high-risk situations leakage rates remain almost unchanged. Here, additional techniques may help the surgeon to protect the anastomosis and prevent leakage. We give an overview of some of the latest developments on experimental and clinical techniques for induction of anastomotic healing. METHODS: We performed a review of the current literature on approaches to improve anastomotic healing. RESULTS: Many promising approaches with a high clinical potential are in the developmental pipeline. Highly experimental approaches like inhibition of matrix metalloproteinases, stem cell therapy, hyperbaric oxygen therapy, induction of the hypoxic adaptive response, and the administration of growth factors are still in the preclinical phase. Other more clinical developments aim to strengthen the anastomotic suture line mechanically while shielding it from the influence of the microbiome. Among them are gluing, seaming the staple line, attachment of laminar biomaterials, and temporary intraluminal tubes. In addition, individualized bowel preparation, selectively reducing certain detrimental microbial populations could become the next stage of bowel preparation. Compression anastomoses are evolving as an equivalent technique additional to established hand-sewn and stapled anastomoses. Fluorescence angiography and flexible endoscopy could complement intraoperative quality control additionally to the air leak tests. Virtual ileostomy is a concept to prepare the bowel for the easy formation of a stoma in case of leakage. CONCLUSION: A variety of promising diagnostic and prophylactic measures that may support the surgeon in identifying high-risk anastomoses and support them according to their potential deficits is currently in development.

The Biology of Anastomotic Healing-the Unknown Overwhelms the Known.

BACKGROUND: Anastomotic complications are among the most devastating consequences of gastrointestinal surgery. Despite its high morbidity, the factors responsible for anastomotic regeneration following surgical construction remain poorly understood. The aim of this review is to provide an overview of the typical and atypical factors that have been implicated in anastomotic healing. METHODS: A review and analysis of select literature on anastomotic healing was performed. RESULTS: The healing of an anastomotic wound mirrors the phases of cutaneous wound healing- inflammation, proliferation, and remodeling. The evidence supporting much of the traditional dogma for optimal anastomotic healing (ischemia, tension, nutrition) is sparse. More recent research has implicated atypical factors that influence anastomotic healing, including the microbiome, the mesentery, and geometry. As technology evolves, endoscopic approaches may improve anastomotic healing and in some cases may eliminate the anastomosis altogether. DISCUSSION: Much remains unknown regarding the mechanisms of anastomotic healing, and research should focus on elucidating the dynamics of healing at a molecular level. Doing so may help facilitate the transition from traditional surgical dogma to evidence-based medicine in the operating room.

Anastomotic leak in colorectal cancer patients: New insights and perspectives.

Anastomotic leak (AL) remains a potentially life-threatening sequela of colorectal surgery impacting on mortality, short- and long-term morbidity, quality of life, local recurrence (LR) and disease-free survival. Despite technical improvements and the identification of several surgery- and patient-related factors associated to the risk of AL, its incidence has not significantly changed over time. In this context, the clarification of the mechanisms underlying anastomotic healing remains an important unmet need, crucial for improving patients' outcomes. This review concentrates on novel key findings in the etiopathogenesis of AL, how they can contribute in determining LR, and measures which may contribute to reducing its incidence. AL results from a complex, dynamic interplay of several factors and biological processes, including host genetics, gut microbiome, inflammation and the immune system. Many of these factors seem to act in concert to drive both AL and LR, even if the exact mechanisms remain to be elucidated. The next generation sequencing technology, including the microbial metagenomics, could lead to tailored bowel preparations targeting only those pathogens that can cause AL. Significant progress is being made in each of the reviewed areas, moving toward translational and targeted therapeutic strategies to prevent the difficult complication of AL.

Ameliorated healing of biliary anastomosis by autologous adipose-derived stem cell sheets.

INTRODUCTION: Cell sheets consisting of adipose-derived stem cells (ADSCs) have been reported to be effective for wound healing. We conducted this study to clarify the efficacy of ADSC sheets in wound healing at the duct-to-duct biliary anastomotic site in pigs. METHODS: Eleven female pigs (20-25 kg) were divided into two groups: biliary anastomosis with an ADSC sheet (n = 6) or without an ADSC sheet (n = 5). To follow the transplanted ADSCs, PKH26GL-labeled sheets were used in one of the ADSC pigs. Two weeks prior to laparotomy, ADSCs were isolated from the lower abdominal subcutaneous adipose tissue. After three passages, ADSCs were seeded on temperature-responsive culture dishes and collected as cell sheets. ADSC sheets were gently transplanted on the anastomotic site. We evaluated specimens by PKH26GL labeling, macroscopic changes, infiltration of inflammatory cells, and collagen content. RESULTS: Labeled ADSCs remained around the bile duct wall. In the no-ADSC group, more adhesion developed at the hepatic hilum as observed during relaparotomy. Histopathological examination showed that the diameter and cross-sectional area of the bile duct wall were decreased in the ADSC group. In the no-ADSC group, a large number of inflammatory cells and more collagen fibers were identified in the bile duct wall. CONCLUSIONS: The present study demonstrated that autologous ADSC sheet transplantation reduced hypertrophic changes in the bile duct wall at the anastomotic site. A long-term follow-up is required to evaluate the efficacy of this mechanism in prevention of biliary anastomotic strictures.

Correlation between invasive microbiota in margin-surrounding mucosa and anastomotic healing in patients with colorectal cancer.

BACKGROUND: Impaired anastomotic healing is one of the major complications resulting from radical resection in colorectal cancer (CRC). Accumulating evidence suggests that intestinal microbiota is correlated with anastomotic healing. AIM: To explore the microbiota structural shift in margin-surrounding mucosa and evaluate the predictive ability of selected bacterial taxa for impaired anastomotic healing. METHODS: Margin-surrounding mucosa samples derived from 37 patients were collected to characterize the microbial community structure by 16s rRNA gene sequencing. The patients were divided into two groups according to the healing status of anastomoses: well-healing group (n = 30) and impaired-healing group (n = 7). Statistic differences in bacteria taxa were compared by Wilcoxon test and chi-squared test. The predictive ability of the selected bacterial taxa for the healing status of anastomoses was evaluated by the area under the receiver operator characteristic curve. RESULTS: Community structure shifts were observed in the impaired-healing group and well-healing group. Six bacterial species were found to be significantly correlated with anastomotic healing, and among these species, Alistipes shahii, Dialister pneumosintes, and Corynebacterium suicordis were considered as the predictive factors. Taking the known risk factor age into consideration, Alistipes shahii, Dialister pneumosintes, and Corynebacterium suicordis improved predictive ability for the healing status of anastomoses. CONCLUSION: These data show that Alistipes shahii, Dialister pneumosintes, and Corynebacterium suicordis could be considered as supplementary factors in the prediction of anastomosis healing status in patients after CRC radical resection.

Effect of Alprostadil on Colorectal Anastomoses Under Relative Ischemia.

BACKGROUND: Anastomotic leak after colorectal surgery, which remains a serious clinical problem that causes augmented morbidity and mortality, is usually favored by ischemia. The aim of this study was to determine whether alprostadil may improve anastomotic wound healing under ischemic condition. METHODS: Ninety-three adult Wistar rats were randomized into three groups: control, ischemia (by devascularization along the first 2 cm at each anastomotic end), and ischemia plus alprostadil. Resection of a colonic segment at the colorectal junction and an anastomosis was performed. Animals were euthanized at 8 d. Surgical site infection, anastomotic leak, and grade of intra-abdominal adhesions using a validated scale were determined. Bursting pressure and tension were calculated and histologic examination of the anastomosis was performed. RESULTS: The ischemic group revealed an increased anastomotic leak rate (14/31 versus 3/31) and a lower bursting pressure and tension when compared to control group, validating therefore the experimental model. After intraperitoneal injection of alprostadil, anastomotic leak rate was significantly lower (5/31) and the bursting pressure and tension were significantly increased. Histologic examination revealed a lower presence of inflammatory cells, and a significantly higher neovascularization and a higher presence of fibroblasts in treated animals when compared with the ischemic group. CONCLUSIONS: Alprostadil may have a positive effect on colonic anastomotic wound healing under relative ischemic condition. Alprostadil administration increases anastomotic bursting pressure, decreases leak rate, and reverses most of the histological changes caused by blood flow decrease. These protective effects could be caused by vasodilation, stimulation of neovascularization, and immunomodulatory properties.

Factors Favoring and Impairing Healing of Tracheal Anastomosis.

The factors governing successful healing of and impairing of tracheal and bronchial anastomosis are best understood by reviewing the normal histologic changes accompanying healing, governing factors, and biochemical advances made in the last 5 decades. Normal wound healing factors, also relevant to tracheal and bronchial reconstruction, rely on precise handling of tissues without interfering with tissue perfusion, careful selection and placement of sutures, and steps to minimize tension. Impairments of satisfactory healing are well recognized in gastrointestinal surgery and apply to tracheal and carinal resection, and sleeve bronchial resection.

Does the application of Ankaferd Blood Stopper rectally have positive effects on the healing of colorectal anastomosis and prevention of anastomotic leakage? An experimental study.

The purpose of this experimental study was to evaluate the potential effects on the healing of colorectal anastomoses of the rectal administration of Ankaferd Blood Stopper (ABS). Thirty Wistar-Albino male rats were randomly separated into 3 groups. In the sham group, only laparotomy and colonic mobilization was performed. In the other 2 groups, colon transection and anastomosis were carried out. Saline (2 mL, 0.9% NaCl) was given rectally via a feeding tube for 10 days after the surgical procedure in the sham and control groups. In Group 3 (ABS group), the rats were treated with rectally administered ABS (2 mL/day) for 10 days. In all groups, after the measurement of bursting pressures, tissue samples were collected for the measurement of tissue hydroxyproline and prolidase levels, and for histopathological evaluation on postoperative day 11. The rectal administration of ABS showed positive effects on bursting pressures, tissue prolidase and hydroxyproline levels, and the histopathological findings of colonic anastomosis. The rectal application of ABS had positive effects on the healing of colorectal anastomosis. As a natural product, it may be used effectively and safely to achieve better healing results after colorectal anastomosis.