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Multiple studies have documented the safety of intestinal anastomosis after resection for necrotizing enterocolitis (NEC). We sought to evaluate a large population of infants with surgical NEC and assess outcomes after primary anastomosis versus enterostomy. The Pediatric Health Information System database was used to identify infants with Bell Stage 3 NEC who underwent an intestinal resection for acute disease between 2016 and 2021. Demographics and preoperative physiology were assessed, and nutritional, infectious, and surgical outcomes were analyzed. Two hundred twenty-two infants at 38 children's hospitals were included. Thirty-five (15.8%) were managed with a primary anastomosis. Among infants who underwent a resection within 10 d of their first operative intervention and survived for at least 3 d, a primary anastomosis was used in 26 (13.7%). These patients were older but had similar weight and physiological status at the time of resection as those managed with an enterostomy. The incidence of wound and infectious complications, duration of parenteral nutrition and length of stay were similar after anastomosis or enterostomy. In a large, geographically heterogenous population of infants with NEC, only 15.8% were managed with a primary anastomosis after intestinal resection. Survivors who underwent resection within 10 d were demographically and physiologically comparable to those who underwent enterostomy and had similar surgical outcomes. While there are clearly indications for enterostomy in some infants with NEC, these data confirm the conclusions of smaller, single-center studies that a primary anastomosis should be considered more frequently. [ABSTRACT FROM AUTHOR]

General surgery residents need to master the hand-sewn bowel anastomosis (HSBA) technique. However, practice opportunities outside of the operating room are rare, and commercial simulators are often costly. The objective of this study is to assess the efficacy of a new, affordable silicone small bowel simulator, made with a three-dimensional (3D) printed mold, as a training tool to learn this technique. This was a single-blinded pilot randomized controlled trial comparing two groups of eight junior surgical residents. All participants completed a pretest using an inexpensive, custom developed 3D-printed simulator. Next, participants randomized to the experimental group practiced the HSBA skill at home (eight sessions), while those randomized to the control group did not receive any hands-on practice opportunities. A posttest was done using the same simulator as for the pretest and practice sessions, and the retention-transfer test was performed on an anesthetized porcine model. Pretests, posttests and retention-transfer tests were filmed and graded by a blinded evaluator using assessments of technical skills, quality of final product, and tests of procedural knowledge. The experimental group significantly improved after practicing with the model (P = 0.01), while an equivalent improvement was not noted in the control group (P = 0.07). Moreover, the experimental group's performance remained stable between the posttest and the retention-transfer test (P = 0.95). Our 3D-printed simulator is an affordable and efficacious tool to teach residents the HSBA technique. It allows development of surgical skills that are transferable to an in vivo model. [ABSTRACT FROM AUTHOR]

The vertebrate cardiovascular system is made up by a hierarchically structured network of highly specialised blood vessels. This network emerges during early embryogenesis and evolves in size and complexity concomitant with embryonic growth and organ formation. Underlying this plasticity are actin-driven endothelial cell behaviours, which allow endothelial cells to change their shape and move within the vascular network. In this review, we discuss the cellular and molecular mechanisms involved in vascular network formation and how these intrinsic mechanisms are influenced by haemodynamic forces provided by pressurized blood flow. While most of this review focusses on in vivo evidence from zebrafish embryos, we also mention complementary findings obtained in other experimental systems. [ABSTRACT FROM AUTHOR]

To minimize complications associated with the construction of the hand-sewn aortic anastomosis, alternative experimental methods have been pursued. This study aimed to evaluate the efficacy of experimental anastomotic devices in relation to time and point of rupture of the anastomosis in comparison to the conventional technique. An electronic search was performed using MEDLINE, Scopus, Science Direct, and Cochrane Library databases by two independent authors. Our exclusion criteria referred to studies reporting results solely from end-to-side anastomosis, results on vessels other than the aorta, studies that did not involve animal experiments, and non-English publications. The last search date was January 1, 2020. The meta-analysis included 22 studies with 34 anastomosis samples and a total of 316 animals. The pooled mean automated anastomosis time was 10.38 min, and the mean point of rupture was 32.7 N. In the subgroup analysis of automated anastomosis time by device category, the anastomotic stenting technique reported significantly lower anastomosis time but also showed significantly lower point of rupture. Comparing the efficacy of experimental devices and the hand-sewn technique, our pooled analysis showed that automated devices significantly decrease the time needed to perform the anastomosis (weighted mean difference −7.24 min). On the other hand, the automated anastomosis is also associated with decreased tensile strength (weighted mean difference −20.68 N). Although experimental devices seem to offer a faster anastomosis, they lack endurance when compared with the hand-sewn technique. Further research is needed for the development of an "ideal" anastomotic technique. [ABSTRACT FROM AUTHOR]

The study aimed to perform continuous and dynamic observation on the blood flow changes in a rat abdominal model of supercharged flaps to examine the roles of arterial and venous supercharging in preventing distal flap necrosis. Eighteen rats were divided into three experimental groups. The left-sided flaps in all groups were used as controls such that the subxiphoid perforator vessels served as the only pedicle. Experimental groups I, II, and III consisted of supercharged right-sided flaps. Group I, the arteriovenous supercharging group, had flaps supercharged by the suprapubic perforator arteries and veins. Group II, the arterial supercharging group, had flaps supercharged by the suprapubic perforator arteries. Group III, the venous supercharging group, had flaps supercharged by the suprapubic perforator veins. Laser-induced near-infrared fluorescence angiography was performed before and after surgery. As revealed by near-infrared fluorescence angiography, the control group and venous supercharging group exhibited rapid reductions in blood supply and loss of arterial perfusion in distal areas. The distal flap necrosis was much smaller in the venous supercharging group than in the control group. Both the arteriovenous supercharging group and the arterial supercharging group exhibited adequate perfusion and resulted in full postoperative survival of the flaps. These findings indicated that the distal arterial hypoperfusion is the major cause of the distal venous stasis and necrosis in the flaps. Sufficient arterial supercharging ensures the distal arterial perfusion and therefore diminishes the occurrence of distal flap necrosis. [ABSTRACT FROM AUTHOR]

Biomedical imaging devices that utilize the optical characteristics of hemoglobin (Hb) have become widespread. In the field of gastroenterology, there is a strong demand for devices that can apply this technique to surgical navigation. We aimed to introduce our novel multispectral device capable of intraoperatively performing quantitative imaging of the oxygen (O 2) saturation and Hb amount of tissues noninvasively and in real time, and to examine its application for deciding the appropriate anastomosis point after subtotal or total esophagectomy. A total of 39 patients with esophageal cancer were studied. Tissue O 2 saturation and Hb amount of the gastric tube just before esophagogastric anastomosis were evaluated using a multispectral tissue quantitative imaging device. The anastomosis point was decided depending on the quantitative values and patterns of both the tissue O 2 saturation and Hb amount. The device can instantaneously and noninvasively quantify and visualize the tissue O 2 saturation and Hb amount using reflected light. The tissue Hb status could be classified into the following four types: good circulation type, congestion type, ischemia type, and mixed type of congestion and ischemia. Postoperative anastomotic failure occurred in 2 cases, and both were mixed cases. The method of quantitatively imaging the tissue O 2 saturation and Hb level in real time and noninvasively using a multispectral device allows instantaneous determination of the anastomosis and related organ conditions, thereby contributing to determining the appropriate treatment direction. [ABSTRACT FROM AUTHOR]

Abstract Purpose Colorectal cancer is globally the third most common cancer. Anastomotic complications remain to be an important issue for colorectal surgery. The aim of this study was to investigate the protective effects of thymoquinone (TQ) on the healing process of left colonic anastomosis in an experimental model. Methods Thirty-two male rats were divided into two groups, as the TQ group and the control group. TQ was administered to the TQ group, whereas the control group was given a standard feed and water for 2 wk. Following the creation of a left colonic anastomosis, subjects in both groups were sacrificed on the postoperative (PO) third and seventh days. Anastomotic burst pressures were measured mechanically. Immunohistochemical stainings for proliferating cell nuclear antigen, cluster of differentiation (CD) 31, CD45 were performed, and the matrix metalloproteinase-2 levels were measured. Histologic total scores were calculated according to Ehrlich-Hunt model. A value of P < 0.05 was considered as statistically significant. Results One rat in the control group that died on the PO fourth day was excluded. Anastomotic burst pressures on the PO seventh day were higher in the TQ group than the control group (P < 0.01). Histopathological total scores on the PO third and seventh days were higher in the TQ group (P < 0.01). In addition, the TQ group revealed lower matrix metalloproteinase-2 scores on the PO third day and higher hydroxyproline levels on the PO seventh day (P < 0.05 and P < 0.01, respectively). Conclusions The use of TQ in colorectal surgery cases with left-sided colonic anastomosis resulted with increased anastomotic burst pressures and increased tissue hydroxyproline levels. [ABSTRACT FROM AUTHOR]

Abstract Background Magnetic compression technique (MCT) is useful for construction of digestive tract anastomoses in pigs and dogs. This study determined the efficacy of MCT for performing colonic anastomosis in rats. Methods Twenty male Sprague–Dawley rats (230-280 g) were randomly apportioned to a study group that underwent colonic anastomosis with MCT or a control group subjected to hand-sewn colonic anastomosis. The groups were compared for time to construct the anastomosis, survival rate, and postoperative complications. Animals were euthanized at 1 mo postsurgery to study the burst pressure and histology of the anastomoses. Results The study group required significantly less time to construct the anastomosis (6.50 ± 1.58 min) than did the control (15.6 ± 2.22 min). The survival rate of the study group (100%) was significantly higher than that of the control group (60%). In the control group, three rats developed anastomotic leakage and one rat developed anastomotic obstruction. No anastomotic leakage or obstruction was observed in the study group. The burst pressures of the two groups were similar. Histology showed that the study group had better alignment of the tissue layers and less inflammation compared with the control group. Conclusions MCT is a safe and feasible technique for colonic anastomosis in rats, with better postoperative outcomes compared with hand-sewn anastomosis. [ABSTRACT FROM AUTHOR]

Background Early diagnosis of anastomotic leakage is the most important factor in reducing its morbidity and mortality. Anastomotic integrity monitoring of the leukocyte count (WBC), C-reactive protein (CRP), and neutrophil-lymphocyte ratio (NLR) are commonly used laboratory parameters. The availability of follow-up presepsin anastomotic integrity was investigated in this study. Materials and methods This study included patients who had gastrointestinal anastomosis due to major abdominal surgery between January 2016 and February 2017. Blood samples were collected to determine the WBC, CRP, NLR, and presepsin values before the anastomosis was performed and then taken on postoperative days 1, 3, and 5. Results This is a prospective nonrandomized study with 100 consecutive patients enrolled in the anastomosis group (male/female, 42:58). WBC, CRP, NLR, and presepsin values are based on certain days in the complication group, and the complication group increased with statistical significance. Presepsin had a specificity of 98.63% in determining anastomotic leak. Conclusions Presepsin can be used as a supplemental marker with CRP and NLR for anastomotic integrity. [ABSTRACT FROM AUTHOR]

Arterial thrombus formation is directly related to the mechanical shear experienced by platelets within flow. High shear strain rates (SSRs) and large shear gradients cause platelet activation, aggregation and production of thrombus. This study, for the first time, investigates the influence of pulsatile flow on local haemodynamics within sutured microarterial anastomoses. We measured physiological arterial waveform velocities experimentally using Doppler ultrasound velocimetry, and a representative example was applied to a realistic sutured microarterial geometry. Computational geometries were created using measurements taken from sutured chicken femoral arteries. Arterial SSRs were predicted using computational fluid dynamics (CFD) software, to indicate the potential for platelet activation, deposition and thrombus formation. Predictions of steady and sinusoidal inputs were compared to analyse whether the addition of physiological pulse characteristics affects local intravascular flow characteristics. Simulations were designed to evaluate flow in pristine and hand-sutured microarterial anastomoses, each with a steady-state and sinusoidal pulse component. The presence of sutures increased SSR max in the anastomotic region by factors of 2.1 and 2.3 in steady-state and pulsatile flows respectively, when compared to a pristine vessel. SSR values seen in these simulations are analogous to the presence of moderate arterial stenosis. Steady-state simulations, driven by a constant inflow velocity equal to the peak systolic velocity (PSV) of the measured pulsatile flow, underestimated SSRs by ∼ 9% in pristine, and ∼ 19% in sutured vessels compared with a realistic pulse. Sinusoidal flows, with equivalent frequency and amplitude to a measured arterial waveform, represent a slight improvement on steady-state simulations, but still SSRs are underestimated by 1–2%. We recommend using a measured arterial waveform, of the form presented here, for simulating pulsatile flows in vessels of this nature. Under realistic pulsatile flow, shear gradients across microvascular sutures are high, of the order ∼ 7.9 × 10 6 m −1 s −1 , which may also be associated with activation of platelets and formation of aggregates. [ABSTRACT FROM AUTHOR]

Heterokaryon formation is an essential step in asexual recombination in Fusarium oxysporum . Filamentous fungi have an elaborate nonself recognition machinery to prevent formation and proliferation of heterokaryotic cells, called heterokaryon incompatibility (HI). In F. oxysporum the regulation of this machinery is not well understood. In Neurospora crassa , Vib-1, a putative transcription factor of the p53-like Ndt80 family of transcription factors, has been identified as global regulator of HI. In this study we investigated the role of the F. oxysporum homolog of Vib-1, called Suf, in vegetative hyphal and conidial anastomosis tube (CAT) fusion and HI. We identified a novel function for an Ndt80 homolog as a nutrient-dependent regulator of anastomosis. Strains carrying the SUF deletion mutation display a hyper-fusion phenotype during vegetative growth as well as germling development. In addition, conidial paring of incompatible SUF deletion strains led to more heterokaryon formation, which is independent of suppression of HI. Our data provides further proof for the divergence in the functions of different members Ndt80 family. We propose that Ndt80 homologs mediate responses to nutrient quality and quantity, with specific responses varying between species. [ABSTRACT FROM AUTHOR]

This study investigates the extent to which individual aspects of suture placement influence local haemodynamics within microarterial anastomoses. An attempt to physically quantify flow characteristics of blood past microvascular sutures is made using computational fluid dynamics (CFD) software. Particular focus has been placed on increased shear strain rate (SSR), a known precipitant of intravascular platelet activation and thrombosis. Measurements were taken from micrographs of sutured anastomoses in chicken femoral vessels, with each assessed for bite width, suture angle and suture spacing. Computational geometries were then created to represent the anastomosis. Each suture characteristic was parameterised to allow independent or simultaneous adjustment. Flow rates were obtained from anonymised Doppler ultrasound scans of analogous vessels during preoperative assessment for autologous breast reconstruction. Vessel simulations were performed in 2.5 mm ducts with blood as the working fluid. Vessel walls were non-compliant and a continuous Newtonian flow was applied, in accordance with current literature. Suture bite angle and spacing had significant effects on local haemodynamics, causing notably higher local SSRs, when simulated at extremes of surgical practice. A combined simulation, encompassing subtle changes of each suture parameter simultaneously i.e. representing optimum technique, created a more favourable SSR profile. As such, haemodynamic changes associated with optimum suture placement are unlikely to influence thrombus formation significantly. These findings support adherence to the basic principles of good microsurgical practice. [ABSTRACT FROM AUTHOR]

Background Recently, a nickel–titanium (NiTi) memory-shape device has been successfully used in gastrointestinal anastomosis. The aim of this study was to investigate the feasibility and safety of the device. Methods Four databases, reference lists, and the World Health Organization International Clinical Trials Registry Platform were systematically searched for randomized controlled trials assessing the clinical efficacy of a NiTi memory-shape device compared with that of a stapler in gastrointestinal or colorectal anastomosis. Results Seven randomized controlled trials regarding the use of compression anastomosis clips (CACs) were enrolled for meta-analysis. The use of CACs was associated with a significant reduction in hospital duration (mean = −0.88 d; 95% confidence interval [CI], −1.38 to −0.38), the time to flatus (mean = −0.36 d; 95% CI, −0.08 to −0.04), and the start of oral intake (mean = −0.45 d; 95% CI, −0.83 to −0.06), as well as a nonsignificant change in postoperative complications and mortality. These clinical outcomes did not significantly change with the use of compression anastomosis rings. Conclusions Colonic anastomosis with a CAC is likely to reduce hospital duration, time to flatus, and the start of oral intake without influencing mortality or postoperative complications and may be a safe and preferable choice in colonic anastomosis. Further well-designed trials should be performed to determine the safety and efficacy of the newly developed compression anastomosis ring in both ileocolic and colorectal anastomosis. [ABSTRACT FROM AUTHOR]

Background Segmental resection of esophagus with primary anastomosis is prohibited because of the risk of dehiscence. We previously have shown that replacement of a segment of cervical esophagus with a tracheal segment of the same length could successfully be performed in a canine model. In this study, we sought to assess the feasibility of replacement of the esophageal defect with a shorter segment of trachea. Methods In five mongrel dogs weighting 20–30 kg, under general anesthesia and after a cervical incision, 8 cm of the cervical esophagus was resected and replaced by a 4-cm segment of the adjacent trachea. The animals were evaluated clinically for signs and symptoms of stenosis and dehiscence and then euthanized after 2 mo of follow-up. Results All dogs recovered from surgery and started regular diet on the seventh postoperative day. No clinical or endoscopic sign of stenosis or voice change was seen. Squamous metaplasia and atrophy of mucosal glands and cartilage were detected in the histopathologic examination of the replaced segments. Conclusions Replacement of a cervical esophageal defect with a shorter segment of trachea can be performed successfully in dogs. This procedure can be potentially used for the treatment of cervical esophageal lesions in humans. [ABSTRACT FROM AUTHOR]

Background Isoperistaltic stapled side-to-side anastomosis (SSSA), which is a modified technique from conventional antiperistaltic SSSA, has the benefits of antiperistaltic SSSA but requires less intestinal mobility. The aim of this randomized controlled trial was to evaluate short-term outcomes of isoperistaltic SSSA comparing them with antiperistaltic SSSA during colon cancer surgery. Materials and methods We conducted a randomized controlled trial of patients with colon cancer who underwent elective curative resection and had enough intestinal mobility at anastomosis. The primary outcome was the presence of anastomotic failure, including leakage, hemorrhage, and stenosis. Results Between July 2012 and January 2014, forty patients were enrolled (20 patients in each group). The study was suspended on detecting excess morbidity in the isoperistaltic SSSA group. No significant differences were observed in all preoperative backgrounds between the two groups. Anastomotic leakage was seen in two patients in the isoperistaltic SSSA group, compared with none in the antiperistaltic SSSA group, although the difference was not statistically significant (P = 0.487). One patient in the antiperistaltic SSSA group had anastomotic stenosis, which improved conservatively, compared with none in the isoperistaltic SSSA group (P = 1.000). No anastomotic hemorrhage was seen in either group. There was no significant difference in the median postoperative hospital stay (P = 0.313). Conclusions This study did not show any short-term advantage or disadvantage of isoperistaltic SSSA compared with that of antiperistaltic SSSA. However, considering that anastomotic leakage occurred only in the isoperistaltic SSSA group, additional modifications are recommended to perform safe isoperistaltic SSSA for colon surgery. [ABSTRACT FROM AUTHOR]

Background Anastomotic leakage rates remain unacceptably high, warranting reconsideration of current anastomotic technique. Anastomotic healing may improve by abrading the serosal surface of bowel ends that are invertedly anastomosed, based on the concept that serosal damage evokes inflammatory adherent processes. It is studied if local abrasion leads to stronger anastomoses and reduces leakage. Methods Ninety-eight Wistar rats were allocated to six groups. Either a regular anastomosis (RA) or abraded anastomosis (AA) was constructed in the proximal colon. Animals were sacrificed at day 3 (groups RA3 and AA3, n = 2 x 17) or day 5 (groups RA5 and AA5, n = 2 x 17). Groups RA-Dic and AA-Dic (n = 2 x 15) received diclofenac from day 0 until sacrifice on day 3 to impair anastomotic healing. Outcomes were leakage, bursting pressure, breaking strength, adhesions, and histological appearance. Results Both in abraded (AA3 and AA5) and control (RA3 and RA5) groups without diclofenac, 1 of 17 anastomoses leaked (6%). Leak rate was 9 of 15 (60%) in group AA-Dic and 8 of 15 (53%) in RA-Dic (P = 1.0). The bursting pressure in group RA3 (127 ± 44 mm Hg) was higher (P = 0.006) compared with group AA3 (82 ± 34 mm Hg), breaking strength was comparable (P = 0.331). Mechanical strength was similar between groups RA5 and AA5. Abrasion did not increase mechanical strength in the diclofenac groups. Adhesion formation was not different between groups. Histology showed dense interserosal scar formation in abraded groups, compared with loose connective tissue in control anastomoses. Conclusions Abrasion of serosal edges of large bowel ends invertedly anastomosed does not improve anastomotic strength, neither does it reduce leakage in anastomoses compromised by diclofenac. [ABSTRACT FROM AUTHOR]

Background Saphenous vein grafts (SVGs) are frequently used for multi-vessel coronary artery bypass grafting and peripheral arterial bypasses; however, the estimated 40% failure rate within the first 5 y due to intimal hyperplasia (IH) and the suequent failure rate of 2%-4% per year pose a significant clinical problem. Here, we report a surgical model in sheep intended to study IH development in SVGs, which can also be used for the evaluation of potential alternative treatments. Materials and methods Autologous bilateral SVGs were implanted as femoral artery interposition grafts using end-to-side anastomoses in adult sheep (n = 23), which were survived for 30 (n = 6), 90 (n = 7), 180 (n = 7), or 365 (n = 3) days. Post-implant, mid-term, and pretermination angiograms were quantified, and harvested SVGs were evaluated using quantitative histomorphometry. Results We describe a peripheral arterial surgical technique that models the progression of SVG pathology. Angiographic analysis showed a progressive dilation of SVGs leading to worsening diametrical matching to the target artery and reduced blood flow; and histomorphometry data showed an increase in IH over time. Multivariable regression analysis suggested that statistically significant (P < 0.05) time-dependent relationships exist between SVG dilation and both reduction in blood flow and IH development. Conclusions Bilateral SVGs implanted onto the femoral arteries of sheep produced, controlled and consistent angiographic and histomorphometric results for which direct correlations could be made. This preclinical investigation model can be used as a robust tool to evaluate therapies intended for cardiovascular pathologies such as occlusive IH in SVGs. [ABSTRACT FROM AUTHOR]

Background The use of fascial perforating vessels as recipients for microvascular composite tissue autotransplants has led to vessel diameter discrepancy becoming an increasingly common finding. Little evidence, however, is available to direct the choice of anastomotic technique where a discrepancy exists. We have been studying two methods of anastomosing arteries where a small-to-large discrepancy exists-a 45° section of the smaller vessel, and invaginating the smaller vessel inside the larger. As part of this work, this study examines intimal hyperplasia and healing of the two methods. Materials and methods A previously described paired Wistar rat femoral axis model was used. Anastomoses were performed, one on each side, and specimens were harvested in groups at 24 h, 1 wk, 6 wk, and 8 mo. Inflammation, necrosis, and fibrosis in each layer of the vessel wall and intimal hyperplasia were each scored by an assessor blinded to the group and anastomotic technique. Results Significant differences in healing were found. The invagination technique induced less inflammation, and caused less endothelial and medial necrosis than the oblique cut end-to-end method. Intimal hyperplasia was most pronounced at 6 wk, but no evidence of a difference in the severity of intimal hyperplasia between the two methods was found. Conclusions The invaginating anastomosis causes less inflammation and less vessel wall necrosis than the oblique end-to-end method in this model. This finding, alongside results from previous work, suggests that this is the better method to deal with a small-to-large microarterial diameter discrepancy in the range 1:1.5 to 1:2.5. [ABSTRACT FROM AUTHOR]

We developed a new microscopy procedure to study anastomoses in the model ascomycete Podospora anserina and compared it with the previous method involving the formation of balanced heterokaryons. Both methods showed a good correlation. Heterokaryon formation was less quantifiable, but enabled to observe very rare events. Microscopic analysis evidenced that anastomoses were greatly influence by growth conditions and were severely impaired in the IDC mutants of the PaMpk1 , PaMpk2 , IDC1 and PaNox1 pathways. Yet some mutants readily formed heterokaryons, albeit with a delay when compared to the wild type. We also identified IDC 821 , a new mutant presenting a phenotype similar to the other IDC mutants, including lack of anastomosis. Complete genome sequencing revealed that IDC 821 was affected in the orthologue of the Neurospora crassa So gene known to control anastomosis in several other ascomycetes. [ABSTRACT FROM AUTHOR]

Highlights: [•] Tube fusion (anastomosis) is a key process in the development of interconnected tubular networks. [•] Tracheal development in Drosophila and angiogenesis in vertebrates involve tube fusion events. [•] Tube fusion requires tip cell specification, cell–cell recognition and contact formation, cell shape changes, lumen formation, and luminal fusion. [•] We highlight similarities and differences between tube fusion in Drosophila tracheal development and angiogenesis in vertebrates. [Copyright &y& Elsevier]

Abstract: Background: Arterialized orthotopic liver transplantation (OLT) in the mouse mimics human liver transplantation physiologically and clinically. The present method of sutured anastomosis for reconstruction of the hepatic artery is complex and is associated with high incidence of complications and failure. This makes the endpoint assessment of using this complex model difficult because of the many variables of the technical aspect. Methods: A total of 14 pairs of donors and recipients from syngeneic male mice were used for arterialized OLT. The grafts were stored in University of Wisconsin solution at 4°C for less than 4 h, and the recipients underwent OLT using a two-cuff technique. The arterial reconstruction was facilitated by the use of a single stent connecting the donor liver artery segment to the recipient common hepatic artery. Results: All 14 recipients survived with the time for arterial reconstruction ranging from 4–10 min. Patency of the artery was confirmed by transecting the artery near the graft 2 and 14 d after transplantation. At day 2, five of the six arteries transected were patent and at day 14, seven of the remaining eight were patent for an overall patency rate of 85.7%. Conclusions: The stent-facilitated arterial reconstruction can be done quickly with a high patency rate. This model expands the translational research efforts to address marginal livers such as steatotic livers. [Copyright &y& Elsevier]

Abstract: Background: Sunitinib (Sutent) is a Food and Drug Administration–approved receptor tyrosine kinase inhibitor found to reduce postoperative adhesion formation in animal models. The objective of the present study was to evaluate anastomotic healing and potential drug-related toxicities after short-term sunitinib administration in New Zealand White rabbits. Materials and methods: Under an approved study protocol, 40 rabbits underwent a laparotomy followed by colonic transection and anastomosis. Animals were randomly assigned to treatment with oral sunitinib (10 mg/kg/d) or placebo, received one preoperative dose followed by 10 postoperative doses, and were divided into two groups following the procedure: group I animals were euthanized on completion of drug treatment and group II animals were euthanized 30 d after completion of treatment. Prior to study completion, animals underwent an echocardiogram and laboratory test results were obtained. At necropsy, intestinal bursting strength (in mmHg) was evaluated. Results: All animals survived until designated euthanasia. There was no evidence of intra-abdominal sepsis or intestinal obstruction. Sunitinib-treated animals were found to have lower intestinal anastomotic strength compared with placebo-treated animals, as measured by bursting pressure at euthanasia, and a greater percentage of bursting at the anastomosis. On echocardiography, all ejection and shortening fractions were within established normal reference values. There were no significant differences in liver enzymes between animals. There were no wound infections, dehiscence, or delayed wound healing in any animal. Conclusions: These results caution against the administration of sunitinib in cases involving intestinal anastomoses because of the elevated risk of anastomotic leak. No evidence of cardiotoxicity, hepatotoxicity, or detrimental effect on wound healing was found in any animal. [Copyright &y& Elsevier]

Background: In the first posttransplant month, the most frequent complications are due to technical problems related to complex vascular and bile duct reconstructions during the operation. Moreover, despite great improvements in suturing technique and materials, severe organ ischemia-reperfusion caused by time-consuming hand suturing is still an important factor in graft survival. During the operation, severe hypotension, hypoxic acidosis, hyperkalemia, and renal dysfunction may occur during the anhepatic phase due to the prolonged venous clamping time required for hand suturing. Therefore, hand suturing is a handicap in the development of further advancements in liver transplantation. In this study, we aimed to test a new “mechanical installation method” for rapid vascular reconstruction. Methods: The magnetic pinning-ring device was developed consisting of paired magnetic rings coated with titanium oxide and embedded in a polypropylene shell. The rings were equipped with alternately spaced holes and titanium pins. Forty adult mongrel dogs were randomly divided into groups: A (n = 16), all vascular and bile duct reconstruction by magnetic ring without venous bypass; B (n = 16), all vascular and bile duct reconstruction by hand suturing with venous bypass; C (n = 8), sham transplantation group, transection of all vessels and common bile duct followed by anastomosis with the magnetic rings without liver transplantation. From groups A and B, dogs were randomly selected as donors (n = 8) or recipients (n = 8) of liver transplantations. We recorded operation time, vascular and bile duct anastomosis time, anhepatic time, administration of supplemental fluids during operation, and survival; blood samples were collected for the detection of liver damage (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and tumor necrosis factor α level. Patency was confirmed using ultrasound scans at various time points as late as 24 wk after surgery. Angiography was used to evaluate the anastomoses formed with magnetic rings. In group C, gross observation, histologic staining, and scanning electron microscopy were used to evaluate the vessels and bile ducts 12 wk postoperatively. Results: In group A, the total operation time, inferior vena cava, and portal vein anastomosis times were significantly shortened, and the anhepatic phase was reduced to about one-fifth that of group B, which was a significant difference between the two groups (P < 0.01). The mean total operative time was 2.54 ± 0.45 h. In order to maintain adequate blood pressure, the mean fluid volume infused was 800.56 ± 60.56 mL in the recipients of group A, which was lower than that in group B (2241.67 ± 390.78 mL, P < 0.01). Use of a pressor agent in group A was unnecessary. After operation, five of eight animals in group A survived more than 7 d after operation. The main cause of death was acute rejection. Only three of eight animals in group B survived more than 1 wk after operation due to chronic anastomotic bleeding, kidney failure, heart failure, and gastrointestinal bleeding. There was a statistically significant difference (P < 0.01) between the short-term survival rate in the two groups (75.0% versus 37.5%). The ALT (1544.46 ± 286.27) U/L and AST (1710.74 ± 252.27) U/L levels after operation in the animals with hand suturing were significantly higher than those in the sutureless group (ALT = 1116.41 ± 210.55 U/L; AST = 1176.95 ± 248.25) U/L after reperfusion (P < 0.01). The serum tumor necrosis factor α levels (45.56 ± 10.78) ng/L in group B were significantly higher than those of group A (26.64 ± 10.84) ng/L after reperfusion (P < 0.01). Re-endothelialization was confirmed in all vessels in group C, with neither formation of aneurysms nor thickening of the vascular wall noted after 12 wk. The bile duct anastomoses also healed well. Conclusions: The magnetic pinning-ring device offers a simple, fast, reliable, and efficacious technique for nonsuturing vascular and bile duct anastomoses. Use of this device shortens operation time, maintains a high patency rate, and improves the healing of tissue. Application of the magnetic ring anastomosis technique can effectively reduce the complications caused by hand suturing, and can reduce the extent of ischemia-reperfusion injury, leading to smoother operations and improved prognosis. [ABSTRACT FROM AUTHOR]

Highlights: [•] Delivery of Cre recombinase by anastomosis excised fungal loxP-flanked marker genes. [•] The method is time and cost saving. [•] The method allows unlimited recycling of fungal marker genes. [•] The method results in marker gene-free excision strains. [•] The method was applied to Cryphonectria parasitica and Metarhizium robertsii. [Copyright &y& Elsevier]

Abstract: Aim: Intestinal anastomoses are always risky in patients who develop intra-abdominal sepsis. In this study, the effects of combined glutamine and growth hormone (GH) on healing of intestinal anastomosis following intestinal repair in the rat intra-abdominal sepsis was induced. Material and methods: Forty Sprague Dawley Albino rats at 10 weeks weighing between 180 and 240 g were included in the study. All the animals were divided into five groups comprising eight rats each. In the control group, no treatment was given in addition to the routine oral nutrition before and after surgery. In the other groups, following surgery, oral glutamine was given at a dose of 1 mg/kg/d in the glutamine group, subcutaneous GH was given at a dose of 1 mg/kg/d in the GH group, and combined glutamine and GH were administered at the same doses in the glutamine + GH group. In rats, a clinical model mimicking intestinal fistula was generated and fistula repair was performed, and the bursting pressure of the repair area and tissue hydroxyproline level of the repair area were calculated. Results: Compared with the control group, glutamine, GH, and combined groups displayed significantly higher mean bursting pressures and tissue hydroxyproline levels. Conclusion: In order to decrease the risks originating from impaired mechanisms due to intra-abdominal sepsis, and to make anastomosis safer, combined use of glutamine and GH increases the bursting pressure of anastomosis. While the use of either of these two substances alone is effective, combined use makes this effect more prominent. [Copyright &y& Elsevier]

Abstract: Background: The optimal management of colon injury patients requiring damage control laparotomy (DCL) is controversial. The objective of this study was to assess the safety of colonic resection and anastomosis versus fecal diversion in trauma patients requiring DCL. Methods: Patients with traumatic colon injuries undergoing DCL between 2000 and 2010 were identified by the database and chart review. Those who died within 48h were excluded. Patients were divided into two groups: those undergoing one or more colonic anastomoses with or without distal colostomy (group 1) and those undergoing colostomy only or one or more colonic anastomoses with a protecting proximal ostomy (group 2). Variables were compared using Wilcoxon rank sum, χ2, or Fisher exact tests as appropriate. Results: Sixty-one patients were included (group 1, n =28 and group 2, n =33). Fascial closure rates (group 1, 50% versus group 2, 61%; P =0.45), hospital length of stay (29 versus 23d; P =0.89), and in-patient mortality (11% versus 12%; P =1.0) were similar between groups. There were a total of 11 anastomotic leaks, five of which were related to non-colonic enteric repairs. Colonic anastomosis leak rates were 16% overall (six of the 38 patients), 14% in group 1 (four of the 28 patients), and 20% in group 2 (two of the 10 patients). Compared with patients who did not leak, patients who leaked had a higher median age (37 versus 25y; P =0.05), greater likelihood of not achieving facial closure before post-injury day 5 (18% versus 2%; P =0.003), and a longer hospital length of stay (46 versus 25d; P =0.003). Conclusions: Outcomes after colonic injury in the setting of DCL were similar regardless of the surgical management strategy. Based on these findings, a strategy of diversion over anastomosis cannot be strongly recommended. [Copyright &y& Elsevier]

Background: Alterations of thyroid hormones in colorectal surgery were previously studied. The aim of the present study was to determine the effects of triiodothyronine (T3) supplementation on anastomotic healing after segmental colectomy. Material and Methods: Thirty male Wistar albino rats were divided into sham (n = 6), control (n = 12), and experimental (n = 12) groups. Sham group rats were immediately sacrificed after segmental colonic resection. Control and experimental group rats underwent resection and anastomosis. Experimental group rats received a single dose of T3 (400 μg/100 g) in postoperative day 1. Half of both control and experimental group rats were sacrificed on postoperative d 3 and the remaining half were sacrificed on postoperative d 7. Hydroxiproline (HP), myeloperoxidase (MPO), thyroid stimulating hormone (TSH), free T3 (FT3), and free thyroxine (FT4) levels, bursting pressure, and histologic analyses of the anastomotic segments were compared. Results: FT3 levels significantly decreased in control groups rats compared with the sham group (P < 0.01). However, T3 hormone given rats had no decline in FT3 levels. Anastomotic bursting pressure was significantly higher in the experimental group rats on postoperative d 7 (P = 0.015). Histopathologic analyses of the anastomotic segments determined significantly more severe edema and necrosis in control group rats (P < 0.05). Collagen deposition in the anastomotic tissue was significantly higher in experimental group rats on postoperative d 7 (P = 0.015). Conclusion: Anastomosis after colon resection is associated with decreased FT3 level. T3 supplementation ameliorates the reduction in FT3 and seems to provide constructive therapeutic effects on anastomotic healing. [ABSTRACT FROM AUTHOR]

Abstract: We describe a novel putative mycovirus infecting the conifer root-rot fungus Heterobasidion annosum sensu lato. This virus, designated as Heterobasidion RNA virus 6 (HetRV6), is taxonomically distant from all previously known viruses of Heterobasidion species, but somewhat related to the Curvularia thermal tolerance virus and the Fusarium graminearum virus 4. Based on a population analysis including 35 virus strains from Heterobasidion abietinum, Heterobasidion parviporum, Heterobasidion annosum sensu stricto and Heterobasidion occidentale, HetRV6 showed a considerable degree of geographical and host-related differentiation. The North American and Eurasian virus populations were clearly separated. In Eurasia, we observed cases of discrepancy between virus and host taxonomy, suggesting interspecies virus transfer. HetRV6 was also successfully transmitted between the three European species H. abietinum, H. annosum and H. parviporum. Based on growth rate tests on agar plates and spruce stem pieces, HetRV6 seemed to be cryptic or slightly mutualistic to its host. [Copyright &y& Elsevier]

Background: We have accumulated multiple lines of evidence supporting the ability of HB-EGF to protect the intestines from injury and to augment the healing of partial-thickness scald burns of the skin. The aim of the current study was to investigate the role of heparin-binding EGF-like growth factor (HB-EGF) in intestinal anastomotic wound healing. Materials and Methods: HB-EGF (–/–) knockout (KO) mice (n = 42) and their HB-EGF (+/+) wild type (WT) counterparts (n = 33), as well as HB-EGF transgenic (TG) mice (n = 26) and their (WT) counterparts (n = 27), underwent division and reanastomosis of the terminal ileum. In addition, WT mice (n = 21) that received enteral HB-EGF (800 μg/kg) underwent the same operative procedure. Anastomotic bursting pressure was measured at 3 and 6 d postoperatively. Tissue sections were stained with hematoxylin and eosin to assess anastomotic healing, and Picrosirus red to assess collagen deposition. Immunohistochemistry using anti-von Willebrand factor antibodies was performed to assess angiogenesis. Complications and mortality were also recorded. Results: HB-EGF KO mice had significantly lower bursting pressures, lower healing scores, higher mortality, and higher complication rates postoperatively compared with WT mice. Collagen deposition and angiogenesis were significantly decreased in KO mice compared with WT mice. Conversely, HB-EGF TG mice had increased anastomotic bursting pressure, higher healing scores, lower mortality, lower complication rates, increased collagen deposition, and increased angiogenesis postoperatively compared with WT mice. WT mice that received HB-EGF had increased bursting pressures compared with non-HB-EGF treated mice. Conclusion: Our results demonstrate that HB-EGF is an important factor involved in the healing of intestinal anastomoses. [ABSTRACT FROM AUTHOR]

Background: Nuclear factor (NF)-κB plays an essential role in inflammation. We tested this role by administering NF-κB-inhibitors into rats undergoing a well-established model of colonic anastomotic healing. Methods: Wistar rats underwent laparotomy, descending colonic transection, and handsewn reanastomosis. The animals were randomized to receive either a selective NF-κB inhibitor (parthenolide 0.5 mg/kg or resveratrol 0.5 mg/kg) or an equal volume of water by gavages before operation and then daily after surgery. Animals were sacrificed either immediately after anastomotic construction (d 0) or at the third, fifth, or seventh postoperative day. Results: Both parthenolide and resveratrol treatment led to early significant increases in plasma levels of IL-6. On d 7, hydroxyproline levels were significantly higher in the parthenolide and resveratrol groups. A similar pattern was observed with the bursting pressure. In contrast, gelatinase activity (MMP-2 and MMP-9 expression) was significantly higher in the control group on postoperative d 3. On d 3, expression of NF-κB activity was up-regulated in the anastomotic area. Both parthenolide and resveratrol completely attenuated NF-κB activity. Study groups also developed more marked inflammatory cell infiltration and collagen deposition on histology analysis. Conclusions: Parthenolide and resveratrol significantly improved healing and mechanical stability of colonic anastomoses in rats during the early postoperative period. Both agents may be acting to accelerate the host reparative process as well as to enhance protection of the anastomotic wound bed. [Copyright &y& Elsevier]

Abstract: A colony-print immunoassay (CPIA) using an anti-dsRNA antibody was developed to visualize the distribution of four unrelated mycoviruses with dsRNA genomes, a partitivirus (RnPV1), mycoreovirus (RnMyRV3), megabirnavirus (RnMBV1), and an unidentified virus (RnQV1), in mycelia of the white root rot fungus, Rosellinia necatrix. CPIA revealed different distribution patterns within single colonies for each virus. Both RnPV1 and RnMBV1 were distributed throughout single colonies, RnMyRV3 was absent from some colony sectors, and RnQV1 exhibited varied accumulation levels between sectors. RnMyRV3 and RnQV1 were transmitted to the recipient virus-free colonies of virus-infected and virus-free colony pairs more slowly than were RnPV1 or RnMBV1. The presence of RnMyRV3 in recipient colonies restricted horizontal transmission of RnPV1 and RnMBV1. These results imply that one or more mechanisms are present in host–virus and virus–virus interactions that restrict the spread of viruses within and between colonies. [Copyright &y& Elsevier]

Background: Postoperative anastomotic strictures produce significant morbidity after esophagectomy. Previous reports have described a variable association between the diameter of the circular end-to-end anastomosis (EEA) stapler commonly used in esophagogastric anastomoses and the incidence of stricture formation. Stapler technology has improved. We investigated an association between stapler diameter and the incidence of postoperative anastomotic strictures in a contemporary series. This has renewed importance given the limited diameter of trans-oral staplers that are being increasingly used. Methods: Retrospective chart review revealed that of 194 patients undergoing an esophagectomy over a 10-y period (10/1998–8/2008) at our institution, an EEA stapler was used in 91. EEA size information and follow-up were available in 89 patients. Patients were divided into two groups based on EEA size: ‘small’ = 23–25 mm (n = 24) and ‘large’ = 28–33 mm (n = 65). Patients with strictures were identified based on symptoms of dysphagia requiring an esophageal dilation procedure. Patients with postoperative leaks were excluded when analyzing for the association of stricture with EEA size, as postoperative leaks are known to be associated with stricture. Wilcoxon and Fisher’s exact tests were used for statistical analysis; a 5% α error was accepted. Results: Fifteen (16.8%) of 89 patients developed a stricture postoperatively. The anastomotic leak rate was 3.3%. There was no statistically significant association between EEA size group and stricture formation (P = 0.7506). Conclusions: No association was found between the size of the EEA stapler used and stricture formation. EEA size should be determined at surgery by the native esophageal diameter. [ABSTRACT FROM AUTHOR]

Objective: To compare anastomotic complications of stapled versus hand-sewn cervical esophago-gastric anastomosis. Methods: All patients undergoing esophageal resection are entered into a prospectively maintained database. The database was queried to identify patients who had near total esophagectomy with cervical esophago-gastric anastomosis. The effect of anastomotic technique and surgeon experience on anastomotic complications, leak, and stricture were analyzed. Results: Eighty-one patients underwent open or minimally invasive esophagectomy and gastric pull-up with or without thoracic mobilization. Eighteen patients had hand-sewn anastomosis and 63 had a partially stapled anastomosis. There was no significant difference between leak rate (22% (4/18) versus 7% (5/63) P = 0.09) and anastomotic stricture rate (38% (7/18) versus 26% (17/63), P = 0.34) between the two groups. Dividing the experience chronologically into three groups of 27 reveals a trend towards decreased leak rate with experience. The leak rate was only 3.7 % (1/27) in the most recent group compared with 14.8% (4/27) in the first group (P = 0.17). Conclusions: In our experience, there was no significant difference in anastomotic complications between hand-sewn and stapled anastomosis. However, there is a decreasing trend in anastomotic complications with increasing surgeon experience. [Copyright &y& Elsevier]

Abstract: A mixture between 1% sodium myristate and guanidine hydrochloride at a molar ratio of 1 in water forms a gel of membranes below a phase transition of ca. 21°C and a viscous limpid and isotropic solution above. As observed by both TEM and AFM, we report the formation of interconnected superstructures in that latter phase. Those assemblies exhibit a size of ca. 4–40nm width and several tens of μm length with unexpected disconnections and re-connections between them having the appearance of an anastomosis-like superstructure. [Copyright &y& Elsevier]

Background: Anastomotic leakage is the major complication after colorectal surgery. To date, animal experiments concerning colorectal anastomosis focus on anastomotic healing instead of anastomotic leakage. This study aims to develop a new experimental model for colorectal anastomotic leakage. Methods: A control group, receiving an anastomosis with 12 interrupted sutures, was compared to a group receiving an anastomosis with 6 interrupted sutures. When the leakage rate was observed to be too low, the number of sutures was decreased stepwise, to 5 or less. Each group contained 9 “C57Bl6–mice”. After 7 d the Anastomotic Bursting Pressure (ABP) was determined. Results: In the first experiment, one mouse (11.1%) in the case group and none in the control group developed leakage. Average ABP was 152,2 mmHg in the control group and 138,8 mmHg in the case group (P =0,111). In the second experiment, case group receiving an anastomosis with 5 sutures, 4 mice (44.4%) in the case group developed leakage. This experiment was repeated twice resulting in leakage rates of 33.3% and 44.4%. The average overall ABP in the case group was 142,7 mmHg vs. 179,9 mmHg (P =0,022) in the control group. The mice without leakage showed a stabilization of average weight loss around day 2 and 3 and a decrease afterwards. The mice with leakage showed a decrease only after day 5. The difference in wellness-scores between the groups with- and without leakage was 2 points, increasing during follow-up. Conclusions: The model of anastomotic leakage caused by creating an anastomosis with 5 interrupted sutures is feasible. Weight loss and wellness-scores are good predictors of leakage. [Copyright &y& Elsevier]

Background: Arteriovenous grafts often fail due to stenosis caused by venous anastomotic intimal hyperplasia (IH) and vascular smooth muscle cell (VSMC) proliferation. We examined the effects of inhaled carbon monoxide (CO), a product of heme-oxygenase-1 degradation of heme, on IH in a porcine arteriovenous graft model. Materials and methods: Eighteen Yorkshire pigs were divided into three groups (N = 6/group): (1) CO 100 ppm preoperatively for 1 h; (2) CO 250 ppm preoperatively for 1 h and intraoperatively; and (3) air-treated controls. Animals underwent end-to-side placement of polytetrafluoroethylene grafts connecting the common femoral artery and vein in both groins. Intimal thickness of the venous anastomosis at 30 days was measured blinded. The effect of CO on pig VSMC proliferation was studied in cell culture using [3H]thymidine incorporation. Results: Pigs in the group receiving CO 250 ppm showed significantly less IH compared to animals in the group receiving 100 ppm and the air-treated group (267.5 ± 21.4, 824 ± 145.8, and 914.8 ± 133.7 pixels, respectively, P < 0.0001). This effect was not observed when comparing the 100 ppm group to the air-treated group. COHb levels were significantly elevated in the 100 ppm and 250 ppm compared to air-treated pigs (5.8 ± 0.47, 13.2 ± 1.0 versus 2.3 ± 0.11%, respectively, P < 0.001). Oxygen saturation, respiratory rate, and hemodynamics were not significantly different between the groups. CO induced VSMC growth arrest compared to air in vitro (11.9 ± 4 versus 20.3 ± 5 103 counts/min/well, P < 0.01). Conclusion: A single exposure to a low concentration of inhaled CO (250 ppm) confers protection against intimal proliferation of VSMCs when given perioperatively in a clinically relevant model of arteriovenous grafts. These data are the first to suggest, in a clinically relevant model, the potential role for CO in clinical applications. [Copyright &y& Elsevier]

Introduction: Lipo-prostaglandin E1 (PGE1) is a new preparation of PGE1 in which it is bound to lipids to slow PGE1 release and delay its rate of metabolism. We investigated the change of the blood flow on impaired microcirculation of the ischemic gastric tube in pigs after saline, unmodified PGE1, and lipo-PGE1 administration. Materials and methods: The gastric tube was constructed using 15 domestic pigs under general anesthesia, and saline, unmodified PGE1, and lipo-PGE1 were infused continuously at a rate of 0.05 μg/kg/min for 10 min. Tissue blood flow (TBF) and the serum PGE1 concentration were analyzed before administration, after administration for 10 min, and 10 min after the end of administration. Results: There were no obvious changes in TBF during the administration of saline. However, TBF during treatment with unmodified PGE1 and lipo-PGE1 was significantly increased to 13.0 ± 1.3 and 13.9 ± 1.3 ml/min/100 g, respectively (paired t-test; P < 0.01). Although TBF was significantly decreased to 8.0 ± 1.0 ml/min/100 g on 10 min after the end of unmodified PGE1 administration (paired t-test; P < 0.01), it was maintained over 10 ml/min/100 g in lipo-PGE1 group. The serum PGE1 concentration during treatment with unmodified PGE1 and lipo-PGE1 was significantly increased to 229 ± 21 and 225 ± 9 pg/ml (paired t-test; P < 0.01), however, it was significantly decreased to 59 ± 5 and 131 ± 17 pg/ml (paired t-test; P < 0.01), respectively, on 10 min after the end of administration. However, the serum PGE1 concentration in lipo-PGE1 group was significantly higher than that in unmodified PGE1 group (unpaired t-test; P < 0.01). Conclusion: Lipo-PGE1 infusion leads to the objectively measurable improvement and the prolonged action in the blood perfusion of the gastric tube in pigs. Therefore, treatment with lipo-PGE1 infusion can increase TBF at the anastomotic site, and it may be beneficial for preventing anastomotic leakage in boluses for a couple of times a day. [Copyright &y& Elsevier]

Background: Previous formulations of cyanoacrylate, though very effective, proved to have too high a tissue reactivity to be used internally. A novel cyanoacrylate compound with less tissue reactivity was recently developed. The objective of this study was to assess this novel cyanoacrylate compound for the use as vascular suture line sealant. Materials and methods: Twelve adult female sheep received a 6 mm PTFE interposition graft in each iliac artery, for a total of 24 grafts. Using oxidized cellulose (Surgicel) as a control, two formulations of a new cyanoacrylate compound (named “compound A” and “compound B”) were assessed during this trial. Hemostatic efficiency was measured at the time of operation by the assessment of bleeding time and amount of blood loss. Long-term graft patency was assessed angiographically at 4, 6, and 18 months. Tissue reaction at 2 weeks, 1, 6, and 18 months was assessed grossly by vascular surgeons and microscopically by a blinded pathologist. Results: Average time to hemostasis was 37.6, 50.6, and 219 s in group A, group B, and oxidized cellulose control groups, respectively (P ≤ 0.001 for both compounds versus control). There were no significant differences between groups with regards to graft patency. Histopathology analysis demonstrated mild to moderate tissue reaction at 2 weeks and 1 month in the cyanoacrylate groups compared with controls at 1 month (ANOVA P = 0.004). Mild tissue reaction was seen at 6 months and 18 months, with no significant differences between groups (ANOVA P = 0.08, 0.62, respectively). Conclusions: The novel cyanoacrylate compound examined in this study is a highly effective suture line sealant with only mild tissue reactivity and no significant effects on graft patency when studied over an 18 month period. [Copyright &y& Elsevier]

Postnatal neovascularization is essential for wound healing, cancer progression, and many other physiological functions. However, its genetic mechanism is largely unknown. In this report, we study neovascularization in regenerating adult zebrafish fins using transgenic fish that express EGFP in blood vessel endothelial cells. We first describe the morphogenesis of regenerating vessels in wild-type animals and then the phenotypic analysis of a genetic mutation that disrupts blood vessel regeneration. In wild-type zebrafish caudal fins, amputated blood vessels heal their ends by 24 h postamputation (hpa) and then reconnect arteries and veins via anastomosis, to resume blood flow at wound sites by 48 hpa. The truncated vessels regenerate by first growing excess vessels to form unstructured plexuses, resembling the primary capillary plexuses formed during embryonic vasculogenesis. Interestingly, this mode of vessel growth switches by 8 days postamputation (dpa) to growth without a plexus intermediate. During blood vessel regeneration, vessel remodeling begins during early plexus formation and continues until the original vasculature pattern is reestablished at ∼35 dpa. Temperature-sensitive mutants for reg6 have profound defects in blood vessel regeneration. At the restrictive temperature, reg6 regenerating blood vessels first fail to make reconnections between severed arteries and veins, and then form enlarged vascular sinuses rather than branched vascular plexuses. Reciprocal temperature-shift experiments show that reg6 function is required throughout plexus formation, but not during later growth. Our results suggest that the reg6 mutation causes defects in branch formation and/or angiogenic sprouting. [Copyright &y& Elsevier]

Background. The CorLink™ Automated Anastomotic Device (AD) was developed to create a sutureless vein-to-aorta anastomosis without the need to clamp the aorta. This study examined the effectiveness and safety of this device in an animal model.Materials and methods. Forty-seven vein-to-aorta anastomoses using the AD and 27 control hand-sutured anastomoses were constructed in 28 sheep. The distal part of these grafts were connected either to the main pulmonary artery (40 AD, 20 control), or to the sheep’s brachiocephalic trunk (7 AD, 7 control). Procedural details focusing on deployment, leakage, and early patency rates were examined. Sheep were sacrificed after periods ranging from 1 to 180 days. Specimens were examined grossly and histologically.Results. All but three attempts to construct an anastomosis were successful (2 AD, 1 control). All anastomoses were patent immediately after their construction. There was no difference between control and AD anastomoses in respect to flow rates at the end of operation and before sacrifice. No metal breaks were detected. Fourteen of the 47 AD anastomoses and 6 of the control anastomoses (29.8% versus 22.2% P = ns) were occluded at autopsy. Histological findings characteristic of the healing process, were evenly distributed between AD and control anastomoses in both models. Intimal thickening was found in a notable number of anastomoses, but without any significant difference between the AD and control sutured (44.7% versus 40.7% P = ns).Conclusions. The AD proved safe and effective for the construction of proximal vein-to-aorta anastomoses as compared to control hand-sutured anastomoses. [Copyright &y& Elsevier]

Objective. The purpose of this study was to compare the hemostatic efficacy of the common surgical hemostatic agents with fibrin sealant (FS) and to assess their functional strength to secure hemostasis in lieu of placing additional sutures.Methods. End-to-end anastomosis of transected abdominal aorta was performed in moderately anticoagulated rabbits using 4 or 6 interrupted sutures. The suture line was covered either with gauze alone (“untreated”) or with gauze plus Gelfoam, Avitene, Surgicel, FloSeal, or FS, following which blood flow was restored. Blood loss was absorbed by gauze and measured. The surviving rabbits were recovered and the repaired vessel was examined histologically 4 weeks after operation. The investigators were blinded to the treatment groups. Aortic anastomoses using 8 or 12 sutures (untreated) were also performed.Results. Untreated 4-suture anastomosis of aorta resulted in a profuse hemorrhage with an average 108.0 ± 19.2 (mean ± SD) ml blood loss and 100% mortality (n = 4). FS application sealed the anastomoses, prevented blood loss (P < 0.01 vs untreated) and exsanguination of the rabbits (n = 4). Other hemostatic agents reduced the bleeding to varying degrees compared to the untreated animals (Gelfoam 66.4 ± 17.6, Avitene 80.6 ± 34, Surgicel 66.7 ± 16.7, FloSeal 44.2 ± 8.5 ml blood loss, n = 4/group), but the changes were not statistically significant. One to three rabbits in each group survived the operation. Six-suture aortic anastomoses, untreated, resulted in 67.7 ± 21.8 ml blood loss and 100% survival (n = 6). Application of FS produced immediate and sustained hemostasis in all the animals (P < 0.01 vs untreated). Other hemostatic agents also reduced the bleeding (Gelfoam 42.5 ± 10, Avitene 50.9 ± 12.4, Surgicel 32.1 ± 14, FloSeal 33.9 ± 5.4 ml blood loss, n = 6/group), but the changes were not statistically significant. The 8- and 12-suture aorta repairs resulted in a moderate blood loss (43.9 ± 19 and 21.3 ± 14.9 ml, respectively), followed by a stable hemostasis that precluded the need to use any hemostatic agent. The aortic cross-clamping time of the 12-suture and time to hemostasis for both the 8- and the 12-suture techniques were significantly longer than those of the 4-suture plus FS application (P < 0.01, P < 0.01 and P < 0.05, respectively).Conclusion. In a moderate coagulopathy, FS was proven to be the most efficacious hemostatic agent, producing immediate and sustained hemostasis at the arterial anastomotic site. This high efficacy is in part attributed to the strong tissue adhesive property of this agent. FS application may potentially ease the anastomosis and shorten the duration of timely critical vascular procedures. [Copyright &y& Elsevier]

Abstract: Background: Anastomotic leakage is a feared complication after esophagectomy. The purpose of this study was to investigate whether the use of a fibrin-thrombin coated collagen patch (TachoSil; Nycomed, Zurich, Switzerland), applied as a sealant, would strengthen the esophagogastric anastomosis and stimulate anastomotic healing in a rat model. Methods: Hand sewn, end-to-side esophagogastric anastomoses were performed in 54 rats. Animals were randomized for an unsealed or sealed anastomosis. Rats were sacrificed on postoperative d 0, 3, 5, and 7. Primary parameter was bursting pressure. Secondary outcomes were complications, weight, and immunohistochemical staining for collagen formation and fibroblast activity. Results: Bursting pressure at d 0 and 3 was significantly increased when a sealant was used (55.1 ± 4.6 mmHg versus 102.4 ± 7.3 mmHg, P < 0.010; and 19.7 ± 3.3 mmHg versus 34.6 ± 4.9 mmHg, P < 0.050 respectively). There was no difference in bursting pressure at d 5 and 7 between unsealed and sealed anastomoses (60.9 ± 18.2 mmHg versus 53.4 ± 6.6 mmHg, P = 0.690; and 118.8 ± 20.2 mmHg versus 97.2 ± 8.3 mmHg, P = 0.374 respectively). Application of sealant independently influenced bursting pressure (P < 0.010). Increased fibroblastic activity was noticed at d 7 in sealed anastomoses (P < 0.050). There were no differences in weight gain between groups. Conclusions: Additional sealing of the anastomosis increased anastomotic strength during early postoperative recovery when anastomotic strength is at its weakest. The findings indicate that sealing of the anastomosis has the potential to prevent leakage after esophagectomy in humans. [Copyright &y& Elsevier]

Background: Anastomotic leakage following colorectal surgery still occurs all too frequently, and this complication is difficult to predict. A nonfunctional stoma may reduce the risk of clinically relevant leaks but is overtreatment for most patients. More accurate assessments of the risk of anastomotic leakage would be very helpful in tailoring treatment in colorectal surgery. Therefore, a Colon Leakage Score (CLS) was developed and tested. Material and Methods: The CLS was developed based on information from the literature and expert opinions. It was tested in a retrospective cohort of consecutive patients undergoing left-sided colorectal surgery with primary anastomosis in a teaching hospital in The Netherlands. Results: In the test cohort, 10 of 121 patients who were not treated with a nonfunctional stoma experienced anastomotic leakage. The mean CLS in the leakage group was 16 versus eight in the group that did not have a leak (P < 0.01). Using receiver-operating characteristics, the area under the curve (AUC) showed that the CLS was a good predictor (AUC = 0.95, CI 0.89–1.00) of anastomotic leakage. Furthermore, logistic regression analysis with CLS as a predictor for anastomotic leakage showed an odds ratio of 1.74 (95% CI 1.32–2.28, P < 0.01). Conclusions: The CLS can predict the risk of anastomotic leakage following left-sided colorectal surgery. After further validation, this score may help the surgeon make a more individualized, safer decision regarding whether to perform an anastomosis or make a (nonfunctional) stoma. [ABSTRACT FROM AUTHOR]

Introduction: Anastomotic failure is one of the most frequent complications in abdominal surgery. During anastomotic healing. the strength of the intestinal tissue nearby is closely related to the accumulation of collagen in interlinked scar tissue. This in turn is influenced, among other things, by single groups of matrixmetalloproteinases, especially collagenases (MMP-1, -8, and -13) and gelatinases (MMP-2 and -9). EPO is known to induce the expression of tissue-inhibitor-of-matrixmetalloproteinases-1 (TIMP-1) and thereby to down-regulate MMPs. Materials and Methods: We used a rat as an experimental model and applied a high dose of EPO (5U/g BW s.c.), one dose 24 h before operation (as pre-conditioning) and one dose directly after performing a colonic anastomosis. After 3 and after 5 d, respectively, immunohistochemical stainings for MMP-2, -8, and -9 as well as TIMP-1 were carried out and evaluated semiquantitatively for each layer of the colonic wall. Sirius-red staining and cross-polarization microscopy were evaluated and the collagen I/III ratio calculated. Anastomotic and colonic tissue distal to the anastomosis were used to determine collagen content. Results: We found increased bursting pressure 5 d post-surgery after applying erythropoietin. It was thus shown that EPO influences collagen metabolism and changes the collagen I/III ratio in the colon distal to the anastomosis. The evaluation of immunohistochemistry did not show the expected ubiquitous up-regulation of TIMP-1 and down-regulation of MMPs. Nevertheless, correlations between TIMP-1, MMP-8, and collagen I/III ratio could only be established after the application of EPO. Conclusion: Contrary to our hypothesis, the picture of TIMP-1 and of the regulation of the MMPs after the application of EPO is not as clear as expected. EPO improves anastomotic bursting strength and the correlation of TIMP-1, MMP-8, and collagen type I/III ratio can only be seen after the application of EPO. [ABSTRACT FROM AUTHOR]