European Surgical Research最新文献

Background: Wound healing of the skin is a very complex biological activity. For a better understanding, an attempt is made to describe and subdivide the different players (cell types and signaling molecules), patterns (different regeneration or repair mechanisms), and processes (division of the overall process into categories, phases, and steps). However, this is always based on different points of view. On the one hand, the temporality of the phases and on the other hand, the dominant activity in each step can play a role. In addition, classifications according to wound theory and wound treatment are possible.

Summary: To gain an initial overview of (human) skin wound healing, simple classifications are advantageous for understanding and thus deserve to exist. The complexity of the underlying biology of skin wound healing takes on a multidimensional configuration upon closer examination, in which new actors are constantly being identified, making the events more precise and comprehensible but also significantly confusing when viewed as a whole. From this point of view, the healing process must be categorized so that the observer does not get lost in the multitude of interacting processes. In view of the steadily increasing knowledge, which includes in parallel the physiological as well as the pathophysiological processes of wound healing, the classification according to function in the sense of consecutive and overlapping phases seems the most convenient and considers the corresponding processes more precisely. Despite that many mechanisms and specific cellular functions in wound healing have been identified, many underlying (patho-)physiological processes still remain unknown.

Key messages: Currently, a substantial part of research activities in medicine is limited to molecular levels, while evidence for therapies currently in use is lacking or newly gained knowledge is quite far from clinical applicability and reality. This article aimed to shed more light on the various classifications of skin wound healing and presents the underlying paradigms starting from simple approaches and ending with more detailed concepts.

Introduction: We investigated the effect of the gastrojejunostomy position on the postoperative oral intake in patients who have undergone pancreaticoduodenectomy (PD).

Methods: We investigated 119 patients who underwent PD between June 2013 and December 2019 and examined the effect of the horizontal and vertical distance rates of the gastrojejunostomy position on the postoperative oral intake. The patients were categorized as having poor or good oral intake based on whether their intake was up to half the required calorie intake.

Results: There were significant differences in the number of cases with grade B or C postoperative pancreatic fistula (good, 20.3% vs. poor, 60.0%; p < 0.001), horizontal distance rate (good, 0.57 vs. poor, 0.48; p = 0.02), and postoperative hospitalization period (good, 15 vs. poor, 35 days; p < 0.001). However, there was no significant difference in the vertical distance rate (good, 0.67 vs. poor, 0.71; p = 0.22). The horizontal distance rate was the independent risk factor for postoperative poor oral intake at 2-3 weeks (risk ratio, 3.69; 95% CI: 1.48-9.20).

Discussion: The oral intake was greater in patients whose gastrojejunostomy position in PD was farther from the median, suggesting the necessity of intraoperative placement of the gastrojejunostomy position as far from the median as possible.

Introduction: Sheep are frequently used in translational surgical orthopedic studies. Naturally, a good pain management is mandatory for animal welfare, although it is also important with regard to data quality. However, methods for adequate severity assessment, especially considering pain, are rather rare regarding large animal models. Therefore, in the present study, accompanying a surgical pilot study, telemetry and the Sheep Grimace Scale (SGS) were used in addition to clinical scoring for severity assessment after surgical interventions in sheep.

Methods: Telemetric devices were implanted in a first surgery subcutaneously into four German black-headed mutton ewes (4-5 years, 77-115 kg). After 3-4 weeks of recovery, sheep underwent tendon ablation of the left M. infraspinatus. Clinical scoring and video recordings for SGS analysis were performed after both surgeries, and the heart rate (HR) and general activity were monitored by telemetry.

Results: Immediately after surgery, clinical score and HR were slightly increased, and activity was decreased in individual sheep after both surgeries. The SGS mildly elevated directly after transmitter implantation but increased to higher levels after tendon ablation immediately after surgery and on the following day.

Conclusion: In summary, SGS- and telemetry-derived data were suitable to detect postoperative pain in sheep with the potential to improve individual pain recognition and postoperative management, which consequently contributes to refinement.

Background: Tympanic membrane perforations (TMPs) are a common complication of trauma and infection. Persisting perforations result from the unique location of the tympanic membrane. The wound is surrounded by air of the middle ear and the external auditory canal. The inadequate wound bed, growth factor, and blood supply lead to circular epithelialization of the perforation's edge and premature interruption of defect closure. Orthotopic animal models use mechanical or chemical tympanic membrane laceration to identify bioactive wound dressings and overcome premature epithelialization. However, all orthotopic models essentially lack repetitive visualization of the biomaterial-wound interface. Therefore, recent progress in 3D printing of customized wound dressings has not yet been transferred to the unique wound setup of the TMP. Here, we present a novel application for the mice dorsal skinfold chamber (DSC) with an epithelialized full-thickness defect as TMP model.

Methods: A circular 2-mm defect was cut into the extended dorsal skinfold using a biopsy punch. The skinfold was either perforated through both skin layers without prior preparation or perforated on 1 side, following resection of the opposing skin layer. In both groups, the wound was sealed with a coverslip or left unclosed (n = 4). All animals were examined for epithelialization of the edge (histology), size of the perforation (planimetry), neovascularization (repetitive intravital fluorescence microscopy), and inflammation (immunohistology).

Results: The edge of the perforation was overgrown by the cornified squamous epithelium in all pre-parations. Reduction in the perforation's size was enhanced by application of a coverslip. Microsurgical preparation before biopsy punch perforation and sealing with a coverslip enabled repetitive high-quality intravital fluorescence microscopy. However, spontaneous reduction of the perforation occurred frequently. Therefore, the direct biopsy punch perforation without microsurgical preparation was favorable: spontaneous reduction did not occur throughout 21 days. Moreover, the visualization of the neovascularization was sufficient in intravital microscopy.

Conclusions: The DSC full-thickness defect is a valuable supplement to orthotopic TMP models. Repetitive intravital microscopy of the epithelialized edge enables investigation of the underlying pathophysiology during the transition from the inflammation to the proliferation phase of wound healing. Using established analysis procedures, the present model provides an effective platform for the screening of bioactive materials and transferring progress in tissue engineering to the special conditions of tympanic membrane wound healing.

Although rat liver transplantation (LT) is useful in training surgeons to perform microsurgery, mastering these surgical techniques remains difficult. Systematized training protocols that enable learning of the proper skills in a short period of time are needed. The present study describes an efficient five-step rat LT training protocol for surgeons designed to be mastered within 3 months through continuous training. The first step was to review all procedures by watching full videos of rat LT and to watch actual LT operations performed by a skilled surgeon, enabling recognition of the anatomy of rat abdominal organs. The second step was to perform ten donor operations, including ex vivo graft preparation, to learn the atraumatic and delicate techniques. The third step was to perform ten LTs, with the goal of achieving an anhepatic time <20 min and surviving until the next day. The fourth step was to perform ten additional LTs, with the goal of achieving 7 days of survival. The fifth step was to perform 5-10 more LTs, with the goal of achieving 7 days of survival in five consecutive LT operations. Systematizing the training was found to increase its efficiency. Furthermore, determining the specific number of operations in advance is useful to maintain motivation for training. Mastering efficient rat LT will not only enhance the success of preclinical research but will enable young surgeons to better perform vascular anastomoses under a microscope in humans.

Introduction: Preoperative carbohydrate oral (CHO) drinks attenuate the surgical stress response; however, the effects of CHO supplementation on the neutrophil-to-lymphocyte ratio (NLR) as an inflammatory and immunology-based predictor remain unclear. This study evaluated the effects of preoperative CHO loading on NLR values and complications following open colorectal surgery compared with a conventional fasting protocol.

Methods: Sixty eligible participants having planned for routine and open colorectal cancer surgery from May 2020 to January 2022 were prospectively and randomly allocated to either the control (fasting) group, whose members discontinued oral intake beginning the midnight before surgery, or the intervention (CHO) group, whose members consumed a CHO solution the night before surgery and 2 h prior to anaesthesia. NLR was assessed at 06:00 h before surgery (baseline) and at 06:00 h on postoperative days 1, 3, and 5. The incidence and severity of postoperative complications were assessed by Clavien-Dindo Classification up to postoperative day 30. All data were analysed using descriptive statistics.

Results: Postoperative NLR and delta NLR values were significantly higher in controls (p < 0.001; p < 0.001). Control group participants also demonstrated grade IV (n = 5; 16.7%, p < 0.01) and grade V (n = 1; 3.3%, p < 0.313) postoperative complications. There were no major postoperative complications in the CHO group.

Conclusion: Preoperative CHO consumption reduced postoperative NLR values and the incidence and severity of postoperative complications following open colorectal surgery, compared with a preoperative fasting protocol. Preoperative carbohydrate loading may improve recovery following colorectal cancer surgery.

Introduction: Calcium is an essential co-factor in the coagulation cascade, and hypocalcemia is associated with adverse outcomes in bleeding patients, including trauma patients, women with postpartum hemorrhage, and patients with intracranial hemorrhage. In this retrospective, single-center, cohort study, we aimed to determine whether admission-ionized calcium (Ca++) is associated with higher rates of therapeutic interventions among patients presenting with acute nonvariceal upper gastrointestinal bleeding (NV-UGIB).

Methods: Adult patients admitted due to NV-UGIB between January 2009 and April 2020 were identified. The primary outcome was defined as a need for clinical intervention (two or more packed cell transfusions, need for endoscopic, surgical, or angiographic intervention). Univariate and multivariable logistic regression analyses were performed to determine whether Ca++ was an independent predictor of the need for therapeutic interventions. Propensity score matching was performed to adjust the imbalances of covariates between the groups.

Results: A total of 434 patients were included, of whom 148 (34.1%) had hypocalcemia (Ca++ <1.15 mmol/L). Patients with hypocalcemia were more likely to require therapeutic interventions than those without hypocalcemia (48.0% vs. 18.5%, p < 0.001). Specifically, patients with hypocalcemia were more likely to require endoscopic intervention for control of bleeding (25.0% vs. 15.7%, p = 0.03) and multiple packed cell transfusions (6.8% vs. 0.3%, p < 0.001). Additionally, they had significantly longer hospital stay (5.0 days [IQR 3.0-8.0] vs. 4.0 days [IQR 3.0-6.0], p = 0.01). After adjusting for multiple covariates, Ca++ was an independent predictor of the need for therapeutic intervention (aOR 1.62, 95% confidence interval [CI] 1.22-2.14, p < 0.001). The addition of Ca++ to the Modified Glasgow Blatchford score improved its accuracy in the prediction of therapeutic intervention from AUC of 0.68 (95% CI 0.63-0.72) to 0.72 (95% CI 0.67-0.76), p = 0.02. After incorporation of the propensity score, the results did not change significantly.

Conclusion: These findings suggest that hypocalcemia is common and is associated with an adverse clinical course in patients with NV-UGIB. Measurement of Ca++ on admission may facilitate risk stratification in these patients. Trials are needed to assess whether the correction of hypocalcemia will lead to improved outcomes.

Introduction: The aim of this work was the evaluation of surface modification in surgery of normally used hernia implants and thus improving their antimicrobial properties. The modification consisted of applying hybrid nanolayers with immobilized antiseptic substances (metal cations of Ag, Cu, and Zn) by sol-gel method which ensures prolonged effect of these substances and thus enables a greater resistance of the implant towards infection. In this work, attention is drawn to the issue of applying hybrid nanolayers, activation of mesh surfaces by physical plasma modification or ultraviolet C (UV C) radiation, and influence of these modifications on the mechanical properties of the final meshes. Next work will continue concentrating on the issue of antimicrobial efficacy and eventual toxicity of the prepared layers.

Materials and methods: Present-day materials of the most commonly used types of implants for reconstruction of the abdominal wall in surgery (polypropylene, polyester, polyvinylidenefluoride) were tested. Optimum conditions of application of nanolayers by sol-gel method and their thermal stabilization were examined first. Surface modification was verified by scanning electron microscope. The surface of implants was first activated for better adhesion by plasma treatment or UV radiation after preliminary tests. Maximum strength and ductility after activation and hybrid nanolayer modification were objectively measured on a universal Testometric tensile testing machine.

Results: The results of surface activation of the meshes (by both plasma treatment or UV C radiation) provided similar and satisfactory results, and particular conditions differed based on the type of material of the mesh. Usage of antimicrobial sol AD30 diluted by isopropyl alcohol in 1:1 proportion appear to be optimal. All tested cases of meshes activated by plasma treatment or UV C radiation and with applied nanolayer concluded in a slight reduction of mechanical properties in modified meshes in comparison with the original ones. However, a slight reduction of test values was not of clinical importance.

Conclusion: It was verified that surface modification of implants by sol-gel method is effective and technically possible, providing hopeful results.

Introduction: Animal models for preclinical research of subarachnoid hemorrhage (SAH) are widely used as much of the pathophysiology remains unknown. However, the burden of these models inflicted on the animals is not well characterized. The European directive requires severity assessment-based allocation to categories. Up to now, the classification into predefined categories is rather subjective and often without underlying scientific knowledge. We therefore aimed at assessing the burden of rats after SAH or the corresponding sham surgery to provide a scientific assessment.

Methods: We performed a multimodal approach, using different behavior tests, clinical and neurological scoring, and biochemical markers using the common model for SAH of intracranial endovascular filament perforation in male Wistar rats. Up to 7 days after surgery, animals with SAH were compared to sham surgery and to a group receiving only anesthesia and analgesia.

Results: Sham surgery (n = 15) and SAH (n = 16) animals showed an increase in the clinical score the first days after surgery, indicating clinical deterioration, while animals receiving only anesthesia without surgery (n = 5) remained unaffected. Body weight loss occurred in all groups but was more pronounced and statistically significant only after surgery. The analysis of burrowing, open field (total distance, erections), balance beam, and neuroscore showed primarily an effect of the surgery itself in sham surgery and SAH animals. Only concerning balance beam and neuroscore, a difference was visible between sham surgery and SAH. The outcome of the analysis of systemic and local inflammatory parameters and of corticosterone in blood and its metabolites in feces was only robust in animals suffering from larger bleedings. Application of principal component analysis resulted in a clear separation of sham surgery and SAH animals from their respective baseline as well as from the anesthesia-only group at days 1 and 3, with the difference between sham surgery and SAH being not significant.

Discussion/conclusion: To our knowledge, we are the first to publish detailed clinical score sheet data combined with advanced behavioral assessment in the endovascular perforation model for SAH in rats. The tests chosen here clearly depict an impairment of the animals within the first days after surgery and are consequently well suited for assessment of the animals' suffering in the model. A definitive classification into one of the severity categories named by the EU directive is yet pending and has to be performed in the future by including the assessment data from different neurological and nonneurological disease models.

Introduction: Ultrasound (US) imaging enables tissue visualization in high spatial resolution with short examination times. Thus, it is often applied in preclinical research. Diagnostic US, including contrast-enhanced US (CEUS), is considered to be well-tolerated by laboratory animals although no systematic study has been performed to confirm this claim. Therefore, the aim of this study was to screen for possible effects of US and CEUS examinations on welfare of healthy mice. Additionally, the potential influence of CEUS and molecular CEUS on well-being and therapy response to regorafenib was investigated in breast cancer-bearing mice.

Material and methods: Forty healthy Balb/c mice were randomly assigned for examination with US or CEUS (3×/week) for 4 weeks. Untreated healthy mice and mice receiving only isoflurane anesthesia served as controls (n = 10/group). Ninety-four 4T1 tumor-bearing Balb/c mice were allocated randomly to the following groups: no imaging, isoflurane anesthesia, CEUS, and molecular CEUS. They either received 10 mg/kg regorafenib or vehicle solution daily by oral gavage. Animals were examined three times within 2 weeks. CEUS measurements were performed using phospholipid microbubbles, and phospholipid microbubbles targeting the vascular endothelial growth factor receptor-2 were applied for molecular CEUS. Welfare evaluation was performed by daily observational score sheets, measuring the heart rate, Rotarod performance, and fecal corticosterone metabolites twice a week. On the last day, pathological changes in serum corticosterone concentrations, hemograms, and organ weights were obtained. Moreover, a potential influence of isoflurane anesthesia, CEUS, and molecular CEUS on regorafenib response in tumor-bearing mice was examined. Analysis of variance and Dunnett's post hoc test were performed as statistical analyses.

Results: Severity parameters were not altered after repeated US and CEUS examinations of healthy mice, but spleen sizes were significantly lower after isoflurane anesthesia. In tumor-bearing mice, no effect on animal welfare after repeated CEUS and molecular CEUS could be observed. However, leukocyte counts and spleen weights of tumor-bearing mice were significantly lower in animals examined with CEUS and molecular CEUS compared to the control groups. This effect was not visible in regorafenib-treated animals.

Conclusions: Repeated US and (molecular) CEUS have no detectable impact on animal welfare in healthy and tumor-bearing mice. However, CEUS and molecular CEUS in combination with isoflurane anesthesia might attenuate immunological processes in tumor-bearing animals and may consequently affect responses to antitumor therapy.