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European Surgical Research. Europaische Chirurgische Forschung. Recherches Chirurgicales Europeennes[JOURNAL]
European Surgical Research. Europaische Chirurgische Forschung. Recherches Chirurgicales Europeennes[JOURNAL]
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200 papers
Postoperative Severity Assessment in Sheep.
Zentrich E, Wassermann L, Struve B … +13 more , Selke K, Buettner M, Keubler LM, Reifenrath J, Angrisani N, Kempfert M, Krause A, Bellmann O, Kopaczka M, Merhof D, Bankstahl M, Bleich A, Häger C
Eur Surg Res · 2023 · PMID 35843208 · Publisher ↗
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,...
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.
Interferon Regulatory Factor 4 (IRF4) Promotes Lipopolysaccharide-Induced Colonic Mucosal Epithelial Cell Proliferation by Regulating Macrophage Polarization.
Hu L, Li S, Li H … +2 more , Lai B, Wen H
Eur Surg Res · 2022 · PMID 35780774 · Publisher ↗
INTRODUCTION: Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the mucosa of colon and rectum. Interferon regulatory factor 4 (IRF4) mediates macrophage anti-inflammatory phenotype (a...
INTRODUCTION: Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the mucosa of colon and rectum. Interferon regulatory factor 4 (IRF4) mediates macrophage anti-inflammatory phenotype (alternatively activated macrophages [M2]). This study aimed to investigate the mechanism of IRF4 in lipopolysaccharide (LPS)-induced colonic mucosal epithelial cell proliferation via the regulation of macrophage polarization. METHODS: Human bone marrow-derived macrophages were subjected to interleukin 4 (IL-4) induction. M2 macrophages were identified using flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). IRF4 expression in M2 macrophages was detected using Western blot and qRT-PCR. IRF4 expression was silenced in M2 macrophages. IL-10 mRNA expression and protein level were detected using qRT-PCR and Western blot. The binding relation between IRF4 and IL-10 was verified using dual-luciferase and chromatin immunoprecipitation assays. Macrophages under different treatments were cocultured with LPS-induced human colonic mucosal epithelial cells. The levels of inflammatory factors (TNF-α, IL-6, and IL-1β) were detected using enzyme-linked immunosorbent assay. The proliferation of inflammatory cells was measured using Cell Counting Kit-8 assay, and the healing of inflammatory cells was detected using wound healing assay. RESULTS: M2 macrophages alleviated LPS-induced inflammatory responses. IRF4 bound to IL-10 and promoted IL-10 expression. Inhibition of IRF4 reduced IL-10 expression and attenuated the alleviating effect of M2 macrophages on inflammatory responses. Inhibition of IRF4 combined with IL-10 overexpression enhanced the promoting effect of M2 macrophages on inflammatory healing. CONCLUSION: IRF4 promoted colonic mucosal epithelial cell proliferation by increasing IL-10 expression and regulating macrophage polarization to M2 phenotype, which might be related to UC mucosal healing.
The Long and Winding Road to Clinical Xenotransplantation: A Personal Journey.
Cooper DKC
Eur Surg Res · 2022 · PMID 35764060 · Full text
BACKGROUND: The recent clinical pig-heart transplant carried out at the University of Maryland in Baltimore is hopefully the first of many xenotransplants that will resolve the problem of the lack of availability of orga...
BACKGROUND: The recent clinical pig-heart transplant carried out at the University of Maryland in Baltimore is hopefully the first of many xenotransplants that will resolve the problem of the lack of availability of organs from deceased human donors. I offer my personal recollections of how xenotransplantation research has progressed since the mid-1980s, when the pig-to-nonhuman primate (NHP) organ transplant model was established. SUMMARY: Initially, hyperacute rejection or early antibody-mediated rejection was almost uniform. Among the milestones that were subsequently achieved are (i) the introduction of the first genetically engineered pigs that expressed a human complement regulatory protein, CD55, which was associated with prolonged graft function, extending to several weeks; (ii) the observation that conventional immunosuppressive therapy did not prevent an adaptive immune response, whereas the administration of an agent that blocked the CD40/<underline>CD154</underline> T-cell costimulation pathway was successful in this respect; (iii) the identification of the major pig carbohydrate xenoantigen as galactose-α1,3-galactose (Gal), followed by gene editing to delete its expression, and the demonstration of prolonged survival of organs from these pigs in NHPs; (iv) the resolution of coagulation dysfunction between a pig and primate by the introduction of genes for human coagulation regulatory proteins; (v) the recognition of a prolonged systemic inflammatory response to a xenograft and its suppression either by drug therapy or by further gene editing, and (vi) identification of two pig "non-Gal" xenoantigens and the production of triple-knockout (TKO) pigs. However, although many humans do not have antibodies against TKO pig cells, all Old World NHPs do have antibodies against these cells. This has provided an unexpected new barrier to testing TKO pig organ transplants in NHPs. KEY MESSAGES: The optimal gene-edited pig for clinical xenotransplantation may be one with 10 genetic manipulations. A pig with this genetic background provided the heart for the recent first clinical xenotransplant. In view of the current barrier to progress in the TKO pig-to-NHP model, the time has surely come when we need to consider moving from the laboratory to the clinic. Selection of patients for the first clinical trials is briefly discussed.
The Open Field Test as a Tool for Behaviour Analysis in Pigs: Recommendations for Set-Up Standardization - A Systematic Review.
Schulz M, Zieglowski L, Kopaczka M … +1 more , Tolba RH
Eur Surg Res · 2023 · PMID 35732140 · Full text
INTRODUCTION: The open field test (OFT) is a common tool to assess anxiety and behavioural changes in rodents. It has been adapted to pigs with no systematic investigation of how environmental changes may alter the perfo...
INTRODUCTION: The open field test (OFT) is a common tool to assess anxiety and behavioural changes in rodents. It has been adapted to pigs with no systematic investigation of how environmental changes may alter the performance of pigs. Currently, the number of published studies including the OFT in domestic pig models is increasing without standardization. METHODS: Our review aimed to investigate the open field (OF) set-ups in published studies and the similarities between performance and published parameters. RESULTS: Following the PRISMA guidelines for reviews, we selected 69 studies for inclusion in this systematic review. We determined the specific set-up conditions such as dimensions, duration, and time of day for most of the included studies; we found high variability across studies with respect to these test specifics. DISCUSSION: Our results indicate the inconsistent implementation of the set-up, including dimensions, timing, parameters, and additional combined tests (e.g., new object tests). Based on our findings, we have made recommendations for the performance of the OFT, according to the current literature.
Effect of the Gastrojejunostomy Position on the Postoperative Amount of Oral Intake in Pancreaticoduodenectomy.
Iida H, Maehira H, Maekawa T … +8 more , Mori H, Nitta N, Takebayashi K, Kojima M, Kurihara M, Bamba S, Sasaki M, Tani M
Eur Surg Res · 2023 · PMID 35709689 · Full text
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...
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.
Preoperative Physical Activity Level Measurement by Accelerometer for Predicting Post-Hepatectomy Complications: A Prospective Observational Study.
Iida H, Maehira H, Mori H … +6 more , Takebayashi K, Kojima M, Kaida S, Ueki T, Miyake T, Tani M
Eur Surg Res · 2023 · PMID 35636396 · Full text
INTRODUCTION: Recently, accelerometers have received much attention around the world. This study examined whether the preoperative physical activity level measured by an accelerometer could be a useful predictor of post-...
INTRODUCTION: Recently, accelerometers have received much attention around the world. This study examined whether the preoperative physical activity level measured by an accelerometer could be a useful predictor of post-hepatectomy complications. METHODS: Between December 2016 and December 2020, the physical activity levels of 185 patients were measured using an accelerometer 3 days before hepatectomy and from postoperative day 1 to 7. The patients without postoperative complications (n = 153) and those with postoperative complications (n = 32) were compared using either the χ2 test or Fisher's exact test for nominal variables; continuous variables were analyzed using either Student's t test or Mann-Whitney U test. Differences were considered statistically significant when the p value was <0.05. Risk factors for postoperative complications following hepatectomy were also investigated. RESULTS: The number of patients with an anatomical resection was significantly higher in patients with postoperative complications (p = 0.001). Furthermore, laparoscopic hepatectomy was performed in 65.4% of patients without postoperative complications and in 25.0% of those with postoperative complications; the difference was statistically significant (p < 0.001). The average preoperative physical activity level was 150.6 kcal/day in patients without postoperative complications and 84.5 kcal/day in those with postoperative complications (p = 0.001). Multivariate analysis identified blood loss, operative time, and preoperative physical activity level as independent risk factors for postoperative complications. DISCUSSION/CONCLUSION: Patients with lower preoperative physical activity levels are at a high risk of developing postoperative complications after hepatectomy. Hence, preoperative physical activity level measurement may be useful in predicting post-hepatectomy complications.
A Rat Model of Esophagogastric Anastomotic Stricture.
Li N, Fei X, Li C … +3 more , Zhao T, Jin H, Chen H
Eur Surg Res · 2022 · PMID 35605582 · Publisher ↗
Esophagogastric anastomosis stricture is one of the most common postoperative complications after esophagectomy; yet, its pathogenesis is still not fully understood, and the treatment and prevention of anastomotic strict...
Esophagogastric anastomosis stricture is one of the most common postoperative complications after esophagectomy; yet, its pathogenesis is still not fully understood, and the treatment and prevention of anastomotic stricture are limited due to the lack of a proper animal model. The insufficient blood supply in the gastric tube is considered a risk factor for postoperative anastomotic strictures. In this study, we used thermal imaging to develop a stable rodent model with esophagogastric anastomotic stricture caused by ischemia. Briefly, 30 male Sprague-Dawley rats have been divided into the control group and the ischemia group. The esophagogastric ischemia anastomosis was performed with the help of intraoperative thermal imaging to identify the poor perfusion area. An unpaired t test with Welch's correction was used to analyze the difference between the two groups. On postoperative day 84, in the control group, no anastomosis stricture was observed, while in the ischemia group, 12 out of 15 animals (80%) developed obvious anastomosis stricture which could not let a 2.7-mm endoscope pass through. The diameter of the anastomosis in the control group and the ischemia group were 2.80 ± 0.15 mm and 1.73 ± 0.44 mm (p < 0.01), respectively (evaluated by endoscopy examination and barium radiography). H&E stain and Masson's trichrome showed that the anastomosis in the ischemia group had more connective tissue hyperplasia and collagen deposition than control group. Thus, this new rat model can be used as a platform to further investigate the potential interventions for prevention of esophagogastric anastomotic stricture.
Welfare Assessment on Healthy and Tumor-Bearing Mice after Repeated Ultrasound Imaging.
Girbig RM, Baier J, Palme R … +3 more , Tolba R, Rix A, Kiessling F
Eur Surg Res · 2023 · PMID 35398847 · Full text
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...
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.
Severity Assessment in Rats Undergoing Subarachnoid Hemorrhage Induction by Endovascular Perforation or Corresponding Sham Surgery.
Bach-Hagemann A, Harder E, Warner L … +5 more , Conzen-Dilger C, Schmidt TP, Pinkernell S, Palme R, Lindauer U
Eur Surg Res · 2023 · PMID 35385845 · Full text
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 we...
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.
Soluble Urokinase Receptor Levels Are Not Affected by the Systemic Inflammatory Response to Anesthesia and Operative Trauma.
Laou E, Papagiannakis N, Tsiaka A … +6 more , Tsapournioti S, Chatzikallinikidis K, Mantzaflaras G, Karadontas I, Eugen-Olsen J, Chalkias A
Eur Surg Res · 2022 · PMID 35385841 · Publisher ↗
INTRODUCTION: Soluble urokinase plasminogen activator receptor (suPAR) is an emerging biomarker of the level of chronic systemic inflammation and the general condition of the patient. We aimed to investigate the impact o...
INTRODUCTION: Soluble urokinase plasminogen activator receptor (suPAR) is an emerging biomarker of the level of chronic systemic inflammation and the general condition of the patient. We aimed to investigate the impact of general anesthesia and major surgery on perioperative suPAR and C-reactive protein (CRP) levels. METHODS: This study included patients undergoing elective major noncardiac surgery with an expected duration of ≥2 h under general anesthesia. Inclusion criteria were age ≥18 years and American Society of Anesthesiologists' physical status I-IV. Blood was drawn 30 min prior to induction of anesthesia (preoperatively), as well as 30 min after emergence from anesthesia (postoperatively). Plasma suPAR levels were determined using the suPARnostic® Quick Triage lateral flow assay. CRP measurements were performed by particle-enhanced immunoturbidimetric assay. RESULTS: The difference in preoperative and postoperative suPAR levels was not statistically significant (7.7 [5.28-10.4] ng/mL vs. 7.15 [5.68-9.8] ng/mL, p = 0.462). CRP levels increased significantly during surgery (0.81 [0.24-2.1] mg/dL vs. 5.76 [2.2-8.75] mg/dL, p < 0.001). No correlation was observed between CRP and suPAR levels, both preoperatively (rho = 0.127; p = 0.208) and postoperatively (rho = 0.017; p = 0.87). A statistically significant increase was also observed in postoperative white blood cell count (7.576 vs. 10.711, p < 0.001). CONCLUSION: General anesthesia and operative trauma did not affect perioperative suPAR levels despite the activation of systemic inflammatory response.
139th Congress of the German Society of Surgery (DGCH).
Eur Surg Res · 2022 · PMID 35367991 · Publisher ↗
Abstract loading — click title to view on PubMed.
139th Congress of the German Society of Surgery (DGCH).
Eur Surg Res · 2022 · PMID 35358974 · Publisher ↗
Abstract loading — click title to view on PubMed.
Blockage of CX3CL1 Attenuates Platelet and Leukocyte Recruitment in Murine Hepatic I/R.
Funken D, Brüggemann A, Mende K … +3 more , Lerchenberger M, Rentsch M, Khandoga A
Eur Surg Res · 2023 · PMID 35279656 · Full text
INTRODUCTION: The chemokine fractalkine (CX3CL1) is critically involved in the pathophysiology of different inflammatory diseases and myocardial ischemia-reperfusion (I/R). This study aimed to analyze the role of CX3CL1...
INTRODUCTION: The chemokine fractalkine (CX3CL1) is critically involved in the pathophysiology of different inflammatory diseases and myocardial ischemia-reperfusion (I/R). This study aimed to analyze the role of CX3CL1 in the activation of platelets and leukocytes during hepatic I/R. METHODS: Under inhalation anesthesia, C57BL6 mice were subjected to warm hepatic I/R (90 min/240 min). The animals were pretreated either with a function-blocking anti-mouse CX3CL1 antibody or IgG control administered systemically before ischemia. Sham-operated animals served as controls (n = 7 each group). The inflammatory response and sinusoidal perfusion failure were evaluated by intravital microscopy. Hepatic transaminases plasma levels and histopathological tissue damage were determined as markers of hepatocellular injury. RESULTS: Sinusoidal perfusion failure, leukocyte recruitment to the liver, and transaminase activities were sharply increased upon I/R compared to sham-operated mice. Firm adhesion of platelets and concordantly leukocytes to endothelial cells is reduced significantly by a function-blocking anti-CX3CL1 antibody. We demonstrate that inhibition of CX3CL1 signaling attenuates leukocyte adhesion in the postischemic liver but does not significantly ameliorate overall perfusion failure and hepatocellular injury. DISCUSSION/CONCLUSION: Our in vivo data demonstrate a mild attenuating effect of CX3CL1 blockade on platelet and leukocyte, but not CD4+ T cell accumulation and activation in hepatic I/R injury. We report a significant effect of blocking chemokine CX3CL1 on sinusoidal perfusion failure without considerably improving overall hepatocellular injury during early reperfusion.
Effects of Oral Pirfenidone on Colon Anastomosis Healing and Adhesion Formation in Rats.
Betancourt-Vicencio S, Prieto-Aldape MR, Alvarez-Villaseñor AS … +12 more , Fuentes-Orozco C, Cortes-Flores AO, Castillo-Cardiel G, Sánchez-Martínez JA, Reyes-Elizalde EA, González-Hernández PG, Zamora-Inzunza JG, Romero-Arredondo VA, Barbosa-Camacho JF, Brancaccio-Pérez IV, Guzmán-Ramírez BG, González-Ojeda A
Eur Surg Res · 2022 · PMID 35196655 · Publisher ↗
INTRODUCTION: Many experimental studies have examined multiple drugs or treatments to improve the healing of intestinal anastomoses. Synthetic prostacyclin analogs, immunosuppressants, erythropoietin, growth hormone, ins...
INTRODUCTION: Many experimental studies have examined multiple drugs or treatments to improve the healing of intestinal anastomoses. Synthetic prostacyclin analogs, immunosuppressants, erythropoietin, growth hormone, insulin-like growth factor type 1, synthetic metalloproteinases inhibitors, and hyperbaric oxygen therapy have produced promising results in low-risk models of anastomosis dehiscence. However, in high-risk models, only hyperbaric oxygen therapy has been shown to be useful. Pirfenidone (PFD), a commonly used antifibrosing drug, has not been shown to be effective for this purpose. Our objective was to evaluate the effects of PFD on anastomosis healing and adhesion genesis in a low-risk rat model of dehiscence of colonic anastomosis. METHODS: An experimental study was conducted on 40 healthy Wistar rats randomly assigned to the control group or PFD experimental group (20 rats in each group). Colon anastomosis was performed 3 cm above the peritoneal reflection using the same technique in all animals. Mechanical resistance was studied by measuring bursting pressure. Adhesions were evaluated macroscopic and histologically using common staining techniques. Animals received the first PFD dose 12 h after surgery at a dose of 500 mg/kg one a day (SID) for 5 consecutive days. On day 6, the animals were reoperated on to measure the bursting pressure in situ and to classify adhesions macroscopically, and the anastomosed colon was resected for histological analysis. RESULTS: There were no deaths, complications, or anastomosis dehiscence in either group. The mean bursting pressure was 120.8 ± 11 mm Hg and 135.5 ± 12.4 in the control and PFD groups, respectively (p < 0.001). The adhesions were less dense and had less inflammatory cell infiltration in the PFD group (p < 0.02 and 0.002, respectively). Collagen content was slightly higher in the PFD group (p = 0.04). CONCLUSIONS: Our results revealed favorable effects of PFD in this low-risk colon anastomosis model; for example, the bursting pressure was higher, and the macroscopic adhesions were soft and exhibited less inflammatory infiltration and higher collagen content in the PFD group than in the control group. The results showing that PFD treatment was associated with better healing of minor adhesions seem to be paradoxical because the therapeutic indications for this drug are directed at treating fibrosing diseases.
Treatment with the 5-Lipoxygenase Antagonist Zileuton Protects Mice from Postoperative Ileus.
Enderes J, Mallesh S, Stein K … +5 more , Wagner M, Lysson M, Schneiker B, Kalff JC, Wehner S
Eur Surg Res · 2022 · PMID 35184063 · Publisher ↗
INTRODUCTION: Previous work of our group showed that lipoxygenase (LOX) pathways become activated upon surgical manipulation of the bowel wall and revealed a beneficial immune modulating role of the LOX-derived anti-infl...
INTRODUCTION: Previous work of our group showed that lipoxygenase (LOX) pathways become activated upon surgical manipulation of the bowel wall and revealed a beneficial immune modulating role of the LOX-derived anti-inflammatory mediator protectin DX in postoperative ileus (POI). While we found a particular role of 12/15-LOX in the anti-inflammatory LOX action during POI, the role of 5-LOX, which produces the pro-inflammatory leukotriene B4 (LTB4), remained unknown. The purpose of this study was to investigate the role of 5-LOX within the pathogenesis of POI in a mouse model. METHODS: POI was induced by intestinal manipulation (IM) of the small bowel in C57BL/6, 5-LOX-/-, and CX3CR1GFP/+. Mice were either treated with a vehicle or with the synthetic 5-LOX antagonist zileuton or were left untreated. Cellular localization of 5-LOX and LTB4 release were visualized by immunofluorescence or ELISA, respectively. POI severity was quantified by gastrointestinal transit (GIT) and leukocyte extravasation into the muscularis externa (ME) by immunohistochemistry. RESULTS: 5-LOX expression was detected 24 h after IM within infiltrating leukocytes in the ME. LTB4 levels increased during POI in wild type but not in 5-LOX-/- after IM. POI was ameliorated in 5-LOX-/- as shown by decreased leukocyte numbers and normalized GIT. Zileuton normalized the postoperative GIT and reduced the numbers of infiltrating leukocytes into the ME. DISCUSSION/CONCLUSION: Our data demonstrate that 5-LOX and its metabolite LTB4 play a crucial role in POI. Genetic deficiency of 5-LOX and pharmacological antagonism by zileuton protected mice from POI. 5-LOX antagonism might be a promising target for prevention of POI in surgical patients.
Frailty Predicts Postoperative Complications following Pancreaticoduodenectomy.
Li V, Awan A, Serrano PE
Eur Surg Res · 2022 · PMID 35172304 · Publisher ↗
INTRODUCTION: Frailty is a clinically recognizable state of decreased reserve and function across physiologic systems, characterized by an inability to cope with acute stressors. A validated modified frailty index (mFI)...
INTRODUCTION: Frailty is a clinically recognizable state of decreased reserve and function across physiologic systems, characterized by an inability to cope with acute stressors. A validated modified frailty index (mFI) was used to evaluate the impact of frailty on postoperative complications following pancreaticoduodenectomy. METHODS: Data from consecutive patients undergoing pancreaticoduodenectomy from 2011 to 2020 were collected retrospectively at a high-volume tertiary care hepatopancreatobiliary hospital. Based on an 11-item mFI, patients were grouped by high (≥0.27) and low mFI. The main outcome was postoperative complications (Clavien-Dindo classification). The impact of frailty on complications was analyzed by evaluating baseline and operative characteristics using multivariable logistic regression. Secondary outcomes included postoperative mortality, length of hospital stay, and intensive care unit (ICU) admission, which were analyzed using univariable logistic regression. RESULTS: There were 64/554 patients (12%) with high mFI. Low and high mFI had similar characteristics, including proportion of pancreatic adenocarcinoma (low mFI = 247/490 [50%] vs. high mFI = 31/64 [48%], p = 0.767), intermediate or hard pancreatic texture (low mFI = 75/191 [39%] vs. high mFI = 6/19 [32%], p = 0.512), operative room time (low mFI = 370 min vs. high mFI = 368 min, p = 0.630), and drain placement (low mFI = 355/490 [72%] vs. high mFI = 48/64 [75%], p = 0.642). The mFI score was an independent predictor for the development of any type of postoperative complications (OR 1.44, 95% CI 1.02-2.10) and major postoperative complications (OR 1.44, 95% CI 1.05-1.98) by multivariable analysis. High mFI patients had a higher 90-day mortality rate (high mFI = 7/64 [11%] vs. low mFI = 20/490 [4.1%], p = 0.017), a longer median length of hospital stay (high mFI = 11 days vs. low mFI = 8 days, p = 0.016), and a higher rate of ICU admission (high mFI = 47/64 [73%] vs. low mFI = 211/490 [43%], p < 0.001). CONCLUSION: Among patients who are considered surgical candidates, the mFI can identify those at high risk of developing postoperative complications. This tool can be used to accurately discuss postoperative risk with patients undergoing pancreaticoduodenectomy.
European Surgical Research: The Future Is Bright!
Dor FJMF, Vollmar B
Eur Surg Res · 2022 · PMID 35172303 · Full text
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Left Ventricular Wall Reconstruction with Autologous Vascularized Tunica Muscularis of Stomach in a Porcine Pilot Model.
Schilling T, Meyer T, Brandes G … +8 more , Hartung D, Tudorache I, Nolte I, Wacker F, Hilfiker A, Höffler K, Haverich A, Cebotari S
Eur Surg Res · 2023 · PMID 35134805 · Full text
INTRODUCTION: Surgical replacement of dysfunctional cardiac muscle with regenerative tissue is an important option to combat heart failure. But, current available myocardial prostheses like a Dacron or a pericardium patc...
INTRODUCTION: Surgical replacement of dysfunctional cardiac muscle with regenerative tissue is an important option to combat heart failure. But, current available myocardial prostheses like a Dacron or a pericardium patch neither have a regenerative capacity nor do they actively contribute to the heart's pump function. This study aimed to show the feasibility of utilizing a vascularized stomach patch for transmural left ventricular wall reconstruction. METHODS: A left ventricular transmural myocardial defect was reconstructed by performing transdiaphragmatic autologous transplantation of a vascularized stomach segment in six Lewe minipigs. Three further animals received a conventional Dacron patch as a control treatment. The first 3 animals were followed up for 3 months until planned euthanasia, whereas the observation period for the remaining 3 animals was scheduled 6 months following surgery. Functional assessment of the grafts was carried out via cardiac magnetic resonance tomography and angiography. Physiological remodeling was evaluated histologically and immunohistochemically after heart explantation. RESULTS: Five out of six test animals and all control animals survived the complex surgery and completed the follow-up without clinical complications. One animal died intraoperatively due to excessive bleeding. No animal experienced rupture of the stomach graft. Functional integration of the heterotopically transplanted stomach into the surrounding myocardium was observed. Angiography showed development of connections between the gastric graft vasculature and the coronary system of the host cardiac tissue. CONCLUSIONS: The clinical results and the observed physiological integration of gastric grafts into the cardiac structure demonstrate the feasibility of vascularized stomach tissue as myocardial prosthesis. The physiological remodeling indicates a regenerative potential of the graft. Above all, the connection of the gastric vessels with the coronary system constitutes a rationale for the use of vascularized and, therefore, viable stomach tissue for versatile tissue engineering applications.
Long-Term Outcomes of Left versus Right Laparoscopic Living Donor Nephrectomy with Multiple Renal Arteries.
Karayagiz AH, Besli S, Yilmaz G … +3 more , Ozdemir E, Cakir U, Berber I
Eur Surg Res · 2022 · PMID 35100577 · Publisher ↗
OBJECTIVES: The objective of this study was to compare the long-term graft outcomes of left-versus-right donor nephrectomy with multiple renal arteries (MRAs), and therefore creating a reference for the expansion of the...
OBJECTIVES: The objective of this study was to compare the long-term graft outcomes of left-versus-right donor nephrectomy with multiple renal arteries (MRAs), and therefore creating a reference for the expansion of the potential living kidney donor pool. METHODS: Laparoscopic live donor nephrectomy cases between May 2010 and October 2020 were included in this retrospective cross-sectional study. The data relating to donor and recipient demographics, surgical and anatomical characteristics, recipient, and graft status were retrieved and compared using nonparametric statistical methods and multivariate regression. Analyses were fit for survival factors. RESULTS: A total of 1,009 recipients were included in this retrospective cross-sectional study with their donors. 16.7% of the donors had been discovered to have more than one renal artery supplying the donated kidney. The acute rejection rate was 12.8%. Death-censored graft survival at postoperative year 5 for single renal artery (SRA) transplants was 89.6%, 89.5% for left-sided MRAs, and 88.2% for right-sided ones. CONCLUSIONS: Both right donor nephrectomy and left donor nephrectomy are safe procedures with no significant negatively impacted rates for neither survival nor complications of the recipients in the long-term, compared to SRA ones.
Toward Evidence-Based Severity Assessment in Mouse Models with Repeated Seizures: (II.) Impact of Surgery and Intrahippocampal Kainate.
Buchecker V, Koska I, Pace C … +4 more , Talbot SR, Palme R, Bleich A, Potschka H
Eur Surg Res · 2023 · PMID 35073547 · Full text
INTRODUCTION: Chronic epilepsy models require neurosurgical procedures including depth electrode implants. The intrahippocampal kainate model is a frequently used chronic paradigm, which is based on chemoconvulsant admin...
INTRODUCTION: Chronic epilepsy models require neurosurgical procedures including depth electrode implants. The intrahippocampal kainate model is a frequently used chronic paradigm, which is based on chemoconvulsant administration and status epilepticus induction during the surgical procedure. This experimental approach raises the question of the extent to which this approach affects postsurgical recovery. In addition to the short- and long-term impact of the surgical intervention, a potential impact of highly frequent electrographic seizure events needs to be considered in the context of severity assessment. METHODS: Various behavioral, biochemical, and telemetric parameters were analyzed in four experimental groups of mice: 1st naive, 2nd with transmitter implants, 3rd with transmitter and electrode implants, and 4th with transmitter implants, electrode implants, and kainate-induced status epilepticus. RESULTS: During the early postsurgical phase, transmitter implants caused a transient impact on Mouse Grimace scores and intragroup increase of fecal corticosterone metabolites. Additional craniotomy was associated with an influence on total heart rate variability and fecal corticosterone metabolites. Heart rate and Irwin score increases as well as a prolonged increase in Mouse Grimace scores pointed to an added burden related to the induction of a nonconvulsive status epilepticus. Data from the chronic phase argued against a relevant influence of frequent electrographic seizures on behavioral patterns, fecal corticosterone metabolites, heart rate, and its variability. However, Irwin scores indicated long-term changes in some animals with increased reactivity, body tone, and Straub tail. Interestingly, selected behavioral and telemetric data from the early post-status epilepticus phase correlated with the frequency of electrographic seizure events in the chronic phase. CONCLUSION: In conclusion, our findings argue against the pronounced impact of highly frequent electrographic seizures on the well-being of mice. However, an increased level of nervousness in a subgroup of animals should be considered for handling procedures and refinement measures. In the early postsurgical phase, several parameters indicate an influence of the interventions with evidence that the nonconvulsive status epilepticus can negatively affect the recovery. Thus, the development and validation of refinement efforts should focus on this experimental phase. Finally, the datasets suggest that simple readout parameters may predict the long-term consequences of the epileptogenic insult. Respective biomarker candidates require further validation in the follow-up studies in models with subgroups of animals with or without epilepsy development.
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