Searches / European Surgical Research. Europaische Chirurgische Forschung. Recherches Chirurgicales Europeennes[JOURNAL]

European Surgical Research. Europaische Chirurgische Forschung. Recherches Chirurgicales Europeennes[JOURNAL]

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C-Reactive Protein in the Prediction of Localization of Gastrointestinal Perforation.

Grupp K, Grotelüschen R, Uzunoglu FG … +6 more , Hofmann B, König A, Perez D, Bockhorn M, Izbicki JR, Bachmann K

Eur Surg Res · 2019 · PMID 31743923 · Publisher ↗

AIM: Information regarding the localization of the anatomic site of gastrointestinal (GI) tract perforation is essential for the following surgical procedure. The purpose of this study was to evaluate the significance of... AIM: Information regarding the localization of the anatomic site of gastrointestinal (GI) tract perforation is essential for the following surgical procedure. The purpose of this study was to evaluate the significance of C-reactive protein (CRP) and other circulating markers for the prediction of the localization of intra-abdominal hollow organ perforation. METHODS: Measurements of serum markers were analyzed in 423 patients with GI tract perforations, who were divided according to the intraoperative diagnosis into colorectal and upper GI tract perforation groups. RESULTS: Levels of CRP were higher in patients with colorectal perforations than in upper GI tract perforations (p < 0.001). Moreover, high levels of CRP were associated with increased mortality of patients with hollow organ perforations (p = 0.009), which was largely driven by the subset of patients with perforations of the upper GI tract (p = 0.001). CONCLUSION: Increased CRP levels predict worse clinical outcome in patients with intra-abdominal hollow organ perforations and are associated with perforations in the colorectal tract. Thus, CRP might be a useful marker for preoperative risk stratification and prediction of the localization of the perforation site.

A New Percutaneous Approach to Treat Combined Right Ventricular and Respiratory Failure: The "Aachen Cannula".

Hima F, Gümmer M, Prescher A … +7 more , Altarawneh B, Zayat R, Hatam N, Ernst L, Kalverkamp S, Spillner J, Arias-Pinilla J

Eur Surg Res · 2019 · PMID 31743901 · Publisher ↗

INTRODUCTION: Right ventricular failure (RVF) on its own is a life-threatening condition. Often it manifests as a two-organ failure in the final phase of several lung diseases. Mechanical circulatory support is a proven... INTRODUCTION: Right ventricular failure (RVF) on its own is a life-threatening condition. Often it manifests as a two-organ failure in the final phase of several lung diseases. Mechanical circulatory support is a proven treatment of RVF but remains challenging. Our objective is to develop a novel, simplified, and minimally invasive cannula approach to treat both RVF and respiratory failure. METHODS: We conceptualized a dual lumen cannula approach to allow oxygenated right-to-left shunting at an atrial level to decompress right-sided circulation. A minimally invasive approach through percutaneous, transjugular insertion and transseptal placement should enable patients to be non-sedated and even ambulatory. In an iterative design, pre-prototyping, prototyping, and anatomic fitting process, such a cannula was generated and tested in both cadaveric and fluid dynamic studies. RESULTS: After various modifications and improvements, a 27-Fr 255-mm-long double-lumen cannula with an inner line (oxygenated blood return to patient into the left atrium) of 18 Fr and an inflatable balloon (with a volume of approximately 1 mL) at the outflow tip was produced - one version with a straight head and another one with a curved head. In our anatomic studies, the "Aachen Cannula" allowed an easy transjugular introduction and advancement into the right atrium by Seldinger technique. Transseptal placement was achieved by puncture (Brockenbrough needle) in combination with dilatation and was then secured in place with the stabilizing balloon, even under slight tension. The cannula prototype enabled a flow of up to 3.5 L/min, at which common pressure drops were observed. CONCLUSION: In conclusion, we successfully conceptualized, designed, and verified a minimally invasive one-cannula approach for the treatment of either isolated right heart failure and even combined RVF and respiratory failure through our transseptal Aachen Cannula. This concept may also be carried out in ambulatory conditions. Moreover, this approach completely avoids recirculation issues and ensures reliable oxygenated coronary as well as cerebral perfusion.

Evaluation of the Site and Frequency of Lymph Node Metastasis with Non-Functioning Pancreatic Neuroendocrine Tumor.

Izumo W, Higuchi R, Furukawa T … +4 more , Yazawa T, Uemura S, Shiihara M, Yamamoto M

Eur Surg Res · 2019 · PMID 31734661 · Publisher ↗

BACKGROUNDS: The optimal lymph node dissection range in patients with non-functioning pancreatic neuroendocrine tumors is not yet clear. In this study, we investigated the site and frequency of lymph node metastasis and... BACKGROUNDS: The optimal lymph node dissection range in patients with non-functioning pancreatic neuroendocrine tumors is not yet clear. In this study, we investigated the site and frequency of lymph node metastasis and the significance of lymph node dissection in patients with non-functioning pancreatic neuroendocrine tumors. METHODS: This retrospective study analyzed 74 patients who underwent a curative pancreatectomy for non-functioning pancreatic neuroendocrine tumors between 2000 and 2016. The site and frequency of lymph node metastasis and clinicopathological factors were evaluated. RESULTS: The rate of synchronous lymph node metastasis was 17.6%, with 11.1 and 29.4% for tumors with diameters of 10-19 mm and ≥20 mm, respectively. Lymph node metastasis was not observed for tumors with a diameter <10 mm. Lymph node metastasis was observed along the anterior (17a: 13.3%, 17b: 12.5%) and posterior (13a: 5.9%, 13b: 26.7%) surfaces of the pancreatic head and the superior mesenteric artery (14p: 12.5%, 14d: 7.7%) in patients with non-functioning pancreatic head neuroendocrine tumors, in the common hepatic (8a: 5.3%), splenic (10: 14.3%, 11p: 17.6%, 11d: 12.5%), and super mesenteric artery (14d: 14.3%) in patients with non-functioning pancreatic body neuroendocrine tumors, and only in the splenic artery (11p: 8.3%, 11d: 7.7%) in patients with non-functioning pancreatic tail neuroendocrine tumors. Grade 2 (HR = 6.21) and synchronous lymph node metastasis (HR = 10.4) were significant risk factors for disease-free survival. The 5-year disease-free survival was 95.7, 72.6, and 0% in patients with 0, 1, and 2 prognostic factors, respectively. CONCLUSIONS: This study clarified the site and frequency of lymph node metastasis and the optimal range of lymph node dissection in patients with non-functioning pancreatic neuroendocrine tumors.

MiR-21 Promotes the Invasion and Metastasis of Gastric Cancer Cells by Activating Epithelial-Mesenchymal Transition.

Xiao T, Jie Z

Eur Surg Res · 2019 · PMID 31722341 · Publisher ↗

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors. It is likely to occur in lymph nodes and is prone to distant metastasis in its early stages, which portends a poor prognosis. Previous studies h... BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors. It is likely to occur in lymph nodes and is prone to distant metastasis in its early stages, which portends a poor prognosis. Previous studies have shown that miRNA-21 was abnormally highly expressed and associated with early metastasis in GC, but the mechanism by which it regulates the invasion and metastasis of GC has not been elucidated. METHODS: Epithelial-mesenchymal transition (EMT) is an important pathologic basis of tumor invasion and metastasis, and in this study, the relationship between miRNA-21 and EMT in GC invasion and metastasis was investigated using RT-qPCR, Western blot, and wound scratch and transwell assays. RESULTS: We found that miRNA-21 expression in GC cell lines was higher than in a gastric mucosal epithelial cell line. After transfection with an miRNA-21 mimic, the upregulation of EMT was found to promote migration and invasion of MGC-803 cells. However, the downregulation of EMT was found to accompany the inhibition of invasion and migration of GC cells after downregulation of miRNA-21 expression due to the transfection of an miRNA-21 inhibitor. CONCLUSIONS: These findings suggest that miRNA-21 might promote the invasion and metastasis of GC by upregulating EMT.

The Mechanism of Electroacupuncture at Zusanli Promotes Macrophage Polarization during the Fibrotic Process in Contused Skeletal Muscle.

Yan M, Wang R, Liu S … +4 more , Chen Y, Lin P, Li T, Wang Y

Eur Surg Res · 2019 · PMID 31694021 · Publisher ↗

INTRODUCTION: Currently, many clinical experiments are being conducted to study the effect of acupuncture on skeletal muscle contusions, and its therapeutic effect has been confirmed to some extent. However, the mechanis... INTRODUCTION: Currently, many clinical experiments are being conducted to study the effect of acupuncture on skeletal muscle contusions, and its therapeutic effect has been confirmed to some extent. However, the mechanism of recovery by electroacupuncture (EA) in skeletal muscles after blunt trauma remains unknown. OBJECTIVE: To determine whether EA at Zusanli can contribute to the regeneration of contused skeletal muscle and the molecular mechanism involved. METHODS: Masson's trichrome staining and hematoxylin and eosin staining were used to measure the area of fibrotic tissue and determine the number of centrally nucleated muscle fibers respectively. The different immune phenotypes of macrophages were determined by flow cytometry. Then, ELISA was used to analyze the levels of interleukin-4 (IL-4), IL-6, interferon-α (IFN-α) and interferon-γ (IFN-γ) in the injured tissue. Finally, the expression of MyoD in the tissue was detected by quantitative real-time polymerase chain reaction. RESULTS: EA at Zusanli helped regenerate contused skeletal muscle by alleviating fibrosis and increasing the size of the regenerating myofibres in the injured skeletal muscle. EA at Zusanli increased the number of M2 macrophages and decreased the number of M1 macrophages in contused skeletal muscle. EA at Zusanli decreased the level of cytokine IFN-γ and increased the levels of IL-4, interleukin-13 (IL-13), and IFN-α, which promoted macrophage polarization during the fibrosis recovery process in the contused skeletal muscle. EA at Zusanli could increase the expression of MyoD in tissues. CONCLUSIONS: EA at Zusanli promoted macrophage polarization during the fibrotic process in contused skeletal muscle by decreasing cytokine IFN-γ and increasing IL-4, IL-13, and IFN-α, which contributed to the regeneration of the contused skeletal muscle.

Interferon-Gamma and Tumor Necrosis Factor-Related Weak Inducer of Apoptosis Expression in Neoangiogenesis in Colorectal Polypoid Lesions.

Ruffolo C, Toffolatti L, Massani M … +9 more , Pozza A, Campo Dell'Orto M, Saadeh LM, Ferrara F, Benvenuti S, Dei Tos AP, Bassi N, Kotsafti A, Scarpa M

Eur Surg Res · 2019 · PMID 31597147 · Publisher ↗

BACKGROUND: Interferon gamma (IFNγ) and tumor necrosis factor-related weak inducer of apoptosis (TWEAK) molecules seem to have a potential effect on angiogenic factors such as vascular endothelial growth factor (VEGF). T... BACKGROUND: Interferon gamma (IFNγ) and tumor necrosis factor-related weak inducer of apoptosis (TWEAK) molecules seem to have a potential effect on angiogenic factors such as vascular endothelial growth factor (VEGF). The aim of this study was to assess a possible interplay between IFNγ and TWEAK cytokines and VEGF machinery in the different steps of colorectal carcinogenesis. METHODS: A total of 92 subjects with colonic adenoma or cancer who underwent screening colonoscopy or surgery were prospectively enrolled. Polypoid lesion tissue samples were collected and frozen. Real-time reverse transcription polymerase chain reaction for IFNγ, TWEAK, and VEGF-A mRNA expression was performed. Immunoassays for VEGF-A, VEGF-C, VEGFR-1, VEGFR-2, and VEGFR-3 were also performed. Nonparametric statistics, receiver operating characteristic curve analysis, and logistic multiple regression analysis were used. RESULTS: IFNγ and TWEAK mRNA expression was higher in patients with T2 or more advanced colorectal cancer than in those with adenomas or T1 cancer (p < 0.001 and p = 0.01, respectively). IFNγ and TWEAK mRNA expression levels directly correlated with VEGF-A mRNA expression levels (rho = 0.44, p < 0.001 and rho = 0.29, p = 0.004, respectively). On the contrary, IFNγ and TWEAK mRNA expression levels inversely correlated with VEGF-C protein levels (rho = -0.29, p = 0.04 and rho = -0.31, p = 0.03, respectively). Similarly, IFNγ and TWEAK mRNA expression levels inversely correlated with VEGFR2 protein levels (rho = -0.38, p = 0.033 and rho = -0.40, p = 0.025, respectively). CONCLUSION: This study showed that in colorectal polypoid lesions, IFNγ and TWEAK expressions are directly correlated to VEGF-A expression but inversely correlated with VEGFR2 levels, suggesting a possible feedback mechanism in the regulation of VEGF-A expression.

Systematic Surgical Assessment of Deceased-Donor Kidneys as a Predictor of Short-Term Transplant Outcomes.

Tierie EL, Roodnat JI, Dor FJMF

Eur Surg Res · 2019 · PMID 31480061 · Full text

BACKGROUND: Short-term kidney graft dysfunction is correlated with complications and it is associated with a decreased long-term survival; therefore, a scoring system to predict short-term renal transplant outcomes is wa... BACKGROUND: Short-term kidney graft dysfunction is correlated with complications and it is associated with a decreased long-term survival; therefore, a scoring system to predict short-term renal transplant outcomes is warranted. AIM: The aim of this study is to quantify the impression of the organ procurement surgeon in correlation with the following kidney transplant outcomes: immediate graft function (IGF), delayed graft function (DGF), and primary nonfunction (PNF). Results are compared to factors associated with the 1-year outcome. METHODS: A regional prospective pilot study was performed using deceased-donor organ assessment forms to be filled out by procurement surgeons after procurement. Data were gathered on kidney temperature, perfusion, anatomy, atherosclerosis, and overall quality. RESULTS: Included were 90 donors who donated 178 kidneys, 166 of which were transplanted. Variables that were significantly more prevalent in the DGF-or-PNF group (n = 65) are: large kidney size (length, p = 0.008; width, p = 0.036), poor perfusion quality (p = 0.037), lower diuresis (p = 0.039), fewer hypotensive episodes (p = 0.003), and donation-after-circulatory-death donors (p = 0.017). Multivariable analysis showed that perfusion quality and kidney width significantly predicted the short-term outcome. However multivariable analysis of long-term outcomes showed that the first measured donor creatinine, kidney donor risk index, IGF vs. DGF+PNG, and kidney length predicted outcomes. CONCLUSIONS: Results show that short-term graft function and 1-year graft function indeed are influenced by different variables. DGF and PNF occur more frequently in kidneys with poor perfusion and in larger kidneys. A plausible explanation for this is that these kidneys might be insufficiently washed out, or even congested, which may predispose to DGF. These kidneys would probably benefit most from reconditioning strategies, such as machine perfusion. A scoring system including these variables might aid in decision-making towards allocation and potential reconditioning strategies.

Vein Suturing Results in Worse Lung Graft Outcomes Compared to the Cuff Method.

Zampieri D, Azzollini N, Vuljan S … +9 more , Pezzuto F, Fiori S, Mister M, Todeschini M, Rodriguez Ordonez PY, Marulli G, Rea F, Calabrese F, Casiraghi F

Eur Surg Res · 2019 · PMID 31480059 · Publisher ↗

BACKGROUND: The rat orthotopic lung transplant model is not widely used yet because of the complexity of the procedure, in particular, venous anastomosis. Here, we performed a rat orthotopic lung transplantation using ei... BACKGROUND: The rat orthotopic lung transplant model is not widely used yet because of the complexity of the procedure, in particular, venous anastomosis. Here, we performed a rat orthotopic lung transplantation using either the suture (ST) or cuff (CT) method for vein anastomosis. OBJECTIVES: To compare the vein ST and CT techniques in terms of operative time, success, recipient survival, and early histological outcomes was the objective of this study. METHODS: A total of 24 left lung transplants in rats were performed. Twelve syngeneic (Lewis to Lewis) and 12 allogeneic (Brown-Norway to Lewis) lung transplants were performed using either the vein ST or the CT procedure. Arterial and bronchial anastomoses were performed with the CT technique. Graft histological damage was evaluated 3-7 days post-transplant in all rat lungs. RESULTS: The surgical success rate was 75% in both the ST and CT groups. Failures related mainly to vein bleeding (n = 2 in the ST group) and thrombosis (n = 1 in the ST group; n = 2 in the CT group). Total ischemia time was longer in the ST group (122 ± 25 min in ST group vs. 83 ± 10 min in CT group, mean ± SD), due to prolonged warm ischemia time (60 ± 12 min in the ST group vs. 21 ± 5 min in the CT group, mean ± SD), reflecting the time required to complete the vein ST procedure. The prolonged warm ischemia time resulted in significantly higher vascular inflammation in syngeneic grafts (2.3 ± 1.2 ST group vs. 0 in the CT group, mean ± SD) and in increased severity of ischemia/reperfusion injury and acute graft rejection (3.6 ± 0.4 in the ST group vs. 2.6 ± 0.4 in the CT group, mean ± SD) in allogeneic lung transplants. CONCLUSIONS: The vein ST technique is a more time-consuming procedure than the CT method and the prolonged anastomosis time has a deleterious impact on transplant outcomes. These findings suggest that warm ischemia time - one of the modifiable transplant factors - should be considered a major risk factor in lung transplantation, particularly in the setting of donation after cardiac death.

Myostatin Upregulation in Patients in the Chronic Phase of Severe Burn Injury Leads to Muscle Cell Catabolism.

Wallner C, Huber J, Drysch M … +5 more , Schmidt SV, Wagner JM, Dadras M, Lehnhardt M, Behr B

Eur Surg Res · 2019 · PMID 31302645 · Publisher ↗

BACKGROUND: Burn injury leads to a hypercatabolic response and ultimately muscle wasting with drastic implications for recovery of bodily functions, patient's quality of life (QoL), and long-term survival. Several treatm... BACKGROUND: Burn injury leads to a hypercatabolic response and ultimately muscle wasting with drastic implications for recovery of bodily functions, patient's quality of life (QoL), and long-term survival. Several treatment options target the body's initial stress response, but pharmacological approaches to specifically address muscle protein metabolism have only been poorly investigated. OBJECTIVE: The aim of this study was to assess the role of myostatin and follistatin in burn injury and its possible implications in muscle wasting syndrome. METHODS: We harvested serum from male patients within 48 h and again 9-12 months after severe burn injury (>20% of total body surface area). By means of myoblast cultures, immunohistochemistry, immunoblotting, and scratch assay, the role of myostatin and its implications in post-burn muscle metabolism and myoblast proliferation and differentiation was analyzed. RESULTS: We were able to show increased proliferative and myogenic capacity, decreased myostatin, decreased SMAD 2/3, and elevated follistatin concentrations in human skeletal myoblast cultures with serum conditioned medium of patients in the acute phase of burn injury and conversely a reversed situation in patients in the chronic phase of burn injury. Thus, there is a biphasic response to burn trauma, initiated by an anabolic state and followed by long-term hypercatabolism. CONCLUSION: We conclude that the myostatin signaling pathway plays an important regulative role in burn-associated muscle wasting and that blockade of myostatin could prove to be a valuable treatment approach improving the rehabilitation process, QoL, and long-term survival after severe burn injury.

Hepatic Stellate Cells Play a Functional Role in Exacerbating Ischemia-Reperfusion Injury in Rat Liver.

Takahashi T, Yoshioka M, Uchinami H … +4 more , Nakagawa Y, Otsuka N, Motoyama S, Yamamoto Y

Eur Surg Res · 2019 · PMID 31132769 · Publisher ↗

PURPOSE: The involvement of hepatic stellate cells (HSCs) with ischemia-reperfusion (I/R) injury in rat liver was examined using gliotoxin, which is known to induce HSC apoptosis. METHODS: Male Sprague-Dawley rats were u... PURPOSE: The involvement of hepatic stellate cells (HSCs) with ischemia-reperfusion (I/R) injury in rat liver was examined using gliotoxin, which is known to induce HSC apoptosis. METHODS: Male Sprague-Dawley rats were used. HSC was represented by a glial fibrillary acidic protein (GFAP)-positive cell. Liver ischemia was produced by cross-clamping the hepatoduodenal ligament. The degree of I/R injury was evaluated by a release of aminotransferases. Sinusoidal diameter and sinusoidal perfusion rates were examined using intravital fluorescence microscopy. RESULTS: Gliotoxin significantly decreased the number of GFAP-positive cells 48 h after dosing (2.50 ± 0.19% [mean ± SD] in the nontreated group vs. 1.91 ± 0.46% in the gliotoxin-treated group). Liver damage was significantly suppressed by the pretreatment with gliotoxin. Sinusoidal diameters in zone 3 were wider in the gliotoxin group (10.25 ± 0.35 µm) than in the nontreated group (8.21 ± 0.50 µm). The sinusoidal perfusion rate was maintained as well in the gliotoxin group as in normal livers, even after I/R. CONCLUSIONS: Pretreatment with gliotoxin significantly reduced the number of HSCs in the liver and further suppressed liver injury following I/R. It is strongly suggested that HSCs play a functional role in exacerbating the degree of I/R injury of the liver.

Bolus Administration of Polyamines Boosts Effects on Hepatic Ischemia-Reperfusion Injury and Regeneration in Rats.

Doi J, Fujimoto Y, Teratani T … +6 more , Kasahara N, Maeda M, Tsuruyama T, Iida T, Yagi S, Uemoto S

Eur Surg Res · 2019 · PMID 31055575 · Publisher ↗

BACKGROUND: It was demonstrated that polyamines ameliorate ischemia-reperfusion injury (IRI) and promote regeneration in the liver. An optimal protocol of polyamine treatment remains unknown in the clinical setting. We e... BACKGROUND: It was demonstrated that polyamines ameliorate ischemia-reperfusion injury (IRI) and promote regeneration in the liver. An optimal protocol of polyamine treatment remains unknown in the clinical setting. We examined 2 types of administration methods using rat models. METHODS: Experiment 1: evaluation of pharmacokinetics of polyamines. Experiment 2: for 3 days preoperatively and 5 days postoperatively, polyamines were given to male Lewis rats in the following three groups: the control group, no polyamine administration; the chow group, 0.05% polyamines mixed in chow; the bolus group, polyamines (200 μmol/kg) given by gastric tube once a day. All rats received 70% hepatectomy after 40 min of warm IRI. Postoperatively, IRI and regeneration were evaluated with assessment of serum levels of hepatic enzymes, histology and immunohistochemistry of liver tissue, and measurement of remnant liver weight. RESULTS: The blood concentrations of polyamines in the portal vein increased at 1 h of bolus administration, while they did not increase without the bolus. The bolus group was significantly associated with lower serum levels of aspartate/alanine aminotransferases (p < 0.05), decreased hepatocyte congestion, vacuolization and necrosis in histopathological scoring (p < 0.05), a lower number of TUNEL-positive hepatocytes (p < 0.05), higher remnant liver weight at 24, 48, and 168 h (p < 0.05), and a higher Ki-67 labeling index (24 h, p < 0.01) compared with the chow group. CONCLUSION: The bolus administration of polyamines was more effective in ameliorating IRI and promoting regeneration than chow administration. Perioperative bolus administration of polyamines might be an optimal treatment, when clinically applied.

Microvascular Mechanisms of Polyphosphate-Induced Neutrophil-Endothelial Cell Interactions in vivo.

Du F, Wang Y, Ding Z … +2 more , Laschke MW, Thorlacius H

Eur Surg Res · 2019 · PMID 30909276 · Publisher ↗

BACKGROUND: Polyphosphates (PolyPs) have been reported to exert pro-inflammatory effects. However, the molecular mechanisms regulating PolyP-provoked tissue accumulation of leukocytes are not known. The aim of the presen... BACKGROUND: Polyphosphates (PolyPs) have been reported to exert pro-inflammatory effects. However, the molecular mechanisms regulating PolyP-provoked tissue accumulation of leukocytes are not known. The aim of the present investigation was to determine the role of specific adhesion molecules in PolyP-mediated leukocyte recruitment. METHODS: PolyPs and TNF-α were intrascrotally administered, and anti-P-selectin, anti-E-selectin, anti-P-selectin glycoprotein ligand-1 (PSGL-1), anti-membrane-activated complex-1 (Mac-1), anti-lymphocyte function antigen-1 (LFA-1), and neutrophil depletion antibodies were injected intravenously or intraperitoneally. Intravital microscopy of the mouse cremaster microcirculation was used to examine leukocyte-endothelium interactions and recruitment in vivo. RESULTS: Intrascrotal injection of PolyPs increased leukocyte accumulation. Depletion of neutrophils abolished PolyP-induced leukocyte-endothelium interactions, indicating that neutrophils were the main leukocyte subtype responding to PolyP challenge. Immunoneutralization of P-selectin and PSGL-1 abolished PolyP-provoked neutrophil rolling, adhesion, and emigration. Moreover, immunoneutralization of Mac-1 and LFA-1 had no impact on neutrophil rolling but markedly reduced neutrophil adhesion and emigration evoked by PolyPs. CONCLUSION: These results suggest that P-selectin and PSGL-1 exert important roles in PolyP-induced inflammatory cell recruitment by mediating neutrophil rolling. In addition, our data show that Mac-1 and LFA-1 are necessary for supporting PolyP-triggered firm adhesion of neutrophils to microvascular endothelium. These novel findings define specific molecules as potential targets for pharmacological intervention in PolyP-dependent inflammatory diseases.

Abstracts: 136th Congress of the German Society of Surgery (DGCH).

Eur Surg Res · 2019 · PMID 30884487 · Publisher ↗

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Intraoperative Sentinel Node Mapping in the Colon: Potential and Pitfalls.

Currie AC

Eur Surg Res · 2019 · PMID 30799407 · Publisher ↗

Sentinel lymph node mapping (SLNM) may play a significant role in future delivery of colon cancer surgery because of an increase in early-stage, node-negative disease due to national bowel cancer screening programmes. Tr... Sentinel lymph node mapping (SLNM) may play a significant role in future delivery of colon cancer surgery because of an increase in early-stage, node-negative disease due to national bowel cancer screening programmes. Traditionally, colon lymphatic drainage has not been thought relevant as the operative approach cannot be tailored. Recent advances in local and endoscopic risk-reducing interventions for colonic malignancy have caused a rethink in approach. SLNM was initially attempted with blue dye techniques with limited success. Technological improvement has allowed surgeons to use near-infrared (NIR) light and NIR active tracers such as indocyanine green. This review provides an overview of the current status of intraoperative lymph node mapping in the colon, identifies challenges to the delivery of the techniques, and discusses potential solutions that may help SLNM play a role in improving the delivery of surgical care for patients with colon cancer.

Kinetics of Hepatic Volume Evolution and Architectural Changes after Major Resection in a Porcine Model.

Bekheit M, Bucur PO, Audebert C … +3 more , Miquelestorena-Standley E, Vignon-Clementel I, Vibert E

Eur Surg Res · 2019 · PMID 30759434 · Publisher ↗

BACKGROUND: The hepatic volume gain following resection is essential for clinical recovery. Previous studies have focused on cellular regeneration. This study aims to explore the rate of hepatic regeneration of the porci... BACKGROUND: The hepatic volume gain following resection is essential for clinical recovery. Previous studies have focused on cellular regeneration. This study aims to explore the rate of hepatic regeneration of the porcine liver following major resection, highlighting estimates of the early microarchitectural changes that occur during the cellular regeneration. METHODS: Nineteen large white pigs had 75% resection with serial measurements of the hepatic volume, density, blood flow, and architectural changes. RESULTS: The growth rate initially was 45% per day, then rapidly decreased and was accompanied by a similar pattern of hepatic fat deposition. The architectural changes showed a significant increase in the Ki67 expression (p < 0.0001) in the days following resection with a peak on the 2nd day and nearly normalized on day 7. The expression of CD31 increased significantly on the 2nd and 3rd days compared to the pre-resection samples (p = 0.03). Hepatic artery flow per liver volume remained at baseline ranges during regeneration. Portal flow per liver volume increased after liver resection (p < 0.001), was still elevated on the 1st postoperative day, then decreased. Correlations were significantly negative between the hepatic volume increase on day 3 and the hepatic oxygen consumption and the net lactate production at the end of the procedure (r = -0.82, p = 0.01, and r = -0.70, p = 0.03). CONCLUSION: The volume increase in the first days - a fast process - is not explained by cellular proliferation alone. The liver/body weight ratio is back to 50% of the preoperative value after 3 days to close to 100% volume regain on days 10-15.

Can Surgical Registrars Accurately Identify the Urgent from the Non-Urgent Patient Presenting with Acute Abdominal Pain?

de Burlet KJ, Lam ABM, Harper SJ … +2 more , Larsen PD, Dennett ER

Eur Surg Res · 2019 · PMID 30726832 · Publisher ↗

BACKGROUND: Acute abdominal pain is a common surgical presentation with a wide range of causes. Differentiating urgent patients from non-urgent patients is important to optimise patient outcomes and the use of hospital r... BACKGROUND: Acute abdominal pain is a common surgical presentation with a wide range of causes. Differentiating urgent patients from non-urgent patients is important to optimise patient outcomes and the use of hospital resources. The aim of this study was to determine how accurately urgent and non-urgent patients presenting with abdominal pain can be identified. METHODS: A prospective study of consecutive patients admitted with abdominal pain was undertaken. Urgent patients were classified as requiring treatment (theatre, intensive care unit, endoscopy, or radiologic drainage) within 24 h. Differentiation between urgent and non-urgent was made on the basis of the initial assessment prior to the use of advanced imaging. Outcomes were compared to a final classification based on final diagnosis as adjudicated by an expert panel. RESULTS: Of the 301 patients included, 93 (30.9%) were deemed urgent based on initial assessment, compared to 83 (27.6%) on final diagnosis. Overall sensitivity for recognising urgent patients was 74.7% and specificity 89.9%, and overall accuracy was higher for senior registrars compared to junior registrars (p = 0.015). Urgent patients more often looked unwell or had peritonism on examination (39.8 vs. 17.4% and 56.6 vs. 14.7%, respectively, p < 0.001 for both). CONCLUSIONS: Registrars can accurately differentiate urgent from non-urgent patients with acute abdominal pain in the majority of cases. Accuracy was higher amongst senior registrars. The "end-of-the-bed-o-gram" and clinical examination are the most important features used for making this differentiation. This demonstrates that there is no substitute for exposure to acute presentations to improve a trainee's diagnostic skill.

Vascular Biomaterial Banking in Academia.

Hakimi M, Wortmann M, Böckler D … +3 more , Schirmacher P, Herpel E, Peters AS

Eur Surg Res · 2019 · PMID 30726831 · Publisher ↗

BACKGROUND/PURPOSE: To establish a high-quality vascular biomaterial bank to serve vascular research teams and act as a basis for translational medicine. The aim was to collect and store material so that investigation in... BACKGROUND/PURPOSE: To establish a high-quality vascular biomaterial bank to serve vascular research teams and act as a basis for translational medicine. The aim was to collect and store material so that investigation into the pathogenesis of vascular disease would be possible employing methods based on histopathology and/or molecular biology. METHODS: The Vascular Biomaterialbank Heidelberg (VBBH) evolved as part of an established, partly accredited biobank complex at the University of Heidelberg (BioMaterialBank Heidelberg - BMBH). The BMBH provided infrastructure regarding legal and quality issues as well as safety, protocols for specimen collection, data management, and publication of results. Protocols were modified where necessary to accommodate specific needs of vascular tissue research. Correct identification of vascular biomaterial is controlled by certified vascular surgeons and pathologists at biobank entry and exit. Pseudonymized clinical data are attached to every specimen. RESULTS: The VBBH provides standardized operating procedures (SOP) regulating the request, processing, and delivery of material to researchers, as well as project tracking. Tissue samples for a research project are requested by filling out an online application form. Within 3-5 working days, a scientific board, including a member of the VBBH and a member of the BMBH, decide upon acceptance or rejection of the research project. Criteria determining acceptance include whether enough samples are available for the particular investigation and whether planned methods are judged adequate to successfully complete the research project. Through tracking of all ongoing studies involving specimens from the VBBH, methods for tissue conservation are continually being optimized. The VBBH platform has supported numerous high-ranking publications involving diverse medical departments and reflects a gain in translational medicine. CONCLUSIONS: SOPs and controls by certified specialists ensure the high quality of specimens obtained through the VBBH. Research performed by vascular surgeons can be facilitated by using the VBBH.

Downregulation of SPARC Is Associated with Epithelial-Mesenchymal Transition and Low Differentiation State of Biliary Tract Cancer Cells.

Aghamaliyev U, Gaitantzi H, Thomas M … +13 more , Simon-Keller K, Gaiser T, Marx A, Yagublu V, Araos J, Cai C, Valous NA, Halama N, Kiesslich T, Ebert M, Grützmann R, Rückert F, Breitkopf-Heinlein K

Eur Surg Res · 2019 · PMID 30650425 · Publisher ↗

BACKGROUND: Biliary tract cancers (BTCs) have a poor prognosis. BTCs are characterized by a prominent desmoplastic reaction which possibly contributes to the aggressive phenotype of this tumor. The desmoplastic reaction... BACKGROUND: Biliary tract cancers (BTCs) have a poor prognosis. BTCs are characterized by a prominent desmoplastic reaction which possibly contributes to the aggressive phenotype of this tumor. The desmoplastic reaction includes excessive production and deposition of extracellular matrix proteins such as periostin, secreted protein acidic and rich in cysteine (SPARC), thrombospondin-1, as well as accumulation of α-smooth muscle actin-positive cancer-associated fibroblasts and immune cells, secreting growth factors and cytokines including transforming growth factor (TGF)-β. In the present study, we investigated the expression of SPARC in BTC as well as its possible regulation by TGF-β. METHODS: Expression levels of Sparc, TGF-β1 and its receptor ALK5 were evaluated by quantitative real-time PCR in 6 biliary tract cell lines as well as 1 immortalized cholangiocyte cell line (MMNK-1). RNAs from tumor samples of 7 biliary tract cancer patients were analyzed for expression of Sparc, TGF-β type II receptor (TbRII) as well as Twist and ZO-1. MMNK-1 cells were stimulated with TGF-β for 24 h, and Sparc, ZO-1 and E-Cadherin expressions were determined. The presence of SPARC protein was analyzed by immunohistochemistry in tumor specimens from 10 patients. RESULTS: When comparing basal Sparc transcript levels in diverse BTC cell lines to MMNK-1 cells, we found that it was strongly downregulated in all cancer cell lines. The remaining expression levels were higher in highly differentiated cell lines (CCSW1, MZChA1, MZChA2 and TFK-1) than in less differentiated and undifferentiated ones (BDC, SKChA1). Expression of Sparc in BTC patient samples showed a significant positive correlation with expression of the epithelial marker ZO-1. In contrast, the mesenchymal marker Twist and the TbRII showed a trend of negative correlation with expression of Sparc in these samples. TGF-β exposure significantly downregulated Sparc expression in MMNK-1 cholangiocytes in vitro in parallel to downregulation of epithelial markers (E-Cadherin and ZO-1). Finally, SPARC immunostaining was performed in 10 patient samples, and the correlation between absence of SPARC and survival times was analyzed. CONCLUSIONS: These data imply that a decrease in SPARC expression is correlated with dedifferentiation of BTC cells resulting in enhanced EMT being possibly mediated by TGF-β. Thereby SPARC levels might be a marker for individual prognosis of a patient, and strategies aiming at inhibition of SPARC downregulation might have potential for new future therapies.

The Short- and Long-Term Outcomes in Elderly Patients with Hepatocellular Carcinoma after Curative Surgery: A Case-Controlled Study with Propensity Score Matching.

Okamura Y, Sugiura T, Ito T … +3 more , Yamamoto Y, Ashida R, Uesaka K

Eur Surg Res · 2018 · PMID 30554221 · Publisher ↗

BACKGROUND: With aging populations increasing in developed countries, the prevalence of elderly patients with hepatocellular carcinoma (HCC) is expected to rise. The aim of this study was to determine the short- and long... BACKGROUND: With aging populations increasing in developed countries, the prevalence of elderly patients with hepatocellular carcinoma (HCC) is expected to rise. The aim of this study was to determine the short- and long-term outcomes of HCC surgery in elderly patients (≥75 years) using propensity score matching. METHODS: The study group included 421 patients who underwent hepatectomy as their initial treatment with curative intent. The patients were divided into elderly (n = 111) and non-elderly (n = 310) groups. We applied propensity score matching - taking into consideration patient background, blood examination, and tumor factors - to minimize the effect of potential confounders. We then compared the results before and after the propensity matching. RESULTS: Before propensity matching, the elderly group included significantly more patients with a high American Society of Anesthesiologists physical status (p < 0.001). In addition, they were taking antihypertensive drugs or an anticoagulant (both p < 0.001). The severe postoperative complications and the overall survival rates for these elderly patients were significantly poorer than for the non-elderly patients (p = 0.015 and p = 0.030, respectively). We then chose 70 patients from each group for whom the preoperative confounding factors were balanced and compared the two groups. The factors identified before matching (severe complications and overall survival rates) were no longer relevant, i.e. there were no significant differences between the two groups. CONCLUSION: Hepatectomy for HCC in elderly patients is justified.

Biology-Based Surgery: The Extent of Lymphadenectomy in Cancer of the Colon.

Willaert W, Cosyns S, Ceelen W

Eur Surg Res · 2018 · PMID 30544106 · Publisher ↗

The progression of colon cancer (CC) involves hematogenous and lymphatic spread to locoregional lymph nodes (LN), distant LN, and metastatic sites including the liver. The biological mechanisms that govern CC progression... The progression of colon cancer (CC) involves hematogenous and lymphatic spread to locoregional lymph nodes (LN), distant LN, and metastatic sites including the liver. The biological mechanisms that govern CC progression remain elusive. The Halsted model assumes an orderly, stepwise progression from the primary tumor to nearby nodes, henceforth to anatomically more distant nodes, and ultimately to distant organs. The Fisher model, on the other hand, regards the release of metastatic cells as early and essentially random events. The underlying biology has important implications for the ideal extent of surgery: when the Fisher model is correct, efforts to remove apical (central), extramesenteric, or para-aortic LN are unlikely to affect the oncological outcome. Recent data from phylogenetic studies suggest that cancer cell populations differ genetically among different LN stations and from distant metastases. Circulating tumor cells and other liquid biomarkers can be detected in the circulation of patients with early-stage disease. Local recurrence in CC is uncommon, and it is associated with a high risk of systemic progression and poor survival. Clinical studies comparing standard colectomy with extensive surgery (high ligation of the inferior mesenteric artery, complete mesocolic excision, D3 dissection, and para-aortic or extramesenteric node dissection) show that these techniques increase the LN count, while any beneficial effect on the risk of local recurrence or disease-free survival is at present uncertain due to the lack of controlled trials. Ongoing randomized trials comparing extensive vs. standard surgery for CC will generate important answers.
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