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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
Effects of Preoperative Oral Carbohydrate Loading on Neutrophil/Lymphocyte Ratio and Postoperative Complications following Colorectal Cancer Surgery: A Randomized Controlled Study.
Rizvanović N, Nesek Adam V, Kalajdžija M … +3 more , Čaušević S, Dervišević S, Smajić J
Eur Surg Res · 2023 · PMID 36940663 · Publisher ↗
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-...
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.
Time-Related Evidence of Intestinal Oxidative Stress in Obstructive Jaundice-Induced Rats.
Angelis A, Kostakis ID, Lilimpakis K … +5 more , Kalaitzopoulou E, Papadea P, Skipitari M, Georgiou CD, Vagianos C
Eur Surg Res · 2023 · PMID 36921589 · Publisher ↗
INTRODUCTION: Obstructive jaundice is known to affect intestinal permeability and facilitate bacterial translocation through related mechanisms. This study was conducted to evaluate the alterations concerning blood bioch...
INTRODUCTION: Obstructive jaundice is known to affect intestinal permeability and facilitate bacterial translocation through related mechanisms. This study was conducted to evaluate the alterations concerning blood biochemistry and levels of several markers of oxidative stress (OS) in blood and intestinal mucosa caused by obstructive jaundice and how these fluctuate over time, in order to further explore the possibility of intervening in the OS path in future experiments. METHODS: A total of 54 albino Wistar rats were randomly divided into three groups (control, sham operated, and bile duct ligation) and sacrificed at specific time intervals (12 h and 2, 7, and 14 days). The intestinal barrier function was evaluated by measuring endotoxin levels in portal, aortic, and peripheral blood. Also, basic biochemical parameters were simultaneously measured in peripheral blood. Tissue samples collected from the terminal ileum were homogenized for determining the OS markers, lipid peroxidation, and protein-free radical-induced oxidation. RESULTS: We designed this experiment to examine the alterations in enteric mucosa primarily in relation to OS in a period of 14 days. During this time period, we investigated in specific time intervals not only OS fluctuations but also other liver function parameters, as well as CRP and endotoxin levels. The alterations were monitored in relation to time after bile duct ligation. CONCLUSION: Bile duct ligation in rats causes OS versus post-ligation time progression of the common bile duct. OS was increased by ∼50% compared to control/sham and peaked at 7 days and at least up to 14 days post-ligation. This phenomenon was accompanied with a deranging of liver function after ligation, as anticipated, but not in all measured parameters; biochemical and endotoxin levels followed the same pattern.
Rapamycin Does Not Act as a Dietary Restriction Mimetic in the Protection against Ischemia Reperfusion Injury.
van den Akker E, Dor FJMF, IJzermans JNM … +1 more , de Bruin RWF
Eur Surg Res · 2023 · PMID 36878202 · Publisher ↗
INTRODUCTION: Short-term fasting protects against renal ischemia reperfusion injury (IRI). mTOR signaling is downregulated and may be involved in its protective effect. Rapamycin is considered a possible mimetic as it in...
INTRODUCTION: Short-term fasting protects against renal ischemia reperfusion injury (IRI). mTOR signaling is downregulated and may be involved in its protective effect. Rapamycin is considered a possible mimetic as it inhibits the mTOR pathway. This study examines the effect of rapamycin on renal IRI. MATERIAL AND METHODS: Mice were divided into four groups: ad libitum (AL), fasted (F), AL treated with rapamycin (AL+R), and F treated with rapamycin (F+R). Rapamycin was administered intraperitoneally 24 h before bilateral renal IRI was induced. Survival was monitored for 7 days. Renal cell death, regeneration, and mTOR activity were determined 48 h after reperfusion. Oxidative stress resistance of human renal proximal tubular and human primary tubular epithelial cells after rapamycin treatment was determined. RESULTS: All F and F+R mice survived the experiment. Although rapamycin substantially downregulated mTOR activity, survival in the AL+R group was similar to AL (10%). Renal regeneration was significantly reduced in AL+R but not in F+R. After IRI (48 h), pS6K/S6K ratio was lower in F, F+R, and AL+R groups compared to AL fed animals (p = 0.02). In vitro, rapamycin also significantly downregulated mTOR activity (p < 0.001) but did not protect against oxidative stress. CONCLUSION: Rapamycin pretreatment does not protect against renal IRI. Thus, protection against renal IRI by fasting is not exclusively mediated through inhibition of mTOR activity but may involve preservation of regenerative mechanisms despite mTOR downregulation. Therefore, rapamycin cannot be used as a dietary mimetic to protect against renal IRI.
Analysis on Efficacy of Hepatic Artery Infusion Chemotherapy with or without Lenvatinib for Unresectable Hepatocellular Carcinoma.
Yuan W, Yue W, Wen H … +2 more , Wang X, Wang Q
Eur Surg Res · 2023 · PMID 36812900 · Publisher ↗
INTRODUCTION: For patients with advanced hepatocellular carcinoma (HCC), hepatic artery infusion chemotherapy (HAIC) is a common and mature treatment, but the safety and efficacy of HAIC combined with lenvatinib for adva...
INTRODUCTION: For patients with advanced hepatocellular carcinoma (HCC), hepatic artery infusion chemotherapy (HAIC) is a common and mature treatment, but the safety and efficacy of HAIC combined with lenvatinib for advanced HCC patient treatment remains unclear. Therefore, this study compared the safety and efficacy of HAIC with or without lenvatinib in unresectable HCC patients. METHODS: We retrospectively analyzed 13 unresectable advanced HCC patients who received HAIC monotherapy or combination therapy of HAIC and lenvatinib. Overall survival (OS), disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), incidence of adverse events (AEs), and changes in liver function were compared between the two groups. We applied a Cox regression analysis to evaluate the independent risk factors affecting survival outcomes. RESULTS: The ORR in the HAIC+lenvatinib group was markedly increased compared to the HAIC group (p < 0.05), while the DCR in the HAIC group was higher (p > 0.05). No notable difference was found between the two groups in median OS and PFS (p > 0.05). Compared to the HAIC+lenvatinib group, more patients had improved liver function in the HAIC group after treatment, but the difference was not dramatical (p > 0.05). The AEs incidence was 100.00% in both groups, which was relieved with corresponding treatment. Besides, Cox regression analysis did not identify independent risk factors related to OS and PFS. CONCLUSION: Combination therapy of HAIC and lenvatinib notably performed better than the HAIC monotherapy in patients with unresectable HCC in terms of ORR and was well tolerated, which deserves further investigation with large-scale clinical trials.
Animal Welfare: Severity Assessment in Experimental Research.
Bleich A, Vollmar B, Tolba RH
Eur Surg Res · 2023 · PMID 36754043 · Publisher ↗
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Predictive Value of Body Composition Parameters for Postoperative Complications in Patients Who Received Pancreaticoduodenectomy.
Cai Z, Yang Y, Fu X … +2 more , Mao L, Qiu Y
Eur Surg Res · 2023 · PMID 36754029 · Publisher ↗
INTRODUCTION: Sarcopenia and visceral obesity have been identified as risk factors for postoperative complications following hepatobiliary and colon surgery. However, the correlation between body composition parameters a...
INTRODUCTION: Sarcopenia and visceral obesity have been identified as risk factors for postoperative complications following hepatobiliary and colon surgery. However, the correlation between body composition parameters and morbidity following pancreatectomy remains unclear. This study aimed to assess the predictive value of body composition parameters measured from preoperative CT images for postoperative complications following pancreaticoduodenectomy (PD). METHODS: A retrospective study of patients who underwent PD between January 2018 and January 2021 was performed. Areas of subcutaneous adipose tissue, visceral adipose tissue, total abdominal muscle area, and mean muscle radio-attenuation were measured from preoperative CT images. Postoperative complications were categorized according to the Clavien-Dindo classification, and comprehensive complication index (CCI) scores were calculated. Logistic regression analysis was performed to identify factors associated with clinically relevant postoperative pancreatic fistula (CR-POPF) and high CCI score (≥26.2). RESULTS: From the data collected on 129 study patients, sarcopenia, visceral obesity, and myosteatosis were detected in 47 (36.4%), 38 (29.4%), and 50 (38.7%) patients, respectively. CR-POPF developed in 51 (39.5%) patients, the overall median CCI score was 30.8 (22.6-36.2), and high CCI scores were identified in 70 (54.3%) patients. Multivariate analysis indicated sarcopenia and visceral obesity were independent risk variables for CR-POPF. Preoperative sarcopenia, visceral obesity, age, preoperative biliary drainage, and a positive culture of postoperative drainage were predictors of high CCI scores. CONCLUSION: Sarcopenia and visceral obesity were significant predictors of CR-POPF and high CCI score. Preoperative body composition assessment by CT images may help identify high-risk patients who undergo PD.
How Surgical Research Gave Birth to a New Clinical Surgical Field: A Viewpoint from the Dallas Uterus Transplant Study.
Johannesson L, Testa G, da Graca B … +1 more , Wall A
Eur Surg Res · 2023 · PMID 36623496 · Publisher ↗
BACKGROUND: Uterus transplantation (UTx) has come of age in the 21st century, building on the 20th century developments in vascular anastomosis and effective immunosuppressive protocols that have enabled solid organ tran...
BACKGROUND: Uterus transplantation (UTx) has come of age in the 21st century, building on the 20th century developments in vascular anastomosis and effective immunosuppressive protocols that have enabled solid organ transplantation to become the life-extending and life-improving treatment option we know today. However, UTx has the goal of enabling reproduction, meaning that research has focused on establishment of pregnancy and healthy live birth in addition to surgical technique and immunosuppression. SUMMARY: The Dallas Uterus Transplant Study (DUETS), established at Baylor University Medical Center in 2015, is one of four UTx programs in the USA, and it holds the distinction of being home not only to the first US live birth but also the highest volume UTx program worldwide, with 23 uterus transplants performed to date, resulting in 15 live births. Innovations pioneered at our center span all aspects of the UTx process, all seeking to improve success for recipients in terms of achieving pregnancy and live birth, while also minimizing the burden on donors and recipients. They have included the following: (1) a deceased donor hysterectomy approach that allows the uterus to be procured prior to cross clamp; (2) proof of concept with use of only superior uterine veins after procuring both the superior and inferior uterine veins during the donor surgery, enabling the choice of the best option in terms of size and location for outflow, while also preserving ovary viability in living donors; (3) contribution to robot-assisted technique/minimally invasive technique with vaginal extraction of the uterus graft for living donor surgeries, shortening donor recovery times; (4) developing a robot-assisted technique for graft hysterectomies, improving recovery times for recipients at the end of their UTx journey; (5) refining immunosuppression protocols to enable embryo transfer as early as 3 months after induction therapy, increasing recipients' chances for achieving up to two live births during the 5 years posttransplant the UTx protocol specifies; and (6) building on our clinical trial experience to now offer UTx in the U.S. outside the setting of a clinical study. KEY MESSAGES: Our center along with others throughout the world has demonstrated that UTx can be reproducible, result in live births from both living and deceased donors, and be safely introduced as a clinical option. Due to the complexity of UTx as well as the need for long-term multidisciplinary care, centers implementing UTx should have an established abdominal transplant program, a gynecologic surgery program, high-risk obstetric and neonatal care, and institutional support and oversight, and should partner with established UTx programs for protocol development and operative proctoring.
Residents Can Do It! A Training Program in Laparoscopic Liver Surgery for General Surgery Residents.
Popa C, Abdul Halim N, Pestean C … +7 more , Ober C, Elisei R, Al Momani T, Schlanger D, Graur F, Zaharie F, Al Hajjar N
Eur Surg Res · 2023 · PMID 36592620 · Publisher ↗
INTRODUCTION: Laparoscopic liver resections (LLRs) constitute an area of surgery that has been kept away from residents in their hands-on training. The aim of our study is to assess the feasibility and the value of a did...
INTRODUCTION: Laparoscopic liver resections (LLRs) constitute an area of surgery that has been kept away from residents in their hands-on training. The aim of our study is to assess the feasibility and the value of a didactic "step-by-step" program for LLR performed by residents using the swine training model. METHODS: From May 2018 to November 2019, three hands-on workshops were held. The protocol involved the performance of cholecystectomy, liver mobilization, minor and major hepatectomies. The participants' performance results in terms of operative time, blood loss, conversion, trainers' intervention, and intraoperative mortality, were recorded. The first workshop was comprised of 30 residents who previously participated in laparoscopic surgery workshops. In the second workshop, after six residents dropped out due to residency completion, the findings for the remaining 24 residents were compared to those for 24 junior-attending surgeons who did not follow the protocol and had not performed LLR previously, and to another 24 residents in a third workshop, who had not taken the training program before but followed the protocol. RESULTS: All residents fully completed the surgical procedures. Trained residents achieved better operative times and less blood loss compared to junior-attending surgeons (p < 0.017), however, the remaining parameters were comparable. When compared to non-trained residents, those who underwent training achieved significantly better results only in operative times (p < 0.001). CONCLUSION: A continuous LLR "step-by-step" training program on swine for residents is feasible and the "step-by-step" protocol is a valuable tool for a proper surgical education.
A Modified Transversal Two-Suture Microsurgical Intussusception Vasoepididymostomy for the Treatment of Epididymal Obstructive Azoospermia.
Liu Z, Ding Z, Jiang H … +3 more , Yuan Q, Xiao K, Wang B
Eur Surg Res · 2023 · PMID 36574758 · Publisher ↗
INTRODUCTION: We have developed a modified vasoepididymostomy procedure, namely "fenestrated" transversal two-suture microsurgical intussusception vasoepididymostomy. This study aimed to investigate the therapeutic effic...
INTRODUCTION: We have developed a modified vasoepididymostomy procedure, namely "fenestrated" transversal two-suture microsurgical intussusception vasoepididymostomy. This study aimed to investigate the therapeutic efficacy and outcome of this fenestrated vasoepididymostomy for epididymal obstructive azoospermia (OA). METHODS: Microsurgical two-suture transversal intussusception vasoepididymostomy was performed using our modified fenestration technique in 64 OA patients due to epididymal obstruction at our hospital. Fenestration means making an opening on the epididymal tubule wall. The edges of the epididymal tubule "window" were stitched transversally (two stitches) using the two double-armed 9-0 atraumatic sutures. The epididymal tubule was anastomosed to the lumen of the vas deferens. The patency rate and pregnancy rate were assessed. RESULTS: Of the 64 OA patients, 45 received bilateral microsurgical two-suture transversal intussusception vasoepididymostomy, while 19 underwent unilateral microsurgical two-suture transversal intussusception vasoepididymostomy. All of the patients were followed up after the operation. The follow-up period ranged from 4 to 54 months. Among 45 cases of bilateral surgery, the patency rate was 88.89% (40/45), and the natural pregnancy rate was 28.89% (13/45). After the patency was confirmed postoperatively, 3 cases had recurrent OA, of which 2 cases had return of sperm to the ejaculate by oral antibiotics and scrotal self-massage. As for the 19 cases of unilateral microsurgery, the patency rate was 68.42% (13/19), and the natural pregnancy rate was 21.05% (4/19). CONCLUSION: The fenestrated transversal two-suture microsurgical intussusception vasoepididymostomy can achieve a good patency rate in OA patients and did not increase the difficulty and duration of the procedure.
Skin Wound Healing: Of Players, Patterns, and Processes.
Sorg H, Sorg CGG
Eur Surg Res · 2023 · PMID 36417847 · Publisher ↗
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 (...
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.
Indocyanine Green Is a Safe and Effective Alternative to Radioisotope in Breast Cancer Sentinel Lymph Node Biopsy regardless of Patient Body Mass Index.
Ng S, Pitsinis V, Elseedawy EH … +4 more , Brown D, Vinci A, Jones BA, Macaskill EJ
Eur Surg Res · 2023 · PMID 36412622 · Publisher ↗
INTRODUCTION: A recent meta-analysis [Lancet Oncol. 2010;11:908-909] has confirmed high sensitivity of indocyanine green (ICG) fluorescence mapping for sentinel node detection in early breast cancer. Concerns have previo...
INTRODUCTION: A recent meta-analysis [Lancet Oncol. 2010;11:908-909] has confirmed high sensitivity of indocyanine green (ICG) fluorescence mapping for sentinel node detection in early breast cancer. Concerns have previously been raised regarding the efficacy in patients with high body mass index (BMI). MATERIALS AND METHODS: All consecutive patients undergoing sentinel lymph node biopsies (SLNBs) for early breast cancer in NHS Tayside were included in a prospective audit of surgical and pathology findings. All patients included in the study received dual injection of patent blue dye and ICG. Approval was obtained from the local Caldicott guardian for collection and use of personal data. RESULTS: Of 239 cases, all were female patients of mean age 62 years (range 27-93). In 4.2% (10/239) of cases, neither blue dye nor ICG was present in the axilla. Of the remaining 229 SLNB cases in this series, surgeons documented retrieval of 451 nodes, with a mean surgical nodal count per case of 1.97 (range 1-5) and pathological nodal count of 2.15 (range 0-7). Eighty three cases were performed in patients with BMI 30-39.9 and 21 cases with BMI ≥40, with nodal detection rates of 96.4% (80/83) and 95.2% (20/21), respectively, in these groups of patients. Twenty percent (48/229) of cases had nodal metastases on histopathology. CONCLUSIONS: This is a large single-center study which demonstrates the safety and accuracy of the combined ICG and blue dye technique for SLNB in breast cancer. This is represented by nodal detection rates and node positivity rates which are comparable to previous multicenter studies of standard SLNB regardless of BMI.
Introduction of a New ex vivo Porcine Coronary Artery Model: Evaluation of the Direct Vascular Injury after Stent Implantation with and without Dogbone Effect.
Obermaier L, Lehle K, Schmid S … +2 more , Schmid C, Schratzenstaller T
Eur Surg Res · 2022 · PMID 36380648 · Publisher ↗
INTRODUCTION: Neointimal hyperplasia after percutaneous coronary intervention remains a major determinant of in-stent restenosis (ISR). The extent of mechanical vessel injury correlates with ISR. A new ex vivo porcine st...
INTRODUCTION: Neointimal hyperplasia after percutaneous coronary intervention remains a major determinant of in-stent restenosis (ISR). The extent of mechanical vessel injury correlates with ISR. A new ex vivo porcine stent model was introduced and evaluated comparing different stent designs. METHODS: Coronary arteries were prepared from pig hearts from the slaughterhouse and used for ex vivo implantations of coronary stents. One basic stent design in two configurations (dogbone, DB; nondogbone, NDB) was used. Vascular injury was determined according to a modified injury score (IS). RESULTS: Standardized experimental conditions ensured comparable vessel dimensions and overstretch data. DB stents caused more severe IS compared to NDB stents. The mean IS and the IS at the distal end of all stents were significantly reduced for NDB stents (ISMean, DB, 1.16 ± 0.12; NDB, 1.02 ± 0.12; p = 0.018; ISDist, DB, 1.39 ± 0.28; NDB, 1.13 ± 0.24; p = 0.03). DISCUSSION/CONCLUSION: The introduced ex vivo model allowed the evaluation of different stent designs, which exclude unfavorable stent designs.
Stepwise Approach for Acquisition of Microsurgical Skills through Rat Orthotopic Liver Transplantation Experiments.
Hirata M, Yagi S, Ito T … +7 more , Masano Y, Okumura S, Yao S, Miyachi Y, Aoki H, Katano K, Hatano E
Eur Surg Res · 2023 · PMID 36380647 · Publisher ↗
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 sk...
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.
Regulation of FOXO3 on neuronal ferroptosis after intracerebral hemorrhage via modulating NOX4 transcription.
Qin Z, Zhu G, Luo H … +1 more , Deng Y
Eur Surg Res · 2022 Nov · PMID 36380623 · Publisher ↗
INTRODUCTION: Intracerebral hemorrhage (ICH) is known to trigger neuronal ferroptosis while forkhead box O3 (FOXO3) is implicated in ICH. This study aimed to determine the specific effect of FOXO3 on neuronal ferroptosis...
INTRODUCTION: Intracerebral hemorrhage (ICH) is known to trigger neuronal ferroptosis while forkhead box O3 (FOXO3) is implicated in ICH. This study aimed to determine the specific effect of FOXO3 on neuronal ferroptosis after ICH. METHODS: The ICH mouse model was established through the injection of bacterial collagenase type IV and the cell model was established in Hemin-induced HT-22 cells. Subsequently, neurological functions, brain water content, and histopathological changes in mice were assessed. HT-22 cell activity was examined via cell counting kit-8 (CCK-8) method, and the levels of FOXO3, NADPH oxidase 4 (NOX4), and glutathione peroxidase 4 (GPX4) in brain tissues and HT-22 cells were measured. Fe2+ concentration and the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) in the tissues and cells were examined. The binding relationship between FOXO3 and the NOX4 promoter region was determined via chromatin-immunoprecipitation (Ch-IP). Rescue experiments were designed to probe the role of NOX4 in the regulation of FOXO3 on neuronal ferroptosis. RESULTS: FOXO3 was highly-expressed in ICH models while silencing FOXO3 alleviated brain damage, edema, and inflammatory infiltration in ICH mice. Meanwhile, silencing FOXO3 enhanced cell activity, diminished ROS and MDA activities and Fe2+ concentration, and elevated GSH and GPX4 levels in the tissues or cells. FOXO3 could bind to the NOX4 promoter and upregulate NOX4 transcription. NOX4 overexpression partially neutralized the repressive role of silencing FOXO3 in neuronal ferroptosis. CONCLUSION: Silencing FOXO3 attenuated ICH-induced neuronal ferroptosis via down-regulating NOX4 transcription levels, thus ameliorating post-ICH brain damage.
Preoperative Predictive Nomogram Based on Alanine Aminotransferase, Prothrombin Time Activity, and Remnant Liver Proportion (APART Score) to Predict Post-Hepatectomy Liver Failure after Major Hepatectomy.
Maehira H, Iida H, Mori H … +6 more , Nitta N, Maekawa T, Takebayashi K, Kaida S, Miyake T, Tani M
Eur Surg Res · 2023 · PMID 36380617 · Publisher ↗
INTRODUCTION: Post-hepatectomy liver failure (PHLF) is a serious complication associated with major hepatectomies. An accurate prediction of PHLF is necessary to determine the feasibility of major hepatectomy. This study...
INTRODUCTION: Post-hepatectomy liver failure (PHLF) is a serious complication associated with major hepatectomies. An accurate prediction of PHLF is necessary to determine the feasibility of major hepatectomy. This study aimed to assess the association between PHLF and preoperative laboratory and computed tomography (CT) findings. METHODS: Medical records of 65 patients who underwent major hepatectomy and preoperative CT were retrospectively reviewed. We evaluated future remnant liver volume evaluation models and remnant liver hemodynamics, which were assessed by arterial enhancement fraction (AEF) by using preoperative CT. Variables, including CT findings, were compared between patients with and without PHLF after major hepatectomy, and the preoperative PHLF-predicting nomogram was constructed using multivariate logistic regression. RESULTS: The PHLF group included 21 patients (32.3%). The AEF was not significantly different between the two groups. In the future remnant liver volume evaluation models, future remnant liver proportion (fRLP) had the highest concordance index (C-index) in the receiver operating characteristic curve analysis (C-index, 0.755). Multivariate analysis of preoperative evaluable factors revealed that alanine aminotransferase levels (p = 0.034), prothrombin time activity (p = 0.021), and fRLP (p = 0.012) were independent predictive factors of PHLF. A nomogram (APART score) was constructed using these three factors, with a receiver operating curve showing a C-index of 0.894. According to the APART score, scores of 51-60 indicated moderate risk (40.0%), and scores over 60 indicated a high risk of PHLF (83.3%) (p < 0.001). DISCUSSION: The APART score may help predict PHLF in patients indicated for major hepatectomies.
Does Sex Matter in Liver Surgery? Comparison of Severity Assessments between Female and Male Rats after Partial Hepatectomy: A Pilot Study.
Kümmecke AM, Zieglowski L, Ernst L … +2 more , Palme R, Tolba RH
Eur Surg Res · 2023 · PMID 36191560 · Publisher ↗
INTRODUCTION: Current animal-based biomedical research, including studies on liver function and disease, is conducted almost exclusively on male animals to mitigate confounding effects of the estrous cycle. However, live...
INTRODUCTION: Current animal-based biomedical research, including studies on liver function and disease, is conducted almost exclusively on male animals to mitigate confounding effects of the estrous cycle. However, liver diseases afflict both men and women, so translational research findings should also be applicable to female patients. This pilot study investigated sex differences in objective and subjective severity assessment parameters in rats following 50% partial hepatectomy. MATERIALS AND METHODS: This study was performed using Wistar Han rats, in which measurements of body weight, spontaneous motor activity in the open field (OF) (movement distance, movement velocity, rearing frequency), and fecal corticosterone metabolites were conducted at baseline and at multiple times after partial hepatectomy. Subjective postsurgical severity assessments were conducted using modified score sheets. Blood parameters such as leukocyte count and serum aspartate aminotransferase, as well as estrogens and testosterone were measured from samples obtained during partial hepatectomy and at sacrifice. In addition, the amount of resected liver tissue was measured at partial hepatectomy, and the proliferated liver was weighed at sacrifice. RESULTS: Fecal corticosterone metabolite concentrations differed significantly between males and females at baseline and following hepatectomy. Also, leukocyte counts and estrogen concentrations were significantly different between sexes before partial hepatectomy. Alternatively, there were no sex differences in severity assessments, body weight changes, and behavior in the OF at any measurement time point. Liver weight was significantly different in males and females at the time point of partial hepatectomy and sacrifice. CONCLUSION: The results of this pilot study suggest that males and females respond similarly following partial hepatectomy. Examination of both sexes is very important for translation to humans, where both men and women suffer from liver disease. Furthermore, the use of both sexes in animal-based research would improve the utilization of the animal breeding in terms of the 3 Rs. However, due to some limitations, larger scale investigations including a broader spectrum of pathophysiolological, behavioral, and pharmacokinetic measures are planned.
Stem Cell Therapies for Gastrointestinal Anastomotic Healing: A Systematic Review and Meta-Analysis on Results from Animal Studies.
Gaitanidis A, Kandilogiannakis L, Filidou E … +3 more , Tsaroucha A, Kolios G, Pitiakoudis M
Eur Surg Res · 2022 · PMID 36067736 · Publisher ↗
BACKGROUND: Despite considerable progress in surgical techniques, anastomotic leak (AL) is a common complication after gastrointestinal surgery. Stem cells are a promising therapy to improve healing and have been used in...
BACKGROUND: Despite considerable progress in surgical techniques, anastomotic leak (AL) is a common complication after gastrointestinal surgery. Stem cells are a promising therapy to improve healing and have been used in gastrointestinal anastomoses. In this study, we perform a systematic review and meta-analysis to evaluate the efficacy of stem cell therapies in preventing ALs among animal studies. METHODS: A systematic review of the literature was performed by searching PubMed, Web of Science, and the Cochrane Library. We considered all anastomoses of the gastrointestinal tract (excl. biliary) from the esophagus to the rectum. Outcomes included AL rates on postoperative day (POD) 7 and the latest time point reported. RESULTS: Fourteen studies were identified, evaluating stem cells in gastrointestinal anastomoses, of which 1 was on esophageal, 2 on gastric, 2 on small intestinal, and 9 on colorectal anastomoses. Meta-analysis did not show significant differences in AL rates on POD 7 (odds ratio [OR] 0.34, 95% confidence interval [CI]: 0.04-3.15, p = 0.248, I2 = 34.1%, 95% CI: 0-75.2%, Q = 6.07, df = 4, p = 0.194), but there was a nonsignificant trend for lower AL rates at the latest time point reported (OR 0.28, 95% CI: 0.08-1.01, p = 0.052, I2 = 34%, 95% CI: 0-70.8%, Q = 10.6, df = 7, p = 0.157). CONCLUSION: Stem cell therapy may be associated with lower AL rates in gastrointestinal anastomoses, though meta-analysis is severely inhibited by heterogeneous study design. More studies are needed to determine the therapeutic potential of stem cells.
DNA-Damage-Repair Gene Alterations in Genitourinary Malignancies.
Dariane C, Timsit MO
Eur Surg Res · 2022 · PMID 35944490 · Publisher ↗
BACKGROUND: High-fidelity repair of DNA damage repair (DDR) (either single-strand- [SSBs] or double-strand breaks [DSBs]) is necessary for maintaining genomic integrity and cell survival. DDR alterations are commonly fou...
BACKGROUND: High-fidelity repair of DNA damage repair (DDR) (either single-strand- [SSBs] or double-strand breaks [DSBs]) is necessary for maintaining genomic integrity and cell survival. DDR alterations are commonly found in genitourinary malignancies involving either DSB repair by the homologous recombination (HR) repair (HRR) system (BRCA1/2 pathway) or the SSB repair through the poly (ADP-ribose) polymerase (PARP) pathway. PARP inhibitors (PARPi) exploit defects in the DNA repair pathway through synthetic lethality, DSBs being repaired only in HR-proficient cells but not in HR-deficient (HRD) cells. SUMMARY: A growing body of evidence supports the need for identification of germinal and somatic DDR alterations in patients with genitourinary malignancies. PARPi have already shown significant survival benefits in patients harboring HRR mutations in advanced settings, paving the way for precision medicine. KEY MESSAGES: In advanced prostate cancer (PCa), somatic mutations in HRR pathway are observed in up to 27% of metastatic resistant-to-castration PCa (mCRPC), although occurring early in PCa development, and mainly involving BRCA2, ATM, CHEK2, and BRCA1. Overall, germinal alterations are present in roughly 30-50% of cases of HRR alterations, and relative risk of PCa in germinal BRCA2 alteration carriers is 4.65-fold higher compared to noncarriers. Determination of DDR gene status is recommended in metastatic patients, a fortiori in mCRPC setting, since it could be a putative biomarker of response to first line of treatment (androgen-receptor signaling inhibitors [ARSI] vs. taxane-based chemotherapy) and allows to assess eligibility for PARPi use. Thus, olaparib (combined with androgen deprivation therapy) recently improved overall survival in mCRPC HRD patients, after new hormonal therapy (NHT) and led to its approvement for patients with an alteration in 14 of 15 prespecified HRR genes. Moreover, since preclinical data suggested synergic action between PARPi and ARSI, the use of either olaparib or niraparib has also been proposed in combination with NHT, with a radiological progression-free survival improvement when used with abiraterone. In urothelial carcinoma, a DDR gene alteration is identified in 23-54% of patients mostly in muscle-invasive bladder cancer, with a strong association between DDR gene mutation and a higher tumor mutation burden and sensitivity to cisplatin-based chemotherapy and immunotherapy. Recent phase 2 trials supported the use of HRR status to select patients for PARPi treatment in advanced urothelial carcinoma. Finally, in renal cell carcinomas (RCCs), pathogenic germline variants in DDR genes were identified in 7.3% of the cases, and deleterious somatic alterations have also been described as recurrent genomic events in patients with advanced RCC.
A Novel Combination of Keratinocyte and Autologous Microskin Grafting to Repair Full-Thickness Skin Loss.
Yin K, Li D, Shen C … +4 more , Shang Y, Li L, Zhao D, Cheng W
Eur Surg Res · 2022 · PMID 35926477 · Publisher ↗
INTRODUCTION: The high mortality of patients with extensive deep burns is mainly attributed to the extensive burn wound and the scarce autologous skin left for wound repair. The purpose of this study was to explore how t...
INTRODUCTION: The high mortality of patients with extensive deep burns is mainly attributed to the extensive burn wound and the scarce autologous skin left for wound repair. The purpose of this study was to explore how to effectively use the limited remaining autologous skin to repair the extensive deep wound. METHODS: Human keratinocytes harvested from the foreskin were cultured and transfected with epidermal growth factors (EGFs) by an adenovirus vector (Ad-EGF). The expression and the biological activity of EGF in both the normal human keratinocytes and the EGF gene-modified human keratinocytes were quantified by ELISA assay and CCK-8 assay, respectively. The differentiated phenotype of epidermal cells was detected by immunofluorescence staining via CK10, CK14, and CK19 expressions. Rats were subjected to a full-thickness skin loss (3.3 cm × 3.0 cm) on the dorsum, which was repaired with the EGF gene-modified human keratinocyte suspension and autologous microskin and covered with the allogeneic skin. The wound healing was quantified, and the expression of EGF mRNA was measured by RT-PCR. RESULTS: The EGF gene-modified human keratinocytes highly expressed EGF. CK10, CK14, and CK19 as keratinocyte differentiation markers were increased in the EGF gene-modified human keratinocytes. Wound healing was accelerated remarkably by the combination of autologous microskin grafting and EGF gene-modified human keratinocytes in vivo, and a very high EGF mRNA expression was observed in EGF gene-modified human keratinocytes groups on days 7 and 14 compared with other groups. DISCUSSION/CONCLUSION: The EGF gene-modified human keratinocyte suspension may serve as promising seed cells which can effectively secrete EGF to accelerate wound repair in combination with autologous microskin grafting and reduce the autologous skin requirement for wound repair.
Mucosal Recovery after Intestinal Transplantation in the Rat: A Sequential Histological and Molecular Assessment.
Bagge J, Padma AM, Casselbrant A … +2 more , Hellström M, Oltean M
Eur Surg Res · 2023 · PMID 35926441 · Full text
INTRODUCTION: Intestinal cold ischemia and subsequent reperfusion during transplantation result in various degrees of mucosal injury ranging from mild edema to extensive mucosal loss. Mucosal barrier impairment favors ba...
INTRODUCTION: Intestinal cold ischemia and subsequent reperfusion during transplantation result in various degrees of mucosal injury ranging from mild edema to extensive mucosal loss. Mucosal barrier impairment favors bacterial translocation and fluid loss and raises nutritional challenges. The injured intestine also releases proinflammatory mediators and upregulates various epitopes toward an inflammatory phenotype. We studied the process of mucosal injury and repair during the early period after intestinal transplantation from a histological and molecular standpoint. MATERIALS AND METHODS: Adult Sprague-Dawley rats were used as donors and recipients. Donor intestines were perfused and stored in saline for 3 h, then transplanted heterotopically using microvascular anastomoses. Intestinal graft segments were obtained after 20 min, 6 h, 12 h, and 24 h after reperfusion. Histology studies (goblet cell count, morphometry), immunofluorescence, and western blot for several tight junction proteins, apoptosis, and inflammation-related proteins were performed. RESULTS: Cold storage led to extensive epithelial detachment, whereas reperfusion resulted in extensive villus loss (about 60% of the initial length), and goblet cell numbers were drastically reduced. Over the first 24 h, gradual morphologic and molecular recovery was noted, although several molecular alterations persisted (increased apoptosis and inflammation, altered expression of several tight junctions). CONCLUSIONS: The current data suggest that a near-complete morphologic recovery from a moderate mucosal injury occurs within the first 24 h after intestinal transplantation. However, several molecular alterations persist and need to be considered when designing intestinal transplant experiments and choosing sampling and endpoints.
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