European Surgical Research最新文献

Understanding the impact routine research and laboratory procedures have on animals is crucial to improving their well-being and to the success and reproducibility of the research they are involved in. Cognitive measures of welfare offer insight into animals' internal psychological state, but require validation. Attention bias - the tendency to attend to one type of information over another - is a cognitive phenomenon documented in humans and animals that is known to be modulated by affective state (i.e., emotions). Hence, changes in attention bias may offer researchers a deeper perspective of their animals' psychological well-being. The dot-probe task is an established method for quantifying attention bias in humans (by measuring reaction time to a dot-probe replacing pairs of stimuli), but has yet to be validated in animals. We developed a dot-probe task for long-tailed macaques (Macaca fascicularis) to determine if the task can detect changes in attention bias following anesthesia, a context known to modulate attention and trigger physiological arousal in macaques. Our task included the following features: stimulus pairs of threatening and neutral facial expressions of conspecifics and their scrambled counterparts, two stimuli durations (100 and 1,000 ms), and counterbalancing of the dot-probe's position on the touchscreen (left and right) and location relative to the threatening stimulus. We tested 8 group-housed adult females on different days relative to being anesthetized (baseline and 1-, 3-, 7-, and 14-days after). At baseline, monkeys were vigilant to threatening content when stimulus pairs were presented for 100 ms, but not 1,000 ms. On the day immediately following anesthesia, we found evidence that attention bias changed to an avoidance of threatening content. Attention bias returned to threat vigilance by the third day postanesthesia and remained so up to the last day of testing (14-days after anesthesia). We also found that attention bias was independent of the type of stimuli pair (i.e., whole face vs. scrambled counterparts), suggesting that the scrambled stimuli retained aspects of the original stimuli. Nevertheless, whole faces were more salient to the monkeys as responses to these trials were generally slower than to scrambled stimulus pairs. Overall, our study suggests it is feasible to detect changes in attention bias following anesthesia using the dot-probe task in nonhuman primates. Our results also reveal important aspects of stimulus preparation and experimental design.

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.

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.

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.

Introduction: Anastomotic leaks (ALs) are serious postoperative complications. Current experimental studies designed to investigate leaks are based on acute intraoperative dehiscence of the anastomosis. Clinically, however, AL usually happens later in the postoperative course. Presented here is a clinically relevant colonic AL model in swine.

Methods: Seventeen Yorkshire pigs were divided into 2 groups: the control group (n = 6) and the experimental group (n = 11). An enterotomy was performed on the descending colon and an end-to-end handsewn anastomosis was created in the groups. The proximal and distal ends of the suture were exteriorized and tied to a plastic tube. Subsequently, the suture was cut and pulled to induce breakdown of the anastomosis in the experimental group 3-4 h postoperatively. Study endpoints included behavioral changes, clinical assessment, laboratory indicators, and macroscopic indicators of leakage.

Results: Leaks were successfully created in 8/11 of the experimental group animals and confirmed through exploratory relaparotomy. Seven of the experimental pigs showed complete anastomotic breakdown and one showed partial rupture. Fecal peritonitis and enteric spillage were observed macroscopically within the abdomen of the experimental pigs, confirming the presence of a leak. The remaining (3/11) experimental pigs did not experience those findings due to either a tamponade/containment by the abdominal wall or surrounding organs. Statistical significance (p < 0.05) was achieved between the experimental and control cohorts for laboratory and clinical indicators including fever, leukocytosis, and decreased blood potassium.

Conclusion: This animal model generated postoperative induced leak in approximately three-quarters (8/11) of experimental pigs, allowing control over the time of leak onset to simulate clinical settings.

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.

In kidney transplantation (KTx), renal graft thrombosis (RGT) is one of the main reasons for early graft loss. Although evidence-based guidance on prevention of RGT is lacking, thromboprophylaxis is widely used. The aim of this survey was to obtain a European view of the different thromboprophylactic strategies applied in KTx. An online 22-question survey, addressed to KTx professionals, was distributed by email and via platforms of the European Society for Organ Transplantation. Seventy-five responses (21 countries, 51 centers) were received: 75% had over 10 years' clinical experience, 64% were surgeons, 29% nephrologists, and 4% urologists. A written antithrombotic management protocol was available in 75% of centers. In 8 (16%) centers, respondents contradicted each other regarding the availability of a written protocol. Thromboprophylaxis is preferred by 78% of respondents, independent of existing antithrombotic management protocols. Ninety-two percent of respondents indicated that an anticipated bleeding risk is the main reason to discontinue chronic antithrombotic therapy preoperatively. Intraoperatively, 32% of respondents administer unfractionated heparin (400-10,000 international units with a median of 5,000) in selected cases. Despite an overall preference for perioperative thromboprophylaxis in KTx, there is a high variation within Europe regarding type, timing, and dosage, most likely due to the paucity of high-quality studies. Further research is warranted in order to develop better guidelines.

Introduction: Hemorrhage is a challenging complication of pelvic surgery. This study aimed to analyze the causes, management, and factors associated with morbidity in patients experiencing major pelvic hemorrhage during complex abdominopelvic surgery.

Methods: Patients who had major intraoperative pelvic hemorrhage during complex abdominopelvic surgery at 11 tertiary referral centers between 1997 and 2017 were included. Patient characteristics, management strategies to control bleeding, short- and long-term postoperative outcomes were evaluated retrospectively.

Results: There were 120 patients with a mean age of 56.6 ± 2.4 years and a mean BMI of 28.3 ± 1 kg/m2. While 104 (95%) of the patients were operated for malignancy, 16 (5%) of the patients had surgery for a benign disease. The most common bleeding site was the presacral venous plexus 90 (75%). Major pelvic hemorrhage was managed simultaneously in 114 (95%) patients. Electrocauterization 27 (23%), pelvic packing 26 (22%), suturing 7 (6%), thumbtacks application 7 (6%), muscle welding 4 (4%), use of energy devices 2 (2%), and topical hemostatic agents 2 (2%) were the management tools. Combined techniques were used in 43 (36%) patients. Short-term morbidity and mortality rates were 48 (40%) and 2 (2%), respectively. High preoperative CRP levels (p = 0.04), history of preoperative radiotherapy (p = 0.04), longer bleeding time (p = 0.006), and increased blood transfusion (p = 0.005) were the factors associated with postoperative morbidity.

Conclusion: Postoperative morbidity related to major pelvic hemorrhage can be reduced by optimizing the risk factors. Prehabilitation prior to surgery to moderate inflammatory status and prompt action with proper technique to control major pelvic hemorrhage can prevent excessive blood loss in complex abdominopelvic surgery.

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

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

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

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

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

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

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