INTRODUCTION: We aimed to compare implant osseointegration with calcium phosphate (CaP) surfaces and rough subtractive-treated sandblasted/acid etched surfaces (SA) in an in vivo minipig mandible model. MATERIALS AND MET...INTRODUCTION: We aimed to compare implant osseointegration with calcium phosphate (CaP) surfaces and rough subtractive-treated sandblasted/acid etched surfaces (SA) in an in vivo minipig mandible model. MATERIALS AND METHODS: A total of 36 cylindrical press-fit implants with two different surfaces (CaP, n = 18; SA, n = 18) were inserted bilaterally into the mandible of 9 adult female minipigs. After 2, 4, and 8 weeks, we analyzed the cortical bone-to-implant contact (cBIC; %) and area coverage of bone-to-implant contact within representative bone chambers (aBIC; %). RESULTS: After 2 weeks, CaP implants showed no significant increase in cBIC and aBIC compared to SA (cBIC: mean 38 ± 5 vs. 16 ± 11%; aBIC: mean 21 ± 1 vs. 6 ± 9%). Two CaP implants failed to achieve osseointegration. After 4 weeks, no statistical difference between CaP and SA was seen for cBIC (mean 54 ± 15 vs. 43 ± 16%) and aBIC (mean 43 ± 28 vs. 32 ± 6). However, we excluded two implants in each group due to failure of osseointegration. After 8 weeks, we observed no significant intergroup differences (cBIC: 18 ± 9 vs. 18 ± 20%; aBIC: 13 ± 8 vs. 16 ± 9%). Again, three CaP implants and two SA implants had to be excluded due to failure of osseointegration. CONCLUSION: Due to multiple implant losses, we cannot recommend the oral mandibular minipig in vivo model for future endosseous implant research. Considering the higher rate of osseointegration failure, CaP coatings may provide an alternative to common subtractive implant surface modifications in the early phase post-insertion.
BACKGROUND: Neutrophil extracellular traps (NETs) are known to play an important role in the pathophysiology of acute pancreatitis (AP). Activation of the complement cascade has been shown to occur in AP. The aim of this...BACKGROUND: Neutrophil extracellular traps (NETs) are known to play an important role in the pathophysiology of acute pancreatitis (AP). Activation of the complement cascade has been shown to occur in AP. The aim of this study was to examine whether complement component 3 is involved in the generation of NETs in AP. METHODS: AP was induced in wild-type and C3-deficient mice by retrograde infusion of taurocholate into the pancreatic duct. Blood, lung, and pancreas tissue were collected and MPO activity was determined in lung and pancreas tissue. Histological examination of the inflamed pancreas was performed. Plasma levels of CXCL2, MMP-9, IL-6, and DNA-histone complexes as well as pancreatic levels of CXCL1 and CXCL2 were determined by use of enzyme-linked immunosorbent assay. NETs were detected in the pancreas by electron microscopy. The amount of MPO and citrullinated histone 3 in neutrophils isolated from bone marrow was examined using flow cytometry. RESULTS: In C3-deficient mice, challenge with taurocholate yielded much fewer NETs in the pancreatic tissue compared with wild-type controls. Taurocholate-induced blood levels of amylase, tissue injury, and neutrophil recruitment in the pancreas were markedly reduced in the mice lacking C3. Furthermore, MPO levels in the lung, and plasma levels of IL-6, MMP-9, and CXCL2 were significantly lower in the C3-deficient mice compared to wild-type mice after the induction of AP. In vitro studies revealed that neutrophils from C3-deficient mice had normal NET-forming ability and recombinant C3a was not capable of directly inducing NETs formation in the wild-type neutrophils. CONCLUSION: C3 plays an important role in the pathophysiology of AP as it is necessary for the recruitment of neutrophils into the pancreas and ensuring NETs formation. Targeting C3 could hence be a potential strategy to ameliorate local damage as well as remote organ dysfunction in AP.
Knowledge of patient-specific liver anatomy is key to patient safety during major hepatobiliary surgery. Three-dimensional (3D) models of patient-specific liver anatomy based on diagnostic MRI images can provide essentia...Knowledge of patient-specific liver anatomy is key to patient safety during major hepatobiliary surgery. Three-dimensional (3D) models of patient-specific liver anatomy based on diagnostic MRI images can provide essential vascular and biliary anatomical insight during surgery. However, a method for generating these is not yet publicly available. This paper describes how these 3D models of the liver can be generated using open source software, and then subsequently integrated into a sterile surgical environment. The most common image quality aspects that degrade the quality of the 3D models as well possible ways of eliminating these are also discussed. Per patient, a single diagnostic multiphase MRI scan with hepatospecific contrast agent was used for automated segmentation of liver contour, arterial, portal, and venous anatomy, and the biliary tree. Subsequently, lesions were delineated manually. The resulting interactive 3D model could be accessed during surgery on a sterile covered tablet. Up to now, such models have been used in 335 surgical procedures. Their use simplified the surgical treatment of patients with a high number of liver metastases and contributed to the localization of vanished lesions in cases of a radiological complete response to neoadjuvant treatment. They facilitated perioperative verification of the relationship of tumors and the surrounding vascular and biliary anatomy, and eased decision-making before and during surgery.
INTRODUCTION: Since the outermost layer of cancer cells is covered with various glycans, targeting these groups may serve as an effective strategy in cancer therapy. We previously reported that fucosylated glycans are sp...INTRODUCTION: Since the outermost layer of cancer cells is covered with various glycans, targeting these groups may serve as an effective strategy in cancer therapy. We previously reported that fucosylated glycans are specifically expressed on pancreatic cancer cells, and that a protein specifically binding to these glycans, namely rBC2LCN lectin, is a potential guiding drug carrier. In the present study, a novel type of glycan-targeting nanoparticle was developed by modifying the surface of doxorubicin-containing liposomes with rBC2LCN lectin. The efficiency and specificity of this formulation, termed Lec-Doxosome, were examined in vitro and in vivo in human pancreatic cancer models. METHODS: Lec-Doxosome was prepared by a post-insertion method based on the insertion of rBC2LCN lectin into the liposomal surface via a lipid linker. The in vitro cellular binding, uptake, and cytotoxicity of Lec-Doxosome were compared with the corresponding parameters in the unmodified liposomes by applying to human pancreatic cancer cell line (Capan-1) with affinity for rBC2LCN lectin. For the in vivo assay, Lec-Doxosome was intravenously injected once per week for a total of 3 weeks into mice bearing subcutaneous tumors. RESULTS: The in vitro application of Lec-Doxosome resulted in a 1.2- to 1.6-fold higher intracellular doxorubicin accumulation and a 1.5-fold stronger cytotoxicity compared with the respective rates of accumulation and cytotoxicity in the unmodified liposomes. In vivo, Lec-Doxosome reduced the mean tumor weight (368 mg) compared with that in mice treated with unmodified liposomes (456 mg), without causing any additional adverse events. CONCLUSION: It was demonstrated from the results obtained herein that rBC2LCN lectin is a potent modifier, as a means for boosting the efficiency of nanoparticles in the targeting of cancer cell surface glycans.
BACKGROUND: More than 20,000 carotid endarterectomies are performed annually in the Russian Federation. Until now, no studies based on the national carotid data set have been published. The objectives of this study were...BACKGROUND: More than 20,000 carotid endarterectomies are performed annually in the Russian Federation. Until now, no studies based on the national carotid data set have been published. The objectives of this study were to evaluate early outcomes after carotid endarterectomy and to identify potential risk factors for major adverse cardiovascular events. MATERIALS AND METHODS: The retrospective analysis was based on data recorded in a single-center registry, including all carotid endarterectomies performed between 2010 and 2017. A univariate analysis was used to identify the risk factors for perioperative mortality, and predictors of stroke were determined using a multivariate logistic regression model. RESULTS: Data from 1,832 patients with a mean age of 64.1 ± 7.6 years were analyzed. The combined in-hospital mortality was 0.65% (12/1,832). The rate of stroke was 0.7% (13/1,832), and the rate of myocardial infarction was 1.1% (20/1,832). The 30-day stroke-free survival was 99%. A history of stroke (p = 0.02) and chronic obstructive pulmonary disease (COPD; p = 0.0001) were found to be predictive of a lethal stroke. Previous myocardial infarction (p = 0.0001), an advanced stage of congestive heart failure (p = 0.0001), and angina pectoris (p = 0.01) were associated with cardiac-related mortality. Moreover, diabetes mellitus (p = 0.03), COPD (p = 0.0001), and carotid calcinosis (p = 0.006) increased the risk of poor survival due to myocardial infarction. The mean duration of clamping was found to be an independent predictor of any perioperative stroke (OR = 1.109; 95% CI 1.052-1.129; p < 0.0001). CONCLUSIONS: The present retrospective analysis of the local carotid surgery register showed appropriate outcomes after CEA regarding the cumulative incidence of MACE, which is comparable to previously published international register data. A previous history of stroke, myocardial infarction, COPD, a prolonged clamping time during CEA, and diabetes mellitus were found to be factors of high-risk for cardiovascular mortality. A prolonged clamping was identified as an independent predictor of any stroke.
INTRODUCTION: Nowadays, surgical excision remains the gold standard to treat liver metastases of colorectal cancer (CRCLM). However, as more than 50% of patients are not eligible for surgery, other alternatives such as p...INTRODUCTION: Nowadays, surgical excision remains the gold standard to treat liver metastases of colorectal cancer (CRCLM). However, as more than 50% of patients are not eligible for surgery, other alternatives such as percutaneous or intravascular interventional therapies (thermal ablation, chemoembolization, or radioembolization), are quite relevant. Recently, the use of magnetic nanoparticles (MNPs) has been suggested as an adjuvant for these therapies, as they could increase their necrotising effect on the tumour while reducing doses and exposure times of thermal therapies. To investigate the potential curative effect of these compounds, animal models are needed, both for the development of experimental interventional procedures and for MNPs toxicity and distribution assessment. Herein, we describe both an experimental infusion procedure in CRCLM-bearing rats and analytical and histological methods to evaluate MNPs deposits in the tissue. METHODS: Eighteen male WAG/RijHsd rats were subjected to intrahepatic injection of 250,000 colorectal cancer cells. Twenty-eight days later, half of the tumour-positive animals (n = 6) were administered with MNPs while the other half (n = 6) did not receive any injection and were used as control. Under microscope magnification, the splenic artery was carefully and completely dissected, and a catheter was inserted through the splenic artery to the common hepatic artery where 1 mL MNPs suspension was administered in 5 min; then STIR, DP*, and T2 MRI sequences were obtained (and signal intensity measured) and both tumour and liver tissue samples were collected for elemental and histological analyses. CONCLUSION: Our method for selective administration of MNPs is reproducible and well-tolerated and it fairly mimics the approach used in clinical practice when intravascular interventional therapies are applied.
The gut hormone cholecystokinin (CCK) is primarily secreted from I-cells in the duodenum and proximal jejunum. CCK secretion is stimulated by food digests and inhibited by proteases from pancreatic juice. CCK regulates d...The gut hormone cholecystokinin (CCK) is primarily secreted from I-cells in the duodenum and proximal jejunum. CCK secretion is stimulated by food digests and inhibited by proteases from pancreatic juice. CCK regulates digestion and appetite, stimulates pancreatic growth, and participates in pancreatic carcinogenesis. The molecular mechanisms of CCK-induced effects are not fully understood. When the mechanisms are studied in animals, the surgical model of pancreatobiliary diversion (PBD) is frequently used. After animals have had PBD, their CCK secretion is no longer inhibited by pancreas-derived proteases, so circulating CCK is increased. PBD is established in rats and hamsters, but not in mice. In this study, we modified PBD procedures and established the model in the mouse. In an experiment, we performed PBD and sham operation (SO) in two groups of mice (20 mice per group). Twenty days after operation, 75% of the PBD mice and all SO mice survived. When plasma CCK was determined by radioimmunoassay, the PBD group had higher levels than the SO group (p < 0.001). To assess pancreatic growth, we determined pancreatic weight and pancreatic contents of protein and DNA. We also stained pancreatic sections by immunohistochemistry to show the proliferating cells that either expressed the proliferating cell nuclear antigen or were labeled with 5-bromo-2'-deoxyuridine. As a result, the pancreases of the PBD mice were heavier (p < 0.001) and had more protein (p < 0.001), DNA (p < 0.01), and proliferating cells (p < 0.01) than those of the SO counterparts. Thus, pancreatic growth was increased as a result of PBD-induced hypercholecystokininemia. The plasma and pancreatic data demonstrated that the PBD model was a success. This model may be used in CCK-related research. For instance, pancreatic cancer is frequently studied in transgenic mice. PBD may be combined with the cancer model to study the role of CCK in the molecular biology of pancreatic cancer.
INTRODUCTION: Swine had special roles in the development of minimally invasive procedures to treat vesicoureteral reflux, and minipigs have been gaining ground in recent years in experimental pediatric urology as they co...INTRODUCTION: Swine had special roles in the development of minimally invasive procedures to treat vesicoureteral reflux, and minipigs have been gaining ground in recent years in experimental pediatric urology as they combine small size with less vulnerable adult physiology, but their suitability as a model has never been assessed. We therefore compared a landrace piglet with a juvenile minipig to elucidate comparability. METHODS: We evaluated five 3-week old Pietrain piglets and five 3-month old Aachen Minipigs as representatives of landrace and minipig models based on their expected bodyweight being similar to a newborn human. We compared renal weight, volume - via the ellipsoid formula - and ureteral length. In addition, we calculated porcine renal function via Gasthuys' formula. In order to compare the groups with previously published values for infants, we used resampling techniques to allow comparison to humans. RESULTS: Renal weight was higher in humans than in Pietrain piglets (ΔL = 7.6 g; ΔR = 5.4 g) and Aachen Minipigs (ΔL = 11 g; ΔR = 9.4 g). Renal volumes in humans were higher than in both Pietrain piglets (ΔL = 5.6 mL, p < 0.001; ΔR = 3.7 mL, p = 0.004) and Aachen Minipigs (ΔL = 8.1 mL; ΔR = 6.6 mL; both p < 0.001). Ureteral lengths in humans and both pig breeds were comparable as were estimated renal functions between both pig breeds. DISCUSSION AND CONCLUSION: Both landrace piglets and juvenile minipigs are suitable models for experimental pediatric urology as parameters did not differ between them. In addition, the anatomic parameters are comparable or smaller than in infants. This might facilitate translational research as technical failure is less likely in larger organs. Additional research is necessary to cover higher age ranges than those included in the present pilot study.
Ruffolo C, Ferrara F, Trevellin E
… +10 more, Cataldo I, Fornasier C, Pozza A, Campo Dell'Orto M, Angriman I, Dei Tos AP, Bardini R, Massani M, Kotsafti A, Scarpa M
BACKGROUND: Vascular endothelial growth factor (VEGF) is a subfamily of growth factors involved in angiogenesis; CD34+ cells are normally found in endothelial progenitor cells and endothelial cells of blood vessels. Colo...BACKGROUND: Vascular endothelial growth factor (VEGF) is a subfamily of growth factors involved in angiogenesis; CD34+ cells are normally found in endothelial progenitor cells and endothelial cells of blood vessels. Colonic adenomatous polyps may not always be completely removable endoscopically, and a preoperative diagnosis might still be necessary. The aim of the study was to evaluate whether VEGF-A, VEGF-C and CD34 mRNA expression along colorectal carcinogenesis steps can implement NICE (Narrow-Band Imaging International Colorectal Endoscopic) classification in the diagnosis of malignancy in colorectal polypoid lesions. METHODS: Seventy-one subjects with colonic adenoma or cancer who underwent screening narrow-band imaging (NBI) colonoscopy were prospectively enrolled in the MICCE1 project (Treviso center). Polyps were classified according to the NICE classification. Real-time RT-PCR for VEGF-A, VEGF-C and CD34 mRNA expression was performed. Nonparametric statistics, receiver-operating characteristic curve analysis and logistic multiple regression analysis were used. RESULTS: VEGF-A and CD34 mRNA expression was significantly higher in sessile adenomas than in polypoid ones (p < 0.001 and p = 0.01, respectively). VEGF-A, VEGF-C and CD34 mRNA expression was significantly higher in adenocarcinoma than in adenoma (p = 0.01, p = 0.01 and p = 0.01, respectively). The accuracy of VEGF-A, VEGF-C and CD34 mRNA expression for prediction of malignancy was 0.79 (95% CI 0.65-0.90), 0.81 (95% CI 0.66-0.91) and 0.80 (95% CI 0.65-0.90), respectively, while the accuracy of the NICE classification was 0.85 (95% CI 0.72-0.94). The determination coefficient R2, which indicates the amount of the variability explained by a regression model, for NICE classification alone was 0.24 (p < 0.001). A regression model that included NICE classification and VEGF-C mRNA expression showed an R2 = 0.39 as well as a model including NICE classification and CD34 mRNA levels. CONCLUSIONS: This study demonstrated that VEGF-C and CD34 mRNA levels might be useful to stratify colorectal polyps in different risk of progression classes by implementing the accuracy of the NICE classification. Studies on in vivo detection of these markers are warranted.
INTRODUCTION: Portal vein embolization (PVE) is an accepted technique to preoperatively increase the volume of the future remnant liver before major hepatectomy. A permanent material is usually preferred since its superi...INTRODUCTION: Portal vein embolization (PVE) is an accepted technique to preoperatively increase the volume of the future remnant liver before major hepatectomy. A permanent material is usually preferred since its superiority to induce liver hypertrophy over absorbable material has been demonstrated. Nevertheless, the use of an absorbable material generates a reversible PVE (RPVE) capable of inducing significant liver hypertrophy. In small animal models, the possibility to proceed to a repeated RPVE (RRPVE) has shown to boost liver hypertrophy further. The aim of this preliminary study was to assess the feasibility and the tolerance of RRPVE in a large animal model, in comparison with permanent PVE (PPVE) and single RPVE. METHODS: Six swine (2 per group) were assigned either to single RPVE group (using powdered gelatin sponge), RRPVE group (2 RPVEs separated by 14 days) or PPVE group (using N-butyl-cyanoacrylate). The feasibility and tolerance of the procedures were evaluated using portography, liver function tests and histological analysis. Evolution of liver volumes was assessed with volumetric imaging by computed tomography. RESULTS: Embolization of portal branches corresponding to 75% of total liver volume was performed successfully in all animals. Procedures were well tolerated, inducing moderate changes in portal pressure and transient aminotransferase increase. None of the animals developed portal vein thrombosis. After RPVE, complete recanalization occurred at day 11. RRPVE showed a trend for higher hypertrophy, the non-embolized liver to total liver ratio reaching 5.2 ± 1.0% in the RPVE group, 6.8 ± 0.1% in the RRPVE group and 5.0 ± 0.3% in the PPVE group. DISCUSSION/CONCLUSION: In this preliminary comparative study, RRPVE was as feasible and as well tolerated as the other procedures, and resulted in higher liver hypertrophy.
BACKGROUND: Clinical chemistry and hematological tests are widely used to monitor the clinical course of several diseases. However, these parameters are sparse in large-animal models of multiple trauma (MT). Thus, we aim...BACKGROUND: Clinical chemistry and hematological tests are widely used to monitor the clinical course of several diseases. However, these parameters are sparse in large-animal models of multiple trauma (MT). Thus, we aimed to provide these missing data to improve future experimental setups in trauma research. METHODS: Male pigs (German Landrace pigs) were randomized into either an MT group (n = 8) including blunt thoracic trauma, tibial fracture, and controlled hemorrhage or a sham group (n = 8) without any trauma. After trauma induction, all animals received intensive care treatment for 72 h under anesthesia, including mechanical ventilation and volume resuscitation. Blood and urine samples were obtained to measure common hematological and chemical parameters before trauma (0 h), after trauma (1.5 h), during resuscitation (2.5 h), after fracture stabilization (3.5 h), and at 12, 24, 48, and 72 h. Statistical analyses were performed using a linear mixed model (group × time) and Welch's ANOVA. RESULTS: MT led to a perceptible immunological reaction. Between groups, significantly different time courses of leukocyte counts (p = 0.034) and lymphocyte proportions (p = 0.001) were observed. Moreover, MT changed the time course of total protein (p = 0.006). Significantly lower concentrations compared to sham were found in MT at each single time point starting at 1.5 h to the end of the observation period (all p < 0.05). CONCLUSIONS: Our results indicate that a traumatic insult leads to significant alterations in the immune system already shortly after trauma. Together with the additional catabolic reactions observed, these alterations might contribute to the occurrence of later complications. The presented data provide valid references for further experimental setups with prolonged observation times, especially in similar porcine models of MT.
BACKGROUND: Damage control resuscitation forms the cornerstone of management in trauma surgery. Several blood products have been widely used for preoperative transfusions prior to emergency surgeries and for hemorrhage c...BACKGROUND: Damage control resuscitation forms the cornerstone of management in trauma surgery. Several blood products have been widely used for preoperative transfusions prior to emergency surgeries and for hemorrhage control in trauma. Prothrombin complex concentrate (PCC) is now being introduced as an essential component of damage control resuscitation. SUMMARY: We did a comparative descriptive analysis of several single and multi-institutional clinical trials and retrospective cohort studies. The primary focus of these studies was a comparison between PCC and other transfusion modalities including recombinant factor VIIa, fresh-frozen plasma, and fibrinogen based on several vital parameters. The parameters included rapid international normalized ratio reversal, hospital length of stay, cost-effectiveness, mortality rate, and rate of thromboembolic complications. KEY POINTS: Although still awaiting its approval from the FDA for use in traumatic coagulopathy, 4-factor PCC has shown far more convincing results in contrast to former transfusion modalities, even 3-factor PCC. However, more prospective extensive clinical trials on national levels are needed to compare its effectiveness to 3-factor PCC and gather promising recognition in the trauma care fraternity.
BACKGROUND: Electrical stimulation (ES) of several gastrointestinal (GI) segments is a promising therapeutic option for multilocular GI dysmotility, but conventional surgical access by laparotomy involves a high degree o...BACKGROUND: Electrical stimulation (ES) of several gastrointestinal (GI) segments is a promising therapeutic option for multilocular GI dysmotility, but conventional surgical access by laparotomy involves a high degree of tissue trauma. We evaluated a minimally invasive surgical approach using a robotic surgical system to perform electromyographic (EMG) recordings and ES of several porcine GI segments, comparing these data to an open surgical approach by laparotomy. MATERIALS AND METHODS: In 5 acute porcine experiments, we placed multiple electrodes on the stomach, duodenum, jejunum, ileum, and colon. Three experiments were performed with a median laparotomy and 2 others using a robotic platform. Multichannel EMGs were recorded, and ES was sequentially delivered with 4 ES parameters to the 5 target segments. We calculated pre- and poststimulatory spikes per minute (Spm) and performed a statistical Poisson analysis. RESULTS: Electrode placement was achieved in all cases without complications. Increased technical and implantation time were required to achieve the robotic electrode placement, but invasiveness was markedly reduced in comparison to the conventional approach. The highest calculated (c)Spm values were found in the poststimulatory period of the small bowel with both the conventional and robotic approaches. Six of the 20 Poisson test results in the open setup reached statistical significance and 12 were significant in the robotic experiments. CONCLUSIONS: The robotic setup was less invasive, revealed more consistent effects of multilocular ES in several GI segments, and is a promising option for future preclinical and clinical studies of GI motility disorders.
The microcirculation plays a crucial role in the distribution of perfusion to organs. Studies have shown that microcirculatory dysfunction is an independent predictor of morbidity and mortality. Hence, assessment of live...The microcirculation plays a crucial role in the distribution of perfusion to organs. Studies have shown that microcirculatory dysfunction is an independent predictor of morbidity and mortality. Hence, assessment of liver perfusion offers valuable information on the (patho)physiological state of the liver. The current review explores techniques in perfusion imaging that can be used intraoperatively. Available modalities include dynamic contrast-enhanced ultrasound, handheld vital microscopes, indocyanine green fluorescence angiography, and laser contrast speckle imaging. Dynamic contrast-enhanced ultrasound relays information on deep tissue perfusion and is a commonly used technique to assess tumor perfusion. Handheld vital microscopes provide direct visualization of the sinusoidal architectural structure of the liver, which is a unique feature of this technique. Intraoperative fluorescence imaging uses indocyanine green, a dye that is administered intravenously to visualize microvascular perfusion when excited using near-infrared light. Laser speckle contrast imaging produces non-contact large surface-based tissue perfusion imaging free from movement- or pressure-related artefacts. In this review, we discuss the intrinsic advantages and disadvantages of these techniques and their clinical and/or scientific applications.
INTRODUCTION: The advantages of the robotic approach in surgery are undisputed. However, during surgical training, how this technique influences the learning curve has not been described. We provide a tentative model for...INTRODUCTION: The advantages of the robotic approach in surgery are undisputed. However, during surgical training, how this technique influences the learning curve has not been described. We provide a tentative model for analyzing the learning curves associated with observation and active participation in learning different surgical techniques, using functional imaging. METHODS: Forty medical students were enrolled and assigned to 4 groups who underwent training in robotic (ROB), laparoscopic (LAP), or open (OPEN) surgery, and a control group that performed motor training without surgical instruments. Surgical/motor training included six 1-h sessions completed over 6 days of the same week. All subjects underwent functional magnetic resonance imaging (fMRI) scanning sessions, before and after surgical training during. RESULTS: Twenty-three participants completed the study. The 3 surgical groups exhibited different learning curves during training. The main effects of the day of training (p < 0.01) and the group (p < 0.01) as well as a significant interaction of day of training group (p < 0.01) were observed. The performance increased in the first 4 days, reaching a peak at day 4, when all groups were considered together. The OPEN group showed the best performance compared to all other groups (p < 0.04). The OPEN group showed a rapid improvement in performance, which peaked at day 4 and decreased on the last day. Similarly, the LAP group showed a steady increase in the number of exercises they completed, which continued for the entire training period and reached a peak on the last day. However, the participants training in ROB surgery, after a performance initially indistinguishable from that of the LAP group, had a dip in their performance, quickly followed by an improvement and reaching a plateau on day 4. fMRI analysis documented the different involvement of the cortical and subcortical areas based on the type of training. Surgical training modified the activation of some brain regions during both observation and the execution of tasks. CONCLUSIONS: Differences in the learning curves of the 3 surgical groups were noted. Functional brain activity represents an interesting starting point to guide training programs.
BACKGROUND: Mobilization after surgery is recommended to reduce the risk of adverse effects and to improve recovery. The aim of this study was to examine the associations between perioperative physical activity and posto...BACKGROUND: Mobilization after surgery is recommended to reduce the risk of adverse effects and to improve recovery. The aim of this study was to examine the associations between perioperative physical activity and postoperative outcomes in colorectal surgery. METHODS: The daily number of footsteps was recorded from preoperative day 5 to postoperative day 3 in a prospective cohort of patients using wrist accelerometers. Timed Up and Go Test (TUGT), 6 Min Walking Test (6MWT), and peak expiratory flow (PEF) were assessed preoperatively. ROC curves were used to assess the performance of physical activity as a diagnostic test of complications and prolonged length of stay (LOS) of more than 5 days. RESULTS: A total of 50 patients were included. Patients with complications were significantly older (67 years) than those without complications (53 years, p = 0.020). PEF was significantly lower in the group with complications (mean flow 294.3 vs. 363.6 L/min, p = 0.038) while there was no difference between groups for the other two tests (TUGT and 6MWT). The tests had no capacity to discriminate the occurrence of complications and prolonged LOS, except the 6MWT for LOS (AUC = 0.746, p = 0.004, 95% CI: 0.604-0.889). There was no difference in the mean number of preoperative footsteps, but patients with complications walked significantly less postoperatively (mean daily footsteps 1,101 vs. 1,243, p = 0.018). CONCLUSIONS: Colorectal surgery patients with complications were elderly, had decreased PEF, and walked less postoperatively. The 6MWT could be used preoperatively to discriminate patients with potentially increased LOS and foster mobilisation strategies.
INTRODUCTION: Pneumonia is one of the most frequently occurring complications after esophagectomy and is associated with increased operative mortality. Chronic obstructive pulmonary disease (COPD) is known to be a risk f...INTRODUCTION: Pneumonia is one of the most frequently occurring complications after esophagectomy and is associated with increased operative mortality. Chronic obstructive pulmonary disease (COPD) is known to be a risk factor for pulmonary complications and operative mortality. However, in COPD patients preparing for esophagectomy, preventive measures against postoperative pneumonia have not yet been discovered. In this study, we evaluate the effect of perioperative inhaled tiotropium, a long-acting, antimuscarinic bronchodilator used in the management of COPD, on patients with COPD who undergo esophageal cancer surgery. METHODS/DESIGN: This study investigates the effect of perioperative inhaled tiotropium on patients with COPD who undergo esophagectomy. It is an open-label, randomized controlled trial conducted in a single center (EPITOPE study). A total of 32 enrolled patients are randomly assigned in a 1:1 ratio to either conventional management or inhalation of tiotropium in addition to the conventional management. Patients included in the intervention group receive tiotropium Respimat 5 μg (two inhalations of 2.5 μg) for at least 2 weeks before the esophagectomy. Following the esophagectomy, tiotropium is re-delivered, starting as early as possible and continuing until the postoperative evaluation (between 30 and 44 days after the operation). The primary outcome is the incidence of pneumonia within 30 days after esophagectomy. Secondary outcomes are the incidence of cardiovascular complications within 30 days after esophagectomy, the incidence of any postoperative complications within 30 days after esophagectomy, pulmonary function (preintervention, preoperative, and postoperative), walking distance in the incremental shuttle walking test (preintervention, preoperative, and postoperative), the incidence of adverse events, and mortality within 30 days after esophagectomy. DISCUSSION: The EPITOPE study is the first pilot study on the effects of perioperative inhaled tiotropium on patients with COPD undergoing esophagectomy. After completing this study, we will plan a multicenter RCT with the appropriate outcomes in the future.
INTRODUCTION: Intestinal blood flow is often named as a key factor in the pathophysiology of anastomotic leakage. The distribution between mucosal and serosal microperfusion during surgery remains to be elucidated. OBJEC...INTRODUCTION: Intestinal blood flow is often named as a key factor in the pathophysiology of anastomotic leakage. The distribution between mucosal and serosal microperfusion during surgery remains to be elucidated. OBJECTIVE: The aim of this study was to assess if the mucosal microcirculation of the intestine is more vulnerable to a surgical hit than the serosal microcirculation during surgery. METHODS: In an observational cohort study (n = 9 patients), the microcirculation of the bowel serosa and mucosa was visualized with incident dark-field imaging during surgery. At the planned anastomosis, the following microcirculatory parameters were determined: microvascular flow index (MFI), percentage of perfused vessels (PPV), perfused vessel density (PVD), and total vessel density (TVD). Data are presented as median (interquartile range [IQR]). RESULTS: Perfusion parameters and vessel density were significantly higher for the mucosa than the serosal microcirculation at the planned site for anastomosis or stoma. Mucosal MFI was 3.00 (IQR 3.00-3.00) compared to a serosal MFI of 2.75 (IQR 2.21-2.94), p = 0.03. The PPV was 99% (IQR 98-100) versus 92% (IQR 66-94), p = 0.01. The TVD was 16.77 mm/mm2 (IQR 13.04-18.01) versus 10.42 mm/mm2 (IQR 9.36-11.81), p = 0.01, and the PVD was 15.44 mm/mm2 (IQR 13.04-17.78) versus 9.02 mm/mm2 (IQR 6.43-9.43), p = 0.01. CONCLUSIONS: The mucosal microcirculation was preserved, while lower perfusion of the serosa was found at the planned anastomosis or stoma during surgery. Further research is needed to link our observations to the clinically relevant endpoint of anastomotic leakage.
OBJECTIVE: Superior mesenteric artery ischemia and nonocclusive mesenteric ischemia are representative diseases of the vascular emergency known as irreversible transmural intestinal necrosis (ITIN). The receptor for adva...OBJECTIVE: Superior mesenteric artery ischemia and nonocclusive mesenteric ischemia are representative diseases of the vascular emergency known as irreversible transmural intestinal necrosis (ITIN). The receptor for advanced glycation end-products (RAGE) belongs to the immunoglobulin superfamily of extracellular ligands, which also includes high-mobility group box 1 (HMGB-1) and proteins of the S100 family. The HMGB-1 ligands have been implicated in the pathogenesis of various inflammatory disorders. This study was designed to investigate the relation between RAGE and ITIN in a murine acute intestinal ischemic model. MATERIALS AND METHODS: ITIN was induced by clipping the cranial mesenteric artery and the peripheral blood vessels. Mucosal and blood samples were collected and analyzed by reverse-transcription PCR and immunohistochemistry for mucosal inflammation and levels of RAGE-related proteins. The influence of RAGE signaling on intestinal cell reproduction was investigated using the cell scratch test, an in vitro wound-healing assay. Finally, RAGE-related proteins and their respective inhibitors were administered intraperitoneally to ITIN model mice to determine their effects. RESULTS: RAGE-expressing cells were located at the base of the intestinal crypts at day 0. As ITIN progressed, most of the damaged intestinal cells expressed RAGE, and ligands of RAGE such as HMGB-1, S100 A8/A9, and S100β were present in the crypt cells from the bottom to the top. The quantities of S100 A8/A9 and S100β were particularly high, above the levels found in other diseases. When S100 A8/A9 and S100β were applied to small intestinal epithelial cells in vitro, regeneration was significantly impeded. Inflammatory Gr1+ neutrophils and F4/80+ macrophages are involved in tissue ischemia. S100 A8/A9 enhances inflammatory myeloid cell influx. CONCLUSIONS: RAGE-related proteins are elevated in ITIN model mice and impede intestinal regeneration in vitro. RAGE-related proteins may be a new therapeutic target or a new marker for ITIN.