An experimental study on long term outcomes after magnetic esophageal compression anastomosis in piglets.

BACKGROUND/PURPOSE: Previous studies have shown that a patent, watertight esophageal anastomosis can be accomplished safely using specially-shaped magnets in piglets. However, it is unclear whether such a magnetic esophageal compression anastomosis (MECA) remains patent in the long-term. The purpose of this study was to evaluate the long-term outcome of MECA in an experimental pig model over an observation period of 2 months. METHODS: Ten piglets underwent creation of an MECA with custom-made 8 mm magnets and a U-shaped esophageal bypass loop to allow peroral nutrition at eight weeks of life. Two weeks later, the bypass loop was closed surgically, requiring the pigs to swallow via the newly created magnetic compression anastomosis. The pigs were fed soft chow for 2 months. They were monitored for weight gain and signs of dysphagia. At the endpoint of two months, esophagoscopy and contrast esophagography was performed. After removal of the esophagus, the tissues were macroscopiocally and histologically assessed. RESULTS: Six piglets survived until the endpoint. In two pigs, closure of the bypass loop failed, these demonstrated mean weight gain of 792 gs/day [95% Confidence interval 575 to 1009 gs/day]. Weight gain in four pigs that exclusively fed via the magnetic anastomosis averaged 577 gs/day [95% confidence interval 434 to 719 gs/day (p = 0.18)]. There were no signs of dysphagia. All magnets passed with the stool within 16 days. After 2 months, a well-formed magnetic compression anastomosis was visible and easily negotiated with a 6.5 mm endoscope. Esophogram and macroscopic findings confirmed patentency of the esophageal anastomoses. Histopathology showed a circular anastomosis lined with contiguous epithelium. CONCLUSION: MECA creates a long-term functional and patent anastomosis in pigs. This concept may facilitate minimally-invasive esophageal atresia repair by obviating a technically challenging and time-consuming hand-sewn anastomosis.

A Continuous Suture Anastomosis Outperforms a Simple Interrupted Suture Anastomosis in Esophageal Elongation.

INTRODUCTION: Long-gap esophageal atresia represents a distinct entity among the esophageal atresia spectrum. In many patients, achieving a reasonable anastomosis depends on some millimeters of tissue. We aimed to determine what effect the suturing technique would have on esophageal ex vivo elongation as it may determine the strength of a primary anastomosis. MATERIALS AND METHODS: In an analysis of porcine esophagi from animals for slaughter (100-120 days old with a weight of 100-120 kg), we determined esophageal length gain of simple continuous and simple interrupted suture anastomoses subjected to linear traction until linear breaking strength was reached. Statistical power of 80% was ensured based on an a priori power analysis using five specimens per group in a separate exploratory experiment. RESULTS: The simple continuous suture anastomosis in 15 porcine esophagi ( = 4.47 cm, 95% confidence interval: 4.08-4.74 cm) outperformed the simple interrupted suture anastomosis in another 15 esophagi ( = 3.03 cm, 95% confidence interval: 2.59-3.43 cm) in length gain (Δ = 1.44 cm, 95% confidence interval: 0.87-2.01 cm, p < 0.0001). CONCLUSION: Simple continuous anastomoses achieved higher length gain compared with simple interrupted suture anastomoses. This effect warrants an experimental assessment in vivo to assess its potential merits for clinical applicability.

Comparing Aachen Minipigs and Pietrain Piglets as Models of Experimental Pediatric Urology to Human Reference Data.

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.

5-Aminolevulinic Acid Multispectral Imaging for the Fluorescence-Guided Resection of Brain Tumors: A Prospective Observational Study.

Fluorescence-guided surgery with five-aminolevulinic acid (5-ALA) is the state-of-the-art treatment of high-grade gliomas. However, intraoperative visualization of 5-ALA under blue light remains challenging, especially when blood covers the surgical field and thereby fluorescence. To overcome this problem and combine the brightness of visible light with the information delivered with fluorescence, we implemented multispectral fluorescence (MFL) in a surgical microscope, a technique that is able to project both information in real-time. We prospectively examined 25 patients with brain tumors. One patient was operated on two different lesions in the same setting. The tumors comprised: six glioblastomas, four anaplastic astrocytomas, one anaplastic oligodendroglioma, two meningiomas, 11 metastatic tumors, one acoustic neuroma, and one ependymoma. The MFL technique with a real-time overlay of fluorescence and white light was compared intraoperatively to the classic blue filter. All lesions were clearly visible and highlighted from the surrounding tissue. The pseudocolor we chose was green, representing fluorescence, with the surrounding brain tissue remaining in its original color. When blood was covering the surgical field, orientation was easy to maintain. The MFL technique opens the way for precise and clear visualization of fluorescence in real-time under white light. It can be easily used for the resection of all tumors accumulating 5-ALA. Drawbacks of classic PpIX fluorescence such as hidden fluorescence, intraoperative changes could be overcome with the presence of additional white light in MFL technique.

Real-Time Overlapping of Indocyanine Green-Video Angiography With White Light Imaging for Vascular Neurosurgery: Technique, Implementation, and Clinical Experience.

BACKGROUND: Fluorescent-guided techniques in vascular neurosurgery can be demonstrated via black and white indocyanine green videoangiography (ICG-VA). Multispectral imaging (MFL) is a new method, which overlaps fluorescence with the white light and provides a fluorescent white light augmented reality image to the surgeon. OBJECTIVE: To investigate (a) whether MFL can enhance the visualization of the blood-flow with simultaneous visualization of the anatomic structures and (b) if MFL can ergonomically improve the microvascular surgical treatment compared to ICG-VA. METHODS: A digital imaging of the blood flow after intravenous injection of ICG on 7 pigs was performed in real time under white light, standard fluorescence, and MFL. The blood flow was interrupted with a surgical clip, demonstrating the blockage of the blood flow. We prospectively included 30 patients with vascular deformities. The vasculature was visualized on the microscope's monitor and through the microscope's eyepiece. RESULTS: In the animal experiment, the visualization of the anatomy and the blood flow under MFL produced high resolution images. The occlusion of blood vessels demonstrated sufficiently the blockage of tissue perfusion and its reperfusion after clip removal. During all 30 surgical cases, the MFL technique and the direct delivery of the pseudo-colored image through the eyepiece allowed for enhanced anatomic and dynamic data. CONCLUSION: MFL was shown to be superior to the classic ICG-VA, delivering enhanced data and notably improving the workflow due to the simultaneous and precise white light visualization of the blood flow and the surrounding anatomic structures.

Using multidimensional scaling in model choice for congenital oesophageal atresia: similarity analysis of human autopsy organ weights with those from a comparative assessment of Aachen Minipig and Pietrain piglets.

Swine models had been popular in paediatric oesophageal surgery in the past. Although being largely replaced by rodent models, swine experienced a revival with the establishment of minipig models. However, none of them has ever been investigated for similarity to humans. We conducted a pilot study to determine whether three-week old Pietrain piglets and three-month old Aachen Minipigs are suitable for experimental paediatric oesophageal atresia surgery. We tested the operation's feasibility, performed a necropsy, weighed organs, measured organ length and calculated relative weights and lengths, and measured laboratory parameters. We used multidimensional scaling to assess the similarity of the swine breeds with previously published human data. Pietrain piglets had a higher a priori bodyweight than Aachen Minipigs (Δ = 1.31 kg, 95% confidence interval (CI): 0.37-2.23, p = 0.015), while snout-to-tail length was similar. Pietrain piglets had higher absolute and relative oesophageal lengths (Δ = 5.43 cm, 95% CI: 2.2-8.6; p = 0.0062, q1* = 0.0083 and Δ = 11.4%, 95% CI: 5.1-17.6; p = 0.0025, q3* = 0.0053). Likewise, absolute and relative small intestinal lengths were higher in Pietrains, but all other parameters did not differ, with the exception of minor differences in laboratory parameters. Multidimensional scaling revealed three-week old Pietrain piglets to be similar to two-month old humans based on their thoracoabdominal organ weights. This result indicates three-week old Pietrain piglets are a suitable model of paediatric oesophageal atresia surgery, because clinically many procedures are performed at around eight weeks age. Three-month old Aachen Minipigs were more dissimilar to eight-week old humans than three-week old Pietrain piglets.

Using simple interrupted suture anastomoses may impair translatability of experimental rodent oesophageal surgery.

Background/purpose: Irreproducibility and missing translatability are major drawbacks in experimental animal studies. Hand-sewn anastomoses in oesophageal surgery are usually continuous, whereas those in experimental oesophageal surgery are widely performed using the simple interrupted technique. It has been implicated to be inferior in tolerating anastomotic tension, which we aimed to test in rats due to their importance as an animal model in oesophageal surgery.Methods: We determined linear breaking strengths for the native oesophagus (n = 10), the simple interrupted suture anastomosis (n = 11), and the simple stitch (n = 9) in 8-week old Sprague-Dawley rats. Experiments were powered to a margin of error of 10% around the results of exploratory investigations. The comparison of anastomotic resilience between native organ and simple interrupted suture anastomosis was a priori powered to 99%.Results: Native oesophagi sustained traction forces of 4.25 N (95% CI: 4.03-4.58 N), but the simple interrupted suture anastomosis had only 38.6% (Δ= -2.78 N, 95% CI: -2.46 to -3.11 N, p < .0001) of the resilience of native oesophagi.Conclusions: Oesophageal division and re-anastomosis markedly decreases resilience to traction forces compared to the native organ. This effect is even more pronounced in rats compared to other species and might impair transferability of results.

An experimental study on magnetic esophageal compression anastomosis in piglets.

INTRODUCTION: Fashioning a patent, watertight anastomosis in patients with esophageal atresia is a challenging task in pediatric surgery, particularly when performed under tension. A reproducible suture-less alternative would decrease operative time. We evaluated magnetic esophageal compression anastomoses in a novel bypass-loop swine model. METHODS: Eight-week-old piglets underwent thoracotomy to mobilize the esophagus at the carina to create a U-shaped loop. Custom-made 8 mm diameter Neodymium Magnets were inserted into the esophagus proximal and distal to the loop, then mated side-to-side at the future anastomosis site. Pigs were observed for 8 (n = 4), 10 (n = 6), and 12 (n = 2) days and then sacrificed. The magnetic compression anastomosis was evaluated macroscopically, by radiography, burst pressure testing, and histology. RESULTS: All 12 pigs survived until the endpoint. Separation of the magnets occurred at a median of 9 days. Contrast esophagrams showed patency and no leak. All anastomoses withstood pressures well over 13 kPa without leak. Histopathology showed epithelialized circular scar tissue. CONCLUSION: Magnetic compression anastomoses of the esophagus using our specially-designed magnets are formed between the 8th and 10th postoperative day, are patent and mechanically resistant to supraphysiologic intraluminal pressures. These data lay the basis for a potential clinical application in patients born with esophageal atresia. LEVEL OF EVIDENCE: Not applicable (experimental animal study).

Confocal-Assisted Multispectral Fluorescent Microscopy for Brain Tumor Surgery.

Optimal surgical therapy for brain tumors is the combination of complete resection with minimal invasion and damage to the adjacent normal tissue. To achieve this goal, we need advanced imaging techniques on a scale from macro- to microscopic resolution. In the last decade, the development of fluorescence-guided surgery has been the most influential breakthrough, marginally improving outcomes in brain tumor surgery. Multispectral fluorescence microscopy (MFL) is a novel imaging technique that allows the overlapping of a fluorescent image and a white light image in real-time, with delivery of the merged image to the surgeon through the eyepieces of a surgical microscope. MFL permits the detection and characterization of brain tumors using fluorescent molecular markers such as 5-aminolevulinic acid (5-ALA) or indocyanine green (ICG), while simultaneously obtaining high definition white light images to create a pseudo-colored composite image in real-time. Limitations associated with the use of MFL include decreased light imaging intensity and decreased levels of magnification that may compromise maximal tumor resection on a cellular scale. Confocal laser endomicroscopy (CLE) is another novel advanced imaging technique that is based on miniaturization of the microscope imaging head in order to provide the possibility of in vivo microscopy at the cellular level. Clear visualization of the cellular cytoarchitecture can be achieved with 400-fold-1,000-fold magnification. CLE allows on the one hand the intra-operative detection and differentiation of single tumor cells (without the need for intra-operative histologic analysis of biopsy specimens) as well as the definition of borders between tumor and normal tissue at a cellular level, dramatically improving the accuracy of surgical resection. The application and implementation of CLE-assisted surgery in surgical oncology increases not only the number of options for real-time diagnostic imaging, but also the therapeutic options by extending the resection borders of cancer at a cellular level and, more importantly, by protecting the functionality of normal tissue in the adjacent areas of the human brain. In this article, we describe our experience using these new techniques of confocal-assisted fluorescent surgery including analysis on the technology, usability, indications, limitations, and further developments.

Beyond Magnamosis: A Method to Test Sutureless Esophageal Anastomotic Devices in Living Swine by Creating an Esophageal Bypass Loop for Natural Oral Nutrition.

Introduction: Thoracoscopic esophageal atresia repair has become increasingly popular, but is still limited to a few expert centers and has some challenges and shortcomings. One of them has a longer operation time compared with conventional thoracotomy. Magnetic compression anastomosis may contribute toward shorter operation times by avoiding the time-consuming anastomotic suturing. We aimed to establish a method of testing sutureless anastomoses in parallel to having swine eating the natural way. Materials and Methods: We used four juvenile Pietrain swine-aged 8 weeks, weighing 15 kg-to establish a living animal model after preceding cadaver tests. Esophagi were fully mobilized through right-sided thoracotomy to gain sufficient length to create an esophageal loop that served as a bypass for food after magnet deployment. Six hours later, patency of the bypass esophageal loop was assessed by passing an orogastric tube and by allowing swine to drink methylene blue-stained water. We also tested the device stability using the classical burst pressure test. Results: The esophageal lumen was patent for feeding tube. Swine were able to drink and methylene blue colored fluid reached the stomach. Clinical signs of obstruction such as regurgitation or coughing were absent. Magnets sustained burst pressures up to 200,000 Pascal until they became disrupted. At 6 hours after magnet placing, we already saw subtle esophageal mucosa erosions indicating the beginning of anastomotic formation. Conclusion: This animal model is useful to test different magnet designs for sutureless esophageal anastomosis or even future devices for in vivo tissue engineering.

Esophageal Blood Flow May Not Be Directly Influenced by Anastomotic Tension: An Exploratory Laser Doppler Study in Swine.

BACKGROUND: Anastomotic tension has been linked to leakage and stenosis in esophageal surgery in both adults and children. We aimed to determine the effects of esophageal topography, operative technique, and anastomotic tension on esophageal blood flow. MATERIALS AND METHODS: We divided and reanastomosed the esophagi at the carinal level with increasing levels of anastomotic tension in piglets (n = 10) and sham controls (n = 4). We examined esophageal blood flow pre- and postoperatively using laser Doppler flowmetry at the anastomosis and two predetermined proximal and distal points. Blood flow in relation to distance from the anastomosis was examined by multivariate linear regression. RESULTS: Thoracotomy alone did not influence perfusion at the carinal level in shams (Δ = 3.13 laser Doppler units, 95% confidence interval: -3.4 to 9.7, p = 0.2686). We constructed a (F[5,134] = 6.34, p < 0.0001) multinomial regression model based on distance to the anastomotic site and pre-/postoperative measurements (adjusted R 2 = 0.1624). Tissue blood flow was higher distant to the carina, but lower postoperatively and not influenced by the tension resulting from the extent of resection (F[1, 8] = 1.134, p = 0.318). CONCLUSION: Esophageal blood flow is higher at greater distances to the carinal level and hampered by esophageal division and reanastomosis. The extent of resection has less influence than previously assumed. Therefore, leakage and stenosis after esophageal anastomosis may not solely be caused by insufficient anastomotic blood flow.

Esophageal Biomechanics Revisited: A Tale of Tenacity, Anastomoses, and Suture Bite Lengths in Swine.

BACKGROUND: Anastomotic tension has repeatedly been associated with anastomotic leakages after esophagectomy for cancer or esophageal atresia repair. We therefore aimed to determine which anastomotic technique would come as close as possible to the native esophagus in sustaining traction forces. Constant traction for several minutes at esophageal remnants and large suture bites are also considered relevant in long-gap esophageal atresia repair. METHODS: Porcine esophagi were subjected to linear traction using a motorized horizontal test stand. We compared breaking strengths of native esophagi to simple continuous, simple interrupted, stapled, and barbed suture anastomoses. We also investigated the effects of suture bite length and phases of constant traction on breaking strengths and powered all experiments to at least 80% using exploratory investigations (n = 5 per group). RESULTS: Continuous suture anastomoses had a breaking strength comparable to native esophagi (Δ = -5.25 Newton, 95% confidence interval: -10.69 to 0.19 Newton, p = 0.058) and outperformed all other investigated anastomoses (Δ ≥14.01 Newton, p ≤ 0.02). Breaking strength correlated with suture bite length (R = 0.905) and predicted breaking strength for the simple stitch (adjusted R2 = 0.812, p < 0.0001), but not for anastomoses. Phases of incrementally increasing constant traction resulted in higher breaking strengths (Δ = 13.36 Newton, 95% confidence interval: 9.93 to 16.79 Newton, p < 0.0001) and higher length gain (Δ = 1.06 cm, 95% confidence interval: 0.65 to 1.48 cm, p < 0.0001) compared with controls. CONCLUSIONS: Only simple continuous anastomoses achieved the linear breaking strength of native tissue. Our study provides important insights in tolerance to traction forces, but its results have to be corroborated in living animals as anastomotic leakages are multifactorial processes.

Technical Aspects in Esophageal Lengthening: An Investigation of Traction Procedures and Suturing Techniques in Swine.

INTRODUCTION: Traction procedures are useful to preserve the child's own esophagus in long-gap forms of esophageal atresia. To date, it remains unclear what suture size or position of the traction sutures is optimal to account for differences in anatomy and to reduce the risk of traction sutures being torn out of the esophageal tissue. MATERIALS AND METHODS: Explanted porcine esophagi (from swine aged 100-120 days and weighing 100-120 kg) were divided at the carinal level. Traction sutures were either placed circumferentially or only in the dorsal wall and the breaking strength-circumferential disruption of the muscular layer-was measured. Suture size (USP 4-0 vs. 5-0) was also evaluated in a similar way. RESULTS: Neither traction suture position did not influence breaking strengths between circumferentially placed traction sutures or those exclusively placed in the dorsal esophageal wall (Δ = 0.47 N, 95% confidence interval: -2.83 to 3.76 N, p = 0.771, n = 11 per group) nor differing suture sizes of USP 4-0 and USP 5-0 (Δ = 1.46 N, 95% confidence interval: -3.2 to 0.28 N, p = 0.0946, n = 9 per group) affected breaking strengths. CONCLUSION: Suture size and suture positioning do not affect mechanical stability in Foker's procedure and therefore can be adapted as needed according to patient's anatomy and size.

Bodyweight, not age, determines oesophageal length and breaking strength in rats.

BACKGROUND/PURPOSE: Delayed primary repair is still the method of choice in the management of long-gap oesophageal atresia in many centres, but the timing of anastomoses varies. Some assume the infant's bodyweight to be an important factor, whereas others prefer age. We therefore aimed to clarify whether age or bodyweight determined oesophageal length in a rodent model. METHODS: We explanted the oesophagi of 20 Sprague-Dawley rats, aged 15 to 444 days (n = two per time point), measured bodyweight, oesophageal length, weight, and linear breaking strength to measure tissue resilience. Univariate and multivariate regression analyses were conducted to determine the influence of age and bodyweight on oesophageal length and linear breaking strength. RESULTS: All parameters were highly correlated (R > 0.8), except for age and linear breaking strength (R = 0.65). Both age and bodyweight were univariate significant predictors of oesophageal length, weight, and linear breaking strength (p < 0.0001). Multivariate analyses showed bodyweight to be a significant predictor of oesophageal length (p < 0.0001), whereas age was not (p = 0.18) [adjusted R2 = 0.9031]. This was also true for linear breaking strength (p = 0.0007 and p = 0.97, respectively) [adjusted R2 = 0.71]. Moreover, the influence of age was negligible, as the adjusted R2 and the regression coefficient of bodyweight and its 95% confidence interval were almost identical between univariate und multinomial regressions. CONCLUSIONS: Only weight determines oesophageal length and tissue resilience in rodents, whereas age is irrelevant. If a similar relationship exists in humans, it may facilitate choosing the optimum time point for delayed primary anastomosis. LEVEL OF EVIDENCE: IV - Experimental Paper.

Crucial role for Nox2 and sleep deprivation in aircraft noise-induced vascular and cerebral oxidative stress, inflammation, and gene regulation.

Aims: Aircraft noise causes endothelial dysfunction, oxidative stress, and inflammation. Transportation noise increases the incidence of coronary artery disease, hypertension, and stroke. The underlying mechanisms are not well understood. Herein, we investigated effects of phagocyte-type NADPH oxidase (Nox2) knockout and different noise protocols (around-the-clock, sleep/awake phase noise) on vascular and cerebral complications in mice. Methods and results: C57BL/6j and Nox2-/- (gp91phox-/-) mice were exposed to aircraft noise (maximum sound level of 85 dB(A), average sound pressure level of 72 dB(A)) around-the-clock or during sleep/awake phases for 1, 2, and 4 days. Adverse effects of around-the-clock noise on the vasculature and brain were mostly prevented by Nox2 deficiency. Around-the-clock aircraft noise of the mice caused the most pronounced vascular effects and dysregulation of Foxo3/circadian clock as revealed by next generation sequencing (NGS), suggesting impaired sleep quality in exposed mice. Accordingly, sleep but not awake phase noise caused increased blood pressure, endothelial dysfunction, increased markers of vascular/systemic oxidative stress, and inflammation. Noise also caused cerebral oxidative stress and inflammation, endothelial and neuronal nitric oxide synthase (e/nNOS) uncoupling, nNOS mRNA and protein down-regulation, and Nox2 activation. NGS revealed similarities in adverse gene regulation between around-the-clock and sleep phase noise. In patients with established coronary artery disease, night-time aircraft noise increased oxidative stress, and inflammation biomarkers in serum. Conclusion: Aircraft noise increases vascular and cerebral oxidative stress via Nox2. Sleep deprivation and/or fragmentation caused by noise triggers vascular dysfunction. Thus, preventive measures that reduce night-time aircraft noise are warranted.

Pringle maneuver increases the risk of anastomotic leakage after colonic resection in rats.

BACKGROUND: Many centers use the Pringle's maneuver during liver resections. Since this maneuver might impair healing of bowel anastomoses, we evaluated its influence on the healing of colonic anastomosis in rats. METHODS: Male Wistar rats underwent median laparotomy and sigmoid resection with end-to-end anastomosis under inhalation anesthesia. Thereafter, rats received a 25 minutes Pringle's maneuver (PM, group 1) or were kept under anesthesia for the same period of time (group 2). The anastomotic bursting pressure (BP) was measured on postoperative days (POD) 3, 6 and 9. Hematoxylin and Eosin (H&E) staining was used for histopathological evaluation of the anastomosis. The Mann-Whitney U and χ2 -tests were used, p<0.05 values were considered significant. RESULTS: All animals (n=48) lost body weight (BW) until POD3 (95.2% vs. 85.7%, p=0.003), and BW remained lower after PM (106.2% vs. 92.8%, p=0.001). The anastomotic BP was lower in group 1 compared to group 2 on POD 3 (116mmHg vs. 176.28mmHg, p=0.001), POD 6 (182.8mmHg vs. 213mmHg, p=0.029) and POD 9 (197.2mmHg vs. 251.7mmHg, p=0.009), and mortality was higher in group 1 (1 vs. 7, p=0.022). CONCLUSIONS: Pringle's maneuver increases anastomotic complications in rats. Therefore, a Pringle's maneuver should be avoided during simultaneous liver and colorectal surgery.

Resection of C6 gliomas in rats with the aid of the waterjet technique.

OBJECTIVES: While clinically the safety and efficacy of waterjet resection of brain tumors have been shown, evidence that waterjet dissection improves tumor resection radicality in comparison with conventional techniques is still missing. In the present study, resection radicality and tumor-free long-term survival of both techniques were evaluated in a C6-glioma model. MATERIAL AND METHODS: Fifty-thousand C6-glioma cells were stereotactically transplanted in the left frontal lobe of 100 male Sprague-Dawley rats. After MRI-scanning for evaluation of tumor extension, microsurgical tumor resection was performed with conventional techniques (n=50) or with the waterjet dissector at pressures of 6bar (n=50). Twenty-five animals of each group were sacrificed after surgery for histological analysis. For analysis of survival after tumor resection, twenty-five animals of each group were followed-up to analyze tumor-free survival using the Kaplan Meier method. RESULTS: In the waterjet group, the resection cavity was free of C6-tumor cells in 10/25 (40%) rats showing a trend (p=0.3) towards better resection radicality compared to the rats that were treated conventionally (7/10; 28%). R1-resection with up to 250C6 cells/object slice was found in 14/25 (56%) rats after waterjet dissection compared to 6/25 (24%) rats treated conventionally showing significance (p<0.01). Probability of survival was 38% after 2 weeks and 20% after 6 months in the waterjet group compared to 30% and 16% respectively in the conventional group. Diffuse tumor cell spreading with possible influence on survival was shown in 47/50 rats. CONCLUSION: In this experimental model, waterjet tumor resection did reveal significantly better resection radicality compared to the conventional technique. Although a direct transfer of these results to human glioma surgery is prohibited, the waterjet technique might contribute to the best possible resection radicality in human gliomas. Nevertheless, tumor cell spreading remains a major problem. Further studies have to address that the surgical results - in deed - improve the postoperative outcome.

Surface Electromyography Reliably Records Electrophysiologically Evoked Internal Anal Sphincter Activity: A More Minimally Invasive Approach for Monitoring Extrinsic Innervation.

BACKGROUND: Even in the case of minimally invasive pelvic surgery, sparing of the autonomic nerve supply is a prerequisite for maintaining anal sphincter function. Internal anal sphincter (IAS) innervation could be electrophysiologically identified based on processed electromyographic (EMG) recordings with conventional bipolar needle electrodes (NE). This experimental study aimed for the development of a minimally invasive approach via intra-anal surface EMG for recordings of evoked IAS activity. METHODS: Six male pigs underwent nerve-sparing low anterior rectal resection. Electric autonomic nerve stimulations were performed under online-processed EMG of the IAS. EMG recordings were simultaneously carried out with conventional bipolar NE as the reference method and newly developed intra-anal surface electrodes (SE) in different designs. RESULTS: In all experiments, the IAS activity could be continuously visualized via EMG recordings based on NE and SE. The median number of bipolar electric stimulations per animal was 27 (range 5-52). The neurostimulations resulted in significant EMG amplitude increases for both recording types [NE: median 3.0 µV (interquartile range, IQR 2.8-3.5) before stimulation vs. 7.1 µV (IQR 3.9-13.8) during stimulation, p < 0.001; SE: median 3.6 µV (IQR 3.1-4.3) before stimulation vs. 6.8 µV (IQR 4.8-10.3) during stimulation, p < 0.001]. CONCLUSIONS: Intra-anal SE enabled reliable EMG of electrophysiologically evoked IAS activity similar to the conventional recording via NE. The transfer of the method to access platforms for transanal total mesorectal excision or robotics may offer a practical more minimally invasive approach for monitoring extrinsic innervation.

Endothelial LRP1 transports amyloid-ß(1-42) across the blood-brain barrier.

According to the neurovascular hypothesis, impairment of low-density lipoprotein receptor-related protein-1 (LRP1) in brain capillaries of the blood-brain barrier (BBB) contributes to neurotoxic amyloid-ß (Aß) brain accumulation and drives Alzheimer's disease (AD) pathology. However, due to conflicting reports on the involvement of LRP1 in Aß transport and the expression of LRP1 in brain endothelium, the role of LRP1 at the BBB is uncertain. As global Lrp1 deletion in mice is lethal, appropriate models to study the function of LRP1 are lacking. Moreover, the relevance of systemic Aß clearance to AD pathology remains unclear, as no BBB-specific knockout models have been available. Here, we developed transgenic mouse strains that allow for tamoxifen-inducible deletion of Lrp1 specifically within brain endothelial cells (Slco1c1-CreER(T2) Lrp1(fl/fl) mice) and used these mice to accurately evaluate LRP1-mediated Aß BBB clearance in vivo. Selective deletion of Lrp1 in the brain endothelium of C57BL/6 mice strongly reduced brain efflux of injected [125I] Aß(1-42). Additionally, in the 5xFAD mouse model of AD, brain endothelial-specific Lrp1 deletion reduced plasma Aß levels and elevated soluble brain Aß, leading to aggravated spatial learning and memory deficits, thus emphasizing the importance of systemic Aß elimination via the BBB. Together, our results suggest that receptor-mediated Aß BBB clearance may be a potential target for treatment and prevention of Aß brain accumulation in AD.

Towards a glioma model for surgical technique evaluation in the rat.

INTRODUCTION: Evaluation of new surgical techniques in animal models is frequently challenging. This article describes the pitfalls, peculiarities and the final best applicable model for evaluating surgical techniques for glioma resection. METHODS: The C6 glioma cell line and the Sprague-Dawley rat strain were selected. Fifty-thousand glioma cells were stereotactically transplanted in the left hemisphere of 137 male adult rats. Evaluation of solid tumour formation, tumour growth and scheduling of surgical resection was performed by MR scanning at 1, 2, and 4 weeks after transplantation and 3 and 6 months after tumour resection. Microsurgical tumour resection was performed with conventional techniques or with the waterjet dissector at a pressure of 6 bar. One subgroup of each surgical technique was sacrificed directly after surgery for histological analysis. The other subgroup was followed up for long-term analysis. RESULTS: The transplantation site was of great importance. After transplantation of tumour cells posterior to the bregma, intra-ventricular tumour growth with spreading occurred. Homogenous and reproducible tumour growth was achieved after grafting cells lateral - 3 mm, anterior + 1 mm, and - 2.5 mm ventral to the bregma. After development of solid tumours on MR imaging, animals were subjected to surgery. MR and intra-operative findings corresponded well. However, MRI and intra-operative none-detectable perivascular tumour spreading was histologically observed in the majority of cases. CONCLUSIONS: The presented glioma rat model consisting of the C6 cell line and Sprague-Dawley rats as recipients is a well-suited model to investigate surgical techniques and their impact on tumour therapy. However, the site of transplantation, the preparation of cell grafts and the technique of tumour growth evaluation is of utmost importance to achieve reliable results.