Pre-differentiation of mesenchymal stromal cells in combination with a microstructured nerve guide supports peripheral nerve regeneration in the rat sciatic nerve model.

Many bioartificial nerve guides have been investigated pre-clinically for their nerve regeneration-supporting function, often in comparison to autologous nerve transplantation, which is still regarded as the current clinical gold standard. Enrichment of these scaffolds with cells intended to support axonal regeneration has been explored as a strategy to boost axonal regeneration across these nerve guides Ansselin et al. (1998). In the present study, 20 mm rat sciatic nerve defects were implanted with a cell-seeded microstructured collagen nerve guide (Perimaix) or an autologous nerve graft. Under the influence of seeded, pre-differentiated mesenchymal stromal cells, axons regenerated well into the Perimaix nerve guide. Myelination-related parameters, like myelin sheath thickness, benefitted from an additional seeding with pre-differentiated mesenchymal stromal cells. Furthermore, both the number of retrogradely labelled sensory neurons and the axon density within the implant were elevated in the cell-seeded scaffold group with pre-differentiated mesenchymal stromal cells. However, a pre-differentiation had no influence on functional recovery. An additional cell seeding of the Perimaix nerve guide with mesenchymal stromal cells led to an extent of functional recovery, independent of the differentiation status, similar to autologous nerve transplantation. These findings encourage further investigations on pre-differentiated mesenchymal stromal cells as a cellular support for peripheral nerve regeneration.

Hybrid robotic versus hybrid laparoscopic Ivor Lewis oesophagectomy: a case-matched analysis.

OBJECTIVES: Robotic-assisted oesophagectomy for cancer has been increasingly employed worldwide; however, the benefits of this technique compared to conventional minimally invasive oesophagectomy are unclear. Since 2016, hybrid robotic minimally invasive oesophagectomy (R-HMIE) has increasingly replaced hybrid laparoscopic minimally invasive oesophagectomy (HMIE) as the standard of care in our institution. The aim of this study was to compare these procedures. METHODS: Over a 10-year period, 686 patients underwent oesophagectomy at our institution. Out of these patients, 128 patients with cancer were treated with a hybrid minimally invasive technique. Each patient who underwent R-HMIE was matched according to gender, age, comorbidity, American Society of Anesthesiologists classification, Union International Contre le Cancer stage, localization, histology and neoadjuvant treatment with a patient who underwent HMIE. Perioperative parameters were extracted from our database and compared between the 2 groups. RESULTS: After the matching procedure, 88 patients were included in the study. Between HMIE and R-HMIE, no significant differences (P > 0.05) were found in operating time (median 281 vs 300 min), R0 resection rate (n = 42 vs 42), harvested lymph nodes (median 28 vs 24), hospital stay (median 19 vs 17 days) and intensive care unit stay (median 7 vs 6.5 days). Regarding surgical complications, no difference could be observed either (n = 42 vs 44). CONCLUSIONS: Minimally invasive oesophagectomy remains a challenging operation with high morbidity even in a high-volume institution. According to our intra- and short-term results, we have found no difference between R-HMIE and HMIE.

Prognostic Value of Chest-Tube Amylase Versus C-Reactive Protein as Screening Tool for Detection of Early Anastomotic Leaks After Ivor Lewis Esophagectomy.

INTRODUCTION: Intrathoracic anastomotic leaks after esophagectomy are a significant cause of morbidity and death. Early detection and timely management are crucial. This study evaluates the effectiveness of daily drain amylase levels in detecting early leaks after esophagectomy compared with C-reactive protein (CRP). MATERIALS AND METHODS: Between June 2015 and September 2017, 126 esophagectomies were performed in our department. Amylase levels were collected in 80 of these patients, as long right-sided chest tubes were in place. Mostly, chest tubes were removed before postoperative day (POD) 5. CRP levels were measured daily. Early leaks were defined as occurring with the chest tubes in place. According to the obtained receiver operating characteristics curves, amylase levels >335 U/L, and CRP >30 mg/dL were considered positive. Sensitivity and specificity for both drain amylase and CRP were calculated. RESULTS: Overall anastomotic leak rate was 7.5% (6/80). An early disruption occurred in 4 of 80 patients (5%). Three patients had a positive amylase level and none a positive CRP on POD 1. These 3 patients had on POD 2 a positive CRP. The fourth patient presented at POD 2 bilious secretion in the chest tubes. He showed normal amylase and CRP levels on POD 1. Sensitivity and specificity for amylase level and CRP within the first 3 PODs were 0.75 and 0.98 versus 0.75 and 0.85, respectively. The patients with leak were reoperated at POD 2. They were all discharged between PODs 15 and 19. CONCLUSIONS: Amylase level after esophagectomy is a more accurate screening tool for detection of early leaks than CRP. It could facilitate their detection up to 24 hours earlier than CRP.

Evaluation of functional nerve recovery with Visual-SSI--a novel computerized approach for the assessment of the static sciatic index (SSI).

Complete nerve transection (neurotmesis) of the rat sciatic nerve is a well-established animal model. The most frequently used behavioural for evaluation of neurotmesis-induced deficits is the walking track analysis with calculation of the sciatic functional index (SFI). More recently, the static sciatic index (SSI) has been developed, which shows a good correlation with the SFI. However, despite all advantages (high accessibility, easy handling, high accuracy, cost-effectiveness), the SSI is still not widely used. We, therefore, developed a novel programme ("Visual-SSI"), which will be made freely available for the assessment of the SSI. As gold-standard for the treatment of neurotmesis-induced nerve gaps, autologous nerve transplantation studies in the rat sciatic nerve model (n=16 [6 weeks], n=8 [12 weeks]) were carried out to test the effectiveness and feasibility of the Visual-SSI software. We observed a significant recovery starting from the pre-operative condition over the 3rd, 6th, 9th weeks until the 12th week after surgery (p<0.05). Theoretically, the SSI can be calculated from both rearing and normal standing position of the rats and we investigated whether the SSI is affected differentially by these positions. We observed no significant differences between animals in a rearing and normal standing stance (p>0.05). The present method combines efficiency (simplicity of use, rapid and economical setup) with accurate and precise quantification of the functional regeneration in the sciatic nerve lesion model of the rat.

Cell-enrichment with olfactory ensheathing cells has limited local extra beneficial effects on nerve regeneration supported by the nerve guide Perimaix.

The reconstruction of peripheral nerve injuries is clinically challenging, and today, the autologous nerve transplantation is still considered as the only gold standard remedy for nerve lesions where a direct nerve coaptation is not possible. Nevertheless, the functional merits of many biomaterials have been tested as potential substitutes for the autologous nerve transplant. One of the strategies that have been pursued is the combination of bioengineered nerve guides with cellular enrichment. In this present study, we combined the previously evaluated collagen-based and microstructured nerve guide Perimaix with olfactory ensheathing cell enrichment. Rat sciatic nerve defects of 20 mm were either bridged by a cell-seeded or nonseeded nerve guide or an autologous nerve transplant. Animals were monitored for 12 weeks for structural and functional parameters. Seeded cells survived on Perimaix, and following implantation aligned along the microstructured Perimaix framework. Axonal densities within the cell-seeded nerve guides were higher than in the nonseeded nerve guides and were comparable to the autograft. Additionally, cell-seeding had local beneficial effects on myelination within the nerve guide, as myelin sheath thickness was enhanced when compared with the empty scaffold. Nevertheless, for bridging the nerve gap of 20 mm, both the cell-seeded as well as nonseeded scaffolds were equally efficient regarding the functional outcome, which did not differ between the autograft, seeded or nonseeded groups. Our data demonstrate that olfactory ensheathing cell enrichment has local effects on nerve regeneration in combination with the Perimaix nerve guide. Surprisingly, for traversing the lesion gap, additional cell-seeding is not crucial.

In vitro assessment of axonal growth using dorsal root ganglia explants in a novel three-dimensional collagen matrix.

The goal of this study was the development of a bioartificial nerve guide to induce axonal regeneration in the peripheral nervous system (PNS). In this in vitro study, the ability of a novel, 3-dimensional (3D), highly oriented, cross-linked porcine collagen scaffold to promote directed axonal growth has been studied. Collagen nerve guides with longitudinal guidance channels were manufactured using a series of chemical and mechanical treatments with a patented unidirectional freezing process, followed by freeze-drying (pore sizes 20-50 microm). Hemisected rat dorsal root ganglia (DRG) were positioned such that neural and non-neural elements could migrate into the collagen scaffold. After 21 days, S100-positive Schwann cells (SCs) migrated into the scaffold and aligned within the guidance channels in a columnar fashion, resembling "Bands of Büngner." Neurofilament-positive axons (mean length +/- SD 756 microm +/- 318 microm, maximum 1496 microm) from DRG neurons entered the scaffold where the growth within the guidance channels was closely associated with the oriented SCs. This study confirmed the importance of SCs in the regeneration process (neurotrophic theory). The alignment of SCs within the guidance channels supported directional axonal growth (contact guidance theory). The microstructural properties of the scaffold (open, porous, longitudinal pore channels) and the in vitro data after DRG loading (axonal regeneration along migrated and columnar-aligned SCs resembling "Band of Büngner") suggest that this novel oriented 3D collagen scaffold serves as a basis for future experimental regeneration studies in the PNS.