Reconstruction of cervical and upper thoracic esophagus with a free posterior tibial artery perforator flap: A case report.

INTRODUCTION: Esophageal window defect in patients with esophageal resection could be challenging to repair. In this case report, a free posterior tibial artery perforator flap (FPTAPF) was used for semi-circumference patch esophagoplasty. PATIENT CONCERNS: For this 47-year-old male patient with recurrent laryngeal nerve schwannoma invading cervical and upper thoracic esophagus, cervical and upper thoracic esophageal reconstruction following tumor resection was needed DIAGNOSIS:: Pathologic result demonstrated recurrent laryngeal nerve schwannoma. Ultrasound examination detected a tumor (7 cm × 6 cm × 3 cm) located behind the right thyroid lobe, and contrast-enhanced computed tomography scan revealed that tumor was located between the cervical esophagus and trachea, and compressed these structures. INTERVENTIONS: The tumor had a size of 7 cm × 6 cm × 3 cm, and the semi-circumference defect of the cervical and upper thoracic esophagus was about 7 cm in length after complete tumor resection. A 7 cm × 4 cm FPTAPF was designed and harvested for esophageal reconstruction. OUTCOMES: The posterior tibial flap survived well and satisfactory recovery of esophageal function was obtained with no significant complications. No local tumor relapse was indicated by computed tomography during the 2-year postoperative follow-up. CONCLUSION: This case highlights the stable performance of FPTAPF when used for the reconstruction of large esophageal window defect.

Tissue-Engineered Esophagus via Bioreactor Cultivation for Circumferential Esophageal Reconstruction.

The use of biomaterials for circumferential esophageal repair is technically challenging in a rat model, and an optimal scaffold implantation technique with nutritional support is essential. The purpose of this study was to investigate the effects of three-dimensional printed esophageal grafts and bioreactor cultivation on muscle regeneration and reepithelialization from circumferential esophageal defects in a rat model. Here, we designed an artificial esophagus that can enhance the regeneration of esophageal mucosa and muscle through the optimal combination of a two-layered tubular scaffold and mesenchymal stem cell-based bioreactor system. The graft was verified by the performance comparison with an omentum-cultured esophageal scaffold. We also applied a new surgical anastomosis technique and a thyroid gland flap over the implanted scaffold to improve graft survival. Although no regenerated mucosal layer was observed around the implants of the control group, histological examination of the regenerative esophagi along the scaffold revealed that the bioreactor system and omentum-cultured groups showed more than 80% of the mucosal regeneration without a fistula. The regenerated tissues showed that the integration of the esophageal scaffold and its native esophageal tissue was intact and were covered with layers of stratified squamous epithelium with several newly developed blood vessels. Therefore, this study describes a novel approach for circumferential esophageal reconstruction. Impact Statement In vivo functional esophageal reconstruction remains challenging due to anastomosis site leakage and necrosis of the implanted scaffold in a circumferential esophageal defect. Therefore, it is necessary to develop a tissue-engineered esophagus that enables regeneration of esophageal mucosa and muscle without leakage of the esophageal anastomosis. In this study, we proposed an intriguing strategy that combines a mesenchymal stem cell-seeded tubular scaffold with a bioreactor system for esophageal reconstruction and introduced a new surgical anastomosis technique with the thyroid gland flap over the implanted scaffold to improve graft survival. We believe that this system should be a powerful platform for circumferential replacement of the esophagus in a rat model.

Full-thickness oesophageal regeneration in pig using a polyurethane mucosal cell seeded graft.

Malignant oesophageal pathology typically requires resection of a portion of oesophagus. The aim of this study was to investigate attachment and growth of swine oesophageal mucosal cells on electrospun synthetic nanofibre matrices of varying chemistries and to determine whether a mucosal-seeded graft, in a swine animal model, could induce regeneration. Swine mucosal oesophageal cells were isolated and seeded them onto five different matrix materials. Matrix samples were cultured for up to 14 days, after which matrices were analysed for cell attachment. Attachment varied for each of the matrix materials tested, with the most rigid showing the lowest levels of attachment. Importantly, sections of these matrices illustrated that multiple layers of mucosal cells formed, mimicking endogenous oesophageal structure. A tdTomato reporter line (mucosaltdt cells) was created to enable cell tracking. As polyurethane matrix was found optimal through in vitro testing, a graft was prepared using mucosaltdt cells, along with an unseeded control, and implanted into swine for determination of oesophageal regeneration. Mucosal seeded polyurethane grafts initiated full thickness regeneration of the oesophagus, including epithelial, submucosal, and skeletal muscle layers which were highly vascularized. Interestingly, an unseeded graft showed similar regeneration, indicating that the role of cells in the process of oesophageal regeneration is still unclear. The electrospun polyurethane matrix does appear suitable for multilayered cellular attachment and growth of oesophageal mucosal cells, and implantation of polyurethane grafts initiated full thickness regeneration of the oesophagus, indicating potential for oesophageal reconstruction in humans. Copyright © 2016 John Wiley & Sons, Ltd.

Artificial phrenoesophageal ligament. An experimental study in dogs.

This report deals with the preparation of a 'true' artificial phrenoesophageal ligament aimed at restoring effective anchoring of the esophagus to the diaphragm, keeping the esophagogastric sphincter in the abdomen. A total of 24 mongrel dogs were assigned to four groups: (i) Group I (n = 4): the esophageal diaphragm hiatus left wide open; (ii) Group II (n = 8): the anterolateral esophagus walls were attached to the diaphragm by the artificial ligament and the esophageal hiatus was left wide opened; (iii) Group III (n = 5): in addition to the use of the artificial ligament, the esophageal hiatus was narrowed with two retroesophageal stitches; (iv) Group IV (n = 7): the only procedure was the esophageal hiatus narrowing with two retroesophageal stitches. The phrenoesophagogastric connections were released, sparing the vagus nerves. Five animals of groups III and IV, which did not develop hiatal hernia, were submitted to esophageal manometry immediately before and 15 days after surgery. In group I, all animals developed huge sliding hiatal hernias. In group II, two dogs (25%) had a paraesophageal hernia between the two parts of the artificial ligament. In group III, neither sliding hiatal hernia nor paraesophageal hernia occurred. In group IV, two animals (28.6%) developed sliding esophageal hiatus hernia. Regarding esophageal manometry, postoperative significant difference between groups III and IV (P = 0.008) was observed. Thus, the artificial phrenoesophageal ligament maintained the esophagus firmly attached to the diaphragm in all animals and the esophagogastric sphincter pressure was significantly higher in this group.

Atypical Clinical Presentation of a Newer Generation Anti-Fungal Drug-Resistant Fusarium Infection After a Modified Multi-Visceral Transplant.

BACKGROUND Fusarium spp. infections have become an emerging and lethal threat to the immunocompromised patient population, especially those with neutropenia. Recently there have been increased reports in solid organ transplant recipients. Presentation is commonly as soft tissue infections several months post-transplant. With high morbidity and mortality, efficacious antifungal therapy is essential. This remains challenging with limited data and no established clinical breakpoints defined. CASE REPORT We report on a modified multi-visceral transplant patient that developed a Fusarium infection only 7 weeks post-transplant in the native hard palate and esophagus, without any soft tissue lesions, which persisted despite aggressive combination treatment with amphotericin B lipid complex and voriconazole. CONCLUSIONS Fusarium spp. infection in solid organ transplant is a significant challenge without clear diagnostic clinical indicators of infection, or specific time of onset, in addition to possible emergence of a more aggressive drug-resistant strain.

Biomimetic and synthetic esophageal tissue engineering.

BACKGROUND/PURPOSE: A tissue-engineered esophagus offers an alternative for the treatment of pediatric patients suffering from severe esophageal malformations, caustic injury, and cancer. Additionally, adult patients suffering from carcinoma or trauma would benefit. METHODS: Donor rat esophageal tissue was physically and enzymatically digested to isolate epithelial and smooth muscle cells, which were cultured in epithelial cell medium or smooth muscle cell medium and characterized by immunofluorescence. Isolated cells were also seeded onto electrospun synthetic PLGA and PCL/PLGA scaffolds in a physiologic hollow organ bioreactor. After 2 weeks of in vitro culture, tissue-engineered constructs were orthotopically transplanted. RESULTS: Isolated cells were shown to give rise to epithelial, smooth muscle, and glial cell types. After 14 days in culture, scaffolds supported epithelial, smooth muscle and glial cell phenotypes. Transplanted constructs integrated into the host's native tissue and recipients of the engineered tissue demonstrated normal feeding habits. Characterization after 14 days of implantation revealed that all three cellular phenotypes were present in varying degrees in seeded and unseeded scaffolds. CONCLUSIONS: We demonstrate that isolated cells from native esophagus can be cultured and seeded onto electrospun scaffolds to create esophageal constructs. These constructs have potential translatable application for tissue engineering of human esophageal tissue.

Development of novel treatment with a bioabsorbable esophageal patch for benign esophageal stricture.

Using a large animal model, we examined whether circumferential stricture after esophageal endoscopic submucosal dissection (ESD) can be treated by grafting a bioabsorbable esophageal patch. Circumferential ESD was performed on the thoracic esophagus in pigs (n = 6) to create a stricture, for which one of the following interventions was performed: (1) the stricture site was longitudinally incised, and an artificial esophageal wall (AEW) was grafted after placing a bioabsorbable stent (AEW patch group, n = 3); (2) endoscopic balloon dilation (EBD) was performed every other week after stricture development (EBD group, n = 3). In both groups, esophageal fluoroscopy was performed 8 weeks after the interventions, and the esophagus was excised for histological examination of the patched site. In the AEW patch group, esophageal fluoroscopy revealed favorable passage through the patched site. Histologically, the mucosal epithelium and lamina propria had regenerated as in the normal area. In the EBD group, the circumferential stricture site showed marked thickening, and there were hypertrophic scars associated with epithelial defects on the luminal surface. Histologically, defects of the mucosal epithelium and full-thickness proliferation of connective tissue were observed. AEW patch grafting was suggested to be a potentially novel treatment strategy for post-ESD esophageal circumferential stricture.

Tissue engineering of the esophagus.

Esophageal atresia occurs in 1 out of 3000 births. Current treatments involve esophageal replacement by using more distal parts of the gastrointestinal tract, such as the stomach, jejunum, and colon. Significant complications are associated with each treatment option. Tissue engineering may provide a therapeutic alternative for esophageal replacement. This article addresses the progress in esophageal tissue engineering using acellular and cell-seeded approaches. In addition, we discuss the potential direction of future approaches by critically appraising the results in the recent literature.

Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats.

A tissue-engineered oesophageal scaffold could be very useful for the treatment of pediatric and adult patients with benign or malignant diseases such as carcinomas, trauma or congenital malformations. Here we decellularize rat oesophagi inside a perfusion bioreactor to create biocompatible biological rat scaffolds that mimic native architecture, resist mechanical stress and induce angiogenesis. Seeded allogeneic mesenchymal stromal cells spontaneously differentiate (proven by gene-, protein and functional evaluations) into epithelial- and muscle-like cells. The reseeded scaffolds are used to orthotopically replace the entire cervical oesophagus in immunocompetent rats. All animals survive the 14-day study period, with patent and functional grafts, and gain significantly more weight than sham-operated animals. Explanted grafts show regeneration of all the major cell and tissue components of the oesophagus including functional epithelium, muscle fibres, nerves and vasculature. We consider the presented tissue-engineered oesophageal scaffolds a significant step towards the clinical application of bioengineered oesophagi.

Partial esophageal transplantation is possible as part of a multivisceral graft.

We report a case of a 9-year-old female with inflammatory myofibroblastic tumor (IMT), which involved the upper retroperitoneum, visceral vessels, stomach and distal esophagus. Complete resection of the tumor required a multivisceral (MV) transplant. Due to tumor involvement, resection of the distal third of recipient esophagus was necessary. Gastrointestinal continuity was subsequently established via esophagoesophagostomy to donor esophagus en bloc with a standard MV graft. After 1.9 years of follow-up, the patient has no symptoms of dysphagia or reflux. This case illustrates the feasibility of including the distal donor esophagus as part of an MV graft.

[Minimally invasive abdominothoracic esophagus resection by transoral esophagogastrostomy: interdisciplinary challenge]. / Minimalinvasive abdominothorakale Ösophagusresektion mit transoraler Ösophagogastrostomie : Interdisziplinäre Herausforderung.

BACKGROUND: Resection of the esophagus is an invasive 2-cavitiy procedure which requires special anesthesiological expertise during perioperative care. Furthermore, in surgery new minimally invasive techniques are continually being established which place special challenges on the treatment team because the anesthesiologist is decisively involved in the course of surgery. AIM: The aim of this article is to present the development of surgical treatment options for esophageal cancer starting from classical open resection up to the minimally invasive technique of esophagectomy (MIE). Previous experience with MIE on a cohort of patients is presented and the special anesthesiological characteristics of this innovative technique are illustrated. MATERIAL AND METHODS: In the department for general, visceral and transplantation surgery of the University Medical Center of Mainz, minimally invasive abdominothoracic esophageal resection has been carried out since 2010. High thoracic anastomization was performed using the EEA™-OrVil™ system operated by the anesthesiologist. Currently 17 highly selected patients have been surgically treated using this technique. RESULTS: Esophagogastric anastomosis with the EEA™-OrVil™ system was feasible in all patients. Transoral introduction of the gastric probe with the connecting sheath and the angled anvil led to minor dislocation of the double lumen tube in only one patient and could immediately be corrected. Further intraoperative complications did not occur. Four of the 17 patients developed pneumonia which could be controlled by intravenous antibiotics. None of the patients had to be reintubated. One patient developed gastric tube necrosis and died 51 days postoperatively due to massive intracerebral hemorrhage. There were no complications of anastomoses following OrVil™ anastomization. In all patients an R0 resection could be achieved. CONCLUSION: Minimally invasive esophagectomy with transoral anastomization appears to be an enrichment of the minimally invasive spectrum as interdisciplinary cooperation leads to reduced operation time and a more efficient process of anastomization. This also results in decreased one-lung ventilation time which is directly correlated to postoperative pulmonary complications. In particular, the interdisciplinary character of this technique and the necessity for targeted communication proved to be of assistance also in other situations.

Esophageal transplantation in the rat.

PURPOSE: Esophageal replacement surgery has been used to treat long-gap esophageal atresia, caustic esophageal stricture, and esophageal avulsion. Here, we report total esophageal transplantation in rats without vascular anastomosis as an option for esophageal replacement surgery. METHODS: Fourteen total segments of esophageal transplants were harvested from 24-week-old male Sprague-Dawley rats using a harvesting procedure. The segments were transplanted through the mediastinum in the esophageal bed of 15-week-old male Sprague-Dawley rats without adjacent vascular anastomosis using the transhiatal pull-up technique. The ends of the transplanted esophagus were ostomized using cervical and abdominal esophagostomies. An immunosuppressive-treated (IT) group (n = 7) received cyclosporine and cotrimoxazole for 10 days, while an untreated (UT) group (n = 7) received only cotrimoxazole for 10 days. On post-operative day 10, the rats were sacrificed, and the transplant and recipient esophagi were evaluated macroscopically and histopathologically. RESULTS: All transplantations were successful and all transplanted rats survived. Upon macroscopic evaluation, no evidence of complications was observed and all transplanted esophagi in the two groups appeared to exhibit excellent firm tissue; however, mild necrosis was observed in the cervical end of the transplant in one rat in the IT group. Histopathologic examination showed a viable esophageal structure in all rats. Inflammation and muscular atrophy were lower in the IT group than in the UT group, whereas vascularity was higher in the IT group than in the UT group. CONCLUSION: Total esophageal transplantation was performed directly without vascular anastomosis into recipients in a rat model. This procedure should be done in larger animal models before being attempted in humans.

Repair of massive stent-induced tracheoesophageal fistula.

OBJECTIVE: The purpose of this report was to discuss a new surgical procedure in treating esophageal stent related large tracheoesophageal fistula without tracheal resection. METHODS: Clinical records of 5 patients with esophageal stent-related large tracheoesophageal fistulas treated in this hospital between 1997 and 2006 were reviewed. RESULT: All patients had insertion of a covered self-expanding esophageal stent, 1 for benign esophageal stricture and 4 for esophageal perforation resulting from various causes. A double patch technique, in which the esophageal wall was used as a protective patch repairing the defect on the trachea, was performed with an esophagectomy and gastric replacement. No significant complications occurred in the perioperative period. All patients recovered uneventfully. CONCLUSIONS: Use of the adjacent esophageal wall as a patch to close a defect on the trachea is a safe procedure with a favorable outcome. It should therefore be recommended as a reliable surgical procedure in treating massive stent-induced tracheoesophageal fistulas and other complicated tracheoesophageal fistulas that tracheal resection could not safely address. However, the esophagus was damaged to a certain degree.

[Experimental study of preventing postoperative stenosis by modifying artificial esophagus in dogs].

OBJECTIVE: To observe the effect of the modified artificial esophagus on postoperative stenosis in dogs. METHODS: The models of defected esophagus were established in dogs. The double-layered membrane tube (modifying type) was implanted in the test group (n = 10) and the esophageal stent was further inserted when the stenosis occurred. The single pattern tube (original type) was transplanted to the control group (n = 30). The dilation treatment was performed to relieve the postoperative stenosis; alternatively, the esophageal stent was implanted in the unsuccessful dogs. RESULTS: The average artificial esophagus removal time was 19.10 days in the test group, which was significantly lower than 39.07 days in the control group (t = 15.6, P = 0.000). No obstruction after removal was observed in the experimental group. The incidence of postoperative stenosis had no significant difference between these two groups. CONCLUSION: The double-layered membrane tube can make the tube removal safer by shortening the removal time.

Use of a bioengineered skin equivalent for the management of difficult skin defects after pediatric multivisceral transplantation.

BACKGROUND: Primary wound closure is not always possible after pediatric multi-visceral transplantation because of oversized donor organs and/or intestinal or graft edema. We report our experience evaluating the safety and efficacy of Graftskin (Apligraf, Organogenesis, Canton, Mass), a bioengineered bi-layered human skin equivalent, for the management of difficult skin abdominal defects after multivisceral transplantation in a pediatric population. METHODS: A retrospective chart review was performed of pediatric multivisceral transplantation patients who were treated with Graftskin. Adverse events, course of wound reepithelialization, and time for complete closure were recorded. RESULTS: Four patients, 7 to 29 months old, were treated with Graftskin. One patient died because of unrelated reasons. Stimulation of the granulation, reepithelialization, and rapid reduction of the wound surface and depth occurred in the other 3 patients. Complete reepithelialization occurred within 5 months. No adverse events were noted. CONCLUSION: Graftskin was a successful treatment for difficult abdominal skin defects after liver and multivisceral transplantation in children.