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.

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.

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.

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.

Tumor development in organ transplants obtained from carcinogen-exposed rats.

F344 rats were exposed intragastrically to two different dose levels of N-nitrosoheptamethyleneimine (NHMI) resulting in a cumulative dose of either 225 or 450 mg/kg body weight. Tumor development was followed either in situ in the NHMI-exposed animals or in tracheas and esophagi from NHMI-exposed donors after these organs were grafted to isogeneic recipients. Tumor responses in situ and in organ grafts were compared. The results showed that the process of carcinogenesis is not disrupted by the transplantation procedure. The carcinogen dose-response relationship observed in situ was also seen in the transplanted organs. At the high carcinogen dose, the tumor incidence was 100% in situ and transplanted esophagi and 20% in tracheas in situ compared to 25% in tracheal transplants. At the low dose, the tumor incidence was 36% in the esophagi in situ compared to 100% in transplanted esophagi, which suggests a greater sensitivity of the transplant system to detect the carcinogenicity of NHMI. The proportion of carcinomas to papillomas was markedly higher in transplanted esophagi. The tracheal tumor response at both NHMI dose levels showed the same trend but was too low to allow any firm conclusions.

[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.

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.

Esophageal web: a previously unrecognized complication of epidermolysis bullosa.

The course of the esophageal disease in four patients with epidermolysis bullosa dystrophica recessive is examined. Three of four patients experienced web formation, a previously unrecognized finding, and the significance of this lesion in the evaluation and management of these patients is emphasized. One of four patients underwent a successful colonic interposition for severe esophageal disease and the role of this potentially life-saving procedure is discussed.

Analyses of extrathymic T cell differentiation in nu/nu mice by grafting embryonal organs.

Fetal (days 15 to 17) organs such as the small intestine, stomach and pancreas were engrafted under the renal capsules of athymic nude (nu/nu) mice to examine the capacity of these organs to induce the differentiation of T cells. Eight weeks after engraftment, the engrafted organs had differentiated into adult-type organs histologically. In the lamina propria of the engrafted small intestine, large intestine, and stomach, there were clusters of lymphocytes or lymphoid follicles, which included Thy1.2+ or CD4+ T cells. Flow cytometric analyses revealed that the lymphocytes from the lymph nodes of sham-, esophagus-, or pancreas-engrafted mice included very few T cells (1.20%), whereas those from the lymph nodes of the fetal small intestine-, large intestine-, or stomach-engrafted mice included significant numbers of T cells (8.36%) 8 weeks after engraftment, although there were not as many as in the fetal thymus-engrafted mice (17.97%). The peripheral T cells in the small intestine-, large intestine-, or stomach-engrafted mice were of bone marrow origin, and consisted of Thy1.2+, CD3+, and CD4+8-, or CD4-8+ with T cell receptor (TcR) alpha beta cells. Taken together, these findings indicate that not only the murine small intestine and large intestine but also the stomach have the capacity to induce the differentiation of T cells.

Experimental tracheal and tracheoesophageal allotransplantation. Paris-Sud University Lung Transplantation Group.

We investigated the effects of allograft perfusion with a preservative technique and of combined thyrotracheoesophageal implantation on airway epithelium of long segments of thyrotracheal grafts allotransplanted on their own vascular pedicles into immunosuppressed pigs. Four groups of five animals each underwent heterotopic (into the neck) thyrotracheal (group 1) and thyrotracheoesophageal (group 2) and orthotopic thyrotracheal (group 3) and thyrotracheoesophageal (group 4) allotransplantation. Allograft revascularization included (1) interposition of donor right subclavian artery--incorporating the inferior thyroid artery--to recipient right carotid artery (end-to-end fashion) and (2) end-to-side anastomosis of donor anterior vena cava to recipient right external jugular vein. All thyrotracheoesophageal blocks were harvested after inferior thyroid artery perfusion with 4 degrees C Euro-Collins solution. The overall lengths of tracheal and esophageal grafts were 10.7 +/- 2.7 cm and 13.4 +/- 3.6 cm, respectively. In the heterotopic groups, all allografts were viable and histologically normal at postmortem examination and the incidence and severity of airway ischemia and rejections (at equal residual levels of cyclosporine) were not different between groups 1 and 2. In the orthotopic groups, the first two pigs died of airway collapse with histologically normal grafts. In the remaining pigs, temporary airway stenting was inserted and allografts remained viable and histologically intact for their entire length 30 days after transplantation. Transplanted tracheal smooth muscles had concentration-dependent contractions and relaxations similar to those of nontransplanted (native) tracheas. This study documents the feasibility of allotransplanting long tracheal and esophageal segments on their own vascular pedicles and demonstrates that allograft preservation and thyrotracheoesophageal transplantation are equally effective in minimizing airway ischemia. Thyrotracheoesophageal transplantation does not enhance recipient alloimmune response compared with thyrotracheal transplantation alone.

Tracheal reconstruction by esophageal interposition: an experimental study.

The purpose of this study was to assess the possibility of reconstructing a circumferential tracheal defect with autogenous esophagus. In 6 mongrel dogs, a circumferential defect involving seven rings of the cervical trachea was reconstructed by interposing pedicled esophagus. A silicone T tube was used as a stent. The vertical limb of the T tube (usually referred to as the horizontal limb when used in humans) was cut shorter after the cervical wound had healed well, and it eventually was buried subcutaneously. Two dogs died 36 days after operation, and 1 died 28 weeks after operation. In no dog was the cause of death related to the operation or to a respiratory tract complication. Two dogs were put to death 4 weeks and 32 weeks after operation. They were well until then, and all the anastomoses between the trachea and the esophagus had healed fully without formation of granulation tissue. One dog is alive and well 14 months after operation. The vertical limb of the T tube retracted into the subcutaneous space, and there is no open cervical wound. Esophageal interposition might be a feasible technique for tracheal replacement in select groups of patients.

Plastic reconstruction of an extended corrosive injury of the posterior tracheal wall with an autologous esophageal patch.

We report on a patient with an extended corrosive injury of the posterior tracheal wall and left-sided tracheo-esophageal fistula after severe inhalative trauma. Resection of the fistula and necrotic tissue was followed by reconstruction of the posterior tracheal wall with an esophageal patch. Interposition of the stomach was performed to restore upper gastro-intestinal continuity. Revision was necessary due to an anastomotic insufficiency and a recurrent fistula between the trachea and the esophago-gastrostomy on the left side. The stomach was resected and the fistula was covered with a sternocleidomastoideus muscle flap. Several weeks later interposition of the right hemicolon was performed to establish the gastro-intestinal tract and the patient recovered completely, thereafter.

Acquisition of a gastric or duodenal phenotype on heterotropic transplantation of esophagus and bladder tissues in F344 rats.

Cell differentiation is very important but not well understood. In the present study the ability of various tissues to newly-differentiate when transplanted into the fundus or the duodenum in rats was tested. Pieces of esophagus, bladder, diaphragm and trachea from 8-week-old male F344 rats were transplanted into the gastric fundus or duodenum of females and examined after 3 or 6 months. While the diaphragm was not recognizable as a muscle layer in either the stomach or the duodenum, the esophagus and trachea persisted, the latter with the presence of cartilage. Esophagus grafts transplanted into the glandular stomach and duodenum, newly-differentiated into gastric and duodenal mucosa, respectively. Goblet cells with alcian-blue positive mucin appeared in bladder tissue implanted into the duodenum. Six months after the operation, their numbers had increased and cytoplasm alkaline phosphatase (ALP) positivity was noted. Gastrointestinal and also bladder stem cells may thus have multipotential ability for differentiation and may be able to newly-differentiate when transplanted into different environments in the gastrointestinal tract.