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Tissue Engineering

Long-Term Form and Function of Neoesophagus After Experimental Replacement of Thoracic Esophagus With Nitinol Composite Artificial Esophagus

Liang, Jian-Hui*; Zhou, Xing; Zheng, Zhao-Bing*; Liang, Xian-Liang*

Author Information
doi: 10.1097/MAT.0b013e3181d00e2c
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Abstract

Previously, we reported that beyond 3 months postoperation, the slipping of the artificial esophagus has little effect on eating, and experimental animals may achieve a long-term survival.1 Also, using the polyester connecting ring can improve outcome in replacement of the thoracic esophagus with nitinol composite artificial esophagus.2 However, whether the neoesophagus could become a stable eating channel after the graft sloughed out was still doubtful. In this study, we attempted to examine the long-term form and function of the neoesophagus, which survived for more than 42 months after replacement of thoracic esophagus with nitinol composite artificial esophagus with polyester connecting rings in pigs. Our findings are reported in this brief communication.

Materials and Methods

The nitinol composite artificial esophagus with polyester connecting rings was 80 mm in length and 18 mm in diameter. It consisted of an outer layer of a woven type of bare nitinol stent tube with two polyester connecting rings and an inner layer of a grid type of nitinol stent tube covered with integrally fixed silicon rubber film (produced by the Beijing Nonferrous Metal Research Institute, Beijing, China). Healthy experimental pigs were provided by the Guangdong Centre of Laboratory Animal for Medicine.

Three pigs weighing 23–29 kilograms were anesthetized with intravenous ketamine and subsequently placed on controlled ventilation with an endotracheal tube. The thoracic esophagus was exposed through a right thoracotomy in the fifth intercostal space. A 6-cm segment of the mid-thoracic esophagus was resected and replaced with a nitinol composite artificial esophagus with polyester connecting rings. The grafted prostheses were inserted 1 cm into the resulting esophageal stumps; the polyester connecting rings was anastomosed by continuously using Prolene sutures (Ethicon, Inc., Somerville, NJ) with esophageal stumps. The chest cavity was closed with catheter drainage to a water-seal receptacle. Gastrostomy was also performed.

Parenteral antibiotics were administered for 5 days postoperative. Beginning on the second postoperative day, enteral nutrition was carried out with feeding tubes. On the seventh postoperative day, oral feeding was reintroduced and continued to the end of the experiment. The shedding time of the artificial esophagus, eating condition according to Bown's grade,3 and weight changes were recorded. X-ray chest film was performed once a month until artificial esophagus had slipped. Esophagography and endoscopic examination (GIF-Q260, Olympus, Tokyo, Japan) were performed in all pigs at 6 months after the implantation. Pigs, which survived more than 42 months, were put euthanized. Histological examination was performed by light microscopy with Masson's Trichrome staining or H&E staining. Results were analyzed statistically by percentage rate (%) and mean ± standard deviation.

Results

Summarized data from three pigs are shown in Table 1. All pigs were without phanero-dysphagia (Bown's grade I). The slipping time of artificial esophagus ranged from 89 to 170 days. One pig showed shedding time at 89-day postoperation and had severe esophageal stenosis resulting in grave dysphagia (Bown's III). It soon recovered eating by reinsertion of a bare nitinol stent. Weight changes ranged from +125 to +197 kg (average 156.3 ± 36.9 kg). The neoesophagus was shorter in length than resected esophagus (shorten rate: 13.9 ± 3.1) and thinner in thickness than normal esophagus (thickness rate: 53.8 ± 5.5) (Table 2). Esophagography/endoscopic findings showed dilatation of cystic form and no autonomic peristalsis or constrictive motion (Figure 1). Microscopical findings showed that the neoesophagus consisted of fibrous connective tissue and esophageal mucosa (Figure 2).

Table 1
Table 1:
Results in Three Pigs That Underwent Esophagus Replacement
Table 2
Table 2:
Gross Esophageal Findings in Three Pigs
Figure 1.
Figure 1.:
Pig 3. A: X-ray photograph shows location of the grafted prosthesis in body. B: Esophagography reveals dilatation of cystic form of the neoesophagus. C: Endoscopic findings reveal internal surface of the neoesophagus.
Figure 2.
Figure 2.:
Pig 1. A: Shows the lumen of the long-term neoesophagus. Note the internal surface of the regenerated esophagus was completely covered with a lustrous smooth mucosa. B: Photo-micrograph of the neoesophagus reveals that it consisted of continuous connective tissue and stratified squamous epithelium of esophageal mucosa. (H&E ×100). C: Photomicrograph of the junction region between the host and the neoesophagus reveals that the original skeletal muscle layer of esophageal stump was encased by collagenous connective tissue of the neosophagus. (Masson's trichrome stain ×100.)

Discussion

To date, there are very few reports of more than a 3-year follow-up period4,5; therefore, the form and function of the neoesophagus, which survived long-term remained unclear. In this study, results showed that long-term form and function of neoesophagus was a stratified squamous epithelium cover scar tube in construction and had passageway function for food taking allowing long-term survival of the experimental animals. Compared with the neoesophagus after 6-month postoperation, their appearance was very similar and there was no essential difference in their structures. These results suggested that holding esophageal prostheses in place for 6 months was required to form a long-term stable passageway for food taking. After 6 months, even if the grafted prosthesis had slipped, neoesophageal stenosis did not develop.

Generally, the earlier the grafted prosthesis sloughed out, the more severe the neoesophageal stenosis. In view of the impact of artificial esophagus slipping time on neoesophageal passageway function formation and severe esophageal stenosis resulting in grave dysphagia after early graft sloughing, further design improvement of current artificial esophagus is needed. Also, continued search for ways of overcoming severe esophageal stenosis is necessary for transfer of the preclinical experience into clinical practice in the future.

Acknowledgment

Supported by the Guangdong Technology (2004B10401036), the Guangzhou Technology (2004Z3-E0221), and the Guangzhou High Education Bureau Technology Projects Foundation (08A077).

References

1. Liang JH, Huang SZ, Huang JM, et al: Experimental study of construction of the neoesophagus following a nitinol alloy composite artificial esophagus replacement of esophagus. Chin J Thorac Cardiovasc Surg 23: 114–116, 2007.
2. Liang JH, Zhou X, Zheng ZB, Liang XL: Polyester connecting ring improves outcome in nitinol composite artificial esophagus. ASAIO J 55: 514–518, 2009.
3. Bown SG, Hawes R, Matthewson K, et al: Endoscopic laser palliation for advanced malignant dysphagia. Gut 28: 799–807, 1987.
4. Hoferichter J: The reconstruction of the esophagus with synthetic materials. II. New formation of the esophagus by means of a temporary guiding spling. Langenbecks Arch Chir 317: 51–63, 1967.
5. Fukushima M, Kako N, Chiba K, et al: Seven-year follow-up study after the replacement of the esophagus with an artificial esophagus in the dog. Surgery 93: 70–77, 1983.
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