An operation for esophageal carcinoma is regarded as one of the most difficult, partly because the esophagus must be replaced to enable the patient to swallow food.1 Resection of the esophageal lesion results in a gap between the cut ends of the stomach and the esophagus. The stomach, colon, or jejunum is usually used as an esophageal tube.2 Because blood supply should be preserved to prevent necrosis of these esophageal substitutes, they are used along with a pedicle or as a free graft using microvascular anastomosis to the mesenteric vessels.3 To resect an esophageal carcinoma, a thoracotomy is necessary in many cases whereas a laparotomy is performed to mobilize the stomach or intestine.4 In addition to meticulous suturing, thoracotomy and laparotomy, irrespective of being separate or continuous, lead to a longer operation time. The thoracoabdominal approach is extremely invasive such that elderly patients or patients with respiratory dysfunction or medical complications are excluded from consideration for this operation,5 in which cases, the patients can receive only palliative therapy.6,7 If an artificial esophagus is available as an esophageal substitute, additional laparotomy will be unnecessary, thereby reducing the complexity of the operation. Besides, if the artificial esophagus is small enough to be anastomosed entirely under thoracoscopic surgery, operative damage can be minimized. Thus a larger number of patients with esophageal carcinoma can be candidates for esophagectomy.
However, an artificial esophagus that can be put to practical use has not been developed thus far.8,9 The esophagus is not a simple tube for passage of food; it actively transports the food by peristalsis.10 In reality, one can swallow food against gravity, for instance, while doing a handstand. Dysfunction of peristalsis leads to easy aspiration of food.11 In immunocompromised hosts, such as elderly patients, the aspiration of food into the trachea results in aspiration pneumonia, leading to life threatening complications.12 Without the peristaltic function, an artificial esophagus has no practical use. Although a few types of artificial esophagi have been developed, they are basically simple tubes that possess neither peristaltic function nor the lower esophageal sphincter.13 Considering the clinical necessity, an artificial esophagus with peristaltic function has been developed in this study.
In addition to the esophagus, the heart and lungs are also present within the thorax. Unlike the peritoneal cavity, the thorax lacks additional space for a motor or equipment other than an artificial esophagus. Hence, the artificial esophagus must possess built in peristaltic function. With the aim of simulating the esophageal peristalsis, an x-ray contrast study using barium was conducted. Peristaltic movement was analyzed (Figure 1). The study showed that each segment of the esophagus dilated and contracted serially. We were encouraged by the possibility that the peristaltic movement could be achieved by contracting peristaltic muscle actuators placed serially in an annular manner. A shape memory alloy was expected to function as the peristaltic muscle actuator.
Materials and Methods
The artificial esophagus that was developed consisted of a Gore-Tex vascular graft (Japan Gore-Tex Inc., Tokyo, Japan) and a nickel-titanium shape memory alloy coil (NiTi-SMA; BMX150, Toki Corporation, Tokyo, Japan) (Figure 2). Serial pairs of the SMA were placed continuously around the artificial vascular graft in an annular manner. Each pair of SMA was connected to an electrical circuit consisting of memory relay switching (Figure 3). Figure 4 shows the scheme of controlling the current in the electrical circuits. A direct current was passed through each pair of SMAs for 0.4 seconds. We chose an artificial vessel as a tube through which a bolus of food would be passed into the stomach. The artificial vessel has excellent biocompatibility and is airtight and waterproof. The diameter of the artificial vessel was 20 mm, and the diameter of the SMA coil was 0.62 mm. The coil was composed of a shape memory alloy fiber (BMF150, Toki Corporation, Tokyo, Japan). The characteristics of the BMX150 are as follows: standard coil diameter D, 0.62 mm; wire diameter d, 0.15 mm; coil diameter to wire diameter ratio D/d, 4.1; practical maximum force produced, 98–196 mN; kinetic displacement (change in length), 200%; standard drive current, 200–300 mA; standard electric resistance, 400 Ω/m; and allowable upper temperature limit, 50–60°C.
Peristaltic movement was performed in the neck of a 50 kg Saanen goat. After intramuscular administration of atropine sulfate (0.02 mg/kg), anesthesia was induced and maintained with halothane, 5% and 1–2%, respectively. The airway was protected by performing tracheotomy, and a central venous catheter was inserted through the left internal jugular vein.
The surgery consisted of two procedures: resection of cervical esophagus and implantation of the artificial esophagus. After the cervical esophagus was resected through a cervical incision, the artificial esophagus was implanted in the neck of the goat. The animal was cared for in strict compliance with the Research Animal Resource Committee guidelines of Institute of Development, Aging, and Cancer, Tohoku University.
The artificial vessel was implanted after the cervical esophagus was resected. The anastomoses between both ends of the vessel and the ends of the remaining esophagus of the goat were performed by suturing (Prolene, Ethicon, Somerville, NJ). The anastomoses were well performed such that no leaks were observed when the vessel was filled with water. The artificial esophagus was observed under these conditions in which the skin incision was not closed and the vessel was filled with water. Figure 5 shows the entire artificial esophagus system, which includes a memory relay switch circuit and power supply unit. The artificial esophagus implanted in the body of the goat is shown in Figure 6. Although the standard driving current of the BMX is 200–300 mA, we increased the current to 500 mA to heat the BMX because, in an in vitro preliminary experiment, the time until the transformation of the BMX was excessively long. When a direct current of 500 mA at 5 V was applied to the first pair of NiTi-SMA, the alloys in the first part shrank; this initiated the contraction of the first part. The contraction of the next part followed consecutively. Five seconds after the contraction in the first part, the contraction in the last part was completed. The serial contraction was similar to the peristaltic movement observed in the x-ray study using barium.
In this study, we developed a novel artificial esophagus with peristaltic movement. After implantation into the neck of a goat, peristaltic movement was generated in the artificial esophagus by contraction of the NiTi-SMAs. The simulated peristaltic movement was similar to the peristaltic movement observed in the x-ray barium study performed in humans.
Because the purpose of this experiment was to realize peristalsis in the artificial esophagus, we conducted an acute experiment wherein the temperature of NiTi-SMAs was elevated. Similar to the case of an artificial heart, heat control is crucial in the development of artificial organs.14 Because the esophagus is surrounded by other organs, a heat shield, such as a silicone coat, must cover an entire artificial esophagus or only the NiTi-SMAs to prevent burns.15 Heat control will be studied in future experiments.
In the resting state, the peristaltic muscle of the esophagus is relaxed, resulting in the collapse of the entire esophagus. A thick, submucous, elastic, collagenous network, which is located between the muscle layers and the striated, squamous epithelium forming the lining of the esophagus, throws the epithelium into folds whose surfaces oppose one another, obliterating the lumen. During swallowing, the folds are smoothed out in the part of the esophagus occupied by the bolus.16 The bolus is propelled toward the stomach by continuous muscle contraction in the part occupied by the bolus. In this model, the diameter of the artificial esophagus was decided by the diameter of the artificial vessel. The implanted artificial esophagus was shown to be placed suitably behind the trachea. In a chronic experiment to determine the performance of the artificial esophagus, attention must be focused upon the physical compression induced by the artificial esophagus that may result in damage to the surrounding organs such as the trachea, heart, and aorta. Furthermore, the compression of the artificial esophagus may lead to destruction of the anastomoses, resulting in life threatening complications such as mediastinitis.
The force generated by the contraction of NiTi-SMAs should be taken into consideration. In this study, the artificial vessel was filled with water, mainly because the artificial esophagus must be proved to be airtight and waterproof. Transit time required to move water from the proximal end of artificial esophagus to the distal end was 5 seconds. In clinical use, an artificial esophagus must exhibit the ability to propel any food material by its peristaltic movement. We used serial pairs of NiTi-SMAs as muscle actuators. If the contracting force in the artificial esophagus is not sufficient, the force can be increased by the addition of more NiTi-SMAs in parallel. Further studies should be conducted to measure the propulsive force using materials with different viscosities or elasticities.
The artificial esophagus that we developed uses a Gore-Tex vascular graft as a supporting tube. Because the lumen of an artificial esophagus is directly connected to the outer environment, it poses some risk of infection.17 Although the vascular graft is biocompatible, it is more prone to infection than esophageal substitutes, such as the stomach and colon. Once infection occurs, the damage to the artificial esophagus may lead to life threatening complications, including sepsis and esophagotracheal fistula. In the future, this will be prevented by the reconstruction of the esophageal epithelium, using tissue engineering.18
Because an acute study was conducted to confirm that the developed artificial esophagus functioned in a living animal, the cervical wound was not closed so as to observe the performance of the artificial esophagus. We triggered the peristaltic contraction of the artificial esophagus using a direct current. A swallow sensor may be required to trigger the peristaltic contraction of the artificial esophagus.
We demonstrated the possibilities of developing an artificial esophagus by realizing the peristaltic movement. With the availability of an artificial esophagus, esophageal carcinoma surgery will become easier and less invasive, and it will be possible to perform the surgery entirely by thoracoscopy. It will widen the indication for an esophageal operation such that more patients, including the elderly, can benefit from the operative treatment.
This work was partly supported by the 21st century COE program: Future Medical Engineering based on BioNanotechnology, Health and Labor Science Research Grants for Research on Advanced Medical Technology, the Grant-in-aid for Scientific Research (11480253, 14380386), Japan Science and Technology Agency, Innovation Plaza, Miyagi. The authors thank Mr. Kimio Kikuchi for experimental preparation and kind cooperation and Miss Yoko Ito and Mrs. Hisako Iijima for their excellent technical assistance and kind cooperation.
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