Enterocutaneous fistulas complicating esophageal cancer surgery can become intractable due to substantial exudate, which constantly exposes the surrounding skin to strong irritation and impairs granulogenesis. Also, a large amount of fistula exudate causes considerable pain [3, 4]. For intractable enterocutaneous fistulas arising due to AL, a minimally invasive approach should be considered first. Therefore, surgical treatments such as pedicled myocutaneous flap filling [5] are not among the first-choice treatments. The usefulness of covered stents for fistula closure after esophagectomy has been reported [6, 7]. However, in this case, since the anastomosis was located in the neck, endoscopic placement of the stent was not suitable. Although over-the-scope clip system was reported as one of the treatment options for anastomotic fistula [8], it was technically difficult to grasp all layers of the digestive tract and was abandoned. Intrathecal injection of fibrin glue or cyanoacrylate has been reported as useful treatment for intractable fistulas [9, 10]. The mechanism of action of fibrin glue involves fibroblasts invading and proliferating in the fibrin matrix adhering to the tissue, resulting in tissue repair with angiogenesis. However, it takes several minutes for fibrin to form a stable cross-link and adhere to the tissue, and the adhesion and fixation are weak. Therefore, this method appeared unsuitable for this case, where exudate was constantly emerging, and the pressure was high. Cyanoacrylate preparations have the advantages of quick and high-strength adhesion [11], and so we attempted to close the fistula using Dermabond®, which, however, proved ineffective.
As the excessive exudate was suspected to be one of the causes of delayed wound healing, we first aimed to reduce the amount of exudate. Although drug therapy options include the use of anticholinergic drugs, both oral and intravenous administration may lead to adverse events such as blurred vision, miosis, palpitation, hot flushes, dizziness, and constipation. Meanwhile, scopolamine is known to be transdermally absorbed [12]. Regarding skin permeability, the posterior part of the ear shows high skin permeability. In the USA, a scopolamine patch is an anticholinergic preparation approved for prevention of motion sickness and is commercially available [13]. Scopolamine patches have also been reported to suppress saliva production in cancer patients [14]. In Japan, such patches are not commercially available, and so one was prepared in our hospital in addition to a hydrophilic ointment so that the concentration of scopolamine hydrobromide hydrate was 5%. In our case, from the day of application, the amount of saliva decreased to about half, and only a slight degree of mouth dryness was observed.
NPWT is a physical therapy in which a negative pressure is continuously or intermittently applied to a wound in a closed environment to promote the formation of granulation tissue, adjust the wound bed, and hence facilitate wound healing. It is widely used for acute wounds, such as those that cannot be closed temporarily; open wounds on amputated limbs; and chronic wounds such as pressure ulcers and diabetic foot ulcers [15,16,17]. Endoscopic vacuum-assisted closure treatment is increasingly used for intrathoracic leakage after esophagectomy [18]. On the other hand, there have been few reports of percutaneous NPWT for management of enterocutaneous fistula due to AL after esophagectomy [19]. We speculated that NPWT would be fully applicable to postoperative enterocutaneous fistulas, such as the one in the present case, and would fit the criterion of a minimally invasive approach. It is also thought that a synergistic effect was obtained in the process of fistula closure by using scopolamine ointment in combination. The reduction in the exudate enabled protection of the wound, and granulation was promoted by the continuous negative pressure. A problem with the use of NPWT in intestinal tract communication is the risk of intestinal necrosis associated with continuous negative pressure [20], possibly due to the negative pressure impairing the microcirculation [21]. Therefore, the negative pressure was carefully and gradually initiated in the present case. Meanwhile, this treatment did not require frequent gauze replacement due to continuous drainage and improved the condition of the surrounding skin, not only promoting wound healing but also significantly reducing patient discomfort.
To our knowledge, there is no general definition of the duration of an intractable fistula. In our case, although post-esophagectomy AL was observed, the drainage and the general condition were reasonably good with no serious complications. Therefore, the next treatment was delayed and the hospitalization period became quite long. We suggest that AL that does not improve within 1 month at the latest should be considered as intractable fistula, and in such cases, a combination treatment with scopolamine ointment and NPWT may prove a successful treatment strategy.