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Minimally invasive esophagectomy for esophageal leiomyomatosis
Journal of Pediatric Surgery Case Reports 56 (2020) 101434
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Journal of Pediatric Surgery Case Reports
Minimally invasive esophagectomy for esophageal leiomyomatosis Ryohei Shibata a, Takeshi Saito a, Keita Terui a, Mitsuyuki Nakata a, Shugo Komatsu a, Tetsuya Mitsunaga b, Gen Matsuura b, Hidehito Shibasaki c, Takahiro Kinoshita d, Hideo Yoshida a, Tomoro Hishiki a, * Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan Department of Pediatric Surgery, Matsudo City General Hospital Children's Medical Center, Matsudo, Japan c Department of Surgery, Chibaken Saiseikai Narashino Hospital, Narashino, Japan d Division of Gastric Surgery, National Cancer Center Hospital East, Kashiwa, Japan a
b
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ABSTRACT
Keywords: Esophageal leiomyomatosis Minimally invasive esophagectomy Prone position Achalasia Case report Review of literature
Background: Esophageal leiomyomatosis (EL) is a rare benign tumor defined as a diffuse form of marked hypertrophy in the muscular layer of the esophagus. Relapses have been reported as a result of misdiagnoses of other tumors or achalasia, followed by inappropriate surgical intervention. The endoscopic approach is preferred because of its lesser degree of invasiveness and better cosmesis; however, its effectiveness for treatment of EL is unclear because these tumors are bulkier and more extensive than those in other esophageal diseases. Case presentation: We treated an 11-year-old girl who had been experiencing progressive dysphagia, vomiting, and coughing during sleep since the age of 4 years and was correctly diagnosed with EL using computed tomography and endoscopic ultrasonography. She was successfully treated with total minimally invasive esophagectomy (MIE), combining thoracoscopy and laparoscopy, in the prone position, without any complications or recurrence of symptoms. To our knowledge, this is the first case report of MIE for EL. A review of 84 EL cases (including the present case) revealed a rate of accurate preoperative diagnosis of only 23.8%. Esophagectomy should be employed because the recurrence rate of the non-esophagectomy cases, involving myotomy and tumorectomy, was significantly higher than that of the esophagectomy cases (57.9% vs. 7.7%, p = 0.002). Among 11 relapse cases in the non-esophagectomy cases, esophagectomy was performed in eight. Among the four relapse cases in the esophagectomy group, additional esophagectomy was necessary in three because of insufficient resection of the tumors at the primary esophagectomy. Conclusions: Multimodal imaging contributes to accurate diagnosis and assessment of the extent of the tumors, thus leading to the selection of the appropriate surgical intervention, i.e., radical esophagectomy. Total MIE in the prone position provides excellent exposure of the operative fields; our experience suggests that total MIE is beneficial for EL, as it is for other esophageal tumors.
1. Background Esophageal leiomyomatosis (EL) is an extremely rare benign tumor defined as a diffuse form of marked hypertrophy in the muscular layer of the esophagus [1]. Refractory and long-lasting dysphagia and vomit are caused by esophageal obstruction due to not only tumor compression, but also incomplete relaxation of the lower sphincter and peristaltic abnormality like achalasia [2,3]; thus, surgical intervention plays an important role in many cases.
*
However, an enormous number of relapse cases were reported previously, indicating that the treatment strategy for EL, appropriate diagnosis, and choice of surgical intervention based on understanding the clinical characteristics are not always straightforward. Although, some reviews of the literature were published [1,4–6] to clarify the clinical features of this extremely rare entity, diagnosis, treatment strategy, and outcome were not discussed in detail. Recently, minimally invasive esophagectomy (MIE) [7], which was a combined thoracoscopic and laparoscopic approach to esophagectomy, was used for esophageal cancer or other benign tumors. In ad-
Corresponding author. 1-8-1 Inohana, Chuo-ward, Chiba City, Chiba, 260-8677, Japan. E-mail address: [email protected] (T. Hishiki).
https://doi.org/10.1016/j.epsc.2020.101434 Received 22 February 2020; Received in revised form 12 March 2020; Accepted 13 March 2020 Available online 15 March 2020 2213-5766/© 2020 The Authors. Published by Elsevier Inc. This is an open (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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R. Shibata et al.
Journal of Pediatric Surgery Case Reports 56 (2020) 101434
dition, the prone technique [8] contributed to the optimal visualization of the mediastinum for a gravity-aided retraction. In EL cases as with these tumors, an endoscopic approach would be desirable in the point of invasiveness and cosmesis, yet no case reports about the endoscopic surgery to EL have been published to date. We successfully treated a case of EL in an 11-year-old girl using total MIE in the prone position. To our knowledge, this is the first case report of a successful minimally invasive resection for EL. We also discuss the optimal treatment strategy for this rare entity based on a review of the literature.
vealing diffuse elevated lesions covered by normal mucosa throughout the esophagus, suggestive of submucosal tumors that extended to the fornix of the stomach (Fig. 2-A, B). Endoscopic ultrasonography revealed significantly thickened smooth muscle layers, up to 23 mm at the lower esophagus (Fig. 2-C). Tumor markers were within normal limits, including carcinoembryonic antigen, square cell carcinoma related antigen, neuron-specific enolase, and soluble interleukin-2 receptor. Based on the imaging findings, she was clinically diagnosed with esophageal leiomyomatosis and MIE was performed. In a completely prone position on a Magic Bed™ (Okada medical supply Co., Ltd. Tokyo, Japan) under differential lung ventilation, five trocars were placed in the 3rd, 5th, and 7th right intercostal space on the posterior axillary line and 7th and 9th on inferior angle of the scapular line. This position forced the right lung to shift anteriorly, thereby providing better exposure of the posterior mediastinum. Adhesions around the lower and middle esophagus were separated using a Harmonic ACE™ (Ethicon Endo-Surgery, Inc., Cincinnati, USA). Direct invasion to adjacent organs or vascular structures was not evident. After dividing the arch of the azygos vein and the right bronchial artery, the upper thoracic esophagus was dissected and transected at 6 cm from the superior border of the thoracic esophagus using a 45 mm Echelon Flex™ (Ethicon Endo-Surgery, Inc., Cincinnati, USA). Subsequently, the patient was placed in the lithotomy position and five abdominal trocars were placed. After mobilization of the stomach, separation of adhesions around the cardia and dissection of the crus of the diaphragm, the esophagus was tugged into the abdominal cavity and brought outside of the abdominal cavity through a transumbilical mini-laparotomy. After the esophagus and the proximal
2. Case presentation An 11-year-old girl was referred to our hospital for detailed evaluation of a widened and distorted shadow in the mediastinum revealed on chest X-ray. She had been experiencing progressive dysphagia, vomiting, and coughing during sleep, associated with recurrent pneumonia since the age of 4 years. Her family history was not significant except for esophageal atresia in her younger sister. Hematuria and proteinuria were not identified and serum creatinine was within the normal limits for age. Barium contrast radiography revealed an irregular esophageal wall and retention of the barium with weakened peristalsis of the lowermiddle esophagus and stenosis at the lower esophagus (Fig. 1-A). A contrast-enhanced computed tomography scan revealed massive multiple tumors at the lower third of the esophagus and wall thickening from the upper third of the esophagus to the cardiac part of the stomach. The oral side of the esophageal tumors was extensive and filled with fluid (Fig. 1-B). Gastroduodenal endoscopy was performed, re-
Fig. 1. Barium contrast radiography disclosing an irregular esophageal wall with “Bird's beak sign,” resembling achalasia (A, black arrowheads). Contrastenhanced computed tomography scan showing wall thickening and fluid collection at the upper third of the esophagus (B) and multiple and bulky tumors at the lower third of the esophagus (C, white arrowheads).
Fig. 2. Endoscopy revealing diffuse elevated lesions covered by normal mucosa in the esophagus (A) and fornix of the stomach (B). Endoscopic ultrasonography depicting muscle layer of the lower third of the esophagus to 23 mm © 2
R. Shibata et al.
Journal of Pediatric Surgery Case Reports 56 (2020) 101434
3. Literature review
stomach were resected en bloc, a gastric conduit was created extracorporeally. The conduit was then pulled up to the cervical wound through the mediastinum and was anastomosed to the cervical esophagus by functional end-to-end anastomosis (delta-shaped anastomosis [9]). Surgical time was 7 hours and 39 minutes and the amount of blood loss was 56 g. Macroscopically, the esophagus and the stomach were thickened by confluent cream-colored nodules and the thickness of the esophageal wall measured up to 40 mm in the lower esophagus (Fig. 3-A). Microscopically, mucosal membrane and muscular mucosae were normal. However, the smooth muscle cells outgrew diffusely, resembling those observed in leiomyomas, partly forming a nodular pattern. The inner muscular layer of the muscularis propria was significantly thickened, whereas the outer layer was moderately thickened. Mitotic and atypical cells were absent. The distal margin at the stomach was free of leiomyoma cells, while the proximal esophageal margin was cell-positive. Immunohistochemistry showed positive staining of vimentin, alpha-smooth muscle antigen, and caldesmon; however, myoglobin, CD34, c-kit, S-100, and human melanin black 45 were negative. Based on these pathological findings, the diagnosis of EL was confirmed. Her postoperative course was uneventful and she was discharged on the 9th post-operation day. She remained well for eight years after the surgery except for mild reflux during sleep and mild constipation due to rectal leiomyomatosis.
We searched MEDLINE/PubMed using the keywords (“esophageal leiomyomatosis” OR “leiomyomatosis of the esophagus“ AND English [LA]) within the period 1975, which was when Fernandes defined EL for the first time (1), to 2019. Among 92 articles, we excluded 25 with insufficient descriptions of the individual cases. Among 91 EL cases in 67 articles, 83 cases with detailed descriptions of the treatment modality were extracted. We added our presented case to form a study cohort of 84 EL cases. The age of the patient at the first surgical intervention (for nonsurgical cases, age at diagnosis of EL) ranged from 1 to 79 years (median age: 19.5 years, undescribed in two cases). Female and pediatric patients less than 19 years of age accounted for 65.9% and 51.2% of the extracted cases, respectively. At presentation, using clinical and radiological findings solely, the correct diagnosis of EL had been obtained in only 20 of the 84 cases (23.8%). Benign esophageal tumors such as leiomyoma were the tentative initial diagnosis in 19 cases (22.6%). Three cases (3.6%) were initially misdiagnosed as malignant esophageal tumors. In addition to neoplastic diseases, achalasia was the most frequent initial diagnosis (nine cases; 10.7%) followed by one case each (1.1%) of gastroesophageal reflux [10], hiatal hernia [11], and esophageal perforation [12]. In 30 cases (34.1%), the primary diagnosis was not clearly described.
Fig. 3. The esophagus and stomach wall were significantly thickened by confluent cream-colored nodules (A). On histopathological findings stained with hematoxylin and eosin, normal mucosal membrane and diffuse and intense proliferation of smooth muscle cell like leiomyomas in making a nodular pattern observed (B, C). 3
R. Shibata et al.
Journal of Pediatric Surgery Case Reports 56 (2020) 101434
Among the 61 cases with description on tumor site, the lower third of the esophagus was involved in 59 patients (96.7%). With respect to the proximal end of the leiomyomatosis, the lower third was involved in 18 cases (29.5%), the middle third in 17 (27.9%), and the upper third in 24 (39.3%). The cervical esophagus was involved in ten cases (16.4%), and the cardia and the gastric fundus were involved in 36 cases (59.0%). Among 84 cases with clear descriptions on treatment options, 71 cases underwent surgery, including 52 esophagectomies (ten total or subtotal, ten partial, and 31 unspecified esophagectomies), six tumorectomies, 11 myotomies, and two fundoplications (Fig. 4). The median postoperative observation period ranged from 2 to 372 months (median: 30 months, not described in 27 cases). There were four relapses (7.7%) in the esophagectomy group, including three cases that underwent partial esophagectomy that resulted in insufficient resection. The recurrent cases underwent redo esophagectomy [13–16]. Relapse was frequently observed in cases undergoing tumorectomy (three cases, 50.0%), myotomy (seven cases, 63.6%), and fundoplication (one case, 50.0%). The relapse rate in the nonesophagectomy group was significantly higher than that of the esophagectomy group (57.9% vs. 7.7%, p = 0.002: Fisher's exact test using R 3.6.1). A redo esophagectomy was required in eight of the 11 recurrent cases (72.7%). Death related to EL was reported in three cases (3.6%). A 33-yearold woman died after 12 hours from the esophagectomy; however, the cause of death was not clearly described [17]. A patient who underwent esophagectomy at the age of 20 years died due to bronchospasm related to residual tracheobronchial leiomyomatosis during endoscopic exploration 19 years after the surgery [18]. A 26-year-old woman had coexisting adenocarcinoma of the esophagus on Barrett's epithelium and died from metastatic dissemination 15 months after esophagectomy [18].
third of the esophagus in almost all cases, with cranial extension to the middle third (29.1%) and the upper third (41.0%). This is reasonable because the lower half of the esophagus is composed of smooth muscle only while the upper half is composed of both striated and smooth muscles, with a predominance of striated muscle [19]. To avoid insufficient esophagectomy, a careful evaluation of the extent of the lesion based on both radiological and intraoperative macroscopic findings is mandatory. In our case, the esophageal mass was macroscopically completely removed; however, residual leiomyomatosis was microscopically identified in the proximal margin; nevertheless, her operative course was uneventful. Although the optimal extent of resection is yet to be known, and the necessity for microscopic total resection remains uncertain, at least a macroscopically complete resection is advisable to relieve the patient's symptom and to prevent recurrent symptoms. Whilst the majority of the cases were treated surgically, observation and symptomatic therapy had also been conducted in asymptomatic cases or in patients unwilling to undergo esophagectomy [3,20,21]. Nevertheless, conservative strategies should be chosen under the recognition of possible malignancies, because there were two cases of coexisting malignant tumors (esophageal adenocarcinoma on Barrett's membrane and leiomyosarcoma [18]) in the reviewed cohort. This suggests that periodic endoscopic evaluation should be carried out in non-surgically managed cases. Our experience in the current case suggested the significant effectiveness of MIE in the surgical treatment for EL. For less invasiveness and better cosmesis, we employed total MIE [7] using the “prone technique” [8]. Palanivelu et al. asserted that MIE in the prone position for esophageal cancer was more effective in terms of the technical advantages of esophagectomy, less required surgical time, and a lower incidence of respiratory complications than conventional esophagectomy [22]. Clear visualization of the operative field in the mobilization of the esophagus was easily secured by gravity-aided retraction without the support of an assistant surgeon, avoided bronchial and tracheal injuries, reduced the surgical time and provided preferable ergonomics in terms of the surgeon's standing position. In addition, prone position during anesthesia also helped to increase functional residual capacity of the lungs and promote postural drainage of sputum, which was a significant advantage in terms of oxygenation and ventilation especially in thoracotomy with differential lung or artificial pneumothorax. They concluded that these advantages of prone position during anesthesia contributed to less lung injury and postoperative respiratory complications, including pneumonia and atelectasis.
4. Discussion and conclusions The literature review revealed that correct diagnosis and esophagectomy were necessary for relief from symptoms. After the clinical diagnosis of EL, esophagectomy should be selected because the relapse rate of palliative procedures, including tumorectomy and myotomy, was significantly higher than that of the radical surgery and subsequent esophagectomy was performed as redo surgery in most cases. Furthermore, the recurrence of symptoms in the esophagectomy cases was caused by residual leiomyomatosis. Based on this review, we found that leiomyomatosis occupied the lower
Fig. 4. The treatment option and outcome of 84 esophageal leiomyomatosis cases in the previously reported literature including our case. 4
R. Shibata et al.
Journal of Pediatric Surgery Case Reports 56 (2020) 101434
Authors' contributions
EL is quite different from esophageal cancer and other benign tumors in that the tumors are massively bulky and usually occupy the whole of the esophagus to the fornix of the stomach. Nevertheless, we completed the procedure without any difficulty and complications in an acceptable duration of the surgery and a small amount of blood loss. The gravity-aided retraction was outstandingly effective for visualization of the mediastinum also in the EL patient. In the lateral position, the retraction of the esophagus by forceps for counter traction would be troublesome because of the extremely heavy and bulky tumors, suggesting that MIE in the prone position was more beneficial for esophagectomy in EL. There are some limitations in our report. First, clinical data from published case reports are limited and may sometimes differ from actual findings, as is the case for other reviews of the literature. In particular, we did not determine which imaging modality contributed to the correct diagnosis of EL because of under-reported radiological findings in the literature. Second, the effectiveness and safety of MIE cannot be generalized because our case is the first report of MIE for EL. Further research is needed to validate our finding. In conclusion, the diagnosis of EL should be made carefully using multimodal imaging approaches with attention to the extent of disease. The optimal choice of treatment is radical esophagectomy. MIE in a prone position is appropriate for EL, in spite of the bulky and extensive tumor, as is the case for other esophageal tumors owing to the better exposure of the operative fields.
All authors attest that they meet the current ICMJE criteria for Authorship. References [1] Fernandes JP, Mascarenhas MJ, Costa CD, Correia JP. Diffuse leiomyomatosis of the esophagus: a case report and review of the literature. Am J Dig Dis 1975;20: 684–90. [2] Katzka DA, Smyrk TC, Chial HJ, Topazian MD. Esophageal leiomyomatosis presenting as achalasia diagnosed by high-resolution manometry and endoscopic core biopsy. Gastrointest Endosc 2012;76:216–7. [3] Takahashi K, Ishii Y, Hayashi K, Ikarashi S, Kawai H, Sato Y, et al. Loss of peristalsis of the esophagus due to diffuse esophageal leiomyomatosis. Endoscopy 2017;49:E95–6. [4] Federici S, Ceccarelli PL, Bernardi F, Tassinari D, Zanetti G, Tani G, et al. Esophageal leiomyomatosis in children: report of a case and review of the literature. Eur J Pediatr Surg 1998;8:358–63. [5] Sans N, Galy-Fourcade D, Bloom E, Pradère B, Chiavassa H, Jarlaud T, et al. Imaging of diffuse esophageal leiomyomatosis: two case reports and review of the literature. Eur Radiol 2000;10:134–8. [6] Ziogas IA, Mylonas KS, Tsoulfas G, Spartalis E, Zavras N, Nikiteas N, et al. Diffuse esophageal leiomyomatosis in pediatric patients: a systematic review and quality of evidence assessment. Eur J Pediatr Surg 2019;29:487–94. [7] Nguyen NT, Schauer PR, Luketich JD. Combined laparoscopic and thoracoscopic approach to esophagectomy. J Am Coll Surg 1999;188:328–32. [8] Cuschieri A. Thoracoscopic subtotal oesophagectomy. Endosc Surg Allied Technol 1994;2:21–5. [9] Kanaya S, Gomi T, Momoi H, Tamaki N, Isobe H, Katayama T, et al. Delta-shaped anastomosis in totally laparoscopic Billroth I gastrectomy: new technique of intraabdominal gastroduodenostomy. J Am Coll Surg 2002;195:284–7. [10] Kugelman A, Greif Y, Gershoni-Baruch R, Berkowitz D, Best LA, Guralnik L, et al. Pulmonary presentation of esophageal leiomyomatosis associated with Alport syndrome in childhood. Isr Med Assoc J 2003;5:293–4. [11] Obeidat FW, Lang RA, Löhe F, Graeb C, Rist C, Jauch K-W, et al. Esophageal leiomyomatosis combined with intrathoracic stomach and gastric volvulus. J Soc Laparoendosc Surg 2009;13:425–9. [12] Nicholson AG, Li D, Pastorino U, Goldstraw P, Jeffery PK. Full thickness eosinophilia in oesophageal leiomyomatosis and idiopathic eosinophilic oesophagitis. A common allergic inflammatory profile?. J Pathol 1997;183:233–6. [13] Mothes H, Heidet L, Arrondel C, Richter KK, Thiele M, Patzer L, et al. Alport syndrome associated with diffuse leiomyomatosis: COL4A5-COL4A6 deletion associated with a mild form of Alport nephropathy. Nephrol Dial Transplant 2002; 17:70–4. [14] Hanazaki M, Takata K, Goto K, Katayama H, Yokoyama M, Morita K, et al. Anesthetic management of a patient with Alport-leiomyomatosis syndrome. J Anesth 2009;23:453–5. [15] Oohashi T, Naito I, Ueki Y, Yamatsuji T, Permpoon R, Tanaka N, et al. Clonal overgrowth of esophageal smooth muscle cells in diffuse leiomyomatosis-Alport syndrome caused by partial deletion in COL4A5 and COL4A6 genes. Matrix Biol 2011;30:3–8. [16] Aoyama J, Miyawaki Y, Kato T, Fujiwara N, Sugita H, Sato H, et al. Alportleiomyomatosis syndrome requiring subtotal esophagectomy for refractory gastroesophageal reflux disease after childhood partial esophagogastrectomy: a case report. Gen Thorac Cardiovasc Surg 2019. https://doi.org/10.1007/s11748019-01255-8. Available from:. [17] Muthuphei NM. Diffuse leiomyomatosis of the oesophagus--a case report. S Afr J Surg 1998;36:30–1. [18] Pujol J, Pares D, Mora L, Sans M, Jaurrieta E. Diagnosis and management of diuse leiomyomatosis of the oesophagus. Dis Esophagus 2000;13:169–71. [19] Kallmünzer B, Sörensen B, Neuhuber WL, Wörl J. Enteric co-innervation of striated muscle fibres in human oesophagus. Neuro Gastroenterol Motil 2008;20: 597–610. [20] Memisoglu E, Agarwal B, Akduman I, Prather C, Collins B, Civelek AC. Multimodality diagnostic imaging of diffuse esophageal leiomyomatosis. J Comput Assist Tomogr 2006;30:100–4. [21] Harada A, Maehata Y, Esaki M. Diffuse esophageal leiomyomatosis diagnosed by endoscopic ultrasonography and endoscopic mucosal cutting biopsy. Dig Endosc 2017;29:395–6. [22] Palanivelu C, Prakash A, Senthilkumar R, Senthilnathan P, Parthasarathi R, Rajan PS, et al. Minimally invasive esophagectomy: thoracoscopic mobilization of the esophagus and mediastinal lymphadenectomy in prone position--experience of 130 patients. J Am Coll Surg 2006;203. 7-1.
Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgments We are grateful to the patient for giving us the permission to use her clinical findings in this report. List of abbreviations EL Esophageal Leiomyomatosis MIE Minimally invasive esophagectomy Ethics approval and consent to participate Not applicable. Patient consent For the publication of related clinical information and all of the images within this report, written informed consent was obtained from the patient because she is now more than 20 years of age. Funding This study was not supported by any external sources of funding.
5
Contents lists available at ScienceDirect
Journal of Pediatric Surgery Case Reports
Minimally invasive esophagectomy for esophageal leiomyomatosis Ryohei Shibata a, Takeshi Saito a, Keita Terui a, Mitsuyuki Nakata a, Shugo Komatsu a, Tetsuya Mitsunaga b, Gen Matsuura b, Hidehito Shibasaki c, Takahiro Kinoshita d, Hideo Yoshida a, Tomoro Hishiki a, * Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan Department of Pediatric Surgery, Matsudo City General Hospital Children's Medical Center, Matsudo, Japan c Department of Surgery, Chibaken Saiseikai Narashino Hospital, Narashino, Japan d Division of Gastric Surgery, National Cancer Center Hospital East, Kashiwa, Japan a
b
ARTICLE INFO
ABSTRACT
Keywords: Esophageal leiomyomatosis Minimally invasive esophagectomy Prone position Achalasia Case report Review of literature
Background: Esophageal leiomyomatosis (EL) is a rare benign tumor defined as a diffuse form of marked hypertrophy in the muscular layer of the esophagus. Relapses have been reported as a result of misdiagnoses of other tumors or achalasia, followed by inappropriate surgical intervention. The endoscopic approach is preferred because of its lesser degree of invasiveness and better cosmesis; however, its effectiveness for treatment of EL is unclear because these tumors are bulkier and more extensive than those in other esophageal diseases. Case presentation: We treated an 11-year-old girl who had been experiencing progressive dysphagia, vomiting, and coughing during sleep since the age of 4 years and was correctly diagnosed with EL using computed tomography and endoscopic ultrasonography. She was successfully treated with total minimally invasive esophagectomy (MIE), combining thoracoscopy and laparoscopy, in the prone position, without any complications or recurrence of symptoms. To our knowledge, this is the first case report of MIE for EL. A review of 84 EL cases (including the present case) revealed a rate of accurate preoperative diagnosis of only 23.8%. Esophagectomy should be employed because the recurrence rate of the non-esophagectomy cases, involving myotomy and tumorectomy, was significantly higher than that of the esophagectomy cases (57.9% vs. 7.7%, p = 0.002). Among 11 relapse cases in the non-esophagectomy cases, esophagectomy was performed in eight. Among the four relapse cases in the esophagectomy group, additional esophagectomy was necessary in three because of insufficient resection of the tumors at the primary esophagectomy. Conclusions: Multimodal imaging contributes to accurate diagnosis and assessment of the extent of the tumors, thus leading to the selection of the appropriate surgical intervention, i.e., radical esophagectomy. Total MIE in the prone position provides excellent exposure of the operative fields; our experience suggests that total MIE is beneficial for EL, as it is for other esophageal tumors.
1. Background Esophageal leiomyomatosis (EL) is an extremely rare benign tumor defined as a diffuse form of marked hypertrophy in the muscular layer of the esophagus [1]. Refractory and long-lasting dysphagia and vomit are caused by esophageal obstruction due to not only tumor compression, but also incomplete relaxation of the lower sphincter and peristaltic abnormality like achalasia [2,3]; thus, surgical intervention plays an important role in many cases.
*
However, an enormous number of relapse cases were reported previously, indicating that the treatment strategy for EL, appropriate diagnosis, and choice of surgical intervention based on understanding the clinical characteristics are not always straightforward. Although, some reviews of the literature were published [1,4–6] to clarify the clinical features of this extremely rare entity, diagnosis, treatment strategy, and outcome were not discussed in detail. Recently, minimally invasive esophagectomy (MIE) [7], which was a combined thoracoscopic and laparoscopic approach to esophagectomy, was used for esophageal cancer or other benign tumors. In ad-
Corresponding author. 1-8-1 Inohana, Chuo-ward, Chiba City, Chiba, 260-8677, Japan. E-mail address: [email protected] (T. Hishiki).
https://doi.org/10.1016/j.epsc.2020.101434 Received 22 February 2020; Received in revised form 12 March 2020; Accepted 13 March 2020 Available online 15 March 2020 2213-5766/© 2020 The Authors. Published by Elsevier Inc. This is an open (http://creativecommons.org/licenses/by-nc-nd/4.0/).
access
article
under
the
CC
BY-NC-ND
license
R. Shibata et al.
Journal of Pediatric Surgery Case Reports 56 (2020) 101434
dition, the prone technique [8] contributed to the optimal visualization of the mediastinum for a gravity-aided retraction. In EL cases as with these tumors, an endoscopic approach would be desirable in the point of invasiveness and cosmesis, yet no case reports about the endoscopic surgery to EL have been published to date. We successfully treated a case of EL in an 11-year-old girl using total MIE in the prone position. To our knowledge, this is the first case report of a successful minimally invasive resection for EL. We also discuss the optimal treatment strategy for this rare entity based on a review of the literature.
vealing diffuse elevated lesions covered by normal mucosa throughout the esophagus, suggestive of submucosal tumors that extended to the fornix of the stomach (Fig. 2-A, B). Endoscopic ultrasonography revealed significantly thickened smooth muscle layers, up to 23 mm at the lower esophagus (Fig. 2-C). Tumor markers were within normal limits, including carcinoembryonic antigen, square cell carcinoma related antigen, neuron-specific enolase, and soluble interleukin-2 receptor. Based on the imaging findings, she was clinically diagnosed with esophageal leiomyomatosis and MIE was performed. In a completely prone position on a Magic Bed™ (Okada medical supply Co., Ltd. Tokyo, Japan) under differential lung ventilation, five trocars were placed in the 3rd, 5th, and 7th right intercostal space on the posterior axillary line and 7th and 9th on inferior angle of the scapular line. This position forced the right lung to shift anteriorly, thereby providing better exposure of the posterior mediastinum. Adhesions around the lower and middle esophagus were separated using a Harmonic ACE™ (Ethicon Endo-Surgery, Inc., Cincinnati, USA). Direct invasion to adjacent organs or vascular structures was not evident. After dividing the arch of the azygos vein and the right bronchial artery, the upper thoracic esophagus was dissected and transected at 6 cm from the superior border of the thoracic esophagus using a 45 mm Echelon Flex™ (Ethicon Endo-Surgery, Inc., Cincinnati, USA). Subsequently, the patient was placed in the lithotomy position and five abdominal trocars were placed. After mobilization of the stomach, separation of adhesions around the cardia and dissection of the crus of the diaphragm, the esophagus was tugged into the abdominal cavity and brought outside of the abdominal cavity through a transumbilical mini-laparotomy. After the esophagus and the proximal
2. Case presentation An 11-year-old girl was referred to our hospital for detailed evaluation of a widened and distorted shadow in the mediastinum revealed on chest X-ray. She had been experiencing progressive dysphagia, vomiting, and coughing during sleep, associated with recurrent pneumonia since the age of 4 years. Her family history was not significant except for esophageal atresia in her younger sister. Hematuria and proteinuria were not identified and serum creatinine was within the normal limits for age. Barium contrast radiography revealed an irregular esophageal wall and retention of the barium with weakened peristalsis of the lowermiddle esophagus and stenosis at the lower esophagus (Fig. 1-A). A contrast-enhanced computed tomography scan revealed massive multiple tumors at the lower third of the esophagus and wall thickening from the upper third of the esophagus to the cardiac part of the stomach. The oral side of the esophageal tumors was extensive and filled with fluid (Fig. 1-B). Gastroduodenal endoscopy was performed, re-
Fig. 1. Barium contrast radiography disclosing an irregular esophageal wall with “Bird's beak sign,” resembling achalasia (A, black arrowheads). Contrastenhanced computed tomography scan showing wall thickening and fluid collection at the upper third of the esophagus (B) and multiple and bulky tumors at the lower third of the esophagus (C, white arrowheads).
Fig. 2. Endoscopy revealing diffuse elevated lesions covered by normal mucosa in the esophagus (A) and fornix of the stomach (B). Endoscopic ultrasonography depicting muscle layer of the lower third of the esophagus to 23 mm © 2
R. Shibata et al.
Journal of Pediatric Surgery Case Reports 56 (2020) 101434
3. Literature review
stomach were resected en bloc, a gastric conduit was created extracorporeally. The conduit was then pulled up to the cervical wound through the mediastinum and was anastomosed to the cervical esophagus by functional end-to-end anastomosis (delta-shaped anastomosis [9]). Surgical time was 7 hours and 39 minutes and the amount of blood loss was 56 g. Macroscopically, the esophagus and the stomach were thickened by confluent cream-colored nodules and the thickness of the esophageal wall measured up to 40 mm in the lower esophagus (Fig. 3-A). Microscopically, mucosal membrane and muscular mucosae were normal. However, the smooth muscle cells outgrew diffusely, resembling those observed in leiomyomas, partly forming a nodular pattern. The inner muscular layer of the muscularis propria was significantly thickened, whereas the outer layer was moderately thickened. Mitotic and atypical cells were absent. The distal margin at the stomach was free of leiomyoma cells, while the proximal esophageal margin was cell-positive. Immunohistochemistry showed positive staining of vimentin, alpha-smooth muscle antigen, and caldesmon; however, myoglobin, CD34, c-kit, S-100, and human melanin black 45 were negative. Based on these pathological findings, the diagnosis of EL was confirmed. Her postoperative course was uneventful and she was discharged on the 9th post-operation day. She remained well for eight years after the surgery except for mild reflux during sleep and mild constipation due to rectal leiomyomatosis.
We searched MEDLINE/PubMed using the keywords (“esophageal leiomyomatosis” OR “leiomyomatosis of the esophagus“ AND English [LA]) within the period 1975, which was when Fernandes defined EL for the first time (1), to 2019. Among 92 articles, we excluded 25 with insufficient descriptions of the individual cases. Among 91 EL cases in 67 articles, 83 cases with detailed descriptions of the treatment modality were extracted. We added our presented case to form a study cohort of 84 EL cases. The age of the patient at the first surgical intervention (for nonsurgical cases, age at diagnosis of EL) ranged from 1 to 79 years (median age: 19.5 years, undescribed in two cases). Female and pediatric patients less than 19 years of age accounted for 65.9% and 51.2% of the extracted cases, respectively. At presentation, using clinical and radiological findings solely, the correct diagnosis of EL had been obtained in only 20 of the 84 cases (23.8%). Benign esophageal tumors such as leiomyoma were the tentative initial diagnosis in 19 cases (22.6%). Three cases (3.6%) were initially misdiagnosed as malignant esophageal tumors. In addition to neoplastic diseases, achalasia was the most frequent initial diagnosis (nine cases; 10.7%) followed by one case each (1.1%) of gastroesophageal reflux [10], hiatal hernia [11], and esophageal perforation [12]. In 30 cases (34.1%), the primary diagnosis was not clearly described.
Fig. 3. The esophagus and stomach wall were significantly thickened by confluent cream-colored nodules (A). On histopathological findings stained with hematoxylin and eosin, normal mucosal membrane and diffuse and intense proliferation of smooth muscle cell like leiomyomas in making a nodular pattern observed (B, C). 3
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Among the 61 cases with description on tumor site, the lower third of the esophagus was involved in 59 patients (96.7%). With respect to the proximal end of the leiomyomatosis, the lower third was involved in 18 cases (29.5%), the middle third in 17 (27.9%), and the upper third in 24 (39.3%). The cervical esophagus was involved in ten cases (16.4%), and the cardia and the gastric fundus were involved in 36 cases (59.0%). Among 84 cases with clear descriptions on treatment options, 71 cases underwent surgery, including 52 esophagectomies (ten total or subtotal, ten partial, and 31 unspecified esophagectomies), six tumorectomies, 11 myotomies, and two fundoplications (Fig. 4). The median postoperative observation period ranged from 2 to 372 months (median: 30 months, not described in 27 cases). There were four relapses (7.7%) in the esophagectomy group, including three cases that underwent partial esophagectomy that resulted in insufficient resection. The recurrent cases underwent redo esophagectomy [13–16]. Relapse was frequently observed in cases undergoing tumorectomy (three cases, 50.0%), myotomy (seven cases, 63.6%), and fundoplication (one case, 50.0%). The relapse rate in the nonesophagectomy group was significantly higher than that of the esophagectomy group (57.9% vs. 7.7%, p = 0.002: Fisher's exact test using R 3.6.1). A redo esophagectomy was required in eight of the 11 recurrent cases (72.7%). Death related to EL was reported in three cases (3.6%). A 33-yearold woman died after 12 hours from the esophagectomy; however, the cause of death was not clearly described [17]. A patient who underwent esophagectomy at the age of 20 years died due to bronchospasm related to residual tracheobronchial leiomyomatosis during endoscopic exploration 19 years after the surgery [18]. A 26-year-old woman had coexisting adenocarcinoma of the esophagus on Barrett's epithelium and died from metastatic dissemination 15 months after esophagectomy [18].
third of the esophagus in almost all cases, with cranial extension to the middle third (29.1%) and the upper third (41.0%). This is reasonable because the lower half of the esophagus is composed of smooth muscle only while the upper half is composed of both striated and smooth muscles, with a predominance of striated muscle [19]. To avoid insufficient esophagectomy, a careful evaluation of the extent of the lesion based on both radiological and intraoperative macroscopic findings is mandatory. In our case, the esophageal mass was macroscopically completely removed; however, residual leiomyomatosis was microscopically identified in the proximal margin; nevertheless, her operative course was uneventful. Although the optimal extent of resection is yet to be known, and the necessity for microscopic total resection remains uncertain, at least a macroscopically complete resection is advisable to relieve the patient's symptom and to prevent recurrent symptoms. Whilst the majority of the cases were treated surgically, observation and symptomatic therapy had also been conducted in asymptomatic cases or in patients unwilling to undergo esophagectomy [3,20,21]. Nevertheless, conservative strategies should be chosen under the recognition of possible malignancies, because there were two cases of coexisting malignant tumors (esophageal adenocarcinoma on Barrett's membrane and leiomyosarcoma [18]) in the reviewed cohort. This suggests that periodic endoscopic evaluation should be carried out in non-surgically managed cases. Our experience in the current case suggested the significant effectiveness of MIE in the surgical treatment for EL. For less invasiveness and better cosmesis, we employed total MIE [7] using the “prone technique” [8]. Palanivelu et al. asserted that MIE in the prone position for esophageal cancer was more effective in terms of the technical advantages of esophagectomy, less required surgical time, and a lower incidence of respiratory complications than conventional esophagectomy [22]. Clear visualization of the operative field in the mobilization of the esophagus was easily secured by gravity-aided retraction without the support of an assistant surgeon, avoided bronchial and tracheal injuries, reduced the surgical time and provided preferable ergonomics in terms of the surgeon's standing position. In addition, prone position during anesthesia also helped to increase functional residual capacity of the lungs and promote postural drainage of sputum, which was a significant advantage in terms of oxygenation and ventilation especially in thoracotomy with differential lung or artificial pneumothorax. They concluded that these advantages of prone position during anesthesia contributed to less lung injury and postoperative respiratory complications, including pneumonia and atelectasis.
4. Discussion and conclusions The literature review revealed that correct diagnosis and esophagectomy were necessary for relief from symptoms. After the clinical diagnosis of EL, esophagectomy should be selected because the relapse rate of palliative procedures, including tumorectomy and myotomy, was significantly higher than that of the radical surgery and subsequent esophagectomy was performed as redo surgery in most cases. Furthermore, the recurrence of symptoms in the esophagectomy cases was caused by residual leiomyomatosis. Based on this review, we found that leiomyomatosis occupied the lower
Fig. 4. The treatment option and outcome of 84 esophageal leiomyomatosis cases in the previously reported literature including our case. 4
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Authors' contributions
EL is quite different from esophageal cancer and other benign tumors in that the tumors are massively bulky and usually occupy the whole of the esophagus to the fornix of the stomach. Nevertheless, we completed the procedure without any difficulty and complications in an acceptable duration of the surgery and a small amount of blood loss. The gravity-aided retraction was outstandingly effective for visualization of the mediastinum also in the EL patient. In the lateral position, the retraction of the esophagus by forceps for counter traction would be troublesome because of the extremely heavy and bulky tumors, suggesting that MIE in the prone position was more beneficial for esophagectomy in EL. There are some limitations in our report. First, clinical data from published case reports are limited and may sometimes differ from actual findings, as is the case for other reviews of the literature. In particular, we did not determine which imaging modality contributed to the correct diagnosis of EL because of under-reported radiological findings in the literature. Second, the effectiveness and safety of MIE cannot be generalized because our case is the first report of MIE for EL. Further research is needed to validate our finding. In conclusion, the diagnosis of EL should be made carefully using multimodal imaging approaches with attention to the extent of disease. The optimal choice of treatment is radical esophagectomy. MIE in a prone position is appropriate for EL, in spite of the bulky and extensive tumor, as is the case for other esophageal tumors owing to the better exposure of the operative fields.
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Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgments We are grateful to the patient for giving us the permission to use her clinical findings in this report. List of abbreviations EL Esophageal Leiomyomatosis MIE Minimally invasive esophagectomy Ethics approval and consent to participate Not applicable. Patient consent For the publication of related clinical information and all of the images within this report, written informed consent was obtained from the patient because she is now more than 20 years of age. Funding This study was not supported by any external sources of funding.
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