Diffuse Esophageal Leiomyomatosis in Pediatric Patients: A Systematic Review and Quality of Evidence AssessmentFunding None.
17 August 2018
31 October 2018
21 December 2018 (online)
Background Diffuse esophageal leiomyomatosis (DEL) is a rare disorder characterized by benign hypertrophy of esophageal smooth muscle cells. No rigorous summary of available evidence on how to best manage these patients exists.
Objective To define the clinical features and outcomes of pediatric patients with DEL.
Materials and Methods A systematic literature search of the PubMed and Cochrane databases was performed with respect to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (end-of-search date: October 6, 2018). The algorithm: “esophageal leiomyomatosis AND (children OR pediatric*)” was implemented.
Results Thirty-five studies including a total of 58 patients were analyzed. The female:male ratio was 1.45:1. Mean patient age was 8.54 ± 4.67 years. The most common disease manifestations were dysphagia and gastrointestinal symptoms (90.0%, 95% confidence interval [CI]: 78.2–96.1), followed by failure to thrive (57.9%, 95% CI: 36.2–76.9) and pulmonary symptoms (56.4%, 95% CI: 41.0–70.7). Alport syndrome (AS) was seen in 57.7% (95% CI: 44.2–70.1) of the patients. The most commonly implemented procedure was esophagectomy (85.2%; n = 46/54; 95% CI: 73.1–92.6) with gastric transposition (37.8%; n = 17/45; 95% CI: 25.1–52.4). Postoperative complications developed in 33.3% (n = 15/45; 95% CI: 21.3–48) of the patients. All-cause mortality was 7.0% (95% CI: 2.3–17.2) and disease-specific mortality was 3.5% (95% CI: 0.3–12.6).
Conclusion DEL is an uncommon condition that typically occurs in the setting of AS. Esophagectomy with gastric transposition is the mainstay of treatment. Although complications develop in one-third of the patients, mortality rates are low.
Keywordspediatric surgery - diffuse esophageal leiomyomatosis - Alport syndrome - esophageal neoplasms - esophageal tumors
Study concept and design, and critical revision: Mylonas, Schizas, Ziogas, Tsoulfas, Spartalis, Zavras, and Nikiteas. Data acquisition, analysis and data interpretation, and drafting of the article: Ziogas and Mylonas. Supervision: Mylonas and Nikiteas.
* Ioannis A. Ziogas and Konstantinos S. Mylonas share first co-authorship.
- 1 Liu W, Wong JKL, He Q. , et al. Chinese family with diffuse oesophageal leiomyomatosis: a new COL4A5/COL4A6 deletion and a case of gonosomal mosaicism. BMC Med Genet 2015; 16 (49) 49
- 2 Uliana V, Marcocci E, Mucciolo M. , et al. Alport syndrome and leiomyomatosis: the first deletion extending beyond COL4A6 intron 2. Pediatr Nephrol 2011; 26 (05) 717-724
- 3 Kruegel J, Rubel D, Gross O. Alport syndrome--insights from basic and clinical research. Nat Rev Nephrol 2013; 9 (03) 170-178
- 4 Segal Y, Peissel B, Renieri A. , et al. LINE-1 elements at the sites of molecular rearrangements in Alport syndrome-diffuse leiomyomatosis. Am J Hum Genet 1999; 64 (01) 62-69
- 5 Ray S, Saluja SS, Gupta R, Chattopadhyay TK. Esophageal leiomyomatosis -- an unusual cause of pseudoachalasia. Can J Gastroenterol 2008; 22 (02) 187-189
- 6 Thomas LA, Balaratnam N, Richards DG, Duane PD. Diffuse esophageal leiomyomatosis: another cause of pseudoachalasia. Dis Esophagus 2000; 13 (02) 165-168
- 7 Levine MS, Buck JL, Pantongrag-Brown L, Buetow PC, Lowry MA, Sobin LH. Esophageal leiomyomatosis. Radiology 1996; 199 (02) 533-536
- 8 Federici S, Ceccarelli PL, Bernardi F. , et al. Esophageal leiomyomatosis in children: report of a case and review of the literature. Eur J Pediatr Surg 1998; 8 (06) 358-363
- 9 Bourque MD, Spigland N, Bensoussan AL. , et al. Esophageal leiomyoma in children: two case reports and review of the literature. J Pediatr Surg 1989; 24 (10) 1103-1107
- 10 Guest AR, Strouse PJ, Hiew CC, Arca M. Progressive esophageal leiomyomatosis with respiratory compromise. Pediatr Radiol 2000; 30 (04) 247-250
- 11 Joanna Briggs Institute Critical Appraisal tools. Checklist for Case Reports. Available at: http://joannabriggs.org/research/critical-appraisal-tools.html . Accessed May 4, 2018
- 12 National Heart Lung and Blood Institute. Quality assessment tool for case series studies. Available at: https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools . Accessed May 4, 2018
- 13 Faber K, Jones MA, Spratt D, Tarraza Jr HM. Vulvar leiomyomatosis in a patient with esophagogastric leiomyomatosis: review of the syndrome. Gynecol Oncol 1991; 41 (01) 92-94
- 14 Guillem P, Delcambre F, Cohen-Solal L. , et al. Diffuse esophageal leiomyomatosis with perirectal involvement mimicking Hirschsprung disease. Gastroenterology 2001; 120 (01) 216-220
- 15 Azzie G, Bensoussan A, Spitz L. The association of anorectal leiomyomatosis and diffuse oesophageal leiomyomatosis. Pediatr Surg Int 2003; 19 (06) 424-426
- 16 Livnat G, Best LA, Guralnik L, Bentur L. Pulmonary outcome of Alport syndrome with familial diffuse esophageal leiomyomatosis. Pediatr Pulmonol 2011; 46 (06) 614-616
- 17 Gupta V, Lal A, Sinha SK, Nada R, Gupta NM. Leiomyomatosis of the esophagus: experience over a decade. J Gastrointest Surg 2009; 13 (02) 206-211
- 18 Sugimoto K, Yanagida H, Yagi K, Kuwajima H, Okada M, Takemura T. A Japanese family with Alport syndrome associated with esophageal leiomyomatosis: genetic analysis of COL4A5 to COL4A6 and immunostaining for type IV collagen subtypes. Clin Nephrol 2005; 64 (02) 144-150
- 19 Kilian AK, Ringle T, Waag K-L, Düber C, Neff KW. Pre- and postoperative MRI of esophageal and gastric leiomyomatosis in a pediatric patient. AJR Am J Roentgenol 2005; 184 (3, Suppl): S129-S131
- 20 Lee LS, Nance M, Kaiser LR, Kucharczuk JC. Familial massive leiomyoma with esophageal leiomyomatosis: an unusual presentation in a father and his 2 daughters. J Pediatr Surg 2005; 40 (05) e29-e32
- 21 Anker MC, Arnemann J, Neumann K, Ahrens P, Schmidt H, König R. Alport syndrome with diffuse leiomyomatosis. Am J Med Genet A 2003; 119A (03) 381-385
- 22 Hirschl RB, Yardeni D, Oldham K. , et al. Gastric transposition for esophageal replacement in children: experience with 41 consecutive cases with special emphasis on esophageal atresia. Ann Surg 2002; 236 (04) 531-539 , discussion 539–541
- 23 Kemper MJ, Ganschow R, Helmke K, Muller-Wiefel DE. The child with haematuria and dysphagia. Nephrol Dial Transplant 2000; 15 (10) 1694-1695
- 24 Appignani A, Lauro V, Prestipino M, Centonze N, Dòmini R. Intestinal bypass of the oesophagus: 117 patients in 28 years. Pediatr Surg Int 2000; 16 (5-6): 326-328
- 25 Ueki Y, Naito I, Oohashi T. , et al. Topoisomerase I and II consensus sequences in a 17-kb deletion junction of the COL4A5 and COL4A6 genes and immunohistochemical analysis of esophageal leiomyomatosis associated with Alport syndrome. Am J Hum Genet 1998; 62 (02) 253-261
- 26 Thorner P, Heidet L, Moreno Merlo F, Edwards V, Antignac C, Gubler MC. Diffuse leiomyomatosis of the esophagus: disorder of cell-matrix interaction?. Pediatr Dev Pathol 1998; 1 (06) 543-549
- 27 Dahan K, Heidet L, Zhou J. , et al. Smooth muscle tumors associated with X-linked Alport syndrome: carrier detection in females. Kidney Int 1995; 48 (06) 1900-1906
- 28 Cochat P, Guyot C, Antignac C. , et al. Pathological case of the month. Alport syndrome and diffuse leiomyomatosis. Am J Dis Child 1993; 147 (07) 791-792
- 29 Antignac C, Zhou J, Sanak M. , et al. Alport syndrome and diffuse leiomyomatosis: deletions in the 5′ end of the COL4A5 collagen gene. Kidney Int 1992; 42 (05) 1178-1183
- 30 Lonsdale RN, Roberts PF, Vaughan R, Thiru S. Familial oesophageal leiomyomatosis and nephropathy. Histopathology 1992; 20 (02) 127-133
- 31 Rabushka LS, Fishman EK, Kuhlman JE, Hruban RH. Diffuse esophageal leiomyomatosis in a patient with Alport syndrome: CT demonstration. Radiology 1991; 179 (01) 176-178
- 32 Lerone M, Dodero P, Romeo G. , et al. Leiomyomatosis of oesophagus, congenital cataracts and hematuria. Report of a case with rectal involvement. Pediatr Radiol 1991; 21 (08) 578-579
- 33 Legius E, Proesmans W, Van Damme B, Geboes K, Lerut T, Eggermont E. Muscular hypertrophy of the oesophagus and “Alport-like” glomerular lesions in a boy. Eur J Pediatr 1990; 149 (09) 623-627
- 34 Capps SNJ, Spitz L. Leiomyoma of the oesophagus in a 7-year-old girl. Pediatr Surg Int 1989; 4: 412-414
- 35 Nahmad M, Clatworthy Jr HW. Leiomyoma of the entire esophagus. J Pediatr Surg 1973; 8 (05) 829-830
- 36 Botting AJ, Soule EH, Brown Jr AL. Smooth muscle tumors in children. Cancer 1965; 18: 711-720
- 37 Blank E, Michael TD. Muscular hypertrophy of the esophagus: report of a case with involvement of the entire esophagus. Pediatrics 1963; 32: 595-598
- 38 Guthrie KJ. Idiopathic muscular hypertrophy of oesophagus, pylorus, duodenum and jejunum in a young girl. Arch Dis Child 1945; 20 (104): 176-178
- 39 Hall AJ. A case of diffuse fibromyoma of the oesophagus, causing dysphagia and death. Q J Med 1916; 9: 409-428
- 40 Hinshaw A, El-Baba M. A 7-year-old boy with Alport syndrome and vomiting. Gastroenterology 2018; 155 (02) e15-e16
- 41 Cochat P, Guibaud P, Garcia Torres R, Roussel B, Guarner V, Larbre F. Diffuse leiomyomatosis in Alport syndrome. J Pediatr 1988; 113 (02) 339-343
- 42 Schapiro RL, Sandrock AR. Esophagogastric and vulvar leiomyomatosis: a new radiologic syndrome. J Can Assoc Radiol 1973; 24 (02) 184-187
- 43 Sell Jr HW, Cocco A. Diffuse leiomyomatosis of the gastrointestinal tract in a single patient--esophagus to rectum: case report. Surgery 1997; 122 (03) 637-640