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Myenteric Plexus Abnormalities Associated with Epiphrenic Diverticula§

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Myenteric Plexus Abnormalities Associated with Epiphrenic Diverticula§ European Journal of Cardio-thoracic Surgery 35 (2009) 22—27 www.elsevier.com/locate/ejcts Myenteric plexus abnormalities associated with epiphrenic diverticula§ Thomas W. Rice a,1,*, John R. Goldblum b, Martha M. Yearsley b, Steven S. Shay c, Scott I. Reznik a, Sudish C. Murthy a, David P. Mason a, Eugene H. Blackstone a,d,2 a Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH, USA b Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, USA Downloaded from https://academic.oup.com/ejcts/article/35/1/22/357545 by guest on 24 September 2021 c Department of Gastroenterology, Cleveland Clinic, Cleveland, OH, USA d Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA Received 5 June 2008; received in revised form 18 August 2008; accepted 8 September 2008; Available online 8 November 2008 Abstract Objective: To (1) categorize histologic esophageal myenteric plexus abnormalities in patients undergoing surgical treatment for epiphrenic diverticulum, and (2) correlate histologic changes with associated esophageal motility disorders and hiatal hernia. Methods: From January 1987 to May 2008, 40 patients had surgery for epiphrenic diverticulum. Esophageal manometry was abnormal in 29 (73%); 23 (58%) had hiatal hernia. Esophageal muscle specimens were evaluated for ganglion cell number, myenteric inflammations and myenteric fibrosis. Results: Myenteric plexus abnormalities were present in 31 (78%). Ganglion cells were reduced in 8 (20%) and absent in 13 (33%). Myenteric inflammation was present in 21 (53%) and myenteric fibrosis in 9 (23%). Abnormalities were seen in 10 (83%) with motility disorders only, 5 (83%) with hiatal hernia only, 13 (76%) with both, and 3 (60%) with neither. Abnormalities in diffuse esophageal spasm (n = 3) were similar to those of achalasia (n = 14). Ineffective esophageal motility (n = 6) was strongly associated with hiatal hernia, and abnormalities were similar to those of hiatal hernia without motility disorders (n = 6). All patients with nutcracker esophagus (n = 3) had hiatal hernia and histologic abnormalities, and two patients with hypertensive lower esophageal sphincter (n = 3, hiatal hernia in 2) had myenteric inflammation. Conclusions: Myenteric plexus abnormalities predominate in epiphrenic diverticulum. Disease-specific patterns exist, but are incomplete. These associations and patterns point to causes of distal obstruction, with some commonality. In the absence of associated disorders, myenteric plexus abnormalities may be the sole finding. Isolated epiphrenic diverticulum is uncommon and may reflect an inability to detect abnormalities by current investigative techniques. # 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. Keywords: Motility disorder; Hiatal hernia; Ganglion cells; Myenteric inflammation; Myenteric fibrosis; Achalasia 1. Introduction (Fig. 2), and study of the esophagus distal to the diverticulum has not been performed. Purposes of this report are to (1) Epiphrenic diverticulum is a false pulsion diverticulum categorize histologic myenteric plexus abnormalities in assumed to result from esophageal obstruction distal to an patients undergoing surgery for epiphrenic diverticulum, area lacking external support of periesophageal tissue or a and (2) correlate these histologic changes with associated point of weakness or absence of the muscularis propria esophageal motility disorders and hiatal hernia. (Fig. 1). We hypothesized that this obstruction may result from or be linked with abnormalities of the myenteric plexus, because the main associated disease, achalasia, has known myenteric plexus abnormalities, including loss of ganglion 2. Patients and methods cells and myenteric inflammation and fibrosis [1,2]. Routine histopathology of the resected diverticulum is unrevealing 2.1. Patients § From January 1987 to May 2008, 58 patients with Presented at the 16th European Conference on General Thoracic Surgery, epiphrenic diverticulum underwent surgery at Cleveland Bologna, Italy, June 8—11, 2008. * Corresponding author. Address: Cleveland Clinic, 9500 Euclid Avenue/Mail Clinic. Forty (70%) had a group of preoperative tests, stop J4-1, Cleveland, OH 44195, USA. Tel.: +1 216 444 1921; including esophageal manometry, esophagogastroduodeno- fax: +1 216 445 6876. scopy, and barium esophagram and subsequent postoperative E-mail address: [email protected] (T.W. Rice). 1 assessment of esophageal muscle distal to the diverticulum. Supported in part by the Daniel and Karen Lee Endowed Chair in Thoracic These patients constitute the study group. Surgery. 2 Supported in part by the Kenneth Gee and Paula Shaw, PhD, Chair in Heart Esophageal motility was abnormal in 29 (73%; Table 1), as Research. defined by DeMeester and Costantini [3]. Hiatal hernia was 1010-7940/$ — see front matter # 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejcts.2008.09.025 T.W. Rice et al. / European Journal of Cardio-thoracic Surgery 35 (2009) 22—27 23 Fig. 1. Radiographic evaluation of epiphrenic diverticulum. (A) Barium esophagram of epiphrenic diverticulum in a patient with achalasia. (B) Barium esophagram of Downloaded from https://academic.oup.com/ejcts/article/35/1/22/357545 by guest on 24 September 2021 epiphrenic diverticulum in a patient with hiatal hernia and no motility disorder. (C) Computed tomography of epiphrenic diverticulum (arrow) demonstrating classic position, on the right lateral aspect of the esophagus just above the diaphragm. This is a presumed area of inadequate support or weakness of the esophageal musculature. diagnosed in 23 (58%): by barium esophagram in 7 (30%), features: (1) number of ganglion cells, evaluated in a esophagogastroduodenoscopy in 6 (26%), and both in 10 semiquantitative fashion as normal in number, decreased in (43%). Hiatal hernia and motility disorders coexisted in 17 number, or absent, and (2) presence or absence of myenteric (43%). Diverticulectomy, myotomy, and anterior partial inflammation and fibrosis (Figs. 3—6). The analysis was done fundoplication were performed in 33 (83%) [4], with without knowledge of clinical information or existence of subsequent esophagectomy in 2 (5%). Esophagectomy was motility disorder or hiatal hernia. the first surgery in seven (18%) because their disease was not amenable to primary repair. 2.3.1. Analysis Categorical data are presented as frequencies and percen- 2.2. Tissue procurement tages. These data were approved for use in research by the institutional review board, with patient consent waived. As part of the myotomy performed to relieve distal obstruction, a 2 cm long strip of muscle was removed from the myotomy edge distal to, and 1808 from, the diverticu- 3. Results lectomy site. These strips were subjected to histologic analysis. In esophagectomy patients, a sample of the 3.1. Myenteric plexus abnormalities muscularis propria distal to and opposite the diverticulum was analyzed as part of the pathologic examination of the The myenteric plexus was abnormal in 31 of 40 patients resected specimen. (78%; Table 2). Ganglion cell abnormalities were present in 21 (53%) patients, reduced in number in 8 (20%), and absent in 2.3. Histologic analysis 13 (33%). Myenteric inflammation was present in 21 (53%) patients. Myenteric fibrosis was seen in nine (23%) patients Hematoxylin and eosin stained sections from the esopha- and associated with myenteric inflammation in eight (20%). geal muscle specimens were evaluated for the following Isolated ganglion cell abnormalities were present in nine (23%) patients and isolated myenteric inflammation in eight (20%). Combined abnormalities were present in 14 (35%). Association of these myenteric plexus abnormalities with motility disorders and hiatal hernia is detailed in Table 2.In the text that follows, these associations are amplified. Table 1 Motility disorders and hiatal hernia in epiphrenic diverticulum. Motility disorder No. (% of 40) Hiatal hernia No. % None 11 (28) 6 54 Achalasia 14 (35) 6 43 DES 3 (8) 1 33 HLES 3 (8) 2 67 Nutcracker 3 (8) 3 100 Fig. 2. Low-magnification appearance of a typical epiphrenic diverticulum. IEM 6 (16) 5 83 The squamous mucosa is hyperplastic and there is moderate degree of chronic Total 40 (100) 23 58 inflammation within the lamina propria and superficial submucosa. The sub- mucosa is fibrotic. Because epiphrenic diverticulum is a false pulsion diverti- Key: DES, diffuse esophageal spasm; HLES, hypertensive lower esophageal culum, the muscularis propria and thus the myenteric plexus are absent. sphincter; IEM, ineffective esophageal motility. 24 T.W. Rice et al. / European Journal of Cardio-thoracic Surgery 35 (2009) 22—27 Downloaded from https://academic.oup.com/ejcts/article/35/1/22/357545 by guest on 24 September 2021 Fig. 3. Low-magnification view of myenteric plexus from a patient with Fig. 5. Low-magnification view of myenteric plexus from a patient with no epiphrenic diverticulum and achalasia, showing a normal number of ganglion known motility disorder, revealing a reduced number of ganglion cells. Only a cells (yellow arrowheads) with scattered chronic inflammatory cells. single ganglion cell is identified within the myenteric plexus (yellow arrow- head). Fig. 4. Low-magnification view of myenteric plexus from a patient with Fig. 6. Low-magnification view of myenteric plexus from a patient with diffuse epiphrenic diverticulum and achalasia, revealing complete absence of gang- esophageal spasm,
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