Gastrointestinal Imaging Clinical Observations

Esophageal Motility Disorders After Laparoscopic Nissen Fundoplication Gastrointestinal Imaging Clinical Observations Natasha E. Wehrli 1 Marc S. Levine 1 Stephen E. Rubesin 1 David A. Katzka 2 Igor Laufer 1 Wehrli NE, Levine MS, Rubesin SE, Katzka DA, Laufer I Keywords: achalasia, barium studies, dysphagia, esophageal motility disorders, gastroesophageal reflux disease, Nissen fundoplication, surgical complications DOI:10.2214/AJR.07.2582 Received May 16, 2007; accepted after revision June 29, 2007. M. S. Levine and S. E. Rubesin are consultants for E-Z-EM Company. 1 Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104. Address correspondence to M. S. Levine (marc.levine@uphs.upenn.edu). 2 Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA. AJR 2007; 189:1464 1468 0361 803X/07/1896 1464 American Roentgen Ray Society Secondary Achalasia and Other Esophageal Motility Disorders After Laparoscopic Nissen Fundoplication for Gastroesophageal Reflux Disease OBJECTIVE. The purpose of our investigation was to determine the frequency of secondary achalasia and other esophageal motility disorders revealed on barium studies after laparoscopic Nissen fundoplication and to present the clinical and radiographic findings in these patients. CONCLUSION. Esophageal dysmotility was found in nine (7%) of 138 patients after laparoscopic Nissen fundoplication, including secondary achalasia in three (33%), diffuse esophageal spasm (DES) in two (22%), and a nonspecific esophageal motility disorder in four (44%). Our findings suggest that patients who undergo laparoscopic Nissen fundoplication for gastroesophageal reflux disease are at risk for the development of esophageal motility disorders, including secondary achalasia and DES. Careful evaluation of esophageal motility on postoperative barium studies may help to identify esophageal dysmotility and to differentiate this finding from structural complications of the wrap as a cause of refractory symptoms in these patients. ysphagia is a frequent and sometimes debilitating symptom after D laparoscopic Nissen fundoplication for gastroesophageal reflux disease. This symptom most commonly occurs during the early postoperative period and is usually attributed to edema and inflammation of the fundoplication wrap, causing transient narrowing and obstruction. Other patients may have prolonged postoperative dysphagia secondary to mechanical obstruction of the distal esophagus from a tight fundoplication wrap. A tight wrap can also lead to the gas-bloat syndrome with epigastric pain and bloating and inability to belch because of constriction of the distal esophagus by the wrap. Still other patients may have breakdown of the wrap with recurrent reflux symptoms [1]. In a study in the surgical literature, Stylopoulos et al. [2] reported patients who presented with dysphagia after laparoscopic Nissen fundoplication because of the development of secondary achalasia. To our knowledge, an association between this type of antireflux surgery and secondary achalasia has not been described previously in the radiologic literature. The purpose of our investigation therefore was to determine the frequency of secondary achalasia and other esophageal motility disorders revealed on barium studies after laparoscopic Nissen fundoplication and to present the clinical and radiographic findings in these patients. Materials and Methods Patient Population A computerized search of the radiology database at our university hospital during a 9-year period from 1998 to 2006 revealed 138 patients who underwent barium studies of the esophagus or upper gastrointestinal tract after laparoscopic Nissen fundoplication for treatment of gastroesophageal reflux disease. Patients who had water-soluble contrast examinations during the early postoperative period to rule out perforation were not included. A review of the original radiologic reports from these 138 patients revealed 33 with abnormal esophageal motility. Twenty-four (73%) of these 33 patients were excluded from analysis for one of the following reasons: they had mild, transient esophageal dysmotility that resolved on follow-up barium studies (n = 18); they had esophageal dysmotility on preoperative barium studies (n = 1), esophageal manometry (n = 2), or both (n = 2); or they had scleroderma or other conditions known to be associated with esophageal dysmotility (n = 1). The remaining nine patients (7%) constituted our study group. Five patients (56%) were men and four (44%) were women. The patients had a mean age of 57 years (range, 45 77 years) and a median age of 56 years. Medical records were reviewed by one author to determine the nature and duration of symptoms at the time of the barium study and the treatment and patient course. All but one patient had normal esophageal motility on preoperative barium studies, esophageal manometry, or both. The re- 1464 AJR:189, December 2007

Esophageal Motility Disorders After Laparoscopic Nissen Fundoplication maining patient had mild esophageal dysmotility on manometry with intermittent weakening of primary peristalsis. This patient was included in the study because of a marked change in esophageal motility on postoperative barium studies showing findings of advanced achalasia. Examination Technique These nine patients underwent double-contrast esophagography (n = 3), double-contrast upper gastrointestinal tract examinations (n = 3), or single-contrast upper gastrointestinal tract examinations (n = 3) after Nissen fundoplication. The mean interval between surgery and the barium study was 23 months (range, 2 57 months). Four patients had one or more repeat studies over a mean interval of 14 months (range, 4 26 months). The mean number of repeat studies was 1.5 (range, 1 2). In all patients, the examinations included upright and left posterior oblique double-contrast views of the esophagus and recumbent right lateral double-contrast views of the gastric fundus with an effervescent agent (Baros, Lafayette Pharmaceuticals) and a 250% weight/volume (w/v) barium (E- Z-HD, E-Z-EM) or prone right anterior oblique single-contrast views of the esophagus and recumbent single-contrast views of the fundus with a 50% w/v barium (Entrobar, Lafayette Pharmaceuticals). All of the studies were performed using digital fluoroscopy equipment (Diagnost 76, Philips Medical Systems; or Sireskop SD, Siemens Medical Solutions) by radiology residents or fellows or one of three attending gastrointestinal radiologists, and all were interpreted by the attending radiologists. Esophageal motility was evaluated by having patients swallow multiple discrete boluses of lowdensity barium in the prone, right anterior oblique position using a straw. The patient was asked to swallow one mouthful of barium at a time and then to keep his or her mouth open to refrain from swallowing another mouthful until the first barium bolus reached the stomach. Esophageal motility was considered abnormal if two or more of five separate swallows failed to show the expected aboral progression of primary peristalsis through the esophagus to the gastroesophageal junction [3]. Review of Images The original radiologic reports were reviewed to characterize the patient s esophageal dysmotility based on the findings described in the reports. Decreased primary peristalsis was characterized by diminished strength or velocity (or both) of the peristaltic wave at fluoroscopy, and absent peristalsis was characterized by loss of the peristaltic wave. Nonperistaltic contractions were characterized by a variable number of transient luminal indentations of varying severity. Incomplete opening of the lower esophageal sphincter (LES) was characterized by a focal segment of tapered, beaklike narrowing in the distal esophagus at or adjacent to the gastroesophageal junction. The images from the barium studies were reviewed by a consensus of two experienced gastrointestinal radiologists to assess for esophageal dilatation or delayed emptying of barium from the esophagus and the presence or absence of a hiatal hernia or gastroesophageal reflux. The appearance of the fundoplication wrap was also evaluated to determine if the wrap was intact or if it was partially or fully disrupted. There were no major discrepancies between the original reports and the blinded review. Study Design Radiographic findings were correlated with clinical presentation, treatment, and course in these patients. The radiographic findings were also correlated with the manometric findings in three patients who also underwent postoperative esophageal manometry. The mean interval between the barium studies and manometry was 3 months (range, 3 days 6 months). Institutional Review Board Approval Our institutional review board approved all aspects of this HIPAA-compliant retrospective study and did not require informed consent from any of the patients included in our study. Results Radiographic Findings Esophageal dysmotility was found in nine (7%) of 138 patients after laparoscopic Nissen fundoplication. These patients had three forms of esophageal dysmotility, including secondary achalasia in three (33%), diffuse esophageal spasm (DES) in two (22%), and a nonspecific esophageal motility disorder in four (44%). Three patients had radiographic findings of achalasia with a dilated and flaccid esophagus, absent primary peristalsis, and delayed emptying of barium into the stomach (Figs. 1 and 2). Two of the three patients had normal esophageal motility and the third had mild, intermittent weakening of primary peristalsis on preoperative esophagograms or manometry, so a diagnosis of secondary achalasia was made on the basis of radiographic findings. In all three patients, there was tapered, beaklike narrowing of the distal esophagus directly adjacent to the gastroesophageal junction (Figs. 1 and 2). Because the gastric wrap itself causes tapered narrowing of the distal esophagus, however, we could not assess LES opening in these patients. Two patients had radiographic findings of DES with intermittently weakened or absent primary peristalsis and multiple nonperistaltic contractions of mild to moderate severity during most swallows (neither patient had a classic corkscrew esophagus) (Fig. 3). There was no evidence of esophageal dilatation or of delayed emptying of barium from the esophagus in either of these patients. The remaining four patients had a nonspecific esophageal motility disorder with intermittently weakened or absent peristalsis and occasional mild nonperistaltic contractions. There was no evidence of esophageal dilatation or of delayed emptying of barium from the esophagus in any of these four patients. Barium studies revealed an intact fundoplication wrap surrounding the region of the gastroesophageal junction in eight of the nine patients with esophageal dysmotility. The remaining patient had a slipped wrap with a recurrent hiatal hernia. There was no evidence of gastroesophageal reflux at fluoroscopy in any of these nine patients. Follow-up barium studies in four patients revealed persistence (n = 2) or progression (n = 2) of esophageal dysmotility in two patients with achalasia and two with a nonspecific esophageal motility disorder. Manometric Findings Esophageal manometry revealed absent peristalsis in the body of the esophagus and decreased LES relaxation in one of the three patients with secondary achalasia after Nissen fundoplication (the other two did not undergo manometry). Neither of the two patients with DES on barium studies underwent manometry after surgery. Finally, manometry revealed intermittent weakening of primary peristalsis and occasional simultaneous contractions in two of the four patients with a nonspecific esophageal motility disorder (the other two did not undergo manometry). Clinical Findings All nine patients underwent barium studies because of esophageal symptoms, including dysphagia in seven, recurrent reflux symptoms in four (heartburn, regurgitation, or both), intractable hiccups and regurgitation in one, and nausea and vomiting in one. Four patients had dysphagia for solids only, and three had dysphagia for solids and liquids. Two patients had associated weight loss, and one had a documented episode of aspiration pneumonia. AJR:189, December 2007 1465

Fig. 1 45-year-old man with secondary achalasia after laparoscopic Nissen fundoplication. Upright, left posterior oblique view from single-contrast upper gastrointestinal tract examination shows dilated esophagus with tapered, beaklike narrowing (black arrow) adjacent to gastroesophageal junction and delayed emptying of barium into stomach. There was no evidence of primary peristalsis at fluoroscopy. Clips (white arrows) are seen near gastroesophageal junction from recent fundoplication. Note dilution of barium by fluid in dilated esophagus more proximally. When the patients were stratified on the basis of the type of esophageal dysmotility, two patients with secondary achalasia had dysphagia and one had intractable hiccups and regurgitation. Both patients with DES had dysphagia and one also had nausea and vomiting. The remaining four patients with nonspecific esophageal motility disorders had dysphagia (n = 1), recurrent reflux symptoms (n = 1), or both (n =2). Treatment and Patient Course One of the three patients with secondary achalasia had marked clinical improvement after an esophageal dilatation procedure in the region of the wrap. The other two patients underwent repeat surgery with takedown of the original fundoplication wrap and creation of a shorter, looser wrap in both and an additional Heller myotomy in one. Both of these patients also had marked clinical improvement after surgery. One patient with a nonspecific esophageal motility disorder and a slipped Nissen fundoplication underwent revision of the wrap 4 Fig. 2 49-year-old man with secondary achalasia after laparoscopic Nissen fundoplication. Prone, right anterior oblique view from double-contrast upper gastrointestinal tract examination shows mildly dilated esophagus with beaklike narrowing (black arrow) of distal esophagus near gastroesophageal junction. There was no evidence of primary peristalsis at fluoroscopy. Note surrounding wrap (white arrows) from Nissen fundoplication, which made it difficult to assess lower esophageal sphincter opening. years later with clinical improvement, and another patient with a nonspecific esophageal motility disorder underwent endoscopic dilatation of the wrap with amelioration of symptoms. The remaining two patients with a nonspecific esophageal motility disorder and both patients with DES underwent conservative management with calcium channel blockers or long-acting nitrates. One of these patients had persistent gastroesophageal reflux symptoms and the other three were lost to follow-up. Discussion Gastroesophageal reflux disease is the most common pathologic condition affecting the upper gastrointestinal tract; up to 25% of the population of the Western world experiences heartburn on a monthly basis [4]. Although most patients respond to treatment with histamine receptor antagonists or proton pump inhibitors, laparoscopic Nissen fundoplication has become the gold standard for Fig. 3 45-year-old woman with diffuse esophageal spasm after laparoscopic Nissen fundoplication. Upright, left posterior oblique view from singlecontrast upper gastrointestinal tract examination shows numerous mild to moderate nonperistaltic contractions (arrows) in lower thoracic esophagus. There also was intermittent absence of primary peristalsis at fluoroscopy. Although no lumenobliterating contractions were observed, these findings are compatible with diffuse esophageal spasm. antireflux surgery in patients with medically refractory disease [5]. Laparoscopic Nissen fundoplication is a highly effective form of surgery for patients with intractable gastroesophageal reflux disease. Nevertheless, this procedure has been associated with complications in up to 10% of patients [6], including partial or complete breakdown of the fundoplication wrap with recurrent reflux, a slipped Nissen wrap, and a tight fundoplication wrap with refractory dysphagia or the gas-bloat syndrome [1]. Some investigators have found that there is a greater likelihood of dysphagia developing after laparoscopic Nissen fundoplication when abnormal esophageal motility is present before surgery [7]. As a result, patients who are candidates for this procedure often undergo preoperative esophageal manometry or barium studies to evaluate esophageal motility; the presence of preexisting esophageal dysmotility is considered by some to be a contraindication to a traditional 360 Nissen wrap [7]. 1466 AJR:189, December 2007

Esophageal Motility Disorders After Laparoscopic Nissen Fundoplication We observed the development of secondary achalasia or other esophageal motility disorders in nine (7%) of 138 patients who underwent barium studies after laparoscopic Nissen fundoplication. All but one of these patients had normal esophageal motility on preoperative barium studies or manometry, indicating that this dysmotility developed after the surgery. Since its original description by Stylopoulos et al. [2] in 2002, secondary achalasia has been recognized as an unusual but important complication of Nissen fundoplication [8]. To our knowledge, however, the development of secondary achalasia or of other forms of esophageal dysmotility after Nissen fundoplication has not been described previously in the radiologic literature. In three patients (33%) with esophageal dysmotility, barium studies revealed a dilated, aperistaltic esophagus with delayed emptying and tapered distal esophageal narrowing in the region of the fundoplication wrap (Figs. 1 and 2); these three patients were thought to have developed secondary achalasia as a direct complication of laparoscopic Nissen fundoplication. The distal esophageal narrowing was likely to have been caused by the surrounding gastric wrap, so it was not possible to assess LES function on the barium study in these patients. However, manometry in one patient confirmed the presence of achalasia with absent peristalsis and a hypertensive LES with decreased relaxation of the sphincter during swallowing. Both patients with secondary achalasia and dysphagia had relief of dysphagia after endoscopic dilatation of the LES in one and revision of the fundoplication with a Heller myotomy in the other. We therefore believe that dysphagia in this group of patients was caused by secondary achalasia with absent esophageal peristalsis and LES dysfunction rather than by the gastric wrap itself. Secondary achalasia is most commonly caused by malignant tumor at the gastroesophageal junction, usually originating in the gastric fundus or cardia or, less commonly, by malignant spread of tumors originating in the esophagus, lung, breast, pancreas, uterus, ovary, colon, or prostate [8]. Other nonneoplastic causes of secondary achalasia include Chagas disease in South America and, rarely, amyloidosis. Our findings and those from the earlier study by Stylopoulos et al. [2] indicate that laparoscopic Nissen fundoplication should be included as another cause of secondary achalasia. The pathogenesis of secondary achalasia after Nissen fundoplication remains uncertain. This motility disorder could result from prolonged mechanical obstruction of the distal esophagus by the fundoplication wrap, with loss of peristalsis above the wrap. Alternatively, secondary achalasia could be caused by vagal injury at surgery or by disruption of the myenteric plexus in the distal esophagus during construction of the wrap. In the study by Stylopoulos et al. [2], one patient was found to have disruption of the anterior and posterior branches of the vagus nerve at reoperation; the development of secondary achalasia in this patient was therefore specifically attributed to vagal injury during the original fundoplication. The possibility of vagal injury at surgery is also supported by a previous case report in which the development of secondary achalasia was documented after a highly selective vagotomy near the gastroesophageal junction [9]. Whatever the pathogenesis, secondary achalasia is likely to be encountered more frequently in the future as an increasing number of patients undergo laparoscopic Nissen fundoplication for intractable gastroesophageal reflux disease. Two patients in our series had radiographic findings of DES after laparoscopic Nissen fundoplication with intermittent weakening or absence of primary peristalsis and multiple nonperistaltic contractions (Fig. 3). In some cases, these nonperistaltic contractions may obliterate the lumen, producing a classic corkscrew appearance. As in our study, however, patients with DES frequently have mild or moderate nonperistaltic contractions, and more than 50% of patients have associated LES dysfunction with incomplete opening of the sphincter during swallowing [10]. As a result, some authors believe that DES and achalasia represent opposite ends of an interrelated spectrum of motility disorders and that DES may slowly progress to achalasia. Finally, four patients had nonspecific esophageal motility disorders after laparoscopic Nissen fundoplication. This condition may be manifested by a variety of radiographic and manometric abnormalities that do not meet the strict criteria for achalasia or DES. As in our study, these patients may present with dysphagia or chest pain and can be treated with long-acting nitrates, calcium channel blockers, and even endoscopic balloon dilatation or botulinum toxin injections if there is a component of LES dysfunction [11]. The choice of therapy and clinical response therefore depends on the nature and severity of esophageal dysmotility in these patients. Our investigation has a number of limitations. For this retrospective study, we had to rely on the original reports from the barium studies for a description of esophageal dysmotility because video recordings were not routinely obtained. This prevented us from providing a detailed assessment of esophageal motility and emptying. Our results were also skewed by selection bias because barium studies were performed primarily on symptomatic patients after laparoscopic Nissen fundoplication. Our retrospective study was also limited by the lack of manometric correlation in all cases. Finally, we cannot exclude other unrecognized causes of esophageal dysmotility in our study group. For example, three patients were older than 60 years, and it has been shown that older individuals are more likely to develop esophageal dysmotility, a condition known as presbyesophagus [12]. However, the presence of normal esophageal motility on preoperative barium studies, manometry, or both in all but one patient strongly suggests that this esophageal dysmotility developed as a direct complication of surgery. In conclusion, our findings suggest that patients who undergo laparoscopic Nissen fundoplication for gastroesophageal reflux disease are at risk for the development of esophageal motility disorders, including secondary achalasia and DES. Careful evaluation of esophageal motility on postoperative barium studies may help to identify esophageal dysmotility and to differentiate this finding from structural complications of the wrap as a cause of refractory symptoms in these patients. It is important to establish the diagnosis of secondary achalasia after laparoscopic Nissen fundoplication because these patients may require an esophageal dilatation procedure or surgical revision of the fundoplication with laparoscopic myotomy for amelioration of symptoms. References 1. Thoeni RF, Moss AA. The radiographic appearance of complications following Nissen fundoplication. Radiology 1979; 131:17 21 2. Stylopoulos N, Bunker CJ, Rattner DW. Development of achalasia secondary to laparoscopic Nissen fundoplication. J Gastrointest Surg 2002; 6:368 376 3. Ott DJ, Chen YM, Hewson EG, et al. Esophageal motility: assessment with synchronous video tape fluoroscopy and manometry. Radiology 1989; 173:419 422 4. Moayyedi P, Talley NJ. Gastro-oesophageal reflux disease. Lancet 2006; 367:2086 2100 AJR:189, December 2007 1467

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