End-stage Achalasia Research Articles

Esophagectomy for End Stage Achalasia

Esophageal myotomy is the standard primary therapy for achalasia. However, reports on long-term results of myotomy have suggested a deterioration of outcome over time with many patients presenting with end stage disease several years after esophagomyotomy. Eight patients who had previously undergone esophagomyotomy for achalasia presented with recurrent or worsening symptoms, and after preoperative evaluation, were treated by esophagectomy via laparotomy and right thoracotomy. The mean age at the time of myotomy was 52 years (range 18 to 62 years), and the mean time until esophagectomy was 12.5 years (range 2 to 18 years) after the initial myotomy. The median time until esophagectomy was performed after myotomy was 14 years. All patients in this series gained weight (mean, 23 pounds; range, 9 to 42 lbs) following esophagectomy, and none of the patients complained of dysphagia at follow-up or developed stricture. There were no major complications (including anastomotic leak) or deaths in this series. Five of the patients have been followed a mean of six years and remain well. Esophagectomy is a safe and appropriate treatment option in the setting of recurrent and end stage achalasia.

Invited commentary

The article by Gaissert and colleagues [1Gaissert H.A. Lin N. Wain J.C. Fankhauser G. Wright C.D. Mathisen D.J. Transthoracic Heller myotomy for esophageal achalasia analysis of long-term results.Ann Thorac Surg. 2006; 81: 2044-2049Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar] represents a large series of patients treated by a very experienced group during 4 decades. The authors show that post-esophagomyotomy results are excellent in 91% of patients early after surgery, and that this outcome deteriorates to 61% of patients with long-term follow-up. Early postoperative dysphagia predicts late failure. The addition of fundoplication is not a significant predictor of outcome in their analysis. Finally, sigmoid esophagus is not an independent predictor of failure after esophagomyotomy. Therefore, esophagomyotomy, not esophagectomy with reconstruction, should be the first-line therapy for achalasia patients with sigmoid esophagus. It is essential to maintain a lifelong perspective in treating achalasia, as patients present at a young age, and treatment is considered palliative. An ideal treatment option is safe, durable, and does not preclude further treatment options. Clearly the excellent results presented by Gaissert and colleagues [1Gaissert H.A. Lin N. Wain J.C. Fankhauser G. Wright C.D. Mathisen D.J. Transthoracic Heller myotomy for esophageal achalasia analysis of long-term results.Ann Thorac Surg. 2006; 81: 2044-2049Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar] will serve as a benchmark to compare with other treatments, including minimally-invasive esophagomyotomy methods. Optimal management of the subset of achalasia patients with sigmoid esophagus remains an unresolved issue. Gaissert and colleagues [1Gaissert H.A. Lin N. Wain J.C. Fankhauser G. Wright C.D. Mathisen D.J. Transthoracic Heller myotomy for esophageal achalasia analysis of long-term results.Ann Thorac Surg. 2006; 81: 2044-2049Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar] argue that esophagomyotomy, not esophagectomy, should be the first line of surgical treatment, because transthoracic myotomy is safe and results are comparable with its use in patients without esophageal enlargement. The authors argue that replacing one aperistaltic conduit (i.e., the native esophagus) with another one (i.e., the stomach, colon, or jejunum) does not make sense and does not justify the risks involved. However, the authors’ conclusions are based on results with 12 patients over 40(+) years, in which long-term data was available for only 11 years. In addition, the authors define sigmoid esophagus solely on the basis of size (i.e., diameter > 6 cm). In fact, in most achalasia patients, as the esophagus dilates (> 6 cm), it also lengthens and begins to twist and fold. It is this acquired luminal tortuosity, not luminal diameter, that renders an esophagus as “end-stage.” A dilated, tortuous esophagus will not empty well even with esophagomyotomy, because of its shape. Esophageal replacement for end-stage achalasia can be performed safely and with good results. The report by Banbury and colleagues [2Banbury M.K. Rice T.W. Goldblum J.R. et al.Esophagectomy with gastric reconstruction for achalasia.J Thorac Cardiovasc Surg. 1999; 117: 1077-1085Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar] is an example of this. There were no deaths in their series of 32 patients, and 83% were able to swallow with no or mild dysphagia. Eighty-seven percent felt better after esophagectomy. Median follow-up time was only 43 months; however, as shown in the current study, early failures predict long-term outcome. Furthermore, there is no reason to expect deterioration in the long-term swallowing result after esophagectomy. Transthoracic Heller Myotomy for Esophageal Achalasia: Analysis of Long-Term ResultsThe Annals of Thoracic SurgeryVol. 81Issue 6PreviewSwallowing deteriorates over time in some patients after transthoracic esophagomyotomy for achalasia. The causes of decline are poorly understood. Full-Text PDF

Esophagus-preserving surgery for advanced end-stage achalasia

Advanced end-stage achalasia was treated by esophagus-preserving surgery in four women. Their median age was 46.5 years, and the median duration of symptoms was 17.0 years. Advanced end-stage achalasia was defined as esophageal dilatation to more than 6 cm in diameter and meandering on radiography. Myotomy, fundopexy, and posterior fixation with straightening of the lower esophagus were performed. Myotomy was carried out for 5 cm in the esophagus and 2 cm in the stomach. The outcome of surgery was evaluated by Payne’s criteria and esophageal manometry. Laparotomy was performed in three patients and left thoracotomy plus laparotomy was done in one patient. The outcome of surgery was good to excellent in all cases by Payne’s criteria, and postoperative esophageal manometry showed a longer lower esophageal sphincter (LES) and lowered lower esophageal sphincter pressure (LESP). Preservation of the esophagus should be attempted before performing esophagectomy for advanced achalasia.

Squamous mucosal alterations in esophagectomy specimens from patients with end-stage achalasia.

Achalasia is an esophageal motor disorder in which the primary morphologic changes are found in the myenteric plexus. However, a number of secondary alterations are characteristically found in esophagectomy specimens, including the mucosa. In addition, these patients are at increased risk of developing esophageal squamous cell carcinoma. We studied the squamous mucosal alterations in 35 esophagectomy specimens from patients with end-stage achalasia and compared them with those found in the squamous mucosa near the esophagogastric junction from pediatric autopsies (</=18 years) from patients with no known esophageal disease. A representative block was immunostained for p53 (DO7), CD3, and CD20. p53 immunoreactivity was graded as follows: 0 = no staining; 1+ = rare basal cell staining; 2+ = extensive basal cell staining; 3+ = suprabasilar staining. Intraepithelial lymphocyte counts were performed by counting five high power fields (HPF) and calculating an average/HPF. Ages of achalasia patients at esophagectomy ranged from 21 to 78 years (mean 56 years), including 20 men and 15 women. Disease duration ranged from 1 to 44 years (mean 17 years). In all cases the squamous mucosa from achalasia patients was markedly hyperplastic with papillomatosis and basal cell hyperplasia. p53 staining in the squamous mucosa from achalasia patients was significantly more common than in controls (32 of 35 [91%] vs 1 of 17 [6%]; p <0.05). In all achalasia cases CD3+ cells far outnumbered CD20+ cells. There was a significantly greater number of CD3+ cells in achalasia cases (range 32-239/HPF; mean 107/HPF) compared with controls (range 0.8-12/HPF; mean 6/HPF) (p <0.05). In conclusion, the squamous mucosa in esophagectomy specimens from patients with end-stage achalasia shows significant alterations including marked squamous hyperplasia, an increased frequency of p53 immunoreactivity, and increased numbers of CD3+ cells when compared with controls. These changes may be related to the increased risk of squamous cell carcinoma in these patients.

The nature of the myenteric infiltrate in achalasia: an immunohistochemical analysis.

Achalasia is an esophageal motor disorder characterized by abnormal relaxation of the lower esophageal sphincter and absence of progressive peristalsis in the esophageal body. Previous studies evaluating esophagomyotomy and esophageal resection specimens have shown the presence of myenteric inflammation to be a consistent and early pathologic change in patients with achalasia. Thus, the goal of this study was to determine the immunohistochemical characteristics of the inflammatory infiltrate within the myenteric plexus in patients with clinically early and end-stage achalasia. Using formalin-fixed tissue, we analyzed the immunohistochemical features of the myenteric lymphocytes using antibodies that recognize B cells (CD20), T cells (CD3), T cell subsets (CD8), and the activation state of T cell subpopulations (TIA-1 and granzyme B) in nine patients with clinically early achalasia who underwent esophagomyotomy and 13 patients with clinically endstage achalasia who underwent esophageal resection. The myenteric infiltrate in all nine esophagomyotomy specimens was composed predominantly of T cells (CD3-positive), the majority of which also stained for CD8. In five of nine specimens, the majority of CD8-positive cells stained for TIA-1. In the esophageal resection specimens, the myenteric infiltrate was composed predominantly of CD3-positive T cells in seven of 13 cases. In three cases, there was a predominance of CD20-positive B cells, and in the remaining three cases there were relatively equal numbers of T and B cells. In eight of 13 cases, the majority of T cells stained for CD8. TIA-1 immunoreactivity was found in the majority of CD8-positive cells in nine of 13 cases. In all esophagomyotomy and esophageal resection specimens studied, rare granzyme B-positive cells were detected. In conclusion, the majority of myenteric inflammatory cells in patients with achalasia are CD3-positive T cells, most of which are also CD8-positive, although the relative percentage of such cells appears to decrease with disease progression. Furthermore, many of the CD3-positive/CD8-positive myenteric lymphocytes also express TIA-1, suggesting they are resting or activated cytotoxic T cells. The immunohistochemical demonstration of granzyme B in a subpopulation of these cells supports the contention that achalasia is an immune-mediated disease, although the inciting antigen remains an enigma.

Esophageal and gastric nitric oxide synthesizing innervation in primary achalasia.

We performed a qualitative and quantitative analysis of the nitrinergic neurons in the esophageal and gastric component of the lower esophageal sphincter (LES) and gastric fundus of patients with primary achalasia. Four muscle strips were obtained from the esophagogastric junction (two from the esophageal and two from the gastric side of the LES), and two from the gastric fundus of six patients with endstage achalasia who underwent an esophagogastric myotomy plus hemifundoplication. Control specimens were obtained from eight patients who underwent surgery for cancer of the thoracic esophagus. Fixed sections were processed for NADPH-diaphorase histochemistry and the number (mean +/- SE) of nitrinergic neurons per section was visually quantified in each specimen. In the controls, nitric oxide fibers were distributed to the muscle layer and surrounding myenteric neurons of both the LES and the gastric fundus. By contrast, achalasic patients showed a marked decrease of nitric oxide nerves and labeled neurons in both esophageal and gastric components of the LES and the gastric fundus. Quantitative assessment in achalasic patients showed that the mean number of nitrinergic neurons was dramatically reduced in both the esophageal (0.2 +/- 0.1) and the gastric component (2 +/- 0.6) of the LES as compared to those in controls (15 +/- 5 and 12 +/- 4, respectively; p < 0.05); nitrinergic neurons in the gastric fundus (3 +/- 1) were significantly reduced in comparison to those of controls (10 +/- 2) (p < 0.05). Our results indicate that achalasia is a motor disorder with an intrinsic inhibitory denervation of the esophageal and gastric component of the LES and of the proximal stomach, thus providing further evidence for an extraesophageal extension of the disease.

Esophageal and gastric nitric oxide synthesizing innervation in primary achalasia

OBJECTIVE: We performed a qualitative and quantitative analysis of the nitrinergic neurons in the esophageal and gastric component of the lower esophageal sphincter (LES) and gastric fundus of patients with primary achalasia. METHODS: Four muscle strips were obtained from the esophagogastric junction (two from the esophageal and two from the gastric side of the LES), and two from the gastric fundus of six patients with endstage achalasia who underwent an esophagogastric myotomy plus hemifundoplication. Control specimens were obtained from eight patients who underwent surgery for cancer of the thoracic esophagus. Fixed sections were processed for NADPH-diaphorase histochemistry and the number (mean ± SE) of nitrinergic neurons per section was visually quantified in each specimen. RESULTS: In the controls, nitric oxide fibers were distributed to the muscle layer and surrounding myenteric neurons of both the LES and the gastric fundus. By contrast, achalasic patients showed a marked decrease of nitric oxide nerves and labeled neurons in both esophageal and gastric components of the LES and the gastric fundus. Quantitative assessment in achalasic patients showed that the mean number of nitrinergic neurons was dramatically reduced in both the esophageal (0.2 ± 0.1) and the gastric component (2 ± 0.6) of the LES as compared to those in controls (15 ± 5 and 12 ± 4, respectively; p < 0.05); nitrinergic neurons in the gastric fundus (3 ± 1) were significantly reduced in comparison to those of controls (10 ± 2) ( p < 0.05). CONCLUSIONS: Our results indicate that achalasia is a motor disorder with an intrinsic inhibitory denervation of the esophageal and gastric component of the LES and of the proximal stomach, thus providing further evidence for an extraesophageal extension of the disease.

Esophagectomy with gastric reconstruction for achalasia

Purpose: Achalasia is a degenerative esophageal disorder that may result in esophageal failure necessitating resection for restoration of gastrointestinal function. This study evaluates a protocol of esophageal resection and gastric reconstruction for end-stage achalasia. Methods: Hospital records, radiographic studies, and resection specimens of patients undergoing esophagectomy and gastric reconstruction were reviewed. Patient outcome was defined by an evaluation of symptoms (early satiety, dysphagia, regurgitation, and reflux), dietary restrictions, and ability to maintain or gain weight. Preoperative, operative, and postoperative variables and pathologic features in the resection specimens were analyzed to determine predictors of outcome. Results: In a 10-year period, 32 patients underwent esophagectomy with gastric reconstruction for achalasia; 30 (94%) underwent elective surgery and 2 (6%), emergency surgery. No postoperative deaths occurred. Of 29 patients completing telephone interviews, 24 (83%) had no or mild dysphagia; 21 (72%), no or mild regurgitation; 20 (69%), no or mild reflux; and 19 (66%), no or mild early satiety. Twenty-four (83%) patients had no or minimal dietary restrictions; 26 (90%) had no or minimal social dietary restrictions. Postoperative weight was not different from preoperative weight. Of 30 patients, 26 (87%) felt better after esophagectomy and 25 (83%) would have the operation again. There were few predictors of outcome. Younger patients were more likely to have dysphagia ( P = .03). Conclusions: Esophagectomy with gastric reconstruction relieves preoperative dysphasia and regurgitation in the majority of patients. Dietary function and weight maintenance are excellent, attesting to the durability of the procedure in patients with end-stage achalasia. (J Thorac Cardiovasc Surg 1999;117:1077-85)

Histopathologic features in esophagomyotomy specimens from patients with achalasia

BACKGROUND & AIMS: A previous study evaluating the morphological features of esophagi resected for endstage achalasia showed marked depletion of myenteric ganglion cells, widespread destruction of nerves, and variable chronic inflammation. The aim of this study was to evaluate the histological features in esophagomyotomy specimens from 11 patients with early achalasia, defined as minimal to moderate esophageal dilation without sigmoid deformity. METHODS: The histological features of esophagomyotomy specimens from 11 patients with achalasia were analyzed and compared with the findings of control specimens obtained from 8 patients who underwent esophagectomy for intramucosal adenocarcinoma. RESULTS: Control specimens had normal numbers of ganglion cells (0.70-0.91 ganglion cells per high-power field) and minimal inflammation. Three patients with vigorous achalasia had normal ganglion cell numbers (0.79-0.91 ganglion cells per high- power field) and at least mild myenteric inflammation without neural fibrosis. The remaining 8 patients had few or no ganglion cells (0-0.30 ganglion cells per high-power field) and at least mild myenteric inflammation and neural fibrosis. Ganglionitis was found in 2 cases. Ganglion cell number was inversely correlated with degree of myenteric neural fibrosis (P < 0.001). CONCLUSIONS: Vigorous achalasia has pathological features that are distinct from classic achalasia. The earliest pathological changes consist of myenteric inflammation with injury to and subsequent loss of ganglion cells and injury to and fibrosis of myenteric nerves. (Gastroenterology 1996 Sep;111(3):648-54)

Esophageal resection with colon interposition for end-stage achalasia.

To review the potential benefits of esophageal resection with colon interposition in patients with achalasia. Retrospective review. University-based tertiary care center. Nineteen patients (13 men, six women; median age, 44 years; age range, 26 to 77 years) with achalasia and recurrent or persistent dysphagia despite a variety of previous treatments. Esophageal resection and replacement with colon interposition. Mortality and morbidity of the procedure, symptomatic outcome, nutritional impact, ability to ingest a meal, and overall patient satisfaction. Follow-up results were available in 15 patients. The procedure accounted for no deaths and complications in four patients. Outcome assessment was done at a median of 6 years (range, 1 to 14 years) after resection. Overall, the symptomatic outcome was excellent to good in 12 patients. Eleven of the 15 patients gained weight (median weight loss, 6.3 kg) after the procedure. Thirteen patients were able to eat three meals daily; seven had the capacity to eat a steak dinner; five, an airline meal; and three, a snack. Nine of the 15 patients enjoyed an unrestricted diet. The speed of ingesting a meal was reduced in that most (11 of 15) were the last to finish when eating in a group. Fourteen of the 15 believed that the operation had cured or improved their preoperative symptoms, and a similar percentage were satisfied with the overall outcome of surgery. Most patients (12 of 15) would have the operation again. Esophageal replacement for end-stage achalasia can be accomplished with safety and marked improvement of preoperative symptoms. Despite multiple previous therapeutic failures, normal alimentation was restored in the majority of patients, with 93% judging the operation to be highly beneficial, improving their quality of life. Based on this success, guidelines for resection in end-stage achalasia are established.