Esophageal adenocarcinoma in a patient with surgically treated achalasia

Summary Although squamous cell carcinoma of the esophagus occurs with increased incidence in primary achalasia, esophageal adenocarcinoma has been considered rare in this condition. We report a patient with long-standing achalasia in whom adenocarcinoma of the esophagus occurred many years after Heller esophagomyotomy, presumably related to Barrett's esophagus complicating gastroesophageal reflux disease.     

Barrett's esophagus complicating achalasia after esophagomyotomy. A clinical, radiologic, and pathologic study of 70 patients with achalasia and related motor disorders

Of 70 patients with achalasia and related motor disorders, 3 developed Barrett's esophagus 5, 8, and 15 years after esophagomyotomy. One of the three had dysplastic changes in the Barrett's mucosa. Although an increased incidence of gastroesophageal reflux, esophagitis, and stricture are well-known complications after esophagomyotomy, the development of Barrett's mucosa has been only recently recognized. Diagnosis of Barrett's esophagus in such patients is difficult and requires a high index of awareness by the radiologist and an endoscopic biopsy for definitive diagnosis. The cumulative effects of achalasia and Barrett's esophagus predispose these patients to higher risks of developing esophageal carcinoma.     

Barrett''s Esophagus in a Patient with Achalasia

Barrett's esophagus has been reported in patients with achalasia who have undergone esophagomyotomy. The condition was thought to be acquired from gastroesophageal reflux secondary to the iatrogenically produced incompetent sphincter. We present the case of a patient with Barrett's esophagus and achalasia without any previous surgical intervention.     

Barrett's Metaplasia and Dysplasia in Postmyotomy Achalasia Patients

Three patients who were 8 to 30 years status postmyotomy for achalasia were shown to develop Barrett's columnar metaplasia of the esophagus. In one instance, the patient had multiple areas of severe dysplasia to carcinoma in situ. There have been only a few reports in the world literature of Barrett's metaplasia occurring in postmyotomy achalasia patients. Our experience would indicate it may be a more common complication than previously appreciated. Also, a possible causal relationship between surgical intervention, Barrett's epithelium, and adenocarcinoma in achalasia is suggested.     

Achalasia of the esophagus

56 patients with achalasia of the esophagus were reviewed in a retrospective study to compare the results of a forceful pneumatic dilation with those of a Heller esophagomyotomy. 22 of 33 patients treated with forceful dilation (67%), showed relief of dysphagia and reduction in the average esophageal diameter by barium swallow during the follow-up period (mean=6.5 years). In 2 patients (6%), forceful dilation was complicated by esophageal perforation, promptly diagnosed, and successfully treated at surgery in both patients. 21 out of 23 patients who underwent esophagomyotomy (91%) showed permanent relief of symptoms and improvement by endoscopic and radiographic criteria. There were no significant postoperative complications during the follow-up period ranging between 1.5 and 10.0 years. The results of this study indicate that esophagomyotomy constitutes a more effective therapeutic modality than forceful dilation (P<0.05). Although esophageal dilation has a place in the treatment of early achalasia, esophagomyotomy appears to be a safer and a more successful form of treatment, of particular value in advanced esophageal disease and in those instances where pneumatic dilation fails to result in immediate clinical improvement.     

The cost-effectiveness of treatment strategies for achalasia

Achalasia is a disorder characterized by abnormal motility of the esophageal body and the lower esophageal sphincter, resulting in dysphagia, regurgitation, and chest pain. Treatment options for achalasia include Botulinum toxin injection, pneumatic balloon dilation, and surgical esophagomyotomy. The aim of this study was to determine the cost-effectiveness of these three strategies in the treatment of achalasia in adults. We constructed a Markov cost-effectiveness model comparing Botox injection, pneumatic balloon dilation, and laparoscopic esophagomyotomy as initial treatments of achalasia. Costs and probabilities were derived from the published literature. The utility for symptomatic achalasia was derived from a sample of patients with achalasia. Sensitivity analyses were performed. Over a five-year time horizon, pneumatic dilation was the most cost-effective treatment strategy for achalasia, with an incremental cost-effectiveness ratio of $1348 per quality-adjusted life-year compared to Botox. Although laparoscopic esophagomyotomy was more effective than the other treatment options, it was not cost-effective because of its high initial cost. In conclusion, pneumatic dilation is the most cost-effective treatment option for adults with achalasia. Further studies should examine the long-term relapse rates following treatment with Botox and more precisely determine the quality of life of symptomatic achalasia.     

TP53 mutations in malignant and premalignant Barrett''s esophagus

In order to improve the efficacy of endoscopic surveillance of Barrett's esophagus, markers of neoplastic progression in addition to dysplasia are required. The aim of the present study was to assess TP53 mutational analysis as a method of identifying patients with Barrett's esophagus who are at greatest risk of adenocarcinoma, for whom endoscopic surveillance is most appropriate. TP53 mutational analysis was initially performed on premalignant and malignant tissue from 30 patients undergoing esophagectomy for adenocarcinoma, and on premalignant biopsies from 48 patients participating in a Barrett's surveillance program. Surveillance patients were followed up endoscopically and histologically for a median of 5 years following TP53 assessment. Mutational analysis was performed by single-strand conformation polymorphism analysis and direct DNA sequencing. TP53 mutations were detected in 10 of 30 esophageal adenocarcinomas, and were more common in well-differentiated carcinomas. An identical TP53 mutation was detected in carcinoma and adjacent dysplasia. Two patients with premalignant Barrett's esophagus had TP53 mutations and one of these patients developed adenocarcinoma on follow up whilst the other has not yet progressed beyond metaplasia. No patient without TP53 mutation developed high-grade dysplasia or adenocarcinoma. TP53 mutations are detected in 33% of esophageal adenocarcinomas and in 4% of premalignant Barrett's esophagus in patients undergoing endoscopic surveillance. TP53 mutation can be detected before the development of high-grade dysplasia or carcinoma, and may be useful in stratifying the risk of adenocarcinoma in patients with Barrett's esophagus.     

The incidence of adenocarcinoma and dysplasia in Barrett''s esophagus

OBJECTIVE: The reported incidence of adenocarcinoma in Barrett's esophagus is variable. The aim of this study was to determine the incidence of dysplasia and adenocarcinoma in a population of patients with Barrett's esophagus followed prospectively and to compare these findings with other series. METHODS: All patients enrolled in the Cleveland Clinic Foundation's Barrett's esophagus registry from 1979 to 1995 were followed. Barrett's esophagus was defined as intestinal metaplasia anywhere in the tubular esophagus. The incidence of dysplasia and adenocarcinoma in these patients was recorded systematically. RESULTS: A total of 136 patients (91 male, 45 female) were followed in an endoscopic surveillance program for a mean of 4.2 yr and a total of 570 patient-years of follow-up. Thirty patients (22%) had short segment Barrett's esophagus. Two adenocarcinomas developed during follow-up, yielding an incidence of one per 285 patient-years of follow-up. Low grade dysplasia developed in 24 patients, whereas high grade dysplasia developed in four patients. CONCLUSIONS: Our study suggests that the incidence of adenocarcinoma in Barrett's esophagus is lower than initially thought. However, large multicenter studies are required to clarify the epidemiological and clinical factors related to the development of dysplasia and adenocarcinoma in Barrett's esophagus.     

Pneumatic dilatation or esophagomyotomy treatment for idiopathic achalasia: Clinical outcomes and cost analysis

The choice between pneumatic dilatation and surgical esophagomyotomy as the initial treatment for achalasia is controversial. The aims of this study were to determine the long term clinical outcome and costs of treating achalasia initially with pneumatic dilatation as compared to esophagomyotomy. Of 123 patients undergoing an initial pneumatic dilatation for achalasia at our institution from 1976 to 1986, 71 (58%) received no further treatment for achalasia during a mean follow up of 4.7±2.8 years. Only 15 of these 123 patients (12%) eventually underwent surgical esophagomyotomy, (two for perforation during pneumatic dilatation, 13 for persistent or recurrent symptoms). The degree of dysphagia at follow up was improved to a similar degree in patients treated with an initial pneumatic dilatation as compared to patients treated with an initial esophagomyotomy. Patients with age45, years at time of initial pneumatic dilatation had fewer subsequent treatments for persistent or recurrent symptoms and had less dysphagia on follow up as compared to patients <45 years. Subsequent pneumatic dilatations to treat persistent or recurrent symptoms were less beneficial than an initial pneumatic dilation. The cost of esophagomyotomy was 5 times greater than the cost of pneumatic dilatation. When costs were analyzed to include subsequent treatments of symptomatic patients, the total expectant costs of treating with an initial esophagomyotomy remained 2.4 times greater than treating with an initial pneumatic dilatation. This study suggests that an initial pneumatic dilatation will be the only treatment needed for the majority of patients with achalasia. A treatment regimen starting with penumatic dilatation has less overall costs than starting with esophagomyotomy. For each subsequent pneumatic dilatation, however, the clinical benefit leans toward, surgery.     

Complications during pneumatic dilation for achalasia or diffuse esophageal spasm

A retrospective cohort study was performed to assess risk factors, early clinical characteristics, and outcome of complications in patients undergoing pneumatic dilation. Of 178 patients with achalasia or diffuse esophageal spasm who underwent 236 dilations with a Browne-McHardy dilator, 16 patients experienced a complication (9.0%). Nine major complications developed: perforations (4), hematemesis (2), fever (2), and angina (1). A prior pneumatic dilation and use of inflation pressure ≥11 PSI were independent risk factors by multivariate analysis for developing a complication. An esophagram immediately following the dilation identified three of the four perforations. Three postdilation findings were identified as indicators of patients with an increased risk of having developed a perforation: blood on the dilator, tachycardia, and prolonged chest pain lasting >4 hr after dilation. In all patients incurring a major complication, one of the three indicators, or the complication itself was recognized within 5 hr of dilation. All patients with complications, including the four with perforation who received prompt surgical repair and esophagomyotomy, recovered uneventfully. The symptomatic relief of dysphagia in patients with perforation undergoing emergent surgical repair and esophagomyotomy was similar to patients undergoing elective esophagomyotomy. Conclusions: (1) Pneumatic dilation is a safe treatment of achalasia, with a 1.7% risk of perforation. (2) The risk of developing a complication is increased by having had a previous pneumatic dilation or by use of inflation pressures ≥11 psi. (3) All patients with a major complication were identified within 5 hr after dilation. (4) Complications following pneumatic dilation, if recognized and treated promptly, were not associated with adverse, long-term sequelae.     

Heller''s esophagomyotomy with or without a 360° floppy Nissen fundoplication for achalasia. Long-term results from a prospective randomized study

Heller's esophagomyotomy relieves dysphagia but does not restore esophageal peristalsis. The myotomy may induce reflux and the addition of a 360 degrees fundoplication may be hazardous with regard to the remaining aperistaltic esophagus. The aim of this prospectively randomized clinical trial was to compare the outcome for patients with uncomplicated achalasia who underwent an anterior Heller's esophagomyotomy (H group) with or without an additional floppy Nissen fundoplication (H + N group). Between 1984 and 1995, 20 patients were prospectively randomized to one or other of the performed operations, 10 patients per group. Esophagitis including Barrett's esophagus (n = 2) was seen under medical treatment, in 6 of 9 in the H group but none in the H + N group. No patient in the H + N group required postoperative continuous acid-reducing drugs. Twenty-four-hour esophageal pH-studies in median 3.4 years after surgery showed pathological reflux expressed as a percentage of time below pH 4 of 13.1% in the H group compared to 0.15% (P < 0.001) in H + N group. One patient with recurrent dysphagia in the H + N group later had an esophagectomy. The remaining patients reported significant improvement of dysphagia without symptoms of reflux at 8.0 years follow-up. Heller's esophagomyotomy eliminates dysphagia, but can induce advanced reflux that requires medical treatment. The addition of a 360 degrees fundoplication eliminates reflux without adding dysphagia in the majority of patients and can be recommended for most patients with uncomplicated achalasia.     

Massively dilated esophagus in achalasia: response to pneumatic balloon dilation

OBJECTIVE: Pneumatic balloon dilation is considered by many to be the treatment of choice for achalasia of the esophagus. Patients with untreated, long standing achalasia may develop massively dilated esophagi, sometimes difficult to dilate with a pneumatic balloon and, rarely, may require esophagectomy. We present our experience with nine such patients out of 110 who underwent pneumatic dilation. METHODS: Of 110 patients treated for achalasia by pneumatic balloon dilation, from January 1989 until December 1996, nine patients had massively dilated esophagi with transverse diameter >7 cm. Results of these patients are presented with pre- and postdilation symptom scores and barium esophagograms. This study was conducted at the Department of Gastroenterology, Shaikh Zayed Postgraduate Medical Institute, Lahore, Pakistan. A Microvasive Rigiflex 35 mm (Boston Scientific, Watertown, MA) pneumatic balloon was used for dilation. RESULTS: Although it is often tedious to perform pneumatic dilation in massively dilated esophagus, it was possible to dilate adequately, in all nine cases without complications, with good symptomatic improvement at 12-month follow-up. CONCLUSIONS: We recommend pneumatic balloon dilation in achalasia with massively dilated esophagus as a first line treatment, the failure of which requires surgical intervention.     

Development of Subsquamous High-Grade Dysplasia and Adenocarcinoma After Successful Radiofrequency Ablation of Barrett's Esophagus

Patients with Barrett's esophagus are frequently treated with radiofrequency ablation (RFA). Those that undergo this procedure have a low risk of developing subsquamous intestinal metaplasia, and none have been reported to develop subsquamous dysplasia or cancer. We report the development of subsquamous neoplasia in 3 patients who were treated with RFA for Barrett's esophagus (2 developed adenocarcinoma and 1 developed high-grade dysplasia). The identification of these cases indicates the need for continued surveillance following RFA, even after complete eradication of intestinal metaplasia, and caution for widespread use of ablation, especially in patients with low-risk Barrett's esophagus.     

Chronology of the Barrett's metaplasia-dysplasia-carcinoma sequence.

The objective of this study was to assess the course over time of the Barrett's metaplasia-dysplasia-carcinoma sequence. The method used was a retrospective analysis of the medical records of a patient series with a median follow-up of 25 months. The study was undertaken in a university hospital foregut laboratory. The progress of seven patients was followed through the sequence of Barrett's esophagus, low-grade dysplasia and high-grade dysplasia to cancer. They all underwent subsequent esophagectomy and were found to have intramucosal adenocarcinoma. The main outcome measure was the time from the first diagnosis of intestinal metaplasia to the development of low-grade dysplasia, high-grade dysplasia and adenocarcinoma. Low-grade dysplasia developed in a median of 24 months, high-grade dysplasia after a median of 33 months and cancer after 36 months. All patients underwent esophagectomy with reconstruction and no patient has had a recurrence at a median follow-up of 25 months (range 10-204 months). Patients on Barrett's surveillance who develop early esophageal adenocarcinoma did so within approximately 3 years after the diagnosis of non-dysplastic Barrett's esophagus.     

Effective and safe endoscopic reversal of nondysplastic Barrett's esophagus with thermal electrocoagulation combined with high-dose acid inhibition: a multicenter study

BACKGROUND: Barrett's esophagus is a metaplastic change in the esophageal lining with an increased risk for adenocarcinoma. Multiple endoscopic techniques have been applied in an effort to reverse Barrett's. This is a multicenter trial defining the efficacy and safety of multipolar electrocoagulation combined with high-dose acid inhibition. METHODS: Patients with a 2- to 6-cm segment of Barrett's esophagus without dysplasia were enrolled at 3 centers. They were treated with omeprazole 40 mg twice daily and then with up to 6 sessions with electrocoagulation aimed at eliminating all the endoscopically apparent Barrett's. Four quadrant large-capacity biopsies every 2 cm were centrally assessed for residual intestinal metaplasia. RESULTS: Fifty-eight patients reached the endpoint of failure of visual reversal of Barrett's after 6 treatment sessions or a 6-month follow-up after the last session. Eighty-five percent had visual reversal and 78% both visual and histologic reversal. Four patients had histologic evidence of residual intestinal metaplasia. Transient esophageal symptoms were common. One patient developed a stricture requiring dilation and one required overnight hospitalization for chest pain. CONCLUSIONS: The majority of patients with 2 to 6 cm of nondysplastic Barrett's esophagus can be safely reversed with this combination therapy. Long-term follow-up will be necessary to document the durability of the new squamous epithelium.     

Pneumatic dilation in achalasia.

Pneumatic dilation is the most common first-line therapy for the treatment of achalasia. The aim of dilation is a controlled disruption of circular muscle fibres of the lower esophageal sphincter to reduce the functional obstruction. Several types of dilators and different dilation techniques are used, but the achieved results are similar. The mean success rate is about 80% in the short term, but some patients need redilation in the further course (particularly young patients). Best long term results are obtained if the lower esophageal sphincter pressure can be reduced below 10 mmHg. Major complications are rare after pneumatic dilation; the most serious complication is esophageal perforation, which occurs at a mean rate of about 2.5%. Considering the pros and cons of other effective forms of treatment of achalasia (esophagomyotomy and intrasphincteric injection of botulinum toxin), pneumatic dilation is still the treatment of choice in the majority of patients with achalasia.     

Irreversible Esophageal Motor Dysfunction in Postvagotomy Dysphagia

Postvagotomy dysphagia is typically a temporary phenomenon but a small subgroup of patients appear to develop irreversible motility disorders of the esophagus. Two patients are reported with persistent symptomatic esophageal dysfunction demonstrated by modern hydraulic infusion technics. Both intially lost weight rapidly and then stabilized. The distal esophagus of both was greatly dilated but in one patient, lower esophageal sphincter pressure was normal. Aperistalsis with diminished motor activity was present throughout the body of the esophagus. Dysphagia and objective esophageal abnormalities were refractory to dilations with simple mercury bougies in one patient whose condition was improved by treatment with pneumatic dilation. The cause of this unusual complication is unknown but may involve a nonneoplastic form of secondary achalasia.     

Argon beam plasma coagulation as therapy for high-grade dysplasia in Barrett's esophagus.

BACKGROUND & AIMS: Patients with high-grade dysplasia in Barrett's esophagus have a high chance of developing adenocarcinoma. Previously these patients have undergone resection, however, the management of patients unsuitable for surgical resection is unclear. We have studied the long-term outcome of patients who have undergone endoscopic Argon ablation for high-grade dysplasia in Barrett's. METHODS: Twenty-nine patients (median age, 64 yr; range, 43-85 yr) with high-grade dysplasia in Barrett's, who were unfit or had declined surgery, underwent Argon ablation and received follow-up evaluation over 7 years (mean follow-up, 37 mo; range, 7-78 mo). Treatment was stopped once there was no further histologic evidence of dysplasia. The patients then went on to receive a surveillance endoscopy at 3, 6, and 12 months after ablation, then annually thereafter. RESULTS: High-grade dysplasia responded to treatment in 25 patients (86%); 22 of these had complete regression to neosquamous esophageal mucosa. During follow-up evaluation, no patients died of esophageal adenocarcinoma. Four patients developed cancer, 3 of whom continue with ablation therapy. The fourth patient died of unrelated causes. A single esophageal perforation was the only significant adverse event attributable to therapy. No esophageal strictures occurred and patients returned to normal activity after 24 hours in the majority of cases. Patients who received Argon ablation showed no difference in survival to that of the general population. CONCLUSIONS: Argon beam ablation for high-grade dysplasia in Barrett's esophagus is an effective and safe treatment, especially in patients unfit for surgical resection.     

Barrett's esophagus. Prevalence and incidence of adenocarcinoma

Between January 1973 and January 1989, 241 patients with Barrett's esophagus were treated at the Lahey Clinic Medical Center, Burlington, Mass. Of these patients, 65 presented with adenocarcinoma in Barrett's esophagus for a prevalence rate of 27%. Of 176 patients followed up for a total of 497 patient-years, adenocarcinoma developed in five patients for an incidence of one per 99 patient-years. The development of adenocarcinoma during endoscopic surveillance 1, 2, 2, 4, and 10 years after the initial diagnosis of Barrett's esophagus emphasizes the importance of long-term endoscopic and histologic surveillance. All five patients had severe dysplasia before adenocarcinoma developed. Yearly endoscopic follow-up examination is recommended for all patients with Barrett's esophagus unless mild dysplastic changes are found, in which case surveillance should be increased. Patients with severe dysplasia who are otherwise acceptable candidates for operation should be advised to have esophageal resection.     

Adenocarcinoma arising in Barrett's esophagus

The main goal of this study was to evaluate the development of adenocarcinoma in patients with Barrett's esophagus. During the period from January 1975 to December 1985, a total of 134 patients had endoscopically severe esophagitis and/or Barrett's esophagus. In these patients, 32 (24%) met the macroscopic and histologic criteria for the diagnosis of Barrett's esophagus. A check-up study of these patients was performed in 1987. Adenocarcinoma developed in three patients during the follow-up period of 166.1 patient-years. Dysplasia in the columnar epithelium was found in two of these patients six and 15 months before the diagnosis of adenocarcinoma. The third patient with adenocarcinoma was detected in endoscopic follow-up in 1987. In addition, the endoscopic examination showed unchanged Barrett's epithelium in all but three patients despite the operative and/or medical treatment 3–12 years (mean 6.7 years) earlier. We conclude that Barrett's esophagus is a potential premalignant condition and careful endoscopic surveillance for dysplasia in the columnar epithelium of the distal esophagus is mandatory in patients with Barrett's esophagus.