Carcinoma of the Esophagus and Achalasia
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1 Carcinoma of the Esophagus and Achalasia Juan C. Bolivar, M.D., and Thomas L. Herendeen, M.D. A lmost a century has elapsed since Fagge [5] originally reported in 1872 the association of carcinoma of the esophagus with achalasia. Esophageal cancer continues to develop occasionally in this longstanding benign disease. It tends to be diagnosed late in the majority of cases. The resultant delay in treatment is responsible for the small incidence of resectability and curability of this cancer. It is our purpose to report such a case and to review the pertinent literature. The case is one of epidermoid carcinoma occurring in association with achalasia, treated successfully with preoperative xray therapy, esophagectomy, and transverse colon interposition, and followed for three years. A 52yearold construction worker first entered the hospital in 1950 with dysphagia and postprandial regurgitation. The diagnosis of achalasia was established. Partial symptomatic relief resulted from hydrostatic esophageal dilatation. After one year the patient was lost to followup until he returned with similar symptoms sixteen years later. His complaints at this time were dysphagia, persistent mild substernal pain, postprandial regurgitation exacerbated by the supine position, and a loss of 25 pounds in weight during the previous seven months. Roentgenograms revealed a large esophagus that projected into the right hemithorax (Fig. 1) with two separate areas of narrowing, a long annular constriction in the lower third of the esophagus, and a smooth tapering at the cardioesophageal junction (Fig. 2). Obstruction to the flow of barium was nearly complete. Subsequent esophagoscopy and biopsy 37 cm. from the upper incisor teeth established the diagnosis of epidermoid carcinoma of the esophagus. Preoperative evaluation failed to demonstrate any gross hepatic dysfunction or pulmonary involvement. The colon was found to be suitable for esophageal rep!acement. Xray therapy was administered to the tumor with a total dose of 2,000 rads in three days H61. Three days later the abdomen was explored through a midline abdominal incision. There were no detectable intraabdominal metastases nor any direct extension of the tumor. A suitable length of transverse colon was prepared for interposition between the stomach and the cervical esophagus in an antiperistaltic fashion. A right thoracotomy was then carried out to evaluate resectability. In spite of its large size the carcinomatous esophagus was freely movable. The entire thoracic esophagus and gastric fundus were removed. The colon was then drawn through the right chest and anastornosed end to end to the cervical esophagus through a third incision on the neck. A pyloroplasty, gastrostomy, and tube cecostomy were performed. From the Surgical Service, Veterans Administration Hospital, and the Department of Surgery, Indiana University Medical Center, Indianapolis, Ind. Accepted for publication Jan. 21, Address reprint requests to Dr. Bolivar, Department of Surgery, Indiana University Medical Center, Indianapolis, Ind VOL. 10, NO. 1, JULY,
2 FIG. 1. Bariumcontrast roentgenogram of the esophagus with an extensive filling defect of the lower middle third. A wedge of the right lower lobe of the lung, which was adherent to the esophagus in the area of the tumor, was removed with the specimen. Microscopic examination of this tissue demonstrated it to be free of cancer. The gross length of the esophageal carcinoma was 11.5 cm. Both the proximal and distal ends of the resected esophagus were free of microscopically detectable cancer. A single positive metastatic node was found in the tissue immediately adjacent to the carcinoma. Satisfactory continuity of the interposed colon was demonstrated by barium contrast roentgenography on the fourth postoperative day, and thereafter the patient was given graduated oral feedings. With the exception of a prolonged spontaneous closure of the cecostomy site and a seroma in the chest incision, the postoperative course was uneventful. The patient was discharged on the twentysecond postoperative day. 82 THE ANNALS OF THORACIC SURGERY
3 CASE REPORT: Cancer of Esophagus and Achalasia FIG. 2. Bariumcontrast roentgenogram with the smooth narrowing of the achalasia at the supradiaphragmatic level. Twentyeight months after esophagectomy the patient had an acute obstruction of the small bowel due to adhesions. No gross evidence of intraabdominal metastasis was found at the time of lysis of adhesions. Followup of this patient for three years has not revealed any significant problem. The cervical anastomosis has maintained an adequate lumen without dilatation (Fig. 3). The patient has eaten a regular diet and has maintained his postoperative weight. COMMENT Published series of patients with achalasia were reviewed to determine the incidence of associated carcinoma of the esophagus (Table). The reported incidence varies widely depending upon whether the data were obtained during the life of the patient or at autopsy. The frequency of occurrence of carcinoma in achalasia as determined clinically varies from 0 to 7.7% [la4, 9, 1113]. In sharp contradistinction to this rather infrequent association of the two diseases is the significantly higher incidence of from 20 to 29% [4, 9, 131 found at autopsy of patients who died with achalasia. The low clinical incidence may be due to relatively shorter duration of the achalasia at the time of observation and reporting in some instances as well as to failure to ascertain the cause of death of an appreciable number of patients in some reports, VOL. 10, NO. 1, JULY,
4 BOLIVAR AND HERENDEEN A FIG. 3. Bariumcontrast roentgenographic study of the transverse colon interposed between the cervical esophagus and stomach as it appears (A) 1 year and (B) 3 years following esophagectorny. B notably those of Plummer and Vinson [191 and Vinson [24]. Conversely, the high incidence of carcinoma in the autopsy series may be due to necessary hospitalization of these patients for symptoms caused by the malignancy. If the true incidence lies between the extremes represented by the two types of reports, the possibility of carcinoma in patients with achalasia remains a serious consideration. In 60 of 79 patients reviewed in this report [7, 9, 10, 22, 231 the 84 THE ANNALS OF THORACIC SURGERY
5 CASE REPORT: Cancer of Esophagus and Achalasia Author Plummer & Vinson [19] Vinson [241 Rake [21] Kay [111 Lawrance [I21 Ellis [41 INCIDENCE OF CARCINOMA OF THE ESOPHAGUS AND ACHALASIA Barlow [l] Le Roux [131 CamaraLopez [31 Barrett [la] Belsey [21 JustViera et al. [91 No. No. with with Incidence Acha Carci Clinical Autopsy Year lasia noma (%) (%) "Fifteen patients died of unknown causes. btwelve patients died of unknown causes Ob temporal relationship between the onset of symptoms of achalasia and the diagnosis of carcinoma is specified. The average interval is 20 years and the average age at diagnosis of cancer is 52 years, 10 years earlier than in patients without achalasia [23]. In 167 patients reported in the literature of Western Europe and the western hemisphere the average age at which carcinoma was discovered was 48 years [8]. The relative incidence between sexes of carcinoma of the esophagus (72% in men and 28% in women) [8, 201 is not basically altered by its association with achalasia. In 62 of 79 patients the sex was specified: 49 were men and 13 were women. The incidence of carcinoma of the esophagus with achalasia appears to be very low in Negroes in the reported series [S]. Achalasia does not modify the distribution of carcinoma found in the otherwise normal esophagus: 16% in the upper third, 47% in the middle, and 37% in the lower third [la, 201. The level of the lesion in the esophagus was stated in 63 of the 79 cases reviewed: upper third in 8, middle third in 33, and lower third in 22 (Fig. 4). Carcinoma of the esophagus is more commonly associated with the saccular type than with the fusiform type of dilatation caused by achalasia. It is usually described as being extensive and cauliflower in form [8]. It is usually epidermoid, although an occasional adenocarcinoma has been reported. VOL. 10, NO. I, JULY,
6 BOLIVAR AND HERENDEEN 75 7WITHOUT ACHALASIA 0 1 UPPER THIRD I [MIDDLE THIRD I LLOWER THIRD 1 FIG. 4. Zncidence by location of carcinoma of the esophagus in patients with and without achalasia. In 76 patients in whom histology of the tumor was mentioned, squamous cell carcinoma occurred in 68, adenocarcinoma in 7, and undifferentiated carcinoma in 1. The tumor has a marked tendency to invade the submucosa, spreading for great lengths of 11 to 19 centimeters [8]. Chronic irritation of the esophageal mucosa produced by the stasis and inflammation occurring in achalasia has commonly been suggested as a predisposing factor in the development of this carcinoma [12, 14, 241. In a series of 90 patients with endemic South American megaesophagus treated with a subtotal esophagectomy, 7 had an associated carcinoma of the esophagus and 21 had leukoplakia of the esophagus [8]. Since the majority of carcinomas are located in the middle third of the esophagus and maximum inflammation and irritation are observed in the distal third close to the cardia, it is difficult to accept this as a complete explanation. Furthermore, the reduction of stasis after an esophagocardiomyotomy does not prevent subsequent development of carcinoma. Several cases have been observed in which the lesion developed years after a Heller s operation for achalasia [la, 2, 810]. Delayed diagnosis is the most disturbing finding in these cases [la3, 6, 7, 9, 10, 13, 22, 231. There are several reasons for this delay. 86 THE ANNALS OF THORACIC SURGERY
7 CASE REPORT: Cancer of Esophagus and Achalasia Since the esophagus is already partially obstructed, any change in preexisting symptoms is subtle. The cardinal manifestation of superimposed cancer, unremitting dysphagia, appears late unless the tumor occurs in the distal third. A history of blood in regurgitated material should suggest the cancer, as should the development of weight loss, anemia, and increasing dysphagia. Once cancer is suspected, confirmatio,n of the diagnosis may be difficult because of secondary inflammation and edema and retention of food. These changes hinder endoscopic visualization and obscure the radiological signs of an early neoplasm. In 57 patients with achalasia of the esophagus complicated with carcinoma who are included in one of the most recent collective reviews [81, the esophagogram was falsely interpreted as being negative for malignancy in 18 patients. A thorough esophageal lavage should always precede radiological and endoscopic examination. The presence of tumor may be overlooked even after thorough preparation. Esophagoscopy performed in 46 patients with achalasia and carcinoma of the esophagus reported a false negative diagnosis in 12 patients C81. Despite its limitations, however, esophagoscopy should be performed yearly in all patients with longstanding achalasia. Cytological examination has been recommended as being of great value in excluding associated malignancy in patients with benign lesions whose radiological and esophagoscopic findings are equivocal [ 141. There is nothing to suggest that treatment of carcinoma of the esophagus with and without achalasia should differ. The surgical literature [15, ls] presents data indicating that in patients who are considered good surgical risks, a preoperative course of radiation therapy followed by esophagectomy and proper interposition procedure may offer better functional results than radiation or surgical therapy alone, as well as improved survival [1518, 251. The prognosis when these two diseases are associated is poor. The longest survival recorded in 5 patients with achalasia and carcinoma of the esophagus treated by irradiation alone was nine months [8]. In 30 cases reported in English publications prior to 1961 [23], no radical surgery was possible because of the advanced stage of the cancer. Duration of survival was stated in 14 patients: 13 died within six months after diagnosis; only 1 patient survived a year. Among 49 cases collected in the present review covering the period from 1961 to 1968 [la3, 6, 7, 9, 10, 13, 22, 231, 19 had palliative procedures and 7 had a curative esophagectomy. The time of death was stated for 16 patients: 10 died within six months after operation, 4 died within one year, and 2 survived at least two years and five months. One patient was living (at the time of being reported) in 1967 [9]. The second patient, reported here, is living three years and three months after esophagectomy. VOL. 10, NO. 1, JULY,
8 BOLIVAR AND HERENDEEN SUMMARY A 52yearold man with achalasia who had been asymptomatic for 16 years following treatment by dilatations developed unremitting dysphagia and weight loss of 25 pounds over a sevenmonth period. An esophagogram and esophagoscopy revealed an intrinsic carcinoma of the lower third of the esophagus. A onestage esophagectomy with interposition of the transverse colon was done after a concentrated course of xray therapy. The patient remains asymptomatic and free of detectable recurrence of cancer three years after treatment. Review of 79 published cases shows that this combination of lesions is characterized by delayed diagnosis, low resectability rate, and short survival. Early diagnosis can be achieved only by periodic radiological, endoscopic, and cytological examinations in patients with achalasia. REFERENCES 1. Barlow, D. Problems of achalasia. Brit. J. Surg. 48:642, la. Barrett, N. R. Achalasia of the cardia: Re,flections upon a clinical study of over 100 cases. Brit. Med. J. 1:1135, Belsey, R. Functional disease of the esophagus. J. Thorac. Cardiovasc. Surg. 52:164, CamaraLopez, L. H. Carcinoma of the esophagus as complication of megaesophagus: Analysis of seven cases. Amer. J. Dig. Dis. 6:742, Ellis, F. G. Natural history of achalasia of the cardia. Proc. Roy. SOC. Med. 53:663, Fagge, C. H. A case of simple stenosis of the esophagus followed by epithelioma. Guy. Hosp. Rep. 17:413, Cited by J. F. Crenshaw and R. J. Booher in Achalasia of the cardia with esophageal carcinoma. Gastroenterology 25:385, Gautman, H. P. Esophageal carcinoma following achalasia. Brit. J. Dis. Chest 60:208, Hessler, C. Carcinoma of the esophagus and achalasia. J. Einstein Med. Cent. 11:19, JustViera, J. O., and Haight, C. Achalasia and carcinoma of the esophagus. Surg. Gynec. Obstet. 128:1081, JustViera, J. O., Morris, J. D., and Haight, C. Achalasia and esophageal carcinoma. Ann. Thorac. Surg. 3:256, Katz, R. L., and Hughes, R. K. Carcinoma of the esophagus in association with achalasia. Dis. Chest 46:235, Kay, E. B., and Cross, F. S. Chronic esophagitis: Possible factor in the production of cancer. A.M.A. Arch. Intern. Med. 98:475, Lawrance, K., and Shoesmith, J. H. Review of treatment of cardiospasm. Thorax 14:211, Le Roux, B. T., and Wright, J. T. Cardiospasm. Brit. J. Surg. 48:619, MacDonald, W. C., Brandborg, L. L., Taniguchi, L., and Rubin, C. E. Esophagus exfoliative cytology. Ann. Intern. Med. 59:332, Millburn, L., Faber, L. P., and Hendrikson, F. R. Curative treatment of epidennoid carcinoma of the esophagus. Amer. J. Roentgen. 103:291, Nakayama, K. Concentrated preoperative irradiation therapy. Arch. Surg. (Chicago) 87: 1003, Nakayama, K. Treatment of patients with carcinoma of the esophagus. J. Clin. Radiol. 15:232, THE ANNALS OF THORACIC SURGERY
9 CASE REPORT: Cancer of Esophagus and Achalasia Parker, E. F., and Gregoire, H. B. Combined radiation and surgical treatment of carcinoma of the esophagus. Ann. Surg. 161:710, Plummer, H. S., and Vinson, P. P. Cardiospasm: A report of 301 cases. Med. Clin. N. Amer. 5:355, Postlethwait, R. W., and Sealy, W. C. Surgery of the Esophagus. Springfield, 111.: Thomas, P Rake, G. Epithelioma of the esophagus in association with achalasia of the cardia. Lancet 26:682, Seaman, W. B., Wells, J., and Flood, C. A. Diagnosis problems of esophageal cancer: Relationship to achalasia and hiatus hernia. Amer. J. Roentgen. 90:778, Tanner, N. C., and Smithers, D. W. (Eds.). Tumors of the Esophagus. Edin ~~ burgh: Livingstone, Vinson, P. P. Wilkins, E. W., Jr Treatment of cardiospasm. Southern Med. J. 23:243, Cancer of the esophagus: Recent progress. CA 18:227, Editor s Note: The authors experience does suggest that the increased incidence of esophageal carcinoma in patients with achalasia is real. The early diagnosis of this cancer is dificult, and the presence of achalasia complicates the problem. If there is a causeandeflect relationship between these two disorders, it would seem desirable to advocate early surgical correction of the achalasia in the hope that the development of esophageal carcinoma might he prevented, rather than to rely upon diagnosis of the carcinoma while it is still at a stage in its development when curative excision may be possible. VOL. 10, NO. 1, JULY,
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