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The association of carcinoma of the esophagus with achalasia
The association of carcinoma of the esophagus with achalasia Among 156 patients with achalasia who were treated during a 13 year period, two developed squamous cell carcinoma of the esophagus. The first, a 33-year-old man, developed a carcinoma of the upper third of the esophagus 2 years after the onset of symptoms of achalasia. He was treated by a Heller myotomy and radiation therapy and survived 16.7 months. The second, a 60-year-old man, had had symptoms of achalasia for 15 years. He is alive with suspected recurrence 6 months after undergoing esophagogastrectomy for a carcinoma of the middle and lower thirds. A summary of the literature regarding carcinoma complicating achalasia is presented. This indicates that carcinoma arises in at least 1 to 7 per cent of patients with achalasia. Delay in diagnosis is common. The treatment need not differ from that of carcinoma without achalasia, but the prognosis is dismal. Since there is evidence that retention esophagitis is a premalignant condition, it should be possible to prevent the development of carcinoma in achalasia by early cardiomyotomy in cases in which hydrostatic dilatation is not completely effective. A plea is made for closer surveillance of patients with achalasia so that, if carcinoma supervenes, it may be detected at an early stage.
John R. Hankins, M.D., and Joseph S. McLaughlin, M.D., Baltimore, Md.
Ihe occurrence of carcinoma of the esophagus in a patient with achalasia was first described by Fagge7 in 1872. Since then, the association of the two diseases has been mentioned sporadically in the literature, but only comparatively recently have reports appeared suggesting that the development of the two diseases in the same patient is more than coincidence.'• -'■4li- I0"15, During the past 13 years, 156 patients have been treated for achalasia at the University of Maryland Hospital. Two of these developed carcinoma of the esophagus. Case reports C A S E 1. A 33-year-old black man was admitted for evaluation of dysphagia complicated by hematemesis and melena. The dysphagia had begun suddenly 2 years previously. Shortly after the onset of symptoms he was admitted to another hospital where the diagnosis of cardiospasm was From the Division of Thoracic and Cardiovascular Surgery, University of Maryland School of Medicine, Baltimore, Md. 21201. Received for publication Aug. 9, 1974.
made on the basis of esophagography and esophageal motility studies. He was treated by a single pneumostatic dilatation. This relieved his symptoms for almost 2 years—until about 2 weeks prior to the present admission. At this time dysphagia recurred, accompanied by heartburn, a substernal sensation of fullness, and regurgitation. Hematemesis and melena developed on the day prior to admission. The patient vomited half a basinful of blood on four occasions. Physical examination was not remarkable except for enlargement of the liver, which was palpable 4 cm. below the right costal margin, and the presence of tarry stool in the rectum. The hemoglobin was 14.2 Gm. and the hematocrit, 42 per cent. Esophagograms (Fig. 1) showed marked dilatation of the entire esophagus with tapering of the lower end compatible with achalasia. Esophagoscopy shortly after admission showed no definite source of the bleeding, but an ulcer with ragged borders was visible on the anterior wall of the esophagus at the 20 to 22 cm. level. Biopsy showed squamous cell carcinoma. It should be noted that the ulcerated tumor had not been demonstrated on the initial esophagograms; however, on a subsequent esophagogram, when it was specifically sought, a small area of irregularity was noted on the anterior wall of the esophagus at the level of the suprasternal notch. On a regimen of milk and antacids, the gastro-
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The Journal of
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Thoracic and Cardiovascular Surgery
Fig. 1. Case 1. Esophagogram shows the characteristic megaesophagus of achalasia. The small carcinoma in the upper third of the esophagus is not demonstrated.
Fig. 2. Case 2. Esophagogram just prior to admission demonstrates a dilated esophagus typical of achalasia. It contains an ulcerating neoplasm at the junction of the middle and lower thirds.
intestinal bleeding subsided. Two weeks following admission, a transthoracic Heller procedure was performed. No evidence of metastasis from the esophageal carcinoma was found in the left hemithorax. The patient's convalescence was relatively uneventful. Radiotherapy was administered to the upper esophagus and mediastinum to a dose of 6,650 rads over a period of 6 weeks, beginning 8 days after operation. Thereafter, the patient gained weight and remained relatively asymptomatic for 15 months. At that time, substernal pain and dysphagia recurred. Recurrence of tumor in the mid-esophagus was found on both esophagography and esophagoscopy. A later esophagogram revealed a mediastinal abscess communicating with the esophagus. Keflex was given and a gastrostomy performed. However, his condition continued to deteriorate, and the patient died at home 3 weeks later. He had survived 16.7 months from the beginning of radiation therapy. CASE 2. A 60-year-old white man was admitted with the complaint of dysphagia of 10 to 15 years' duration. During the 4 to 5 months prior to admission, his symptoms worsened and were accompanied by epigastric pain, nausea, regurgitation, hematemesis, and melena. He had lost 20 pounds in weight. Several esophagograms in years past had been reported as showing
"cardiospasm." A more recent esophagogram (Fig. 2) taken just prior to admission demonstrated an ulcerating neoplasm at the junction of the middle and lower thirds of the esophagus in addition to the megaesophagus characteristic of achalasia. Esophagoscopy and biopsy of this lesion established the diagnosis of squamous cell carcinoma. Physical examination revealed no abnormalities except for a systolic murmur at the cardiac apex, believed to be hemodynamically insignificant. Initial laboratory studies were within normal limits. The hemoglobin level was 13.4 Gm. and the hematocrit, 38.8 per cent. Repeat esophagoscopy confirmed the presence of a dilated esophagus with a fungating, necrotic, ulcerating circumferential lesion beginning 32 cm. from the incisors. An esophagogastrectomy was performed through a left thoracotomy, with resection of the distal two thirds of the esophagus and the proximal stomach. No gross tumor was left behind. The anastomosis was carried out deep to the aortic arch. Pathological examination of the specimen revealed a large pedunculated ulcer measuring 7 by 6 cm. in the distal esophagus (Fig. 3). Microscopically, this was a well-differentiated squamous cell carcinoma involving mainly the submucosa and invading the muscular wall only superficially, with no involvement of the periesophageal tissues. The proximal and distal resection margins were free of tumor. No metastasis was seen in any of
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seven periesophageal lymph nodes. In addition, there was marked submucosal edema and chronic esophagitis in the distal third of the esophagus, with absence of ganglia. The patient's postoperative course was smooth. At the time of discharge he reported that he was swallowing better than he had for 15 years. Five months after the operation he developed abdominal distress and weight loss. A gastrointestinal x-ray series showed persistent pyloric spasm. Laparotomy with pyloroplasty was performed. During this operation a mass was palpated adjacent to the body of the pancreas. The lesion appeared to represent lymph node metastasis, although it was not biopsied. The patient was given radiation therapy to this area. At the time of last follow-up he was alive but with evidence of recurrence 6 months after the resection.
Discussion Williams22 in 1956 reviewed the literature and was able to find only 28 cases of esophageal carcinoma complicating achalasia. He concluded that achalasia did not appear to predispose to malignancy. However, a number of other authors, beginning with Rake 17 in 1931, have emphasized that there is an increased incidence of carcinoma of the esophagus in achalasia. Rake found clinically undetected carcinomas in 3 of 15 patients who died from achalasia. In a majority of his cases, examination of the esophagus revealed diffuse mucosal inflammation and ulceration corresponding to the height of the column of stagnating food. In some cases he also observed attempts at healing of the ulceration in the form of epithelial overgrowths or papillomas. These he believed to represent an intermediate stage in the response of the esophageal mucosa to repeated chronic irritation from putrifying food material, the end stage being carcinoma. Actually Guisez8 in 1919 had called attention to the major role played by stasis in the supervention of malignancy in achalasia. Further evidence for the hypothesis that the retention esophagitis of achalasia is a premalignant condition was presented by Camara-Lopes.5 He found leukoplakia of the esophageal mucosa in all 7 of the patients with esophageal carcinoma whom he encountered among 90 cases of achalasia. Reviews of the literature were published
Fig. 3. Case 2. Photograph of the resected specimen, which has been opened longitudinally to show the ulcerated carcinoma. The proximal end of the specimen lies to the left. There is marked dilatation of the esophagus at this level.
by Just-Viera and Haight11 in 1969 and by Bolivar and Herendeen4 in 1970. Most of the reports reviewed by the above authors cite an incidence of 1 to 7.7 per cent in cases in which the diagnosis was made clinically; the incidence was 20 to 29 per cent when the carcinoma was found at autopsy in patients dying with achalasia. The present report analyzes 78 cases reported since the above reviews were published.1' 4 - ,; ' ,2"ls- ,s ' 20' 21 - 23 Fifty-one are from series in which the per cent incidence of carcinoma in achalasia was given (Table j)_i. o, la, i3, is. 2i, 23 jjjg w ide variation in the incidence reported by various authors is probably related to differences in the length of follow-up of patients with achalasia. Symptoms of achalasia are present on the average for 20 years before the diagnosis of carcinoma is made.4 Even so, the average age at which cancer was diagnosed in achalasia patients was 4 8 u to 52 years,4 which is 10 to 14 years younger than in persons without achalasia. In the present review, this temporal relationship was stated in 45 cases. The average interval was identical to that reported by Bolivar and Herendeen 4 —20
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Table I
Author
Year
No. of cases of achalasia
Debray et al.° Akuamoa 1 Lortat-Jacob et al.™ Pierce et al. , ! i Lagache et al. 1 Wychulis et
1968 1969
62 101
1969 1970 1970
279 110
al.2:* Triadu Castell 2 1
1971 1973
1,318 33
53
No. with carcinoma 8* 3
Per cent incidence 6.4 3.0
24 3 5
8.6 2.7 9.4
13t 5
0.53 15.2
•Four of these 8 cases came from other hospitals. Of the 62 patients with achalasia treated by the authors, only 4 (6.4 per cent) developed carcinoma. tSeven of these patients came from the group of 1,318 achalasia cases treated during a 32 year period, an incidence of 0.53 per cent or 41 cases per year per 100,000. The other 6 patients had their initial treatment for achalasia before this time period or elsewhere.
years. However, the average age at diagnosis of carcinoma was greater—55 years. Although achalasia is commoner in women, carcinoma complicating achalasia is more common in men by a ratio of 78 men to 28 women, or 2.8:l. 1 1 In the present review, of a total of 49 cases in which the sex was stated, 45 were men and 4 were women. The disease is apparently rare in Negroes. Just-Viera and Haight,11 in their review, were able to find only 5 cases in this race. In view of the foregoing, Case 1 is unusual in several respects. The man was only 33 years of age when carcinoma was diagnosed, and symptoms of achalasia had been present for only 2 years. Even more noteworthy is the fact that he was a Negro. Another unusual aspect of Case 1 is the fact that the tumor was in the upper third of the esophagus. Carcinomas in the otherwise normal esophagus are located as follows: 16 per cent in the upper, 47 per cent in the middle, and 37 per cent in the lower third.10 However, in recent collective reviews4, n of carcinoma complicating achalasia, there was a slightly greater incidence of middle third lesions and a slightly lower incidence of upper and lower third lesions than is the case in carcinoma with-
out achalasia. Just-Viera and Haight,11 in reviewing 109 cases in which the location was stated, found the following distribution: upper third, 4 cases (3.7 per cent); middle third, 56 cases (51.4 per cent); lower third, 42 cases (38.5 per cent); and more than one segment, 7 cases (6.4 per cent). AH nine carcinomas reported by Belsey 2,3 were in the middle third. In our review, the location of the tumor was specified in 70 cases. The distribution was as follows: upper third in 12, middle third in 23, lower third in 32, and both middle and lower thirds in 3 cases. Carcinoma is more commonly seen in the saccular than in the fusiform type of esophageal dilatation produced by achalasia.4 It frequently extends for great lengths along the esophagus and is often cauliflower in shape, as in Case 2. As regards cell type, our 2 cases were typical in that both tumors were squamous cell carcinomas. Of 77 cases reviewed by Just-Viera and Haight,11 68 were squamous cell carcinoma, 7 adenocarcinoma, 1 an undifferentiated carcinoma, and 1 a carcinosarcoma. Of the 60 cases covered by our review in which the histology of the neoplasm was described, 56 were squamous cell carcinoma and 4 were adenocarcinoma. The diagnosis is frequently delayed. The delay occurs because patients with prolonged swallowing difficulty tend to attribute any change in symptoms to their pre-existing disease, and the alteration in symptoms when carcinoma supervenes may be subtle. Weight loss and a return of, or an increase in, dysphagia are the most common harbingers of malignant change.1 '• 1:> LortatJacob and colleagues13 found blood-stained regurgitation or hematemesis to be the second most prevalent and retrosternal or back pain to be the third most common symptom of malignancy. In this respect both cases presented here are typical, for both patients had renewed or increased dysphagia, hematemesis, and substernal or epigastric discomfort. Delay by the patient is frequently compounded by delay on the part of the physician in making the diagnosis. Even a rela-
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tively large growth may be overlooked on esophagography in an esophagus which is dilated and partly filled with retained food. Esophagoscopy as a means of diagnosing the tumor is limited by these same factors. The small carcinoma of the upper third in Case 1 was missed on two esophagograms and was noted on a third only when it was specifically sought after having been found during esophagoscopy. It is perhaps fortunate that the fiberoptic esophagoscope was used. The lesion might have been missed if the rigid esophagoscope has been employed. Fewer lesions would be missed by these diagnostic procedures if the patient were given only clear liquids for several days and the esophagus thoroughly irrigated through a large-bore tube just prior to the examination. In addition, esophagography must include films taken in the Trendelenburg position. Cytologic study of esophageal secretions and washings, although not needed to make the diagnosis in the 2 cases presented here, is a valuable addition to the diagnostic armamentarium. Such studies have proved positive in some instances in which all other studies were negative.11 The management of carcinoma complicating achalasia is in most instances the same as for carcinoma without achalasia. In 1969, having become dissatisfied with the results from a combined irradiation-resection regimen, we" adopted a philosophy of palliation in the treatment of patients with esophageal carcinoma. With this philosophy the primary goal is restoration of swallowing ability, with cure an important but secondary consideration. Radiation therapy has become the primary mode of treatment for lesions of the upper third, because experience has shown that long-term survival and even cure are possible by this method. Esophagogastrectomy is the method of choice for lesions of the middle and lower thirds. No attempt is made to perform a radical tumor resection or lymph node dissection. Postoperative radiotherapy is given for middle third lesions in cases in which small amounts of tumor have been left behind in the mediastinum. Since adoption of
this approach, the quality of life of the patients so treated has improved greatly, the hospital mortality rate has decreased to well below 10 per cent, and survival rates promise to be as good as, or better than, those achieved under our former regimen. Following this philosophy, we treated patient 1 by radiation therapy and achieved 16 months of satisfactory palliation. Since his achalasia had been inadequately controlled, a Heller procedure was also performed. Case 2 was managed by esophagogastrectomy, which thus far has provided satisfactory palliation. Judging from the literature, the prognosis for carcinoma with achalasia is worse than for carcinoma without achalasia, probably because of delayed diagnosis. Only one 5 year survivor has been recorded thus far,11 although a few patients have been reported to be alive and without evidence of disease after 2 or 3 years. Of 38 surgically treated patients reviewed by Just-Viera and Haight,11 only 6 underwent esophagogastrectomy, 1 of whom also received radiation therapy. There were two postoperative deaths. The remaining 4 patients were alive at intervals of 3 months to 2'/i years after operation. Of the 78 cases reported since the review by Just-Viera and Haight11 in 1969, the type of treatment used was described in 63. Twenty-seven patients were considered unsuitable for operation. Eleven of these were treated by radiotherapy, 1 of whom survived a little over 1 year. Surgical exploration was performed in 36 patients, and resection was possible in 22. There were six postoperative deaths. One patient was reported to be alive at 3 years and another at 2 years. Four others were alive after much shorter or unspecified intervals. The remainder have died, 1 after surviving 26 months, another 25 months, and all the others less than 18 months. In view of our poor ability to cure the disease once it has become symptomatic, more attention should be directed toward both prevention and earlier detection. If the chronic esophagitis resulting from stasis predisposes to malignant change, as the evi-
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dence seems to indicate, then relief of stasis early in the course of achalasia should prevent the development of carcinoma. It is recommended that a Heller cardiomyotomy be performed promptly in patients with achalasia in whom hydrostatic dilatation has not completely relieved cardial obstruction. If the Heller myotomy is not thorough or if it is carried out after megaesophagus has already developed, it may not prevent the development of carcinoma. Two of BelseyV patients developed malignant degeneration 2 and 5 years after a successful Heller operation. Earlier detection should be possible if physicians treating patients with achalasia maintain them under close surveillance. Esophagography, esophagoscopy, and cytologic studies should be performed at yearly intervals and even more frequently if there is a change in symptomatology. REFERENCES
CARDIOVASC. SURG. 59: 335,
1 Akuamoa, C : Achalasia Esophagi and Associated Diseases, Acta Chir. Scand. 135: 421, 1972. 2 Belsey, R.: Functional Disease of the Esophagus, J.
3 4
5
6
7
8
THORAC.
de l'oesophage, Gaz. Hop. Par. 92: 479, 1919. 9 Hankins, J. R., Cole, F. N., Ward, A., Carter, E. A., Weiner, S., and McLaughlin, J. S.: Carcinoma of the Esophagus: The Philosophy for Palliation, Ann. Thorac. Surg. 14: 189, 1972. 10 Just-Viera, J. O., Morris, J. D., and Haight, C : Achalasia and Esophageal Carcinoma, Ann. Thorac. Surg. 3: 526, 1967. 11 Just-Viera, J. O., and Haight, C : Achalasia and Carcinoma of the Esophagus, Surg. Gynecol. Obstet. 128: 1081, 1969. 12 Lagache, G., Combemale, B., and El Hassar, S.: Une statistique de 53 operations de Heller pour megaoesophage idiopathique, Lille Med. 15: 647, 1970. 13 Lortat-Jacob, J. L., Richard, C. A., Fekete, F., and Testart, J.: Cardiospasm and Esophageal Carcinoma: Report of 24 Cases, Surgery 66: 969, 1969. 14 MacDonald, J. B., Waissbluth, J. G., and Langman, M. J. S.: Carcinoma of the Oesophagus and Gastric Surgery, Lancet 1: 19, 1971. 15 Pierce, W. S., MacVaugh, J., and Johnson, J.: Carcinoma of the Esophagus Arising in Patients With Achalasia of the Cardia, J. THORAC.
CARDIOVASC. SURG. 52:
164,
1966. Belsey, R.: Recent Progress in Oesophageal Surgery, Acta Chir. Belg. 7 1 : 230, 1972. Bolivar, J. C , and Herendeen, T. L.: Carcinoma of the Esophagus and Achalasia, Ann. Thorac. Surg. 10: 81, 1970. Camara-Lopes, L. H.: Carcinoma of the Esophagus as a Complication of Megaesophagus: An Analysis of Seven Cases, Am. J. Dig. Dis. 6: 742, 1961. Debray, C , Leymarios, J., Etienne, J.-P., and Cuq, J.-P.: Les cancers developpes sur megaoesophage idiopathique, Arch. Fr. Mai. App. Dig. 57: 5, 1968. Fagge, C. H.: A Case of Simple Stenosis of the Oesophagus, Followed by Epithelioma, Guys Hosp. Rep. 17: 413, 1872. Guisez, J.: De la frequence des stenoses spasmodiques graves et de la precocite du cancer
1970.
16 Postlethwait, R. W., and Sealy, W. C : Surgery of the Esophagus, Springfield, 111., 1961, Charles C Thomas, Publisher, p. 250. 17 Rake, G.: Epithelioma of the Oesophagus in Association With Achalasia of the Cardia, Lancet 2: 682, 1931. 18 Ribet, M., and Laget, J. P.: Cancer sur megaoesophage, Chirurgie 98: 632, 1972. 19 Santy, P., Michaud, P., and Viard, H.: Cancer sur megaoesophage, Lyon Chir. 54: 354, 1958. 20 Seliger, G „ Lee, T., and Schwartz, S.: Carcinoma of the Proximal Esophagus: A Complication of Long-Standing Achalasia, Am. J. Gastroenterol. 57: 20, 1972. 21 Triadu Castell, I.: Valoracion Diagnostica de la Disfagia. I. Megaesofago-Cancer Esofagico, Rev. Esp. Enferm. Apar. Dig. 39: 43, 1973. 22 Williams, J. L.: Carcinoma of the Oesophagus as a Complication of Achalasia of the Cardia, Thorax 11: 268, 1956. 23 Wychulis, A. R., Woolam, G. L., Andersen, H. A., and Ellis, F. H., Jr.: Achalasia and Carcinoma of the Esophagus, J. A. M. A. 215: 1638, 1971.
John R. Hankins, M.D., and Joseph S. McLaughlin, M.D., Baltimore, Md.
Ihe occurrence of carcinoma of the esophagus in a patient with achalasia was first described by Fagge7 in 1872. Since then, the association of the two diseases has been mentioned sporadically in the literature, but only comparatively recently have reports appeared suggesting that the development of the two diseases in the same patient is more than coincidence.'• -'■4li- I0"15, During the past 13 years, 156 patients have been treated for achalasia at the University of Maryland Hospital. Two of these developed carcinoma of the esophagus. Case reports C A S E 1. A 33-year-old black man was admitted for evaluation of dysphagia complicated by hematemesis and melena. The dysphagia had begun suddenly 2 years previously. Shortly after the onset of symptoms he was admitted to another hospital where the diagnosis of cardiospasm was From the Division of Thoracic and Cardiovascular Surgery, University of Maryland School of Medicine, Baltimore, Md. 21201. Received for publication Aug. 9, 1974.
made on the basis of esophagography and esophageal motility studies. He was treated by a single pneumostatic dilatation. This relieved his symptoms for almost 2 years—until about 2 weeks prior to the present admission. At this time dysphagia recurred, accompanied by heartburn, a substernal sensation of fullness, and regurgitation. Hematemesis and melena developed on the day prior to admission. The patient vomited half a basinful of blood on four occasions. Physical examination was not remarkable except for enlargement of the liver, which was palpable 4 cm. below the right costal margin, and the presence of tarry stool in the rectum. The hemoglobin was 14.2 Gm. and the hematocrit, 42 per cent. Esophagograms (Fig. 1) showed marked dilatation of the entire esophagus with tapering of the lower end compatible with achalasia. Esophagoscopy shortly after admission showed no definite source of the bleeding, but an ulcer with ragged borders was visible on the anterior wall of the esophagus at the 20 to 22 cm. level. Biopsy showed squamous cell carcinoma. It should be noted that the ulcerated tumor had not been demonstrated on the initial esophagograms; however, on a subsequent esophagogram, when it was specifically sought, a small area of irregularity was noted on the anterior wall of the esophagus at the level of the suprasternal notch. On a regimen of milk and antacids, the gastro-
355
The Journal of
356
Hankins and
McLaughlin
Thoracic and Cardiovascular Surgery
Fig. 1. Case 1. Esophagogram shows the characteristic megaesophagus of achalasia. The small carcinoma in the upper third of the esophagus is not demonstrated.
Fig. 2. Case 2. Esophagogram just prior to admission demonstrates a dilated esophagus typical of achalasia. It contains an ulcerating neoplasm at the junction of the middle and lower thirds.
intestinal bleeding subsided. Two weeks following admission, a transthoracic Heller procedure was performed. No evidence of metastasis from the esophageal carcinoma was found in the left hemithorax. The patient's convalescence was relatively uneventful. Radiotherapy was administered to the upper esophagus and mediastinum to a dose of 6,650 rads over a period of 6 weeks, beginning 8 days after operation. Thereafter, the patient gained weight and remained relatively asymptomatic for 15 months. At that time, substernal pain and dysphagia recurred. Recurrence of tumor in the mid-esophagus was found on both esophagography and esophagoscopy. A later esophagogram revealed a mediastinal abscess communicating with the esophagus. Keflex was given and a gastrostomy performed. However, his condition continued to deteriorate, and the patient died at home 3 weeks later. He had survived 16.7 months from the beginning of radiation therapy. CASE 2. A 60-year-old white man was admitted with the complaint of dysphagia of 10 to 15 years' duration. During the 4 to 5 months prior to admission, his symptoms worsened and were accompanied by epigastric pain, nausea, regurgitation, hematemesis, and melena. He had lost 20 pounds in weight. Several esophagograms in years past had been reported as showing
"cardiospasm." A more recent esophagogram (Fig. 2) taken just prior to admission demonstrated an ulcerating neoplasm at the junction of the middle and lower thirds of the esophagus in addition to the megaesophagus characteristic of achalasia. Esophagoscopy and biopsy of this lesion established the diagnosis of squamous cell carcinoma. Physical examination revealed no abnormalities except for a systolic murmur at the cardiac apex, believed to be hemodynamically insignificant. Initial laboratory studies were within normal limits. The hemoglobin level was 13.4 Gm. and the hematocrit, 38.8 per cent. Repeat esophagoscopy confirmed the presence of a dilated esophagus with a fungating, necrotic, ulcerating circumferential lesion beginning 32 cm. from the incisors. An esophagogastrectomy was performed through a left thoracotomy, with resection of the distal two thirds of the esophagus and the proximal stomach. No gross tumor was left behind. The anastomosis was carried out deep to the aortic arch. Pathological examination of the specimen revealed a large pedunculated ulcer measuring 7 by 6 cm. in the distal esophagus (Fig. 3). Microscopically, this was a well-differentiated squamous cell carcinoma involving mainly the submucosa and invading the muscular wall only superficially, with no involvement of the periesophageal tissues. The proximal and distal resection margins were free of tumor. No metastasis was seen in any of
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Association of esophageal carcinoma and achalasia
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seven periesophageal lymph nodes. In addition, there was marked submucosal edema and chronic esophagitis in the distal third of the esophagus, with absence of ganglia. The patient's postoperative course was smooth. At the time of discharge he reported that he was swallowing better than he had for 15 years. Five months after the operation he developed abdominal distress and weight loss. A gastrointestinal x-ray series showed persistent pyloric spasm. Laparotomy with pyloroplasty was performed. During this operation a mass was palpated adjacent to the body of the pancreas. The lesion appeared to represent lymph node metastasis, although it was not biopsied. The patient was given radiation therapy to this area. At the time of last follow-up he was alive but with evidence of recurrence 6 months after the resection.
Discussion Williams22 in 1956 reviewed the literature and was able to find only 28 cases of esophageal carcinoma complicating achalasia. He concluded that achalasia did not appear to predispose to malignancy. However, a number of other authors, beginning with Rake 17 in 1931, have emphasized that there is an increased incidence of carcinoma of the esophagus in achalasia. Rake found clinically undetected carcinomas in 3 of 15 patients who died from achalasia. In a majority of his cases, examination of the esophagus revealed diffuse mucosal inflammation and ulceration corresponding to the height of the column of stagnating food. In some cases he also observed attempts at healing of the ulceration in the form of epithelial overgrowths or papillomas. These he believed to represent an intermediate stage in the response of the esophageal mucosa to repeated chronic irritation from putrifying food material, the end stage being carcinoma. Actually Guisez8 in 1919 had called attention to the major role played by stasis in the supervention of malignancy in achalasia. Further evidence for the hypothesis that the retention esophagitis of achalasia is a premalignant condition was presented by Camara-Lopes.5 He found leukoplakia of the esophageal mucosa in all 7 of the patients with esophageal carcinoma whom he encountered among 90 cases of achalasia. Reviews of the literature were published
Fig. 3. Case 2. Photograph of the resected specimen, which has been opened longitudinally to show the ulcerated carcinoma. The proximal end of the specimen lies to the left. There is marked dilatation of the esophagus at this level.
by Just-Viera and Haight11 in 1969 and by Bolivar and Herendeen4 in 1970. Most of the reports reviewed by the above authors cite an incidence of 1 to 7.7 per cent in cases in which the diagnosis was made clinically; the incidence was 20 to 29 per cent when the carcinoma was found at autopsy in patients dying with achalasia. The present report analyzes 78 cases reported since the above reviews were published.1' 4 - ,; ' ,2"ls- ,s ' 20' 21 - 23 Fifty-one are from series in which the per cent incidence of carcinoma in achalasia was given (Table j)_i. o, la, i3, is. 2i, 23 jjjg w ide variation in the incidence reported by various authors is probably related to differences in the length of follow-up of patients with achalasia. Symptoms of achalasia are present on the average for 20 years before the diagnosis of carcinoma is made.4 Even so, the average age at which cancer was diagnosed in achalasia patients was 4 8 u to 52 years,4 which is 10 to 14 years younger than in persons without achalasia. In the present review, this temporal relationship was stated in 45 cases. The average interval was identical to that reported by Bolivar and Herendeen 4 —20
The Journal of
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Hankins and McLaughlin
Thoracic and Cardiovascular Surgery
Table I
Author
Year
No. of cases of achalasia
Debray et al.° Akuamoa 1 Lortat-Jacob et al.™ Pierce et al. , ! i Lagache et al. 1 Wychulis et
1968 1969
62 101
1969 1970 1970
279 110
al.2:* Triadu Castell 2 1
1971 1973
1,318 33
53
No. with carcinoma 8* 3
Per cent incidence 6.4 3.0
24 3 5
8.6 2.7 9.4
13t 5
0.53 15.2
•Four of these 8 cases came from other hospitals. Of the 62 patients with achalasia treated by the authors, only 4 (6.4 per cent) developed carcinoma. tSeven of these patients came from the group of 1,318 achalasia cases treated during a 32 year period, an incidence of 0.53 per cent or 41 cases per year per 100,000. The other 6 patients had their initial treatment for achalasia before this time period or elsewhere.
years. However, the average age at diagnosis of carcinoma was greater—55 years. Although achalasia is commoner in women, carcinoma complicating achalasia is more common in men by a ratio of 78 men to 28 women, or 2.8:l. 1 1 In the present review, of a total of 49 cases in which the sex was stated, 45 were men and 4 were women. The disease is apparently rare in Negroes. Just-Viera and Haight,11 in their review, were able to find only 5 cases in this race. In view of the foregoing, Case 1 is unusual in several respects. The man was only 33 years of age when carcinoma was diagnosed, and symptoms of achalasia had been present for only 2 years. Even more noteworthy is the fact that he was a Negro. Another unusual aspect of Case 1 is the fact that the tumor was in the upper third of the esophagus. Carcinomas in the otherwise normal esophagus are located as follows: 16 per cent in the upper, 47 per cent in the middle, and 37 per cent in the lower third.10 However, in recent collective reviews4, n of carcinoma complicating achalasia, there was a slightly greater incidence of middle third lesions and a slightly lower incidence of upper and lower third lesions than is the case in carcinoma with-
out achalasia. Just-Viera and Haight,11 in reviewing 109 cases in which the location was stated, found the following distribution: upper third, 4 cases (3.7 per cent); middle third, 56 cases (51.4 per cent); lower third, 42 cases (38.5 per cent); and more than one segment, 7 cases (6.4 per cent). AH nine carcinomas reported by Belsey 2,3 were in the middle third. In our review, the location of the tumor was specified in 70 cases. The distribution was as follows: upper third in 12, middle third in 23, lower third in 32, and both middle and lower thirds in 3 cases. Carcinoma is more commonly seen in the saccular than in the fusiform type of esophageal dilatation produced by achalasia.4 It frequently extends for great lengths along the esophagus and is often cauliflower in shape, as in Case 2. As regards cell type, our 2 cases were typical in that both tumors were squamous cell carcinomas. Of 77 cases reviewed by Just-Viera and Haight,11 68 were squamous cell carcinoma, 7 adenocarcinoma, 1 an undifferentiated carcinoma, and 1 a carcinosarcoma. Of the 60 cases covered by our review in which the histology of the neoplasm was described, 56 were squamous cell carcinoma and 4 were adenocarcinoma. The diagnosis is frequently delayed. The delay occurs because patients with prolonged swallowing difficulty tend to attribute any change in symptoms to their pre-existing disease, and the alteration in symptoms when carcinoma supervenes may be subtle. Weight loss and a return of, or an increase in, dysphagia are the most common harbingers of malignant change.1 '• 1:> LortatJacob and colleagues13 found blood-stained regurgitation or hematemesis to be the second most prevalent and retrosternal or back pain to be the third most common symptom of malignancy. In this respect both cases presented here are typical, for both patients had renewed or increased dysphagia, hematemesis, and substernal or epigastric discomfort. Delay by the patient is frequently compounded by delay on the part of the physician in making the diagnosis. Even a rela-
Volume 69 Number 3
Association of esophageal carcinoma and achalasia
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March, 1975
tively large growth may be overlooked on esophagography in an esophagus which is dilated and partly filled with retained food. Esophagoscopy as a means of diagnosing the tumor is limited by these same factors. The small carcinoma of the upper third in Case 1 was missed on two esophagograms and was noted on a third only when it was specifically sought after having been found during esophagoscopy. It is perhaps fortunate that the fiberoptic esophagoscope was used. The lesion might have been missed if the rigid esophagoscope has been employed. Fewer lesions would be missed by these diagnostic procedures if the patient were given only clear liquids for several days and the esophagus thoroughly irrigated through a large-bore tube just prior to the examination. In addition, esophagography must include films taken in the Trendelenburg position. Cytologic study of esophageal secretions and washings, although not needed to make the diagnosis in the 2 cases presented here, is a valuable addition to the diagnostic armamentarium. Such studies have proved positive in some instances in which all other studies were negative.11 The management of carcinoma complicating achalasia is in most instances the same as for carcinoma without achalasia. In 1969, having become dissatisfied with the results from a combined irradiation-resection regimen, we" adopted a philosophy of palliation in the treatment of patients with esophageal carcinoma. With this philosophy the primary goal is restoration of swallowing ability, with cure an important but secondary consideration. Radiation therapy has become the primary mode of treatment for lesions of the upper third, because experience has shown that long-term survival and even cure are possible by this method. Esophagogastrectomy is the method of choice for lesions of the middle and lower thirds. No attempt is made to perform a radical tumor resection or lymph node dissection. Postoperative radiotherapy is given for middle third lesions in cases in which small amounts of tumor have been left behind in the mediastinum. Since adoption of
this approach, the quality of life of the patients so treated has improved greatly, the hospital mortality rate has decreased to well below 10 per cent, and survival rates promise to be as good as, or better than, those achieved under our former regimen. Following this philosophy, we treated patient 1 by radiation therapy and achieved 16 months of satisfactory palliation. Since his achalasia had been inadequately controlled, a Heller procedure was also performed. Case 2 was managed by esophagogastrectomy, which thus far has provided satisfactory palliation. Judging from the literature, the prognosis for carcinoma with achalasia is worse than for carcinoma without achalasia, probably because of delayed diagnosis. Only one 5 year survivor has been recorded thus far,11 although a few patients have been reported to be alive and without evidence of disease after 2 or 3 years. Of 38 surgically treated patients reviewed by Just-Viera and Haight,11 only 6 underwent esophagogastrectomy, 1 of whom also received radiation therapy. There were two postoperative deaths. The remaining 4 patients were alive at intervals of 3 months to 2'/i years after operation. Of the 78 cases reported since the review by Just-Viera and Haight11 in 1969, the type of treatment used was described in 63. Twenty-seven patients were considered unsuitable for operation. Eleven of these were treated by radiotherapy, 1 of whom survived a little over 1 year. Surgical exploration was performed in 36 patients, and resection was possible in 22. There were six postoperative deaths. One patient was reported to be alive at 3 years and another at 2 years. Four others were alive after much shorter or unspecified intervals. The remainder have died, 1 after surviving 26 months, another 25 months, and all the others less than 18 months. In view of our poor ability to cure the disease once it has become symptomatic, more attention should be directed toward both prevention and earlier detection. If the chronic esophagitis resulting from stasis predisposes to malignant change, as the evi-
The Journal of
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Hankins and McLaughlin
Thoracic and Cardiovascular Surgery
dence seems to indicate, then relief of stasis early in the course of achalasia should prevent the development of carcinoma. It is recommended that a Heller cardiomyotomy be performed promptly in patients with achalasia in whom hydrostatic dilatation has not completely relieved cardial obstruction. If the Heller myotomy is not thorough or if it is carried out after megaesophagus has already developed, it may not prevent the development of carcinoma. Two of BelseyV patients developed malignant degeneration 2 and 5 years after a successful Heller operation. Earlier detection should be possible if physicians treating patients with achalasia maintain them under close surveillance. Esophagography, esophagoscopy, and cytologic studies should be performed at yearly intervals and even more frequently if there is a change in symptomatology. REFERENCES
CARDIOVASC. SURG. 59: 335,
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