Cardiospasm

In a follow-up study of 147 patients with achalasia of the esophagus treated by myotomy, 146 patients were traced (58 female and 88 male patients aged 4 to 83 years [median, 46 years]). The living persons were contacted in writing or by telephone. The mean follow-up time after the operation was 23.2 years (range, 6 to 41 years). The cause of death was established for 71 patients. There were three postoperative deaths and two deaths following recurrence. In comparison with the Danish population, the 66 remaining patients were found to have a relatively higher cancer mortality (33.8 percent). Contrary to the expected less than one, ten of 23 patients who died of cancer had a malignant tumor in the esophagus. The mortality rate after 30 years was 66.1 percent, 11.9 percent of the deaths caused by esophageal cancer. It is concluded that there is a connection between achalasia and cancer of the esophagus that ought to be considered in the treatment and follow-up of patients with achalasia.

(Chest 1992; 102:1013-16)

One hundred years ago, the association between achalasia and cancer of the esophagus was described, and in 1969, Just-Viera and Haight[1] found 167 instances suitable for review. The reported incidence was between 1 and 20 percent, but most series were small.

The largest series was described by Ellis,[2] who in a follow-up of 85 patients found that of 24 patients with an established cause of death, seven died of esophageal cancer.

A recent reappraisal questions the concept of a connection between achalasia and esophageal carcinoma, and a follow-up study of 100 patients with achalasia disclosed no instances of cancer of the esophagus.[3]

However, it is our opinion that the design and statistical evaluation of this study is inadequate for the theory to be discarded. We therefore made a follow-up of our 147 patients with achalasia operated on by a myotomy.

MATERIAL AND METHOD

The study is a follow-up of 147 patients. The criteria for entering patients in the study were that they had diagnosed cardiospasm or achalasia of the esophagus and a history of myotomy.

One hundred forty-seven patients who satisfied the criteria were treated in the period 1949 to 1984 at the departments of the University Hospital, Rigshospitalet, in Denmark. One patient living abroad was not found for the follow-up. All the other patients have been traced.

There were 58 female and 88 male patients aged 4 to 83 years (median age, 46 years; mean age, 48.9 years).

Seventy-five patients are still alive and have been contacted in writing or by telephone. Seventy-one have died and we have obtained information on the causes of death from death certificates, where possible supplemented by medical records, autopsy reports, histologic examinations, and reports from general practitioners. Twenty-seven patients had had an autopsy.

The follow-up time has been calculated from the date of operation. The mean follow-up time was 23.2 years (range, 6 to 41 years), which is equivalent to 3,390 observation years in 146 patients. The time interval from the first symptom to the operation was mentioned in 143 records but was not exact in all cases; it ranged from nil to 45 years with a median value of more than three and less than four years.

Statistics

Survival has been calculated by the actuarial method and contingency tables have been evaluated by the [X.sup.2] test. P values of <0.05 were considered significant.

RESULTS

Table 1 shows the cause of death in the group studied in comparison with the causes of death in the Danish population in the year 1965 and in the year 1985.

There were three postoperative deaths and two deaths following treatment for recurrence. Among the remaining 66 deaths in the group studied, a relatively high cancer mortality (34.8 percent) was found as compared with the overall death rate in the Danish population (Table 1), which was 23.2 percent in 1965[4] and had increased to 24.8 percent in 1985.[5] The expected cancer death rate for our patients corrected for age, sex, and year of death was 24.75 percent. the difference between the expected and the observed death rate (34.9 percent) is not statistically significant ([X.sup.2] 3.7026, 0.10>p>0.05).

Table 2 shows the different sites of the malignant tumors. Ten of 23 patients who died of cancer had a malignant tumor in the esophagus. Table 3 provides information about those ten patients. The data on the size of the esophagus derive from the radiologists' reports; roentgenograms were not available. The interval from the time of the operation to the occurrence of death was longer than 19 years for patients younger than 60 years.

During the years 1970 to 1979, the number of new cases of esophageal cancer in Denmark per year was 120 among male patients and 62 among female patients.[6] The five-year survival is less than 5 percent, so almost 180 patients die of cancer of the esophagus each year. Cancer of the esophagus accounted for about 1.5 percent of all cancer deaths in the above period, 1.7 percent in 1965 and 1.2 percent in 1985 (see table 1). As a consequence, the expected number of deaths caused by esophageal cancer among our 66 patients is less than one (0.33). The difference between the expected "less than one patient" and the observed ten patients is highly significant ([X.sup.2] 710.0, p<0.001).

In Figure 1, the actuarial survival of the patients is demonstrated and compared with the survival of a Danish population of the same age and sex (calculated from the 1980 death rates).

As indicated in Figure 1, the actuarial death rate of cancer of the esophagus is 11.9 percent after 30 years, which is equivalent to almost one fifth of the total death rate of 66.1 percent.

DISCUSSION

In an earlier study from our hospital, Akuamoa[7] in 1969 found two cases of ulcerative esophageal cancer among 101 patients with an achalasia diagnosis. Some of those patients are part of our series but with a longer follow-up period, and the present prevalence is 6.9 percent. Our patients have been followed up for such a long time that half of them have died. A series in which the patients have been followed to death provides a final prevalence figure. Among the dead patients, the prevalence is 10 of 71, or 14 percent, but this figure may change during a continued follow-up on the rest of the patients. Our results support the hypothesis of a connection between achalasia and cancer of the esophagus also found in Ellis' series.[2]

Chuong et al[3] found no case of esophageal cancer in 91 of 100 patients with achalasia. They state an incidence of 0/589 person years.[3] In this study,[3] the mean follow-up time after the diagnosis was six years and six months--a much shorter time than the 17.5 years in another study with an incidence of 41 cases per year per 100,000,[8] just as it was shorter than the mean follow-up time of 23.2 years in our study. Like others,[2,9-11] we found that there is an interval of many years from the beginning of the disease to the development of cancer. During the initial years, the incidence/person years in a series will be nil and subsequently, after a few decades, reach a significant value. It is therefore irrelevant to use the incidence/person years to compare series in which the follow-up times are different.

It has been established that the consumption of alcohol and tobacco increases the risk of developing esophageal cancer possibly owing to the content of carcinogens in alcohol and tobacco such as polycyclic aromatic hydrocarbons and nitrosamines.[12] Achalasia is known to cause retention and increased bacterial growth and chemical irritation from the continuous composition of food that culminates in chronic esophagitis. This is supposed to provoke cancer or make the epithelium more sensitive to carcinogens.[1] A high concurrence with chronic esophagitis has been found in endemic areas.[12] It is therefore conceivable that early treatment relieving the retention reduces the risk of esophageal cancer, while late operation on a dilated esophagus does not prevent the development of cancer.[2,11,13] The patients in our series had all been treated by myotomy, but many of them had been treated at a late stage. If it had been possible to divide them into two groups, one of patients whose conditions were diagnosed early and who were treated well, and one of patients treated unsatisfactorily or at a late stage of the disease, it might have shed light on the possibility of early and effective treatment to prevent cancer. Unfortunately, the information available to us about the time from the first symptom to the operation and about the degree of dilatation of the esophagus is inadequate in some patients. However, the diameter of the esophagus was considerably enlarged in all of the ten patients with esophageal cancer when the myotomy was performed, which might indicate disease in an advanced stage. [TABULAR DATA OMITTED]

Reflux can result in the development of Barrett's epithelium with carcinomatous degeneration toward an adenocarcinoma.[14% Adenocarcinoma has been found after myotomy complicated by reflux,[15] but only one of our patients had an adenocarcinoma that might have been caused by this mechanism.

Tumors in patients with achalasia are usually at an advanced stage once they are diagnosed and the prognosis is therefore poor.[10,11,13,16] These patients develop dysphagia late and closer surveillance has been recommended.

CONCLUSIONS

Achalasia is a risk factor for cancer of the esophagus. Early operation, including good drainage of the esophagus, might reduce the risk. Based on our findings, a regular follow-up of patients with achalasia is justified.

REFERENCES

1 Just-Viera JO, Haight C. Achalasia and carcinoma of the esophagus. Surg Gynecol Obstet 1969; 128:1081-95

2 Ellis FG. The natural history of achalasia of the cardia (abridged). Proc R Soc Med 1960; 53:663-66

3 Chuong JJH, DuBovik S, McCallum RW. Achalasia as a risk factor for esophageal carcinoma: a reappraisal. Dig Dis Sci 1984; 29:1105-08

4 Statistical year book: Copenhagen: Danmarks statistik. 1967, Table 41, p 71

5 Statistical year book: Copenhagen: Danmarks statistik. 1987, Table 35, p 34

6 Carstensen B, Jensen OM. Atlas of cancer incidence in Denmark 1970-1979. Copenhagen: Danish Cancer Registry, 1986:65-7

7 Akuamoa G. Achalasia oesophagi and related diseases. Acta Chir Scand 1969; 135;421-27

8 Wychulis AR, Woolam GL, Anderson HA, Ellis FH. Achalasia and carcinoma of the esophagus. JAMA 1971; 215:1638-41

9 Seeliger G, Lee T, Schwartz S. Carcinoma of the proximal esophagus, a complication of long-standing achalasia. Am J Gastroenterol 1972; 57:20-5

10 Pierce WS, MacVaugh H III, Johnson J. Carcinoma of the esophagus arising in patients with achalasia of the cardia. J Thorac Cardiovasc Surg 1970; 59:335-39

11 Carter R, Brewer LA. Achalasia and esophageal carcinoma: studies in early diagnosis for improved surgical management. Am J Surg 1975; 130:114-20

12 Schottenfield D. Epidemiology of cancer of the esophagus. Semin Oncol 1984; 11:92-100

13 Lortat-Jacob JL, Richard CA, Fekete F, Testart J. Cardiospasm and esophageal carcinoma: report of 24 cases. Surgery 1969; 66:969-75

14 Spechler SJ, Goyal RK. Barrett's esophagus. N Engl J Med 1986; 315:362-71

15 Shah AN, Gunby TC. Adenocarcinoma and Barrett's esophagus following surgically treated achalasia. Gastrointest Endosc 1984; 30:294-96

16 Hankins JR, McLaughlin S. The association of carcinoma of the esophagus with achalasia. J Thorac Cardiovasc Surg 1975; 69:355-60

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