Epidemiology of achalasia in central israel rarity of esophageal cancer

Digestive Diseases and Sciences, VoL 38, No. 10 (October 1993), pp. 1920-1925

Epidemiology of Achalasia in Central Israel Rarity of Esophageal Cancer N. ARBER, MD, A, GROSSMAN, MD, B. LURIE, MD, M. HOFFMAN, MD, A, RUBINSTEIN, MD, P. LILOS, MD, P. ROZEN, MD, and T. GILAT, MD

The epidemiology o f achalasia was studied in a predominantly urban, Jewish population o f approximately L3 million, in central Israel, during the years 1973-1983. One hundred sixty-two proven cases were collected, representing all known patients with achalasia in the study area. There were no gender differences. The majority o f cases were diagnosed within two years o f onset o f symptoms, although the median delay in diagnosis was 4. 4 + 5.3years. The disease was rare in the first two decades o f life. The prevalence (in 1983) in the first two decades was 0.7/105 rising to 36.2/105 above age 70. The mean annual inCidence in the years 1973-1978 was 0.8/105. It rose slightly to a mean annual incidence o f 1.1/105 in the years 1979-1983. The prevalence o f the disease in 1973 and 1983 was Z9/105 and 12.6/105, respectively. The age-adjusted prevalence in 1973 was higher in Asian andAfrican born Jews as compared to those born in Europe, America, or Israel This difference disappeared by the year 1983. N o case o f cancer o f the esophagus was found among our patients. This may be due to the nonselected, regional nature o f our series or to the effects o f earlier therapy o f achalasia in recent decades. KEY WORDS: achaiasia; epidemiology; esophageal cancer.

Achalasia was apparently first described in 1674 (i), but it was not until 1913 that the name achalasia was coined (2, 3). It has been described throughout the world and has been reported to be particularly common in Ireland, Sweden, and New Zealand and very rare in Japan and Zimbabwe (1). It may occur at any age from early childhood to the ninth decade. Fi~om the 1930s to the 1970s there was a reported 50% rise in the incidence of achalasia, without sex predilection (1). This apparent increase may reflect improved diagnostic techniques, changes in referral patterns, more complete recording, and an increase in life-sPan (4). There has been no apparent change in the incidence of this disorder during the past two Manuscript received January 20, 1992; revised manuscript received June 12, 1992; accepted June 18, 1992. From the Department of Gastroenterology, Tel Aviv-Sourasky Medical Center, Ichilov Hospital, and Sackler Faculty of Medicine arid Department of Mathematics, Tel Aviv University, Israel. Address for reprint requests: Dr. Tuvia Gilat, Department of GaStroenterology, Ichilov Hospital, 64239 Tel Aviv, Israel.

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decades (4). Despite this considerable body of knowledge, the epidemiology of achalasia has not been extensively studied (5-i2). We conducted an epidemiologic and clinical study of achalasia in a predominantly urban area of central Israel, during the years 1973-1983 and report here the epidemiologic results, The clinical, diagnostic, and treatment features will be reported elsewhere. MATERIALS AND METHODS Study Area and Population. The study area comprised the greater Tel Aviv area between (and not including) Netanya in the north, Rehovot in the south, and including Petach Tikva in the east. This area is located in central Israel with a population of about 1.3 million. As the number of non-Jewish residents living in the study area is small, they were not included in the present study, which is thus confined to the Jewish population. Demographic data were derived from government census figures gathered in the years 1972, 1977, and 1983 (13). As the study period was 1973-1983, the demographic data of the 1972 and 1983 census were mostly used (13).

Digestive Diseases and Sciences, VoL 38, No. 10 (October 1993) 0163-2116/93/1000-1920507.00/0 9 1993PlenumPublishingCorporation

ACHALASIA EPIDEMIOLOGY IN ISRAEL TABLE 1. PATIENTDATA Number of patients Males Females Age at onset (years) Mean -+ SD Range Age at diagnosis (years) Mean - SD Range Time between onset and diagnosis (years) Mean _ so Range Follow-up (years) Mean +- so Range Country of birth (%) (N = 161) Europe, America Asia, Africa Israel

was critically evaluated to determine the reliability of the diagnosis. A complete follow-up, with particular attention to esophageal cancer, was obtained. Som'ees. During a six-year period (1983-1988), all regional hospitals and departments of gastroenterology, within and adjacent to the study area, were repeatedly screened, ineluding gastroscopy and biopsy reports. All patient records with a diagnosis of achalasia or related diagnosis were reviewed. Gastroenterologists in the study area were contacted regarding all their personal patients with achalasia. We thus believe we have identified all known, diagnosed patients with achalasia in the study area. Some patients were last seen between the years 1973-1983 and were subsequently lost to follow-up. The y e a r of the last medical record was considered as the y e a r of the last follow-up. On the other hand, many patients were followed up to as late as 1988. F o r patients wh o died, the medical death certificate was reviewed, as were any hospital records. All patients whose last medical examination was before 1983 were rechecked and efforts were made to contact them or their physician. In addition the Israel Cancer Registry records, which include the entire country, were reviewed. Thus, if a patient moved out of the study area and had an operation for or died of esophageal cancer, he would be listed. N o case was found in the Cancer Registry, providing a valuable check on the completeness of our follow-up, For each patient in the study, a detailed questionnaire was filled out containing demographic and clinical data. Dates of onset, diagnosis, and last follow-up were noted, as well as various clinical manifestations and examinations (documented b y endoscopy, radiology, manometry, or a combination of them). The data were coded and a comput-

162 79 83 43.0 --+ 17.9 1-78 47.7 -- 18.3 2-85 4.4 - 5.3 0-21 9.9 - 8.7 0-52 49.7 29.8 20.5

Criteria for Achaiasia. Patients were considered to have achalasia only if at least the first two of the following three criteria were fulfilled: (1) chronic dysphagia, usually with a dilated esophagus on barium swallow; (2) upper gastrointestinal endoscopy performed to exclude organic esophagogastric diseases such as malignancy or benign peptic stricture; and (3) in 50 cases (31%) a manometric study was also performed, demonstrating absent or incomplete relaxation of a usually hypertensive lower esophageal Sphincter. Absent or impaired peristalsis in the lower esophageal body was also found. Patients. A n extensive study was conducted to locate all patients with achalasia in the study area. Each patient

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Digestive Diseases and Sciences, VoL 38, No. 10 (October 1993)

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Time Elapsed Between Onset & Diagnosis (years) Fig 2. Time elapsed between onset of achalasia and its diagnosis.

erized analysis performed. Statistical differenceswere evaluated using the method of difference between proportions. RESULTS After critical evaluation of the data, 162 cases of achalasia were confirmed in the study area. Their data are shown in Table 1. Eighty-three (51%) were women and 79 were men (49%), giving a male-to-female ratio of 1:1.05, The majority of patients Were between 16 and 75 years of age (mean 43.0 +_ 17.9, range 1-78) at the time of onset of symptoms with a slight peak in the age group 31-35 (Figure 1). Eight percent of the patients ,---,

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were diagnosed within one year, and 64% within three years, with a mean of 4.4 ___5.3 years (range 0-21 years) between onset of symptoms and diagnosis (Figure 2). Mean follow-up time was 9.9 _ 8.7 years, with a median of eight years, and a range of 0-52 years. Sixty-four patients (39%) were followed for at least 10 years, and 17 (10%) had been followed for more than 20 years (up to a maximum of 52 years). Fifty percent of the patients were born in Europe and America, 30% in Asia and Africa, and 20% in Israel. Incidence. The mean annual incidence (Figure 3) of newly diagnosed patients with achalasia was 0.8/

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Digestive Diseases and Sciences, Vol. 38, No. 10 (October 1993)

ACHALASIA EPIDEMIOLOGY IN ISRAEL

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105 in the years 1973-1978. There was a slight rise in the years 1979-1983 to 1.15/105 . Prevalence. The overall prevalence on January 1, 1973, was 7.9/100,000. The overall prevalence on December 31, 1983, was 12.6/100,000. The prevalence in the different age groups in 1973 and 1983 is shown in Figure 4. The disease was more prevalent in higher age groups at both time periods tested and in both sexes (Figures 4 and 5). The prevalence of achalasia was higher in 1983 as compared to 1973. This difference was accounted for by the age groups 50-59 (P < 0.025) and 70+ (P < 0.001). There was a steady rise in the prevalence of achalasia with age. There was no sex difference in the prevalence of achalasia (Figure 5)

except for a small male preponderance in the age group 50-59 and 70+ years. The prevalence of achalasia in central Israel by age and origin is summarized in Table 2. In 1973 the disease was more prevalent in Israelis of Asian and African origin (P < 0.025); this difference between the Jewish community groups disappeared in 1983. Malignancy. There were no cases of esophageal neoplasia in the study population. Mortality. Sixteen deaths (10%) were reported during the years 1977-1987, only six (4%) were related to the disease. The mean age at death was 70.1 ___ 13.7 years (range 36-89 years).

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Age Groups Fig 5. Prevalence of achalasia according to age and sex in 1983. Digestive Diseases and Sciences, Vol. 38, No. 10 (October 1993)

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ARBER ET AL TABLE 2. PREVALENCEoF ACHALASLAINCENTRAl. ISRAELBY AGEANDORIGIN IN 1973Ar~ 1983

On#n A g e groups 1973 0-14 15-29 30-44 45-64 65+ Crude prevalence Age-adjusted prevalence 1983 0-14 15-29 30-44 45-64 65+ Crude prevalence Age-adjusted prevalence

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DISCUSSION

The incidence of achalasia found in central Israel is higher than that reported in many other epidemiological studies (1, 5-8) and is similar to that found in Ireland, Sweden, and New Zealand (9-11). This confirms the marked regional variations of the disease (1, 9, 14). There has been an insignificant increase in the incidence of this disorder from 0.8/105 in 1973 to 1.1/105 in 1983. There was a significant increase in the prevalence of achalasia from 7.92 cases perl00,000 population in 1973 to 12.6/105 in 1983 (P < 0.001). This is similar to the trend in the prevalence of the disease in Great Britain (8, 9). This apparent increase in the prevalence of achalasia in Israel probably reflects the aging of the Israeli population, improved diagnostic techniques, and better treatment of the disease. As in other studies (1, 4, 8), there was a delay in diagnosis. Even though the median delay in diagnosis was 4.4 years, Figure 2 demonstrates that in the majority of cases the diagnosis was made within two years of onset of symptoms. Our study confirms the clinical impression that the disease is unusual in childhood. It is, however, the first report of the prevalence of achalasia in the first two decades of life. In youngsters it was more prevalent in girls; nevertheless, it tended to decrease from 2.2/105 in 1973 to 1.0/105 in 1983, while the prevalence in boys remained constant at 0.5. In contrast to other studies (15-18), there were no familial dusters of cases in our series.

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0.3 4.3 16.5 24.0 32.8 12.6

It is of interest to note (Table 2) that the higher prevalence of achalasia in Jews of Asian and African origin (9.6/105), in comparison to those of European and American origin or native Israelis (6.3/10 5 and 6.1/105, respectively), disappeared in 1983 to reach 13.3/105 , 12.9/105, and 12.2/105, respectively. This suggests that the original difference in 1973 was either coincidental or due to environmental factors. The prevalence of carcinoma was reported to be higher in achalasia patients than expected in the general population, ranging from 0% to as high as 20% (4); however, such high figures were reported in series with a longer duration of follow-up (4, 19) or that were contaminated by patients with primary tumors mimicking achalasia (20). The average prevalence of carcinoma was approximately 3% in several series (4). Nevertheless, in our study, there were no cases of carcinoma. Esophageal cancer is infrequent in Israel (21). This has been attributed to a low exposure to environmental carcinogens. The follow-up of our patients (9.9 _ 8.7 years) was not overly long, even though 81 patients were followed for more than 10 years (up to 52 years). Unlike series from major referral centers, ours is a regional series, thus devoid of selection bias. Earlier therapy with avoidance of esophageal stasis may also be a factor, in comparison to older series. Studies from several areas will be needed to confirm the possibility that earlier and more effective therapy of achalasia has reduced the incidence of esophageal cancer. Digestive Diseases and Sciences, Vol. 38, No. 10 (October 1993)

ACHALASIA EPIDEMIOLOGY IN ISRAEL REFERENCES 1. Mayberry JF, Probert CSJ, Sher KS, Atkinson M: Some epidemiological and aetiological aspects of achalasia. Dig Dis 9:1-8, 1991 2. Hertz AF: The bismuth meal. BMJ S:13, 1913 3. Hertz AF: Achalasia of the cardia. Q J Med 8:300-308, 1916 4. Reynolds JC, Parkman HP: Achalasia. Gastroenterol Clin North Am 18:223-255, 1989 5. Earlam RJ, Ellis FH, Norbrega FT: Achalasia of the oesophagns in a small urban community. Mayo Clin Proc 44:478483, 1960 6. Galen EA, Switz M, Zfass AM: Achalasia: Incidence and treatment in Virginia. Va Med 109:183-186, 1982 7. Mayberry JF, Rhodes J: Achalasia in the city of Cardiff from 1926-1977. Digestion 20:248-252, 1980 8. Mayberry JF, Atkinson M: Studies of the incidence and prevalence of achalasia in the Nottingham area. Q J Med 56:451-456, 1985 9. Mayberry JF, Atkinson M: Variations in the prevalence of achalasia over a decade in Great Britain and Ireland: An epidemiological study based on hospital admissions. Q J Med 62:67-74, 1987 10. Mayberry JF, Mayell M: The epidemiology of achalasia in children. Gut 29:90-93, 1988 11. Mayberry JF, Atkinson M: The incidence of achalasia in

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12. 13. 14. 15. 16.

17.

18. 19.

20.

21.

New Zealand, 1980-1984: An epidemiological study of hospital discharges. J Gastroenterol Hepatol 3:247-252, 1988 Stein CM, Gelfand M, Taylor HG: Achalasia in Zimbabwean blacks. S Mr Med J 67:261-262, 1985 1983 Census of population and housing publications. Jerusalem, State of Israel, Central Bureau of Statistics, 1984 Mayberry JF, Atkinson M: An international study of mortality of achalasia. Hepatogastroenterology 35:80-82, 1988 Dayalan N, Chettur L, Ramakrishnan MS: Achalasia of the cardia in siblings. Arch Dis Child 47:115-118, 1972 Westley CR, Herbst JJ, Goldman S, Wisek WC: Infantile achalasia: Inherited as an autosomal recessive disorder. J Pediatr 87:243-246, 1975 Allgrove J, Clayden GS, Grant DB, Macauley JC: Familial glucorticoid deficiency with achalasia of the cardia and deficient tear production. Lancet 1:1284-1286, 1978 Bosher P, Shaw A: Achalasia in siblings. Clinical and genetic aspects. Am J Dis Child 135:709-710, 1981 Carter R, Brewer LA: Achalasia and esophageal carcinoma. Studies in early diagnosis for improved surgical management. Am J Surg 130:114-118, 1975 Kahrilas PJ, Kishk SM, Helm JF, Dodds WJ, Harig JM, Hogan WJ: Comparison of pseudoachalasia and achalasia. Am J Med 82:439-446, 1987 Israel Cancer Registry: Cancer in Israel. Incidence and Mortality 1978-1980. Jerusalem, Ministry of Health, July 1983

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