Botulinum toxin (300 endotoxin units [EU]) was injected circumferentially in the same session without relief of symptoms within the following days. Histology revealed an invasive, poorly differentiated adenocarcinoma of the cardia. Helicobacter pylori was absent. Endoscopic ultrasound (EUS) revealed a stage IV tumor reaching the aorta with suspected infiltration of the outer layer of the aortic wall (Fig. 4). Pathologic lymph nodes with a diameter up to 8 mm were found along the esophagus. Computed tomography demonstrated an advanced mass at the gastroesophageal junction with enlarged lymph nodes but no signs of distant metastasis. The patient was referred for chemotherapy and responded well, allowing surgical resection 5 months later.
We describe an adolescent male with all clinical features of primary achalasia. The symptoms and findings in a barium study, manometry, and upper endoscopy were consistent with this diagnosis. In patients with achalasia the endoscopist can expect the instrument to pop into the stomach when the LES is passed, a phenomenon that was not present in our patient. Apparently normal mucosa at the gastroesophageal junction does not rule out the possibility of a tumor causing secondary achalasia, because a reasonable number of tumors are infiltrative and therefore not detectable by endoscopy (4,17). It seems to be justified to obtain biopsy specimens in certain patients, especially in those with negative family history for achalasia, because the bleeding risk of 0.01% is minimal (18).
Because all the tests were consistent with the diagnosis of primary achalasia, botulinum toxin (300 EU) was injected circumferentially into the gastroesophageal junction in the same session without relief of symptoms within the following days. In patients with primary achalasia improvement of symptoms can be expected in 70% to 90% within 1 to 2 weeks after injection of botulinum toxin (19,20). Improvement can be delayed up to 2 months (21). In one study, including 60 patients with primary achalasia, 53 subjects (88%) responded to therapy with botulinum toxin. Twenty of these 53 responders improved by day 1, 18 by week 1, and 4 by week 2. In 11 patients (21%), however, it took up to 2 months for symptoms to improve (21). In patients with secondary achalasia only 20% responded to botulinum toxin therapy. Time interval between injection of botulinum toxin and improvement of symptoms in patients with secondary achalasia was 1 day to 1 month (21,22).
It is known that esophageal manometry cannot distinguish between primary achalasia and secondary achalasia because of adenocarcinoma of the gastroesophageal junction (4,13). In one retrospective study Tucker et al. (4) demonstrated, in seven patients with secondary achalasia caused by malignancies, manometric features (aperistalsis, poor LES relaxation, and elevated sphincter pressure) identical with those in patients with primary achalasia. In another retrospective study, the investigators could not discriminate 6 patients with secondary achalasia due to carcinoma from 161 patients with primary achalasia (13). In this study, the two major criteria for the diagnosis of achalasia were aperistalsis of the thoracic esophagus and failure of the LES to relax completely with deglutition. Although mean LES pressure was somewhat lower in patients with primary achalasia compared with patients with secondary achalasia, manometry could not distinguish between the two forms of achalasia. Manometry can confirm the diagnosis of primary achalasia but contributes less in advanced cases with classic radiographic findings and endoscopic appearance.
The incidence of gastric adenocarcinoma is approximately 8 new cases per 100,000 population per year in the United States (23) and approximately 14 per 100,000 in Austria (24). There is a worldwide decline in prevalence and death rate. The disease is uncommon in people under 50 years of age. Mean age at diagnosis is 63 years in the United States and 69 years in Austria. Gastric adenocarcinoma is extremely rare in adolescents (approximately 1 per 40 million per year). It is noteworthy that this extremely low incidence includes the small number of carcinomas that are confined to the region of the cardia.
The literature reports very few cases of adenocarcinoma of the stomach in children and adolescents (6,25–36). Location of the carcinoma can be the gastroesophageal junction, the cardia, antrum, pylorus, or the greater or lesser curve (28). Symptoms of the disease are variable in children. According to the location and extent of the tumor, the main symptoms described included abdominal pain, loss of appetite, weight loss, vomiting, gastroesophageal reflux, heartburn, dysphagia, diarrhea, anorexia, fatigue, weakness, lethargy, anemia, and a palpable abdominal mass. In only one of these patients was dysphagia described as the main symptom (33). In no patient did adenocarcinoma mimic achalasia.
It is not known whether risk factors specific for gastric adenocarcinoma in adults apply to children and adolescents. They include familial adenomatous polyposis, high-grade dysplasia, Barrett's esophagus, intestinal metaplasia, chronic atrophic gastritis, H. pylori infection and hereditary nonpolyposis colorectal cancer (Lynch grade II). Our patient had none of these risk factors. His family history was unremarkable. In addition, we could rule out H. pylori infection.
Many epidemiologic data suggest that the socioeconomic status and other factors influence the risk of development of gastric adenocarcinoma. These studies show that the risk for gastric cancer is influenced by use of alcohol or nicotine, limited access to fresh fruits or vegetables, or low socioeconomic status (37–41). None of these risk factors applied to our patient.
Another risk factor is heartburn or gastroesophageal regurgitation. A recent study showed that the risk of development of esophageal adenocarcinoma is almost eight times higher among patients who have these symptoms (42). In the same study, the risk of development of adenocarcinoma of the gastric cardia was shown to be two times higher in patients with these symptoms. However, our patient had none of these symptoms.
Although adenocarcinoma of the cardia is extremely rare in adolescent patients, the endoscopist should be alert to this disease in patients of any age with dysphagia, even if symptoms, and results of a barium study, upper endoscopy, and esophageal manometry are suggestive of primary achalasia, especially if family history is negative for achalasia. In addition, secondary achalasia should be suspected in patients who do not respond to therapy with botulinum toxin within 2 months.
Because none of the mentioned tests can distinguish between primary achalasia and secondary forms due to carcinoma of the cardia, biopsy specimens should be obtained. It appears that, although there is a minimal risk for complications, a diagnostic procedure such as biopsy would be appropriate when the information obtained could be essential.
In some cases EUS can be an additional diagnostic tool, because lesions of the submucosa and the surrounding area can be identified by EUS.
1. Mayberry JF, Atkinson M. Studies of incidence and prevalence of achalasia in the Nottingham area. Q J Med. 1985; 56:451–6.
2. Katz PO, Richter JE, Cowan R, et al. Apparent complete lower esophageal sphincter relaxation in achalasia. Gastroenterology. 1986; 90:978–83.
3. Clouse RE, Diamant NE. Motor physiology and motor disorders of the esophagus. In: Sleisenger MH, Fordtran JS, eds. Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management.
6th ed. Vol 1. Philadelphia: WB Saunders, 1998:467–97.
4. Tucker HJ, Snape Jr, WJ Cohen S. Achalasia secondary to carcinoma: manometric and clinical features. Ann Intern Med. 1978; 89:315–8.
5. Wong RKH, Johnson LF. Achalasia. In: Castell DO, Johnson LF, eds. Esophageal Function in Health and Disease. New York: Elsevier; 1983:99–123.
6. Mahour GH, Isaacs Jr, H Chang L. Primary malignant tumors of the stomach in children. Pediatr Surg. 1980; 15:603–8.
7. Black RE. Linitis plastica in a child. J Pediatr Surg. 1985; 20:86–7.
8. Schwartz MG, Sgaglione NA. Gastric carcinoma in the young: overview of the literature. Mt Sinai J Med. 1984; 51:720–3.
9. Goldthorn JF, Canizaro PC. Gastrointestinal malignancies in infancy, childhood, and adolescence. Surg Clin North Am. 1986; 66:845–61.
10. Streitz Jr, JM Ellis Jr, FH Gibb SP, et al. Achalasia and squamous cell carcinoma of the esophagus: analysis of 241 patients. Ann Thorac Surg. 1995; 59:1604–9.
11. Wenzl E, Starlinger M, Feil W, et al. Secondary achalasia caused by diffuse infiltrating cardial cancer. Chirurgie. 1988; 59:536–40.
12. Lubke HJ, Berges W, Frieling T, et al. Achalasia as a mask of cardial carcinoma. Dtsch Med Wochenschr. 1988; 113:1997–2002.
13. Kahrilas PJ, Kishk SM, Helm JF, et al. Comparison of pseudoachalasia and achalasia. Am J Med. 1987; 82:439–46.
14. Balthazar EJ, Goldfine S, Davidian MM. Carcinoma of the esophagogastric junction. Am J Gastroenterol. 1980; 74:237–43.
15. McCallum RW. Esophageal achalasia secondary to gastric carcinoma: report of a case and a review of the literature. Am J Gastroenterol. 1979; 71:24–9.
16. Lawson TL, Dodds WJ. Infiltrating carcinoma simulating achalasia. Gastrointest Radiol. 1976; 1:245–8.
17. Tracey JP, Traube M. Difficulties in the diagnosis of pseudoachalasia. Am J Gastroenterol. 1994; 89:2014–8.
18. Reiertsen O, Sjkoto J, Jacobsen CD, et al. Complications of fiberoptic gastrointestinal endoscopy: five years' experience in a central hospital. Endoscopy. 1987; 19:1–6.
19. Pasricha PJ, Rai R, Ravich WJ, et al. Botulinum toxin for achalasia: long-term outcome and predictors of response. Gastroenterology. 1996; 110:1410–5.
20. Cuilliere C, Ducrotte P, Zerbib F, et al. Achalasia: outcome of patients treated with intrasphincteric injection of botulinum toxin. Gut. 1997; 41:87–92.
21. Fishman VM, Parkman HP, Schiano TD, et al. Symptomatic improvement in achalasia after botulinum toxin injection of the lower esophageal sphincter. Am J Gastroenterol. 1996; 91:1724–30.
22. Vallera RA, Brazer SR. Botulinum toxin for suspected pseudoachalasia. Am J Gastroenterol. 1995; 90:1319–21.
23. Kelsen DP. Gastric cancer. In: Fischer DS, eds. Follow-up of Cancer: A Handbook for Physicians.
4th ed. Philadelphia: Lippincott–Raven; 1996:34–55.
24. Rosen H, Klimpfinger M, Jatzko G, et al. Magenkarzinom. In: Smola MG, eds. Manual der chirurgischen Krebstherapie. Wien: Österreichische Ärztekammer; 1999:115–28.
25. Wolach B, Rothschild M, Pomeranz A, et al. Idiopathic non-obstructive hypertrophic cardiomyopathy, vitamin B12 deficiency and gastric adenocarcinoma: an unreported association in a teenager. Eur J Pediatr. 1998; 157:715–8.
26. Katz S, Berernheim J, Kaufman Z, et al. Pernicious anemia and adenocarcinoma of the stomach in an adolescent: clinical presentation and histopathology. J Pediatr Surg. 1997; 32:1384–5.
27. Chatura KR, Nadar S, Pulimood S, et al. Case report: gastric carcinoma as a complication of dyskeratosis congenita in an adolescent boy. Dig Dis Sci. 1996; 41:2340–2.
28. McGill TW, Downey EC, Westbrook J, et al. Gastric carcinoma in children. J Pediatr Surg. 1993; 28:1620–1.
29. Fox KR, Moussa SM, Mitre RJ, et al. Clinical and pathologic features of primary gastric rhabdomyosarcoma. Cancer. 1990; 66:772–8.
30. Hoeffel JC, Nihoul-Fekete C, Schmitt M. Esophageal adenocarcinoma after gastroesophageal reflux in children. J Pediatr. 1989; 115:259–61.
31. Conley ME, Ziegler MM, Borden IV, S et al. Multifocal adenocarcinoma of the stomach in a child with common variable immunodeficiency. J Pediatr Gastroenterol Nutr. 1988; 7:456–60.
32. Goto S, Ikeda K, Ishii E, et al. Carcinoma of the stomach in a 7-year-old boy: a case report and a review of the literature on children under 10 years of age. Z Kinderchir. 1984; 39:137–40.
33. Elliott MJ, Ashcroft T. Primary adenocarcinoma of the gastro-oesophageal junction in childhood: a case report. Scand J Thorac Cardiovasc Surg. 1983; 17:65–6.
34. Siegel SE, Hays DM, Romansky S, et al. Carcinoma of the stomach in childhood. Cancer. 1976; 38:1781–4.
35. Dixon WL, Fazzari PJ. Carcinoma of the stomach in a child. JAMA.
36. Johnston Jr, DP van Heerden JA, Lynn HB, et al. Carcinoma of the stomach in a 10-year-old boy. J Pediatr Surg. 1975; 10:151–2.
37. Kabat GC, Ng SK, Wynder EL. Tobacco, alcohol intake, and diet in relation to adenocarcinoma of the esophagus and gastric cardia. Cancer Causes Control. 1993; 4:123–32.
38. Ramon JM, Serra L, Cerdo C, et al. Dietary factors and gastric cancer risk: a case-control study in Spain. Cancer. 1993; 71:1731–5.
39. Hansson LE, Baron J, Nyren O, et al. Tobacco, alcohol and the risk of gastric cancer: a population-based case-control study in Sweden. Int J Cancer. 1994; 57:26–31.
40. La Vecchia C, Negri E, D'Avanzo B, et al. Electric refrigerator use and gastric cancer risk. Br J Cancer. 1990; 62:136–7.
41. Nomura A, Grove JS, Stemmermann GN, et al. A prospective study of stomach cancer and its relation to diet, cigarettes, and alcohol consumption. Cancer Res. 1990; 50:627–31.
42. Lagergren J, Bergstrom R, Lindgren A, et al. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med. 1999; 340:825–31.