Carcinoma of the esophagus and cardia Diagnostic evaluation in 113 cases Fiberoptic endoscopy with directed biopsy and brush cytology was used to diagnose 73 patients with squamous carcinoma of the esophagus and 40 adenocarcinomas of the gastric fundus invading the lower esophagus. Over-all accuracy of histologic diagnosis in the esophagus was 95.8 per cent and in the cardia, 97.5 per cent. Multiple biopsies (6 to 8) and brush cytology complemented one another in providing a high index of reliable histologic diagnoses. There were no complications. Endoscopy with the fiberoptic scope as now performed is well tolerated and accurate. It appears to be the most reliable means of diagnosis in cancer of the esophagus and cardia and should be performed routinely in all patients with symptoms referable to the esophagus.
Hamilton C. Bruni, M.D., and Robert S. Nelson, M.D., Houston, Texas
The advent of fiberoptic esophagoscopes has changed esophageal endoscopy from a rather difficult, often hazardous procedure to a relatively well-tolerated and routinely applied test. There has been some question as to whether the small biopsy specimen obtained with the flexible fiberoptic esophagoscope would be so inadequate that the diagnosis might be missed in an unacceptable number of patients with carcinoma of the esophagus or carcinoma of the stomach invading the esophagus. The latter type of tumor has been poorly identified in the past by all measures-:'" 1~ when compared with the relatively easily diagnosed epithelial cancers of the esophagus itself. The purpose of the present study is to evaluate the diagnostic accuracy of fiberoptic endoscopy, including directed biopsy and brush cytology, in a significant number of patients with carcinoma of the esophagus and of the gastric fundus with esophageal extension. From the University of Texas Cancer Center, Texas Medical Center, Houston, Texas 77025. Received for publication March 4, 1975.
Materials and methods All patients admitted with a diagnosis of carcinoma of the esophagus and cardia during the period January, 1970, to December, 1973, who had been evaluated by fiberoptic endoscopy were included in the study. There was a total of 113 patients, 73 with squamous carcinomas originating in the esophagus and 40 with adenocarcinomas extending upward from the stomach, with involvement of the cardia. The age and sex distribution are noted in Table I. Instruments used were the Olympus GIF, EF, and JF model fiberoptic endoscopes. Biopsies (from 6 to 8) were obtained in all patients and brush cytology in a smaller but significant number. Adequate radiologic examinations were available in each. Results Carcinoma of the esophagus. A total of 73 patients had carcinoma of the esophagus. X-ray films gave a positive diagnosis in 67 (91.7 per cent). Visualization by endoscopy was correct in 70 (95.8 per cent). Esophageal biopsy at endoscopy provided 367
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Table I. Sex and age distribution in 113 cases of carcinoma of the esophagus and cardia
Sex Male Female Age (yr.) 30-39 40-49 50-59 60-69 70-79 80-89 Totals
Ca esophagus (No. ofpts.]
Ca cardia (No. ofpts.}
50 23
32 8
6 18 33 13 3
3 6 16 9 5 I
73
40
an accurate result in 60 of 64 patients at our institution; in the remaining 9 patients, biopsy had been done elsewhere with positive results. These 9 patients were not included in our totals, since information was lacking as to the type of instrument used. Brush cytology was obtained in all 9 during endoscopic examination and was positive in each instance. Therefore, biopsies taken with the fiberoptic endoscope gave accurate results in 93.7 per cent. Brush cytology was accurate in 46 of 50 patients (92.0 per cent). Forty-one patients had both biopsy and brush cytology, and results were positive in 39 (95.1 per cent accuracy). In 2 of these patients, results of biopsy were positive and cytology negative; in 1 patient, positive cytology corrected a false-negative biopsy result. The over-all accuracy of histologic diagnosis by fiberoptic endoscopy was 95.8 per cent in 73 patients (Table II). Carcinoma of the stomach involving the cardia and lower esophagus. X-ray examination yielded a correct diagnosis of the lesion in 34 of 38 patients. In 2 cases roentgenologic studies were not available. (One of the 4 misdiagnosed lesions was evaluated as esophageal stricture and the other 3, tumor of the stomach, but with no esophageal involvement seen.) All 40 lesions were visualized by endoscopy, with correct diagnoses based on submucosal involvement, mucosal
Table II. Carcinoma of the esophagus: Accuracy of various diagnostic methods Method Roentgenography Endoscopy (visual) Endoscopic biopsy Brush cytology Biopsy + cytology
Percent 73 73 64 50 41
67 70 60 46 39
91.7* 95.8t 93.7 92.0 95.1
'There were 6 errors in x-ray diagnosis: extrinsic mass on the esophagus (3) ; obstruction of the esophagus (1) ; bronchogenic carcinoma involving the esophagus (1); and esophageal ulcer (I). tThere were 3 errors in visual endoscopic diagnosis: Narrowing of the esophagus (1); roughened mucosa (1); and obstruction by extrinsic mass (1).
Table III. Carcinoma of the stomach involving the cardia and lower esophagus: Accuracy of the various diagnostic methods Method
No. ofpts.
Roentgenography Endoscopy (visual) Endoscopic biopsy Brush cytology Biopsy + cytology
38 40 39 27 26
Percent 34 40 37 21 25
89.4* 100 94.8 77.7 96.1
'There were 4 errors in x-ray diagnosis: Benign esophageal stricture (1) and carcinoma of the upper stomach with no cardioesophageal involvement (3).
lesions, or both. Results of endoscopic biopsy were positive for adenocarcinoma in 37 of 39 patients (94.8 per cent). Brush cytology was positive in only 21 of 27 (77.7 per cent), but there was enough overlap in those who underwent both cytologic examination and biopsy so that results in 25 of 26 were positive by one or both methods (96.1 per cent accuracy). Over-all histologic accuracy was 39 of 40 patients (97.5 per cent) (Table III). Discussion The early diagnosis of carcinoma of the esophagus or cardia is frequently impossible due to the insidious nature of the onset of symptoms and patient delay in reporting to the physician. The initial roentgenograms may be nondiagnostic in an appreciable
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number of patients (from 12 to 30 per cent);' It is mandatory that anyone with pain or difficulty on swallowing have both roentgenograms and esophagoscopy for best results. The difficulty of performing esophagoscopy has in the past often made this impossible. Present-day fiberoptic instruments and sedative drugs, however, have made esophagoscopy an acceptable procedure. The only question remaining is that of the accuracy of the examination itself, and particularly the histologic accuracy obtainable with the small biopsy instruments available for fiberoptic esophagoscopes. In the past, various authors have demonstrated that esophageal washings showed tumor cells in a majority of patients with cancer of the esophagus." However, since the lesion can be reasonably well visualized by either roentgenography or endoscopy, esophageal washing appears to be a rather cumbersome method compared to the simplicity of biopsy at the time of esophagoscopy. If the lesion cannot be demonstrated grossly, positive results from washings are of little help," although P-32 scanning will demonstrate the extent of the lesion." The latter situation is an unusual one in our experience, as the great majority of lesions are easily shown and biopsied. The figures in the present study for histologic confirmation are better than average for squamous carcinoma of the esophagus and are considerably superior to any yet published for gastric cancer invading the esophagus.v 5-B, 11 It appears that the fiberoptic instruments are at least as good in diagnosing esophageal lesions and are much better in those involving the cardia. The discrepancy in statistics is unexplained, but the number of biopsies taken may be partially responsible. The biopsy instrument employed with the fiberoptic esophagoscope is quite small, and the tissue fragments are only a fraction of the size of those obtained through the rigid, open-tube esophagoscope. More specimens, from 6 to 8, are necessary to assure adequate coverage of the lesion, but when these are properly obtained, the accuracy rate is superior. The
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comfort and safety of the patient are also considerably improved over the older method. Routine brush cytology helps in the occasional patient in whom the esophageal lumen above the tumor is so narrow that adequate biopsies cannot be obtained. In such patients, the brush may usually be passed through the remaining opening with good cytologic recovery.v 11, 13 Routine use of the fiberoptic endoscope appears to represent the most accurate approach for early histologic diagnosis of carcinoma of the esophagus and cardia. Most esophageal lesions will still be advanced when this diagnosis is made, but the patient will at least have optimal opportunity for cure or palliation. REFERENCES Appelqvist, P.: Carcinoma of the Oesophagus and Gastric Cardia, Acta Chir. Scand. Supp!. 430: 1, 1972. 2 Block, G. E., and Lancaster, J. R.: Adenocarcinoma of the Cardioesophageal Junction, Arch. Surg. 83: 852, 1964. 3 Fierst, S. M.: Carcinoma of the Cardia and Fundus of the Stomach, Amer. J. Gastroentero!. 57: 403, 1972. 4 Hookman, P.: A Comparison of Endoscopic Biopsy and Esophageal Exfoliative Cytology in Establishing the Diagnosis of Carcinoma of the Esophagus, Gastrointest. Endosc. 12: 29, 1966. 5 Kobayashi, S., Prolla, J. C., and Kirsner, J. B.: Brushing Cytology of the Esophagus and Stomach Under Direct Vision by Fiberscopes, Acta Cyto!. 14: 219, 1970. 6 Kobayashi, S., Prolla, J. c., Winans, C. S., and Kirsner, J. B.: The Improved Endoscopic Diagnosis of Gastroesophageal Malignancy: Combined Use of Direct Vision Brushing Cytology and Biopsy, J. A. M. A. 212: 2086, 1970. 7 Kobayashi, S., Yoshii, Y., Winans, C. S., ProlIa, J. C., and Kirsner, J. B.: Use of Direct Vision Biopsy in the Diagnosis of Gastroesophageal Malignancy, Gastrointest. Endosc. 18: 23, 1971. 8 Kobayashi, S., Yoshii, Y., and Kasugai, T.: Selective Use of Brushing Cytology in Gastrointestinal Strictures, Gastrointest. Endosc. 19: 77, 1972. 9 Malmon, H. N., Dreskin, R. B., and Cocco, A. E.: Positive Esophageal Cytology Without Detectable Neoplasm, Gastrointest. Endosc. 20: 156, 1974.
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10 Nelson, R. S.: Radioactive Phosphorus in the Diagnosis of Gastrointestinal Cancer: Recent Results in Cancer Research, New York, 1967, Springer-Verlag, pp. 30, 39. 11 Prolla, J. c., Yoshii, Y., Xavier, R. G., and Kirsner, J. B.: Further Experience With Direct Vision Brushing Cytology of Malignant Tumors of the Upper Gastrointestinal Tract: Histopathologic Correlation With Biopsy, Acta Cytol. 15: 375, 1971.
12 Prolla, J. c, Taebel, D. W., and Kirsner, J. B.: Current Status of Exfoliative Cytology in Diagnosis of Malignant Neoplasms of the Esophagus, Surg. Gynecol. Obstet. 121: 743, 1965. 13 Yoshii, Y., Nobuyoshi, K., Yagi, M., and Kasugal, T.: Endoscopic Biopsy and Cytology in Esophageal and Gastric Carcinoma With the Fiberesophagoscope, Gastrointest. Endosc. 17: 150, 1971.