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Exfoliative Cytologic Study of Gastric and Esophageal Lesions *
Advantages to the Surgeon of the Chymotrypsin Method
HENRY W. MAYO, JR., M.D., HANS J. BRUNS, M.D.,
IRVING A. RomE, M.D., JOHN T. PRIOR, M.D.
From the Departments of Surgery, Medicine and Pathology, State University of New York,
Upstate Medical Center, Syracuse, New York
WITHN the last ten years, there has been Material and Method
renewed interest in exfoliative cytology of This study consists of observations made
the esophagus and stomach.1-14 Several upon patients from the surgical and med-
methods are available,1 satisfactory results ical services of the State University of New
have been reported for each although cer- York, Upstate Medical Center, and a few
tain disadvantages are apparent. private patients. The only criterion of selec-
Abrasive technics include the Ayre tion of patients for this series was the dem-
brush,' the abrasive gastric balloon, 7,14 onstration of abnormal or suspicious x-ray
and the antral balloon.12 Very satisfactory findings in the stomach or esophagus. The
specimens may be obtained by these meth- specimens were obtained by clinician mem-
ods, but they cause significant discomfort bers of a team, and, after staining, were
to the patient, and lack simplicity. The studied during regular meetings by all
abrading instrument may not reach impor- members of this team, under direction of
tant areas of mucosa.12 the pathologist. With some modification,
Simple lavage with saline or Ringer's the method of Rubin 10-13 was used as
solution is easily done, does not require follows:
special equipment, and is virtually non-
traumatic.3 This method yields fewer cells In the fasting patient, a Levin tube is
than the others, but good results have been passed into the stomach through the mouth,
obtained with it. to avoid contamination with nasal cells.
Papain is one of the mucolytic agents Contamination withbothnasalandesophag-
which frees cells from the mucous barrier, eal cells is minimized further by encourag-
and at times, excellent specimens may be ing the patient to expectorate and blow his
obtained by its use.8 Preparation of the nose often. Water is used as a lubricant;
papain solution is time-consuming, and cell oil is avoided because it might prevent ad-
digestion is not uncommon.12 Lavage with herence of cells to the slides. The stomach
a solution of chymotrypsin, another muco- is emptied by aspiration, and the material
lytic agent, is said to yield well preserved obtained is discarded. Next, the stomach is
and abundant cells, and is easily done, be- lavaged vigorously with Ringer's solution
ing practically nontraumatic.4 5 until the return is clear. In cases of pyloric
The purpose of this study has been to obstruction, extra attention must be given
determine the practical value of this chymo- to this step, if necessary over a period of
trypsin method. several days. The chymotrypsin solution
* Presented before the Southern Surgical Asso- used is prepared by adding the contents of
ciation, White Sulphur Springs, West Virginia, a commercially available capsule (CYTO-
December 10-12, 1957. LAVR) of 7,000 Armour units of salt free
733
734 MIAYO, BRUNS, ROTHE AND PRIOR Annals of Surgery
May 1958
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FIG. 1. Smear showing large malignan gastric cell just to of center. (x
it right 450)
chymotrypsin to 500 cc. of 0.1 molar acetate sible, the patients are transported to a loca-
buffer. This buffer is obtained by adding tion close to the centrifuge.
13.6 grams of sodium acetate and 0.6 cc. The supernatant fluid is decanted off and
of glacial acetic acid to 1,000 cc. of distilled discarded, and the sediment transferred to
water, and results in a pH of 5.6. slides upon each of which has been spread
As much of this chymotrypsin solution as one drop of albumen solution. A smear of
the patient can tolerate (usually 150 to 400 this sediment is then made. As a rule one
cc.) is instilled into his irrigated empty slide is made for each 50 cc. centrifuge
stomach. The solution is left in the stomach tube, or three to ten slides for each patient.
for exactly ten minutes. During this time, Glass pipettes are used for transport of the
the patient changes from the upright to the sediment to the slide and preparation of
recumbent position. While recumbent, he the smear. To avoid deterioration of cells
is rotated through 3600, so that the solu- the smears must not become too dry.
tion will cover all areas of the stomach. Smears of proper thickness will be obtained
The stomach is then aspirated as rapidly as with experience. The smears are fixed im-
possible, and the contents placed in stand- mediately in a solution consisting of equal
ard 50 cc. plastic centrifuge tubes, which parts of ether and 95 per cent ethyl alcohol.
are kept in ice in order to avoid further The slides are stained by the Papanicolaou
digestion by the enzyme. The material is technic (Fig. 1-2).
centrifuged immediately, using a refriger-
ated centrifuge at over 5,000 r.p.m. for five Results
minutes. Not more than ten minutes should The results of the study of material ob-
pass between aspiration and fixation of the
cells as described below. To make this pos- tained by the above technic from 50 con-
Volume 147
Number 5 STUDY OF GASTRIC AND ESOPHAGEAL LESIONS 735
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~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~.. ..... :.- . .. ..:....
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~. . .. ;; ..i5;;
:e ,: :. ... X~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~. ........
FIG. 2. Group of malignant gastric cells in center of field. ( x 450)
secutive patients are recorded in Table 1. the benign nature of the pathology, because
Malignant cells were foundin ten instances. the patients were not submitted to opera-
In six of these cases, the diagnosis of malig- tion. This group comprised cases of gastric
nancy was confirmed by later microscopic ulcer, "antral gastritis," peptic esophagitis,
tissue study, and in two cases, the diagnosis and hiatus hernia. There were 16 cases of
was confirmed by death with carcinomato- gastric ulcer; of these, ten subsequently
sis. In one case, the patient refused opera- appeared completely healed on radiologic
tion, and is still alive, although becoming examination, and three showed definite
progressively weaker. In the remaining signs of healing. The other three patients
case, a subtotal gastric resection was car- were lost to radiologic follow up, but are
ried out for a gastric ulcer, and multiple reported to be completely asymptomatic.
sections of this lesion failed to reveal any These 26 cases were followed for an in-
malignancy. On reviewing the smears of the terval of between one and eight months
latter case, since the malignant cells were after the examination, the average length
found to be superimposed on other cells, it of follow up time being 3.3 months. There
was thought that this false positive might were two patients in whose smears no
possibly represent contamination from an- malignant cells were found, but in whom
other specimen which occurred in the proc- malignancywasdemonstratedsubsequently.
ess of passing the slides through the stain. One of these patients developed a gastro-
No malignant cells were found in 40 colic fistula some time after examination,
specimens. In 12 of these cases, the benign and at the time of his death, carcinoma in-
nature of the disease was confirmed by his- volved both the stomach and colon. It is
tologic study of surgical specimens. In 26 possible that this lesion was primary in the
patients, there is no tissue confirmation of colon and invaded the gastric mucosa some
BRUNS, ROTHE AND PRIOR Annals of Surgery
736 MAYO, May 1958
time after chymotrypsin gastric lavage was Case 4. A 63-year-old man disclosed on x-ray
done. The other patient died subsequently examination a gastric ulcer high on the posterior
with a scirrhous carcinoma of the stomach wall toward the lesser curvature. This ulcer was
and carcinomatosis. The pathologic nature not visualized through the gastroscope. The smears
of this lesion, in which the submucosa is obtained by the chymotrypsin gastric lavage
showed no malignant cells. At operation, a large
chiefly involved, might possibly explain this ulcer penetrating into the pancreas was found. Be-
false negative cytologic diagnosis. cause of the surrounding large lymph nodes, it
Thus, in a small series of 50 consecutive was the surgeon's opinion that the lesion repre-
cases with abnormal x-ray findings in the sented carcinoma, and total gastrectomy was per-
esophagus or stomach, the cytologic diag- formed. Microscopic study of the specimen indi-
cated the lesion was benign. This crippling pro-
nosis was presumably correct in 47, and cedure might have been avoided, if results of the
obviously incorrect in three. cytologic study had been thought to be dependable.
The following cases were thought to be Case 5. A 78-year-old man presented on x-ray
of special interest as illustrations of the study a fungating lesion of the greater curvature
potentialities of this method. of the pars media of the stomach. He also had an
enlarged nodular liver, and an elevated alkaline
Case 1. In a 48-year-old man, a lesion of the phosphatase. A positive cytologic diagnosis was
fundus of the stomach was demonstrated, which made. Subsequently, a needle biopsy of the liver
some radiologists thought to be extra-mucosal, al- confirmed presence of metastatic adenocarcinoma,
though others thought this roentgenogram repre- and in view of his rapidly deteriorating state, he
sented gastric carcinoma. This lesion could not was discharged forterminal care, without operation.
be visualized at esophagoscopy. Cancer cells were Case 6. A 67-year-old man was found to have
obtained by gastric lavage (Fig. 1). a large lesser curvature gastric ulcer. The gas-
Case 2. A 76-year-old man had a lesion at the troscopist thought that there was definite evidence
cardia of the stomach on x-ray examination in- of malignancy in the appearance of the ulcer.
terpreted as carcinoma. This lesion was visualized However, cytologic study was negative for malig-
through the esophagoscope, but the biopsy ob- nant cells. Operation was planned, but the patient
tained showed normal mucosa with inflammation. refused surgery. On follow up examination three
A positive cytologic diagnosis was made, and in months later, his ulcer was healed.
view of his poor condition, the patient was dis- Discussion
charged for terminal care and died at home a
month later presumably of carcinomatosis. Un- This series of cases is admittedly small,
fortunately, no autopsy was done. and the follow up time on unconfirmed
Case 3. A 47-year-old man had radiologic conclusive
demonstration of apparent carcinoma of the lower cases is too short to allow any
esophagus. The lesion was visualized through the statements. Yet, the studies suggest strongly
esophagoscope at the 38 cm. level. Biopsy showed that previously reported results may be re-
no evidence of malignancy. A positive cytologic produced. None of the participants had had
diagnosis (Fig. 2) seemed to justify exploration previous experience with the method or
without further esophagoscopy. At exploration, ex- instruction in it.
tensive metastases from a primary adenocarcinoma
of the lower esophagus were found. In particular, cytologic study may be
useful in some special situations, if proven
TABLE 1. Confirmation of 50 Cytologic Diagnoses consistently reliable:
Malignant Benign 1. In the esophagus, in instances in
Confirmed by tissue study 6 12 which a lesion is demonstrated by x-ray,
Confirmed by death due to positive cytology may make unnecessary
carcinomatosis 2 biopsies through the esophagoscope, which
Not confirmed to be false 1 26 involve a certain risk. Moreover, it may be
Diagnosis proved 1 2 impossible to reach the lesion through the
by tissue study in where cytological
Total 10 40 instrument instances
study may be positive (Cases 2, 3).
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