Gastric cancer: Correlation of roentgenological and pathological findings

GASTRIC CANCER: CORRELATION OF ROENTGENOLOGICAL AND PATHOLOGICAL FINDINGS* LEWIS

NEW

YORK

types of gastric cancer give different roentgenoIogica1 findings because of their various gross morphoIogica1 characteristics. Our earIy attempts to fit roentgenoIogica1 findings into one of the many pathoIogica1 cIassif?cations were, I beIieve, recognized by Ewing. The wide variation of these cIass& cations, the ambiguity of the terms empIoyed, and the compIexity of the cIassifications resuIting from the endeavor to combine both gross and microscopica findings, discouraged me in these earIy attempts. You may refer to textbooks for these many pathoIogica1 cIassifications. Even quotations from these, in contradiction with each other, might seem to reffect discredit on their compiIers, which is not my intention. Gross morphoIogy aIone has not been considered suffIcientIy accurate criteria for pathoIogica1 cIassifications. Microscopica criteria aIone, as suggested by Kauffman, seem to be unsatisfactory, because differor at Ieast different ent pathoIogists, schools of pathoIogy, cIassify Iesions differentIy on the same microscopica sections. On the same section of the commoner varieties of cancer, different pathoIogists wiI1 designate the Iesion by various names or terms, and, in the border-Iine cases, there is IittIe or no unanimity of ohinion as to the type of cancer, or even as to whether the Iesion is carcinoma, sarcoma, or granuIoma. There is a surprising divergence of opinion as to whether a Iesion is maIignant or benign. Furthermore, a cIassification based on a combination of gross and microscopica findings is not practica1 for cIinica1 use, firstIy because

V

ARIOUS

* Read at a Round Table Conference

COLE, M.D.

GREGORY

CITY

of the compIexity of combining the two, and secondly because the cIassification cannot be made until after death, or at Ieast unti1 after operation. Therefore it offers no aid in the soIution of the probIem of indications for surgica1 or medica treatment. Purdy Stout’s extremeIy simpIe cIassification (nameIy, the division of cancers into fungating and infiltrating types, in a paper presented at the New York Academy of Medicine in May, Ig34), stimulated me again to attempt an x-ray cIassification based on gross morphoIogy as observed in the Iiving functioning stomach. The roentgenoIogica1 findings of gastric cancer as reveaIed by seria1 roentgenography (muItipIe fXms in rapid succession in the same direction) are not based soIeIy on the so-caIIed “ fiIIing defects” caused by the projection of the growth into the Iumen of the stomach, a condition that wouId constitute true gross morphoIogy of .the inner surface of the stomach. But, by seria1 roentgenography one can aIso show the absence of or abnorma1 peristalsis due to Iack of pIiabiIity of the gastric waI1 caused by the infiItration of the submucosa by cancer ceIIs without growth of the cancer into the Iumen. Gastric peristaIsis is the function of the muscuIaris mucosa and not of the reguIar muscuIar coat, as it has been generaIIy assumed. A few cancer ceIIs onIy, in the superficia1 portion of the submucosa fixed to the muscuIaris mucosa, wiI1 interfere with the function of this muscIe to such an extent as to cause a Iimp in gastric peristaIsis. This finding is most marked in seria1 roentgenograms, and especiaIIy when

on Cancer at the Fiftieth ‘934.

206

Anniversary

of the MemoriaI Hospital,

May 25,

NEW SERIES VOL. XxX1,

No. z

Cole-Gastric

X-ray

reproduced cinematographically. RoentgenoIogica1 findings thus observed may be very marked in a case having such a slight mucosa1 Iesion that, aIthough the cut surface and the inside of the specimen have been carefuIIy examined with the question of mahgnancy in mind, the cancer is not recognized even by a competent pathoIogist. In the vast majority of cases presenting themseIves for roentgenoIogica1 examination, there is IittIe or no diffrcuIty in making a positive or negative diagnosis of gastric cancer on the x-ray findings. In these cases the diagnosis is as easy as and more accurate than the diagnosis of fracture. The pathoIogica1 reports usuaIly prove that “the roentgenoIogica1 diagnosis this is a11 that is correct,” and apparentIy couId be desired. However when the pathoIogicaI report proves that the x-ray diagnosis is wrong, that is another matter, and, although not the subject of this communication, it is, nevertheIess, a mighty interesting one. In other cases the roentgenologist has diffrcuIty in differentiating carcinoma from some other mahgnant or nonmaIignant neopIasm, and the pathoIogists have equal or even greater diffrcuIty in making such a differentia1 diagnosis. We have ampIe proof of this for seven or eight sections have been submitted to a large group of representative pathologists and there is no unanimity in their opinions either as to maIignancy or type of lesion, and in perhaps the most important case the twenty-four pathologists were equaIIy divided. TweIve thought the case maIignant and tweIve considered it benign. An attempt shouId be made to estabIish a definite negative or positive roentgenoIogica1 diagnosis of gastric cancer in every case examined, giving a description of its morphoIogica1 characteristics, nameIy, the size and extent of the growth, its location in the stomach, whether it protrudes abruptIy into the Iumen of the stomach, or whether it is an unprotruding, infiItrative type of Iesion. In the fungatory or protruding type of Iesion with no invasion of the gastric wall adjacent to the

& Pathology

American

Journal

or strrgery

207

tumor-mass, gastric peristaIsis is unobstructed until it reaches the growth. Whereas, in the i&Itrative type of lesion,

Extensive carcinoma.* c, cap; P, peristalsis; indentations of carcinomatous ‘nodules; CC, conica arc3 of constriction; LI, line of invasion.

FIG.

I.

ICN,

the ceIIs invade the submucosa and interfere with gastric peristaIsis for a considerable distance from the main portion of the Iesion. A reIativeIy few cancer ceIIs in this region definiteIy interefere with This interference is gastric peristaIsis. marked because gastric peristaIsis is the function of the rather delicate muscularis mucosa and not the reguIar muscular coat, as has aIready been mentioned. This Iack of pIiability, in reality, is a pathoIogica1 characteristic observed roentgenoIogicalIy in the living, functioning stomach; therefore, it becomes of paramount cIinica1 because it is observabIe besignificance, fore, instead of after, operation or autopsy. Such roentgenoIogica1 findings as these should be used to determine whether a Iesion is suffrcientIy Iimited to the pyloric region or possibIy to the corpus, to permit surgica1 cure or aIIeviation, or whether it invoIves the body of the stomach, cardia or fornix, where surgery is diffrcult or * This identical half-tone was used by the author to illustrate typical findings of gastric carcinoma in the “Journal of the American MedicaI Association,” November 30, 1912. The uninvoIved cap, peristakis ceasing at the line of invasion, indentations of carcinomatous nodules, conica area of constriction, and the line of invasion on the greater curvature described at that time Ieave nothing to be added more than two _ . _ decades later.

208

A merican JournaI of Surgery

Cole-Gastric

X-ray

impossibIe. WhiIe the Iocation and extent of a cancer is important in deciding whether surgica1 procedure either for cure or pahiation is indicated, it must be remembered that a very extensive fungatory growth, even one invoIving the body or offers a far better chance for corpus, surgica1 cure or paIIiation than a much smaIIer growth of the infiItrative type, invoIving onIy a Iimited region of the pyIorus. The roentgenoIogica1 findings discussed in hearty cooperation with the surgeon shouId be used in determining not onIy whether operation is indicated, but the specia1 type of operation best adapted to each particuIar case. A fuI1 recognition on the part of the surgeon of the region of the stomach invoIved, the extent of the Iesion, and whether it is a fungating or infiItrative type, may Iead him to abandon the type of operation he usuaIIy empIoys and to perform one pecuIiarIy adapted to the particuIar case under consideration. RoentgenoIogicaI findings can be utiIized in compiIing a practica1 cIinicopathoIogica1 cIass&ation that may guide one in determining the Iine of treatment and in the soIution of other cancer probIems. This cIassifrcation is based on four roentgenopathoIogica1 characteristics: /a.

(I) Regional churacteristics (How far from the pyIorus is the proxima1 Iine of invasion?)

(2)

Obstructive characteristics. (Does the growth itseIf protrude sufikientIy far into the Iumen of the stominterfere ach to with the passage of food?)

antra1, or pyIoric b. corporea1, or of the body c. cardiac, cIose to the esophagus d. fundic, or invoIving \

& PathoIogy

FEBRUARY, 1936

(3) Infiltrative churucteristics (Is the Iine of invasion sharpIy defined at the periphery of the tumormass or does it taper off graduaIIy?) (4) Protruding churucteristics (Does the Iesion grow abruptIy into the Iumen of the i. protruding stomach? What are j. nonprotruding the surface characteristics of the protrusion-are they smooth or rough and cauIifI ower?) AI1 of these roentgenoIogica1 hndings are practicaIIy identica1 with the gross pathoIogy. The tumor-mass may project into the “ Auid cast” of barium, causing an indentation just as constant as one’s finger prints in a baI1 of putty, even to the whorIs. The infiItrative growth may render the normaIIy pIiabIe gastric waI1 stiff, obstructing or preventing peristaIsis further from the growth than the mucosa1 invoIvement indicates. The correIation of roentgenoIogica1 findings with the morphoIogy of the Iesion, as observed in the gross pathologica specimen (prepared in a specia1 manner so as to Ieave it undistorted by the fixing soIutions) is the theme of this articIe. A further correIation of the gross pathoIogy of the speciaIIy prepared specimen with Iarge microscopical sections is the next step toward the fina1 correIation of the microscopica1 findings observed in a smaI1, IocaI region of the’ Iesion with the roentgenoIogica1 findings in the same region as observed in the Iiving functioning stomach. Another point of correIation between the pathoIogy in the Iiving subject, as observed roentgenoIogicaIIy, and the high-powered microscopica1 observation, is the manner in

New SERIES VOL. XxX1, No.

2

Cole-Gastric

X-ray

which carcinoma, even of the infiItrative type, ends abruptIy at the dista1 base of the pyIoric vaIve at the very point where the muscuIaris mucosa and submucosa terminate. (Figure 27.) The most dista1 or abnorma1 carcinomatous ceIIs and the end of the muscuIaris mucosa and submucosa are usuaIIy observed within a singIe high-powered microscopica fieId. ConsequentIy, carcinomatous or other malignant Iesions of the pyloric end of the. stomach as observed roentgenoIogicaIIy show a reIativeIy norma cap. This finding is so striking that it might possibIy be a key to the Iong-Iocked door of the etioIogy of cancer. In contradistinction to this, nonmaIignant inff ammatory Iesions invoIving the pyIoric region have a definite tendency to transgress the pyIoric vaIve and extend across to invoIve the cap, and visa versa. A specia1 study of malignant and nonmaIignant Iesions in this region is of paramount importance at this time, because of the oft-quoted statement of George HoImes, “that a11 organic Iesions invoIving the pyIorus within one inch or so of the pyIoric vaIve shouId be considered maIignant unti1 proved otherwise,” the inference being that they are to be proved otherwise by surgica1 procedure. In discussing HoIme’s origina articIe on this subject, I expressed the opinion that this was a most pernicious statement, and predicted that it wouId cause the performance of IiteraIIy hundreds of unnecessary pyIorectomies. Since that time I have given the matter stiI1 more serious consideration, and, whiIe many Iesions, uIcerative and nonujcerative in this region are maIignant, for every pyIoric cancer demonstrated roentgenoIogicaIIy in this region, I can show a roentgenogram of a nonmaIignant lesion. Often these are heaIed or, unheaIed uIcers in patients who have Iived for many years without symptoms. This phase of the subject wiI1 be considered Iater. When this paper was presented at the round tabIe discussion, fifty Iantern sIides were shown to iIIustrate the various steps in correIating the roentgenoIogica1 findings

& PathoIogy

American

Journdof

Surgery

209

with both the gross and microscopica findings observed in various stages of maIignant and nonmaIigant Iesions. These steps were as foIIows: I. An x-ray showing the Iiving, functioning stomach with norma pIiabiIity of the uninvoIved region. 2. An x-ray of the Iumen of the gross specimen f3Ied with barium. 3. Photographs of the outside of the gross specimen, both ventra1 and dorsa1 surfaces. 4. An x-ray or photograph of the wax mode1 that heId the specimen in shape during the period of fixation. 5. Photographs of the inside of the gross specimen, both ventra1 and dorsa1 surfaces. 6. Magnified photographs of a Iongitudina1 cut section through the Iesion which show detaiIs that are quite astonishing. 7, Magnified photographs of a Iarge microscopica section of the same region as described in heading 6 stained with various stains, especially Masson’s trichrome soIution, correIating the gross with the microscopica findings. This section shouId be Iarge enough to show the Iesion at the Iine of invasion where pathology joins normaIcy. 8. Low and high-powered photomicrographs showing orthodox and unorthodox microscopic criteria for the diagnosis of cancer. The Iimitation of space and the expense of reproduction necessitates the eIimination of some of these iIIustrations. However, the origina microscopica sections are avaiIabIe to a11 who wish to study them, particuIarIy to those who wish to study and discuss the so-caIIed unorthodox microscopic criteria presented. The remaining portion of this articIe wiI1 be devoted to case reports and to a very simpIe procedure of comparing the roentgenoIogica1 findings with the gross specimens, and then with the Iow and highpowered magnifications as reproduced in photomicrographs. The first case, iIIustrated by the roentgenogram in Figure I. was seIected out of

2 IO

American Journal of Surgery

Cole-Gastric

X-ray

hundreds of cases of cancer to show typica roentgenoIogica1 findings and aIso because of its historica interest and its controversia1 aspect at the time the roentgenoIogica1 examination was made. It was one of the first cases in which I made a positive diagnosis of cancer soIeIy on the roentgenoIogicaI findings. Patient D. S. B., referred to me by Dr. Max Einhorn, was x-rayed on January 27, I 91 I, a report of which foIIows :

“X-ray findings: A series of ten pIates made during inspiration shows the size, shape, and position of the stomach very accurateIy. The greater curvature is about three inches beIow the umbihcus, the Iesser curvature is on a IeveI with the umbiIicus. The position of the pylorus is indicated by the first portion of the duodenum”-(we had not yet recognized this as the cap)-“and shows that the pyIorus is heId we11 up in position. There is aImost compIete absence of bismuth in the pyIoric end of the stomach. The Iumen of the stomach at the pyIorus is reduced to a fine line about the size of a Iead penci1 and is irreguIar in shape. This constricted area is about two and one-half inches Iong, then it diIates into a funnel-shape near the center of the body of the stomach. “Diagnosis: From a study of the pIates one is justified in making a positive diagnosis of an advanced new growth at the pyloric end of the stomach, the Iumen being almost compIeteIy contracted for a distance of about two and one-haIf or three inches.” The patient was subsequently operated on at the Mayo Clinic. In October 1912, almost .two years Iater, at a time of great controversy concerning the vaIue of x-ray in the diagnosis of gastrointestinal lesions, a symposium was given before the Mississippi VaIIey MedicaI Association. This symposium consisted of three papers discussing (a) the reIative vaIue of symptom compIices, or indirect method of diagnosis, as advocated by the Continental schooIs; (b) direct detection of pathoIogica1 lesions, referred by some as the American method; and (c) a discussion tending to prove that neither of these methods was of any vaIue in the diagnosis of gastro-intestinal Iesions. This negative aspect of the controversy was taken by

& PathoIogy

FEBRUARY,1936

Doctor SeIby, then roentgenoIogist at the Mayo CIinic, who said that x-rays were a11 right for the diagnosis of bone, kidney and Iung Iesions, but were of no use for gastrointestina1 Iesions. In November I 9 I 3, still a year Iater, after having Iearned from Doctor Einhorn that the patient had been operated at the Mayo

Clinic, an inquiry ing repIy :

brought

forth the foIIow-

The findings at operation in the case of Mr. D. S. B., “the patient had two uIcers, one in the stomach and one in the duodenim. The uIcer in the stomach was indurated and adherent to the pancreas. There was marked obstruction. There was a pecuIiar soft tumor 4” or 5” from the origin of the jejunum, rendering an anterior gastro-enterostomy necessary. The uIcer in the stomach was aImost continuous with the one in the duodenum. WhiIe a good many gIands were found to be involved, we were unabIe positiveIy to estabIish maIignancy. There were aIso many noduIes in the Iiver, apparentIy secondary to the growth in the stomach .”

This report tended to prove that our diagnosis of gastric cancer was inaccurate. However, Doctor Einhorn later reported that the patient was not improved by the anterior gastroenterostomy and had died of gastric cancer. A postmorten examination was not made, but a postmorten on this incident began to throw some doubt on the accuracy of the yardstick of surgica1 expIoration and Ieads to some thought as to this cure not vitiating the surgica1 statistics of cancer cures. Since 1910-1 I it has been our practice to make a negative or positive diagnosis of gastric cancer in every gastrointestina1 case examined. We are frequentIy asked with what accuracy this can be accomplished. My repIy is that that depends upon the yardstick by which our accuracy is measured,-whether it is the immediate clinica history, surgica1 expIoration, pathoIogica1 findings as observed microscopicalIy, or the fina termination of the case. The accuracy of these yardsticks will. not be stressed at this point. In a very few cases

NEW SERIES

VOL..

XXXI,

No.

2

Coie-Gastric

X-ray

I have been compeIIed to make an equivoca1 diagnosis. In some other cases an equivoca1 diagnosis had to be made because

& PathoIogy

American Journal of Surgery

2 I I

between the noduIes. The gastric waII was pIiabIe al1 the way to the base of the growth. The patient, W. H. D., was

FIG. 4. Photograph of inside of same specimen removal of wax cast.

after

there was no unanimity of opinion among us, or because none of us was willing to make a definite positive or negative diagnosis of malignancy. An extensive fungating growth, which protrudes into the Iumen of the stomach

operated on by Dr. Bancroft at the Fifth Avenue HospitaI, and the Iumen of the specimen was filIed with barium, as shown in roentgenogram Figure 3. This x-ray of the surgica1 specimen is very simiIar to the original x-ray, and almost identical to the wax cast (made by Ming the Iumen with low-melting point paraffin and aIIowing it to harden before the specimen had become

FIG. 3. Roentgenogram of Iumen of surgical fiIIed with barium.

FIG. 5. h,lagnified photograph showing characteristic of growth.

FIG. 2. Gastric carcinoma: fungating cauliflower type. N, Nodular protrusions. s, SUICUSbetween noduIes.

specimen

causing Iarge, deep fingerprints in the barium mass, is shown in roentgenogram Figure 2. Th e cap and descending duodenum were we11 fiIIed, and, strange as it may seem, the stomach evacuated itseIf in a normaI period of time, except for a smaI1 deposit of barium deep in the creases

peduncuIated

distorted and shrunken by the fixing soIution). The interior of this speciaIIy prepared specimen, after the removal of the wax moId, (Figure 4) shows a Iarge fungating growth. The manner in which this growth retracted or drew the gastric wall aImost to

2 I2

American Journal of Surgery

CoIe-Gastric

X-ray

its center is of vast significance. The importance of this significance is indicated by the fact that the gastric waII up to the base of

FIG. 6. Gastric carcinoma: infihrative type, indicated by lack of pIiabiIity of lesser curvature without protrusion and by gradations of density in the invoIved area. I, infiItrated area; P, peduncuIated area.

the pedicle, and even the gastric waII drawn into the growth, is cancer-free. A magnified photograph of a IocaI region (Figure 5) shows the peduncuIated character of this type of cancer, and even the manner in which the pedicIe of the growth is composed of normal gastric constituents rather than of carcinoma. These gross pathoIogica1 findings, which were equaIIy we11recognized in the roentgenoIogica1 findings, indicate that this very extensive growth, invoIving not only the pyIorus but part of the body of the stomach as weI1, was far more favorabIe for operation with hope of cure than a very much smaIIer Iesion of an infiItrative type, even though in this particuIar instance the patient died two weeks postoperativeIy. A casua1 observation of the next roentgenogram (Figure 6) reveaIs a much Iess extensive Iesion than that of the previous case, this one being Iimited to the extreme pyIoric end of the stomach, and therefore presumabIy a more favorabIe case for An intensive study of this operation. however, shows that the roentgenogram, Iesion shades off verv EraduaIIv into the

& PathoIogy

FEBRUARY,1936

uninvoIved portion of the stomach, indicating that it is of the infiItrative type in contradistinction to the fungating type,

FIG. 7. Photograph of the inside of the gross specimen showing infiItrative type on the Iesser curvature and posterior wall with pedunculated tendency on the greater curvature. I, infiltrated area; P, peduncuIated area.

and therefore Iess amenabIe to surgery. This case, Mr. G., was aIso operated on by Dr. Bancroft. A photograph of the gross specimen prepared in the specia1 manner previousIy described shows the Iumen of the stomach (Figure 7) corresponds with that of the roentgenogram. The sudden, deep indentation aIong the greater curvature has some tendency to be peduncuIated as described in the foregoing case, but the growth invades the Iesser curvature and posterior waII aImost to the Iine of resection, thus indicating its infiItrative character. Microscopic sections of this Iesion show such characteristic orthodox criteria of carcinoma that iIIustrations are unnecessary. The aforementioned statement of George HoImes that every organic Iesion invoIving the pyIorus shouId be considered maIignant unti1 proved otherwise Ied my son, Dr. WiIIiam Gregory CoIe, to make an equivicaI diagnosis of cancer on the roentgenoIogica1 findings observed in Figure 8.

NEW SERIES VOL. XxX1, No. z

Cole-Gastric

X-ray

& PathoIogy

American ~~~~~~~~ ,,fsurgery

2I3

Because he was unwilling to state that this Iesion was not maIignant, it was considered necessary to resort to surgical exploration. *

coat was broken and retracted and replaced by connective tissue. There were slight changes in the mucosa adjacent

FIG. 8. Roentgenogram showing pyIoric fibrosis with fan-shaped mu&e the folIowing detail. A, thickened on greater curvature; C, fan-shaped muscle on Iesser curvature destroyed by scar tissue; E, cap; G, Iumen of contracted pyIoric cana1; I, mucosa1 fold.

FIG. 9. Photograph of the IongitudinaIIy cut section. A, thickened fan-shaped muscIe on greater curvature; H, portion of cap removed with specimen; c, fanshaped muscle on Iesser curvature destroyed by scar tissue; E, cap; I:, Iumen of pyIoric antrum; G, Iumen of contracted pyIoric canal; H, proximaI end of section; I, mucosal fold; L, whorIs of scar tissue.

A photograph of the inside of the gross specimen (Figure g) shows a partialIy obstructive Iesion invoIving the pyIoric canaI. The contour of the Iumen of the surgica1 specimen corresponds absoluteIy with the roentgenoIogica1 findings, even to the mucosal foIds aIong the greater curvature at the proxima1 end of the thickened fan shaped muscIe. A magnified photograph of the microscopica section shows the extent of the microscopical materia1 studied, (Figure I o) which incIuded both the greater and Iesser curvatures. AIong the Iesser curvature the reguIar muscular coat is broken and repIaced by connective tissue, which under higher magnification was found to aIso involve and cicatricalize the intramuscuIar spaces between the muscIebundIes in the fan shaped muscIe aIong the greater curvature and prevented its norma reIaxation. This permanent contraction of the pyloric cana prevented Dr. WiIIiam Gregor.): Cole from making a negative diagnosrs of gastric cancer. A photomicrograph of the Iesser curvature (Fig. I I) shows the manner in which the muscuIar * For a compIete report of this case see “The Surgical Clinics of North America,” April 1933, pp. 3q3~.

to this region, but there were no microscopical criteria that wouId justify one in considering this Iesion carcinoma. The

FIG. IO. Low power photomicrograph showing: A, the heaped-up, contracted fan-shaped muscle on the greater curvature; B, the portion of the cap removed at the time of resection; c, a mass of scar tissue in the center of the retracted fan-shaped muscIe on the lesser curvature; D, retracted fan-shaped muscIe; F, Iumen of the pyloric antrum; I, prominent mucosal foId.

patient died of pneumonia before leaving the hospital, so that, according to the ruIing of the American CoIIege of Surgeons, it was cIassified as a surgica1 mortaIity.

2

I4

American Journal of Surgery

CoIe-Gastric

X-ray

& PathoIogy

FEBRUARY. 1936

IncidentaIIy, the patient is just as dead as if he had died of carcinoma some years Iater and his death may be attributable

with connective tissue, which extended into it from the superficia1 area of &eration on the Iesser curvature. The absence

FIG. II. High-power photomicrograph of the Iesser curvature in the region of the scar of the healed uIcer, showing: J, the suhperitoneal patch; K, the regular muscuIar coat; L, whorls of scar tissue; D, retracted fan-shaped muscle; P, muscuIaris mucosa broken and retracted.

FIG. 12. Pyloric carcinoma. IF, Smooth rounded area of infiItration of the fan-shaped mu&e with absence of the mucosa1 foId shown CharacteristicaIIy in CA, cancer. Figure IO (I) ; u, smaII superficial uIceration.

to our fear that this prepyIoric Iesion might be cancer. Based on HoImes dictum. Numerous cases such as the one just mentioned Ied me to be extremeIy cautious concerning a positive diagnosis of carcinoma in the pyIoric region, particuIarIy when the fan shaped muscIe is invoIved. In the foIIowing case, Mrs. R., I erred temporariIy in that I faiIed to make a positive diagnosis of carcinoma on the roentgenoIogica1 findings as iIIustrated in Figure 12. In this roentgenogram a smaI1 area of superficia1 uIceration was recognized on the Iesser curvature about $$ inch proxima1 to the vaIve. This uIcer was surrounded by a smooth area of induration which encircIed the pyIoric region and particuIarIy protruded into the Iumen from the greater curvature. The Iack of a noduIar mass forming finger prints and the absence of irreguIarities in this indurated area due to uIceration Ied me to beIieve that this annuIar constriction resuIted from a contraction of the fan shaped muscIe infiItrated

of rugae in the contracted region was recognized but I did not then reaIize that the smooth curve of the indurated area on the greater curvature, which was singuIarIy free from mucosa1 foIds protruding into it, was such an important diagnostic factor. Therefore, I advised that for three weeks the patient be treated medicaIIy with rest in bed, during which time she gained severa pounds and became practicaIIy symptom free. However, the roentgenoIogica1 findings at the end of this time showed no change whatever (no increase nor decrease). In the fourth week she had a sudden recurrence of symptoms and a pyiorectomy was performed by Dr. Bancroft. The patient survived the operation and remained we11 for nine months but finaIIy died of carcinoma. A photograph of the inside of the gross specimen of this case (Figure I 3) correIated with the roentgenogram (Figure 12) shows that the smooth curve of the unbroken mucosa on the greater curvature is, in reaIity, caused by a carcinomatous inva-

NEW SERIES VOL. XXXI,

No. z

Cole-Gastric

x-ray

sion of the submucosa, which prevents the mucosa from being thrown into foIds. One of the most important points in this whoIe communication is a comparison of this roentgenogram and gross pathoIogica1 specimen with those of the previous case (Figures 8 and g, reported in detai1 by Dr. Wham Gregory Cole), in which a permanent fibrotic contraction of the fan shaped muscIe throws the mucosaI foIds into boId reIief. To formuIate more cIearIy this differentiation between maIignant and nonmaIignant Iesions of the pyIoric cana1, the foIIowing facts shouId be borne in mind : Carcinomatous infltration may be noduIar or may have the irreguIarities of uIcerations, or may be perfectIy smooth or rounded, and curved as iIIustrated in the case of Figures 12 and 13. In contradistinction to this, there is a very Iarge and important group of cases where just as great a degree of pyIoric stenosis is due to a contraction and fibrosis of the fan-shaped muscIe. In these cases the submucosa is not markedIy invoIved by connective tissue and it aIIows the mucosa to be thrown into deep folds, which protrude from the greater curvature into the Iumen of the stomach, giving a characteristic point of differentiation between a Iarge group of nonmaIignant Iesions and various types of carcinomatous invoIvement of this region. This roentgenogram (Figure 14) of patient, Mr. P., shows a Iarge uIcerating Iesion on the greater curvature protruding into the Iumen of the stomach. This examination was made in 1927 before I was aware of the fact that simpIe benign uIcers always occur nearer the Iesser curvature than the greater. As this one was directIy on the greater curvature, we wouId now know that it was maIignant, or at Ieast an uIcerating neopIasm. In this instance, however, our equivoca1 diagnosis did not materiaIIy deIay operation. A Iarge microscopica section, incIuding the crater and both Iips of the uIcer (Figure 13) shows a very marked simiIarity

8; Pathology

American

~~~~~~~

of surgery 2

15

to the roentgenoIogica1 findings, even the size and shape of the overhanging Iip of the crater. It shouId be particuIarIy

FIG. 13. Magnified photograph of inside of gross specimen showing: IF, carcinoma invading fan-shaped u, smaII superficia1 ulcer. mu.&;

noted that the crater does not protrude beyond the norma contour of the stomach. Even this deep crater had not destroyed a11 of the muscuIature, the bundIes being fixed by carcinomatous invasion prior to the deveIopment of the uIcer in the center of the tumor-mass. In contradistinction to, or for comparison with the previous case, we show a photograph of an uIcer on the lesser curvature of the stomach of approximateIy the same shape and size (at Ieast Iarger than the proverbia1 quarter, considered by the Mayos as the borderIine between uIcers that may or may not be maIignant), which was not maIignant (Figure 16). The manner in which the reguIar muscuIar coat in the benign uIcer is broken and the way in which the crater invoIves the intraperitonea1 space beyond the normal contour of the Iumen of the stomach, and many other pathoIogica1 and roentgenoIogicaI characteristics, aid one in differentiating between uIcerating carcinoma and simpIe

216

A mrican

Journalof Surgery

Co&-Gastric

X-ray

benign uIcer, even though the Iesion is Iarger than the proverbia1 quarter. The next case, Mrs. C., represents one

FIG. 14. Ulcerating

carcinoma

on the greater curvature ing into the Iumen; UA,

of the most serious mistakes I have ever my made, and now, whiIe reviewing origina roentgenoIogica1 findings, I fee1 rather confident that I wouId not repeat this error. The mistake was due, in part, to inaccurate observations and, in part, to poor or even very bad judgment, or to the wish that it might not be maIignant. The facts are that there was a very smaI1 area of superficia1 uIceration just above the SUICUS,and furthermore, there was a peristaItic wave between it and the adjacent s&us anguIaris, which I then inter-

& PathoIogy

FEBRIJARY, rg36

preted as a crater instead of the superficia1 mucosa1 erosion above it. (Figure 17.) There was an extremely deep contraction

in the pyloric region. CG, Carcinomatous ulcerating are; in its center.

growth

protrud-

on the greater curvature, which had drawn in the gastric waI1 in a manner similar to that shown in Figure 4. There was Iack of pIiabiIity aIong the Iesser curvature a11 the way from the SUICUSto the pyIoric vaIve. These two findings shouId have made me suspicious of maIignancy, even at the very first examination. The third roentgenoIogica1 examination, made three weeks Iater, (Figure 18) in reaIity shows that the uIcer itseIf had increased in size, but comparing the crater of the uIcer in this second examination with the

FE. I 5. Magnified photograph of gross section showing: c, crater; M, mucosa; MP, muscuIaris propria not broken but infiltrated with carcinoma and retracted; SI, submucosa, infiltrated with carcinoma; P, peritoneum of serosa1 coat, no subperitoneal patch.

FIG. 16. Magnified photograph of simple benign gastric ulcer showing: c, crater; M, mucosa; VP, muscularis propria broken by the ulcer; s2, submucosa, connective-tissue wedge; PP, subperitoneal patch of connective-tissue in intraperitoneal gastric triangle.

218

American Journal of Surgery

Cole-Gastric

X-ray

peristaItic wave I had misinterpreted as an uIcer crater in the first examination, it had apparentIy diminished in size.

& PathoIogy

FEBRUARY,

1936

An expIoratory operation performed by Dr. Bancroft reveaIed the entire abdomen to be studded with a diffuse carcinomatous

I

UI

FIG. I 7. Gastric carcinoma: first roentgenoIogica1 examination showing: LP, lack of pIiabiIity; DS, deep suIcus on greater curvature pointing to the region of the Iesion; UI, uIcerating induration.

One month Iater, in a fourth roentgenoIogica1 examination, the entire Iesser curvature of the pyIoric region remained constant as in the two previous examinations,-a fact which shouId have Ied me to the definite diagnosis of maIignancy at this time. The crater was shaIIower, being fiIIed by growing carcinomatous tissue, and the area of induration had increased,aIso an indication of uIcerating carcinoma. Many series of roentgenoIogica1 examinations over a considerabIe period of time finaIIy led to the one iIIustrated in Figure Ig in which the crater had diminished to a very smaI1 spot, the rugae in the adjacent gastric waI1 had a11 centered toward this crater, the tumor-mass had not protruded into the stomach, and, aIthough it seems inconceivabIe, even at this time I stuck to my diagnosis of a nonmaIignant lesion, aIthough I must confess that at various times during these examinations I had wavered toward a diagnosis of maIignancy.

FK. 18. Roentgenogram made three weeks Iater shows area of induration materiaIIy increased and crater shaIIower. LP, lack of pIiabiIity; DS, deep sulcus on greater curvature pointing to the region of the lesion; UI, uIcerating induration.

growth. The patient died shortIy after operation. At autopsy the stomach (prepared in the specia1 manner previousIy described) showed diffuse carcinoma invoIving the gastric waI1 and the intraperitonea1 space, and by its contraction had shortened the Iesser curvature. (Figure 20.) The growth, however, did not protrude into the Iumen of the stomach. A comparison of the photograph of the inside of the stomach with the Iast roentgenogram shows the correIation between the gross pathoIogy and the roentgenoIogica1 findtoward ings. Even the rugae puckering the crater are exactIy the same in the roentgenogram as they are in the pathoIogica1 specimen. Th is pecuIiar formation of the rugae has in the past been considered an indication of simpIe benign uIcer in contradistinction to malignancy, but in certain types of infiItrative carcinoma, this shortening of the Iesser curvature and

NEW Sswzs

VOL. XxX1, No.

2

Cole-Gastric

X-ray

puckering of the rugae are characteristic of carcinoma. KirkIin of the Mayo CIinic has demonstrated a simiIar case. The onIy,

& PathoIogy

American

~~~~~~~

of surgery

2 19

justify a positive diagnosis of gastric cancer, but the two together, or at Ieast the entire series, showed a definite area of

R

FIG. 19. Roentgenogram made one month later showing: CLC, contraction of the lesser curvature; RGC, retraction of the greater curvature.

I shaII not say excuse, but palliation of my regret, in this diagnostic error was the fact that even at the time of our first examination, the patient had an inoperabIe infiItrating gastric cancer. ConsequentIy my error in diagnosis did not hasten her end-in fact, it probabIy deIayed it. Case, Mr. V., is of specia1 interest from many aspects; the difhculty of roentgenoIogica1 diagnosis; the indefinite surgica1 findings; the contradictory gross and microscopica findings; and the subsequent cIinica1 course of the disease. The patient, with a cIinica1 history more characteristic of uIcer than of cancer, presented himseIf at the Fifth Avenue HospitaI with a roentgenoIogica1 diagnosis of uIcer by another roentgenoIogist. A series of fiIms made by my associate, Dr. R. E. Pound, reveaIed the findings shown in Figures 21 and 22. Neither of these fiIms aIone, nor any singIe fiIm of the entire series, wouId

FIG. 20. Photograph of gross autopsy specimen showing: CLC, contraction of the Iesser curvature; MF, mucosal folds; RGC, retraction of greater curvature.

obstructed peristalsis on the lesser curvature near the pyIorus. Even the Iumen of the pyloric canal showed some variation in size due to the Iack of invoIvement of the greater curvature. The Iesion in this case did not invoIve the fan shaped muscIe on the greater curvature and therefore the findings differ from those iIIustrated in Figures 6 and 8. I made a positive diagnosis of gastric cancer, which was contrary to the cIinica1 history and the previous roentgenoIogica1 diagnosis. We maintained that the Iesion was smaI1, and apparentIy Iimited to the extreme pyIoric end of the stomach and therefore operation for an attempted cure was justifiabIe. The Iate Dr. Francis Honan decided to operate and no Iesion could be found in the pylorus.

220

American

Journal

of Surgay

CoIe-Gastric

X-ray

A smaI1 area of sIightIy increased density WEts paIpabIe on the Iesser curvature of the PY4orus, but this was quite

indefinite,

FIG 21. FIGS. 21 and

22.

and

& PathoIogy

evidence whether stomach

PyIoric (:arcinoma:

there was some question as to whether a pyIorectomy shouId be performed or the incision closed without any radical procedure. At the operation I inspected and paIpated the region. My judgment, based on inspection and paIpation, did not Iead me even then to urge a pyIorectomy. However I reIied on my roentgenoIogica1 findings, as did aIso the surgeon, and the pyIorus was removed as far back as the suIcus. A coIored photograph was made of the inside of this specimen and its cut surface, but the professiona photographer forgot to draw his slide, so the pIate was bIank- a great disappointment to me at that time, and a stiI1 greater one now. That same afternoon I presented the freshIy removed gross specimen intact, except for a IongitudinaI section aIong the greater curvature, to Doctor Ewing. After examining the exterior and interior, he made a IongitudinaI cut aIong the Iesser curvature in the region where I had diagnosed cancer. He took the section to the window, scraped the knife aIong the cut surface, and stated that there was no

FEBRUARY, 1936

of cancer. I am not quite sure he said that I had had a normal removed, or whether at this point

infiltrative

FIG. type.

22.

I myseIf had come to this concIusion. At any rate, he toId me not to be so disturbed or gIum, because something might possibIy be found microscopicaIIy. Two days Iater he toId me that the Iesxon was definitely cancer, the earIiest one he had ever seen. A few days Iater he sent us the foIIowing communication : DEPARTMENT OF PATHOLOGY, CORNELL UNIVERSITY MEDICAL COLLEGE (REPORT ON GASTRIC CARCINOMA) The materiaI received consists of the pyloric portion of the stomach I I cm. Iong and 15 cm. in diameter at its widest part. Surrounding the pyIoric orifice of 6 cm. there is a shght tumefaction of the mucosa, which on the surface is sIightIy noduIar in diameter, where the mucosa is fixed to the muscuIaris and sIightIy eroded. The whoIe area is soft and Iacks the usual induration of carcinoma. On section of the eroded area it is found that the mucosa or the thick opaque layer is 3 or 1 cm. wide. The serosa is normal, but the surrounding fat tissue is slightIy adherent. After fixation in formalin the entire invoIved area, 6 cm., becomes EoardIike, while the rest of the

FIG. 27A. FIG. 23B. portion F ‘IL 23, A and B (B fits on the proximal sections from the uninvolved end of A). Adjace :nt microscopical of the cap to a point beyond the area of induration on the Iesser curvature show the extent of the carcinc ,matous D, faninvo1~ rement. A, uninvoIved c, proximal line of invasion; portion of the cap; B, distal Iine of invasion; nodules; shape, d muscle; G, numerous Pnlarged I\-mph E, subperitoneal invasion; F, muscul ‘ar invasion; H, Car cinomatous mucosa not thickened nor thinned.

222

American Journal of Surgery

Cole-Gastric

X-ray

& PathoIogy

FEBRUARY,1936

stomach remains eIastic. The remaining mucosa shows a marked granuIar surface, indicating advanced atrophic gastritis. Just beyond the

tion of the submucosa by cancer ceIIs. This infiItration, aIthough very scanty, accounts for the induration and restricted mobiIity

FIG. 24. SmaII carcinomatous area, which renders the mucosa neither thicker nor thinner than it is in the mucosa; adjacent uninvoIved area. MM, muscuIaris cc, CarCinOmatOuS criteria; NM, nOrmaI mucosa.

FIG. 25. Carcinomatous invasion of the deeper structures of the gastric wall, which is out of proportion to the primary Iesion in the mucosa as shown in Figure 24. P, Peritoneum; MP, muscularis propria; cc, carcinomatous criteria.

involved area, is a smaI1 poIypoid projection mm. wide, 2 mm. deep, which is the seat of the carcinoma. Microscopic Examination. The stomach is the seat of an infiltrating adenocarcinoma, which extends through the entire waI1, spIitting up the muscIe fibers over a wide area, reaching the peritoneum and involving the bIood vesseIs and nerve trunks. The main structure is simpIe tubuIar gIands of various sizes, but there are numerous areas diffuseIy infiItrated by singIe tumor ceIIs. There are numerous new Iymph foIIicIes. The uIceration is very superficia1. The process arises in the tubuIar gIands of an atrophic gastritis and these gIands show various stages of transformation from simpIe atrophy to carcinoma. Sections taken from the stomach waI1, I I cm. from the pyIorus, show we11 marked chronic interstitia1 gastritis with much overgrowth of Iymphbid tissue and considerabIe fibrosis. Sections taken 7 cm. from the pyIorus on the edge of the boardy area show diffuse infiItra4

observed in this segment. The mucosa in this zone shows very marked chronic interstitia1 gastritis with numerous groups of markedIy atypica1 gIands which show many stages toward, but do not reach, adenocarcinoma. These gIands show how the origina tumor began. It is interesting to note that these changes are identica1 with the ones found on the edges of oId ulcers and are commonly interpreted as cancerous transformation of the ulcer. Epicritical. This case represents one of the earIiest gastric cancers that I have seen, and one of the earIiest that was ever encountered. It is particuIarIy important in that it shows the deveIopment of carcinoma on diffuse chronic interstitia1 gastritis. The superficia1 erosion is characteristic of a Iarge group of pyIoric cancers which seem to deveIop in the same manner. The very wide infiItration of the submocosa aIso expIains why in many of these cases the infiItration becomes aImost universa1

NEW SERIES VOL. XXXI, No.

throughout the very Iimited.

z

stomach,

CoIe-Gastric

X-ray

but

is

ulceration

James Ewing,

M.D.

FIG. 26. Extreme proxima1 Iine of carcinomatous inMP, muscuIaris propria; MM, musvasion showing: cuIaris mucosae; NSM, norma submucosa; cc, carcinomatous cells; Pr_I, proxima1 line of invasion.

A bIock of tissue incIuding the entire Iength of the specimen aIong the Iesser curvature was fixed and mounted, and then cut into five parts to faciIitate the making of thin microscopica sections. These adjacent sections were then mounted, as shown in Figure 23, A and B. The carcinomatous degeneration described by Ewing occurs in severa reIativeIy IocaI regions of extremeIy smaI1 size, separated by very much Iarger areas of mucosa composed of gIanduIar structure, which do not show the orthodox criteria of carcinoma. (Figure 24.) In those regions of the mucosa where the carcinomatous degeneration is most extensive the mucosa is neither thicker nor thinner than normal In onIy one very smaI1 area is the surface of the mucosa broken as if by a superficia1 uIcer-

& PathoIogy

American ~~~~~~~of surgery

223

ation. In many areas of the mucosa the deep proportion adjacent to the convotuted tubuIes shows evidence of cancer

FIG. 27. Distal Iine of carcinomatous invasion, which ends abruptIy in the extreme proxima1 portion of the cap in the same microscopica field in which the MP, muscularis mucosa and submucosa terminate. muscularis propria; MM, muscularis mucosa; N:sM, normal submucosa; cc, carcinomatous ceIIs; DLI, distal line of invasion.

criteria, whereas the superficia1 portion does not show such criteria. In the submucosa, intramuscuIar spaces within the circular muscIes, and the intermuscuIar spaces between the circular and Iongitudina1 muscIes. and even in the subserous coat outside the IongitudinaI muscIe there is an extensive invasion of carcinomatous celIs. (Figure 25.) The Iesion in the submucosa and deeper coats of the stomach is far out of proportion to the slight invasion of the mucosa itself. Ewing’s remarks concerning this being one of the earliest carcinomas he had ever encountered certainIy must refer to the mucosal invoIvement rather than the submucosal, muscuIar and subserous Iesion. The carcinomatous

224

American JOUST 0f Surgery

CoIe-Gastric

X-ray

degeneration of the mucosa itself, not having aItered its thickness, wouId cause no roentgenoIogica1 findings whatever, but the very extensive invasion of the submucosa, far beyond the region of the mucosa1 invoIvement wouId cause the typica Iack of pIiabiIity the basis for roentgenoIogica1 diagnosis of gastric cancer. The very gradual manner in which the carcinomatous tissue in the submucosa tapers off as one approaches the proxima1 periphery of the Iesion (Figure 26) and the very gradua1 invasion of the intramuscuIar spaces in the proxima1 portion of the Iesion is very characteristic of this invasive or infiItrative type of carcinoma. This is in marked contradistinction to the abrupt termination of the cancer at its dista1 or abora1 line of invasion. At this point the carcinoma ends abruptIy in the same microscopica fieId in which the muscuIaris mucosa and submucosa terminate. (Figure 27.) This finding, which is observed in a11 cancers invoIving the pyIoric region, has a very great cIinica1 significance and may be of extreme etioIogica1 bearing as was mentioned earIy in the articIe. In spite of Ewing’s statement that this was one of the earIiest carcinomas he had ever and pathoIogica1 seen, roentgenoIogica1 findings indicate that this was one of the most unfavorabIe cases for surgery that one is IikeIy to encounter. This statement is borne out by the fact that the patient died of carcinomatosis of the entire abdomina1 cavity within sixteen months after the operation. A comparison of this case with that in Figure 3 emphasizes the fact

& Pathology

FEBRUARY, 1936

that operabiIity and prognosis do not depend entireIy or even primariIy on the extent of the Iesion. Lack of pIiabiIity of the gastric waI1 is the most deIicate of the four fundamenta1 findings on which gastrointestina1 roentgenoIogica1 diagnosis is based.* By use of the term “deIicate” we mean that i&Itrative Iesions can be detected by this finding at an earIier stage than by any of the other three fundamenta1 findings. The purpose of this presentation is to stimuIate roentgenoIogists to appIy their findings to a greater variety of the probIems of gastrointestina1 medicine, particuIarIy to gastric cancer and gastric uIcer, but they shouId not do so unti1 they have prepared themseIves to converse rationaIIy in terms of pathology, and until they have Iearned to correIate, from their attendance at operations and autopsies, the surgica1 and pathoIogica1 findings with their own roentgenoIogica1 findings. This presentation is aI.so intended to urge the hearty cooperation of the roentgenoIogist with the surgeon, cIinician and pathoIogist, and it is a pIea to the surgeon and cIinician to consider the roentgenoIogist as a medica coIIeague rather than a Iaboratory technician and to cooperate and consuIt with him concerning the roentgenoIogica1 findings and their appIication to the probIems which he, as a surgeon or cIinician, must of necessity apply. *The four fundamental findings are described by the CoIe CoIIaborators in “RadioIogicaI ExpIoration of the Mucosa of the Castro-IntestinaI Tract.” The Bruce PubIishing Company, Saint Paul and MinneapoIis, 1934.