A CLINICAL AND PATHOLOGIC STUDY OF 739 CASES...

THE PROGNOSIS O F GYNECOLOGICAL CANCER

A CLINICAL AND PATHOLOGIC STUDY OF 739 CASES FROM THE SERVICE OF HOWARD C. TAYLOR AND THOMAB C. PEIGHTAL

THE ROOSEVELT HOSPITAL

HOWARD C. TAYLOR, JR.

The organization of cancer treatment has received wide attention in the last few years and no aspect has evoked more discussion than the relative merits of the cancer institute and the general hospital as agencies for cancer therapy. It was with this question in mind that a careful survey of the results of the treatment of cancer cases by the gynecological division of the Roosevelt Hos- pital was determined upon.

A complete sifting of the files of the years 1910 through 1930 has resulted in a collection of 739 cases, some of which have been previously reported (Taylor and Peightal, Taylor, Jr.) . The number is perhaps not great, but a present average of about fifty malignant cases a year probably entitles us to offer the report as coming from a representative small clinic attempting to do careful cancer work but in no sense of the word specializing in that disease.

A study of this type is in itself of some importance, for the great majority of cancer cases in America are undoubtedly being treated in hospitals comparable in size to our own or perhaps smaller, so that the problems in our service have a wide applica- bility. Furthermore, since the Roosevelt service has never attempted to treat special numbers or types of malignant disease and since few if any patients have been turned away as unsuit- able for the forms of treatment offered by the institution, it is probable that the group to be reported comprises an unusually random sample and that the results represent those obtained or readily obtainable throughout the country. A review of these cases with a discussion of certain errors when they have occurred may therefore be of value to similar clinics in which deficiencies of a special type may be present due to a lack of concentration of the surgical and pathological staff upon the tumor problem and the rarity with which certain forms of tumor are encountered. Fin-

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THE PROGNOSIS OF GYNECOLOGICAL CANCER 2519

ally, as a result of this survey of the development of cancer work on the Roosevelt service over a twenty-one year period, a few definite suggestions in regard to plans of treatment and organization can be made that may be useful to the small clinic with limited clinical material and radiological equipment.

The survey of the work of the Roosevelt clinic has indicated, in fact, that in three directions there is a definite possibility for improvement. These are as follows: (1) a revision of the system of classification and record keeping with the object of facilitating a more accurate and a more continuous knowledge of the results being obtained in all types and classes of cases; (2) an improvement in the coordination of the clinical with the pathological data, so that the newer ideas upon radiosensitivity may be considered in relation to treatment; (3) the agreement upon a more or less standardized form of therapy for cases of a given type. In regard to the first two points it has been possible to review all material, clinical and pathological, back to 1910, and to record it in a system identical with that now planned for the future. This worked-over material has supplied a basis for the determination of the third point, namely a somewhat standardized plan of therapy, and gives a mass of data with which present work is readily comparable.

At the commencement of this study, all cases of cancer treated by the division from 1910 to 1930. were collected, partly from previous lists, partly from a complete review of the files. The cases were then divided into ten groups, carcinoma of the cervix, corpus, ovary, tubes, vulva and vagina, sarcoma of the uterus and ovary, chorionepithelioma, and a miscellaneous group of advanced peritoneal neoplasms of doubtful relation to the pelvic organs. In each group each case received a serial number, beginning with the earliest and continuing to the present. In the future cases will continue to be assigned serial numbers as soon as they come under observation, whether or not treatment is possible. In certain cases, where doubt has existed as to the primary site of the growth, reclassification was made according to certain rules to be referred to later.

Following the completion of the lists, the cases were abstracted upon cards (Fig, 1) containing space for data necessary to classify them from several angles. The card devised for this purpose, which is 11 x 895 inches in size, was evolved from the one used in the survey of end-results of cancer of the cervix by the American

2520 HOWARD C. TAYLOR, JR.

College of Surgeons but has, we believe, certain features more practical for use as a continuous record in a follow-up clinic. In one space in the upper left-hand corner are placed all data directing an investigator to sources of further information, namely the address of the patient herself, of her family doctor, the numbers of history and pathological records, the operating surgeon, and dates of admission. In the upper right-hand corner is the summarized classification, permitting rapid sorting of the cases, namely whether primary or recurrent, degree of advancement, histological type, form of treatment, and end-result, The remainder of the card contains amplifications of the history, examination, and treatment, while the back is reserved entirely for follow-up notes. The four possible results of treatment, as recordable in the upper right-hand corner of the card, are made the criteria for filing. Each corre- sponds to a position of a guide on a folder in a standard letter file, column one carrying the number of the year, two the living and well cases, three those with recurrence, four those dead, five those lost. The cards all start in a folder in column two and are shifted as circumstances require, so that the record is always up to date. The end-results for any year or group of years are thus instantly determinable by a mere process of counting.

An important part of the work was a review of all microscopic slides, with the assignment of the histologic grade where the state of preservation of the material permitted, and a correction of certain errors in diagnosis. These slides and all new microscopic material from malignant tumors are now kept in a special and easily accessible file, constituting a permanent part of the service’s record.

The attitude of the Roosevelt clinic toward methods of cancer treatment is the outcome of a gradual evolution from a purely surgical point of view to one modified by admission of the more definitely accepted indications for irradiation. The present study has not resulted in any radical changes but in the selection of the apparently more favorable methods with which the clinic has already had experience and the formulation of more or less standardized plans of therapy. Such a standardized plan is to be recommended in any clinic for two reasons: (1) to protect the patient from possible neglect of minor details due to forgetfulness or to the point of view that measures which may theoretically improve the end-results by one or two per cent are of insignificant


value to the individual patient, and (2) to have enough cases during a course of years treated by the same method to permit judgment of the efficacy of a plan of treatment. At the same time it has been felt desirable to make the plans somewhat flexible, since the Roosevelt service is better adapted for individualization than for the study of a large group of cases. The types of therapy as now planned will be set forth as each variety of cancer is presented, in the following pages.

Statistics: I n the presentation of statistics the rules laid down by the radiological subcommission of the League of Nations in June 1929 will be followed so far as possible. The end-results for five years will be reported on the basis of every case in the files without deduction for cases in which treatment was interrupted or in which the patient died without recurrence or was lost sight of. This method gives an absolute minimum figure, undoubtedly a little lower than the actual one, since it is notable that in the groups in which only a small number of patients remain untraced there is a relatively high proportion of early and borderline cases among the lost. The League Commission emphasizes further that cases examined but not admitted for treatment should be tabulated, an admonition which is of great importance, since the exclusion of cases regarded as too advanced for treatment at once improves the end-results.

The system of reporting end-results for cancer of the cervix recommended by the League Commission is designed for cases treated by a single therapeutic agent, namely radium, and is not entirely suitable for a group of cases treated by the more complex plan of surgery for some and irradiation for others. The results to follow are reported, nevertheless, as indicative of the relative successes of such a plan and not of a single method of treatment. Furthermore, since the attitude of the service has constantly changed in regard to methods of treatment, particularly in relation to cervical cancer, certain groups of years must be set apart and the results noted separately.

TOTAL CASES After a review of the histories and sections and the exclusion of

any cured case with a doubtful diagnosis, there were 739 cases of malignant tumor of the gynecological organs treated from 1910 to 1930. These were divisible as follows:


Carcinoma of the cervix. .................. 421 Carcinoma of the corpus. .................. 145 Carcinoma of the ovary. .................. 108 Carcinoma of the vulva. .................. 20 Carcinoma of the vagina. ................. 9 Carcinoma of the tubes.. .................. 2 Chorionepithelioma ...................... 3 Sarcoma of the uterus. .................... 9 Sarcoma of the ovary. .................... 5 Sarcoma of pelvic connective tiesue. ........ 1 General peritoneal growths. ............... 21 -

744 Anumber of these were private patients treated on the service by

Dr. William P. Healy and Dr. John W. Warner, to whom we are in- debted for the privilege of including these cases and for their kindness in furnishing data on late results.

In the total of 744, 5 appear twice; i. e. both as carcinoma of the corpus and carcinoma of the ovary.

CANCER OF THE CERVIX CZassi$calion: All cases of epidermoid carcinoma were regarded

as primary in the cervix and not in the vagina if the cervix was at all involved, whereas all cases of adenocarcinoma were regarded as primary in the corpus unless good evidence existed that the body of the uterus was free of disease. This involved the shifting of several cases previously regarded as adenocarcinoma of the cervical canal into the corpus list.

The classification of degree of extension was made according to the customary American plan, namely: early cases, with the disease grossly limited entirely to the cervix; borderline cases, with a questionable spread to the parametria or vaginal walls; advanced cases, with definite invasion of the parametrium or vagina. This classification was made in the older cases from a review of the recorded descriptions and not by the original operator. As such the classification is only approximate, but as this form of division is notoriously inaccurate, the present approximation is probably as serviceable as any. Reports upon early and borderline cases as a group are of little value at best, since the results depend so largely upon the operator’s view of how large to make this favorable group. Practically all the results in this paper are based, therefore, on the total number of cases applying for treatment.

Although the customary division into three groups has been followed in this paper, we plan in the future to use the more com- plicated classification of the League of Nations Commission. The plan has in itself the merit of giving a wider subdivision of cases. Furthermore, the advantages of an internationally uniform system

THE PROGNOSIS O F GYNECOLOGICAL CANCER 2523

are obvious, and it appears unlikely that any more authoritative body exists to support an alternative system. This system of classification follows :

Classification of Carcinoma of the Cervix Uteri into Stages according to the Anatomical Extent of the Growth

Stage I: The growth is strictly limited to the cervix uteri. Uterus mobile.

Stage 11: Lesion spreading into one or more fornices with or without inatration of the parametrium adjacent to the uterus, the uterus retaining some degree of mobility.

Stage 111: (a) Nodular infiltration of the parametria on one or both sides, extending to the wall of the pelvis, with limited mobility of the uterus or massive infiltration of one parametrium with fixation of the uterus.

(b) More or less superficial infiltration of a large part of the vagina, with a mobile uterus.

(c) Isolated metastases in the peIvic glands, with a relativeIy small primary growth.

(d) Isolated metastases in the lower part of the vagina. Generally speaking, all cases not falling into Stages 2 or 4 will be

Stage IV: (a ) Cases with massive infiltration of both parametria

(b) Carcinoma involving the bladder or rectum. (c) The whole vagina infiltrated (rigid vaginal passage), or one vaginal

( d ) Remote metastases.

placed under Stage 3.

extending to the walls of the pelvis.

wall infiltrated along its whole length with fixation of the primary growth.

The 421 cases of cancer of the cervix divide themselves naturally into groups dependent upon the plan of treatment in vogue during the years in which they were admitted to the hospital. These groups are: (1) cases treated entirely by surgery; (2) cases treated by radium and surgery with a high operability rate; (3) cases treated by radium and surgery with a low operability rate; (4) cases treated entirely by irradiation.

Surgical Era (1910-1916) During this period no radium was available in the hospital. The figures cited represent the results in a desperate era, when

operation was the only method of attack and 60 per cent of cases were actually treated by removal of the uterus, although from the modern point of view 70 per cent of these cases were already advanced. Thus, in comparing the success of early purely surgical


means with modern methods of therapy, it must be remembered that the latter has to its advantage the entire and perhaps vitally important effect of the educational campaigns of the last ten years. To compare surgical cures and surgical mortality with radium results one must, therefore, examine the figures of modern surgical experience.

TOTAL CASES, 126 Recurrent, 13 (with one cure by total colpectomy) Primary, 113

Inoperable, 45 (40 per cent) Treatment: None, 10; cautery or trachelectomy, 20; Percy

Results: Operative deaths, 2; cures, 0; 2 patients lived over four cautery, 6; exploratory celiotomy, 9

years Operable, 68 (60 per cent)

Gross extension: Advanced, 46; borderline, 13; early, 9 Complete hysterectomy, 29

Results: Operative mortality, 5 (17 per cent) ; five-year cures, 3 (11 per cent); death or recurrence, 10 (34 per cent); untraced, 11 (38 per cent)

Wertheim operation, 39 Results: Operative mortality, 6 (15 per cent) ; five-year cures,

5 (13 per cent); death or recurrence, 12 (31 per cent); intercurrent disease, 1 (2 per cent); untraced, 15 (38 per cent)

Summary of primary cases Absolutejhe-year rate. . . . . . . . . . . . . . . . . . 8 + 113 = 7.1 per cent With subtraction of untraced treated cases. . . . . . . . . . 9 per cent Operability. .................................... 60 per cent Operative mortality. ............................ 16 per cent Cures of traced operated cases. . . . . . . . . . . . . . . . . . . . 20 per cent Cures of traced cases surviving operation. .......... 26 per cent

Bonney’s recently reported work shows that an absolute five- year rate of 24.4 per cent is obtainable; among private patients, a rate of 37.5 per cent. Kermauner, from the I1 Universitat Frauenklinik of Vienna, reports a series of 976 cases with 63.9 per cent operability, a 9 per cent primary mortality, and a five-year cure in 26.9 per cent of the cases. This mortality is lower than that usually cited by opponents of the Wertheim operation, but becomes still less when the results of the radical vaginal operation are considered. Thus Peham reports a mortality of 6.9 per cent for the years 1921-1924, while Adler, in a series of 1000 cases, found an average primary mortality of 6.1 per cent, which in recent years has fallen to 3.8 per cent. Such results have not been ob-


tained in America, where the radical vaginal operation has not been popular and few operators have had the opportunity of a large number of cases with which to perfect their operative skill.

Era of Radium and Surgery, Operability 43 per cent (191Y-1920) In 1917, 100 milligrams of radium in the form of the salt was

obtained. This was distributed in two 25 mg. and one 50 mg. capsule, each filtered by 1.0 mm. of brass and 0.5 mm. silver. The use of this equipment was at first irregular, since the technic had to be learned entirely from experience. The immediate effects of the new methods were a contraction of the operability to 43 per cent, and an immediate drop in mortality, perhaps on account of the clearing up of infection by the preliminary irradiation. The plan of treatment for the operable cases during these years was the insertion of 100 mg. into the cervical canal for twenty-four hours from one to two weeks before operation, while the inoperable cases were treated with an average total of 4400 milligram hours in two to three applications at weekly intervals.

TOTAL CASES, 84 Recurrent, 6 (no cures) Primary, 78

Palliation only, 4 Radium only, 40

Gross extension: Advanced, 36; cancer of the cervical stump, 4 Results: Five-year cures, 1; dead, 16; lost, 23

Gross extension: Advanced, 12; borderline, 11; early, 2 A. Complete hysterectomy, 15

B. Wertheim operation, 10

Radium and surgery, 25

Results: Five-year cures, 4; dead, 5; lost, 6

ResuIts: Five-year cures, 3; dead, 7 Surgery only, 9

Gross extension: Advanced, 2; borderline, 4; early, 3 A. Complete hysterectomy, 3

B. Wertheim operation, 6 Results: Lost, 3

Results: Five-year cures, 3; dead, 1; lost, 2 Summary of primary cases

Absolute rate five-year cures. . . . . . . . . . . . . . 11 + 78 = 14.1 per cent With subtraction of untraced. . . . . . . . . . . . . . . . . . . . 25 per cent Operability. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 per cent Operative mortality. . . . . . . . . . . . . . . . . . . . . . 0 per cent Absolute rate in operated cases. . . . . . . . . . . . . . . . . . 30 per cent Rate of cure in traced operated cases. . . . . . . . . . . . . . . 44 per cent


Radium and Surgery, Operability 27 per cent (1921-1 023) During the period 1921-1923 only about a quarter of all cases

were regarded as operable and these were treated preoperatively with an average of 2900 milligram hours of radium. The other cases received intracervical irradiation as before, but this, for some unexplained reason, had dropped to an average dose of only 3400 milligram hours and was very irregularly applied, both as re- gards total amounts and spacing of the two applications. A lack of definite plan of irradiation is in these years strikingly evident.

TOTAL CASES, 43 Recurrent, 6 (no cures) Primary, 37

Palliation only, 1 Radium only, 26

Gross extension: Advanced, 16; borderline, 8; early, 2 Results: Five-year cures, 4; dead, 20; lost, 2

Gross extension: Advanced, 4; borderline, 4; early, 2 Complete hysterectomy, 8

Results: Cures, 5 ; dead, 2; lost, 1 Wertheim operation, 2

Results: Cures, 2 Summary of primary cases

Radium and surgery, 10

Absolute rate of five-year cures. . . . . . . . . . . 11 + 37 = 29.7 per cent With subtraction of untraced. . . . . . . . . . . . . . . . . . . . . 32 per cent Operability.. ................................... 27 per cent Operative mortality. ............................ 0 Absolute rate in operated cases. ................... 70 per cent Rate in traced operated cases. .................... 78 per cent

The improvement in the end-results in this era is no doubt in part merely an apparent one, due to a more complete tracing of cases, but the combination of irradiation with surgery has in other hands and in larger series also produced excellent results. The vaginal operation in particular, when followed by the placing of radium in the parametria, has led to unsurpassed figures for five-year cures as shown by Adler's five-year survivals of 32 per cent (of all cases).

The specific effect of the irradiation is indicated more definitely in another series of cases reported from Vienna (Peham), in which, among the patients operated upon, 57.3 per cent remained well five years when postoperative x-ray .irradiation was given, as


compared with 41.5 per cent following operation alone. Early reports of a different procedure from a Belgian clinic (Delporte and Cahen), where transabdominal insertion of radium is combined with vaginal and intracervical irradiation, are also so favorable as to command attention. Aside from the increased cure rate, attention should also be directed to the fact that in the Roosevelt series there were no deaths among the entire 35 patients treated by preoperative radium and hysterectomy. In a larger group treated by the Wertheim operation (BG cases) Mayer also had no deaths, a success attributed by him to the elimination by preoperative irradiation of infection, the chief source of fatalities from the operation alone. Such reductions in mortality indicate again the inaccuracy of many of the opponents of surgery, who assume an inevitably high mortality in radical hysterectomy for cancer. In America, where the Wertheim operation is not now widely practised and where the influence of the Paris and Stockholm schools of irradiation is great, it appears a t present that radium will soon entirely displace surgery in the treatment of cervical cancer. A study of the work being done in other European clinics, less well known in America, gives some indication that surgery alone or combined with irradiation may yet have a renaissance. The success in a small group of cases so treated in the Roosevelt, Hospital inclines us to accept this as a possibility.

Radium and X-ray Era (1924-1930) (1) Five-year Cases (1924-1925): Beginning with the year 1924,

hysterectomy was practically abandoned and the amount of irrstdi- ation cautiously increased. The treatment for the years 1924- 1925 was still by means of two intracervical applications of 100 mg. of radium with a total average dosage of 3300 milligram hours, supplemented in a part of the cases by four exposures of deep x-ray therapy.

TOTAL FIVE-YEAR CASES, 4G Recurrent, 7 (with one cure) Primary, 39

No treatment, 1 X-ray only, 1 Radium only, 13

Gross extension: Advanced, 10; borderline, 3; early, 0 Results: Five-year cures, 2; dead, 8; intcrcurrent disease, 1; lost, 2

23


Radium and X-ray, 21 Gross extension: Advanced, 14; borderline, 4; early, 3 Results: Five-year cures, 4; dead, 17

Gross extension: Advanced, 1; borderline, 1; early, 1 Results: Five-year cure, 1; dead, 1; lost, 1

Radium and hysterectomy, 3

Summary of primary cases Absolute cure rate . . . . . . . . . . . . . . . . . . . . . 7 f 39 = 18.0 per cent With subtraction of lost cases.. . . . . . . . . . . . . . . . . 20 per cent

(2) Three-year Cases (1926-1927) ; During the years 1926-1927, 53 cases were treated, all except 3 by irradiation methods only. X-rays were used much more consistently than theretoforc, and the radium dosage had risen to 4500 milligram hours delivered in two practically equal doses. In this period occurred the only two deaths in the series following radium application. At the end of three years 28 per cent of the primary cases (46) are known to be well, 5 cases are untraceable, the remainder dcnd.

(3) Recent Cases (1968-1930); Sixty-three primary and 5 recurrent cases have been treated in the last three years, :ill by radium and x-rays, with the exception of the following: untreated, 2; radium only, 5 ; radium and hysterectomy, 3 ; hysterectomy only, 1. The last case was one of cancer of the upper cervical canal, untli- agnosed until the operation was well under way and resulting in :i

postoperative death. This case, be i t noted, was the first surgical death since 1916, the only one in 54 hysterectomies undertaken after the advent of radium permitted preoperative irrndiation and a more rigid selection of cases for radical surgery.

These last three years have seen a gradual spreading out of the sources of irradiation, with the use of various appliances for radium in the fornices. The plan has continued to be that of two applications at about a week’s interval, with the total dose varying from 5200 milligram hours in 1928, t o 6800 in 1929, and 6500 in 1930. After experience with a few cases with higher dosage we feel that 7000 to 7500 milligram hours must be the maximum.

Summary of Results The absolute five-year result in the surgical era, 1010-1916

(113 primary cases), was 7.1 per cent cures, but many cases were untraceable. The cures from 1917 to 1920 (78 primary cases), when the operability was 43 per cent, amounted to 14.1 per cent; with subtraction of untraced cases, 25 per cent. From 1921 to 1923 (37 primary cases) the absolute cure rate was 29.7 per cent; with the untraced cases deducted, 32 per cent. In 1924-1925 (39 primary


cases), with therapy reduced practically to irradiation methods, there were five-year cures in 18 per cent; with lost cases deducted, in 20 per cent. These figures may be compared with the following for irradiation methods: Healy, 20 per cent; Ward, 23.1 per cent; Heyman, 23.1 per cent; Lacassagne, 20 per cent (10-30 per cent); Voltz, 15.4-18.2 per cent.

From this survey, it appears probable that the chief criticism should be directed against the inconsistency in treatment. This defect, which has been gradually eliminated, is probably common to the histories of most clinics during the earlier periods of irradiation, but where it persists it may be responsible for certain cases receiving less than the optimum amount of irradiation. It is n defect which, we believe, is liable to be especially prevalent in the smaller clinics where only sporadic cases are treated.

Although the best results in this series were obtained by a combination of radium and surgery, the Roosevelt service intends to continue treatment by radium and x-rays. The present equipment consists of 140 mg. of radium element distributed in two tubes of 25 mg. and one of 50 mg., each filtered by 0.5 mm. of platinum, and eight needles of 5 mg. each filtered by 0.25 mm. of platinum. The latter are readily placed in groups in small brass capsules and are so used, as a rule. The routine treatment consists of 75 to 100 mg. divided about equally between an intra-uterine and vaginal application. The intra-uterine treatment is carried out by the usual method of capsules in rubber tubing extending from the external 0s to the fundus, while the vaginal application is accomplished by capsules placed either in the Kaplan or Regaud type of colpostat or in rubber tubes sutured to the fornices or Iateral cervical walls. For the first application the radium is left in place till 3000 to 3500 milligram hours have been delivered. During the week following, four x-ray treatments are given, the factors for each treatment being as follows: 200 kv, 5 ma, 50 cm. distance, four fields of 400 sq. cm. each with the opposite half of the abdomen or back screened, for severity minutes. The amount delivered to the skin in each field is 675 R units. From one to three weeks after the first radium application a second is made to bring the total dosage to 6500 or 7000 milligram hours, after which the patient is discharged.

In spite of the enthusiasm of many writers for the single con- centrated application or the single protracted treatment with low intensity, we intend to continue with the divided dose. This is based on the belief that the shrinkage following the first dose


brings the periphery of the tumor nearer to the centers of rttdiation when the second application is made and that this purely physical advantage is probably more valid than the theoretical biological advantages of the undivided dose. The x-ray therapy given between radium treatments has also the effect of making the irradiation more or less continuous.

Relation of Histologic Types lo End-results irt Cervical Cancer The study of microscopic sections has not led to any corrobora-

tion of the work of the many writers who have found a definite relationship between histologic structure and prognosis. One hundred and twenty-eight cases in which three-year arid five-year results were known and in which adequate sections were available were studied.

The grading was done entirely on the basis of tissue differentiation and deviation from the architecture of the normal squatnous epithelium. The classification is, therefore, similar in principle to that employed by Healy and Cutler and follows rather closely the original system of Martzloff, for it is clear that , though the latter’s nomenclature referred to cellular types, these in turn correspond in large measure to degrees of architectural differentiation.

The method of Hueper and Schmitz, which has received the widest publicity in the last few years, was considered, but found to be objectionable for several reasons. In the first place, the apparent assignment of only eight possible points out of eighty-four to differentiation (special cell type) is misleading, since several, if not the majority, of the other items are probably dependent upon this one. Even the factors of irregularity in size and shape of cells and nuclei are linked with this process of differentiation ttnd are difficult to evaluate properly in such tissue as squamous carcinoma whose parent cells normally pass through great changes in cell and nuclear size and form. Certain other factors of the ‘[ malignogram,” such as the presence of pencil cells, eosinophilia, and the stroma reaction, are based on ill-proved theoretical con- cepts. Furthermore, it is quite possible that certain factors in the “malignogram,” such as the character of the stroma, should be marked + (plus) for one type of therapy and - (minus) for nn- other. Finally, the recording of the malignancy index in terms of mathematical detail out of all proportion to our knowledge of the meaning arid interrelationships of the component parts, appears unjustifiable.

FIG. 2. SCJUAMOUS CARCINOMA OF THE CERVIX, GRADE I

FIG. 3. SCJUAMOUS CARCINOMA OF nm CERVIX, GRADE I1 2531

I L

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m h i 3 3

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. . . .

. . . .

. . . . . . _ . . . . . . . . . . . . . . . . . . . . - . , .

d . . . ..

2332


The grading of the present cases was recorded first upon a. general impression of the degree of deviation from the normal. Several weeks later the slides were reviewed and graded upon the basis of several factors thought to be particularly indicative of tissue differentiation, namely, four points relative to general architecture (presence of a keratinized layer, presence of a definite basal layer, the sharpness of the epithelial-connective tissue border, and the occurrence of regular stratification) and three points relative to cell type (size and shape of cells and sharpness of cell boundaries). Arbitrary values were assigned, and the grading was determined by the results. The different factors were, as a rule, found to be developed to a parallel degree and so, beyond its requirement of increased study, no special merit can be claimed for the system.

The results of the two methods were found to differ completely in 11 per cent of the cases, a figure which probably represents about a half of the irreducible number of borderline cases which must bc present where an attempt is made to force a completely transitional series into three sharply defined divisions. The cases with contradictory gradings were examined a third time and a grade de- cided upon. No knowledge of the clinical outcome of the cases was permitted till the final value was recorded.

The cases are separately recorded depending on the type of treatment, since increased malignancy may be offset by greater radiosensitivity. See Table I.

The cases treated by surgery may be regarded as somewhat uniform in degree of gross extension but the irradiated cases require subdivision. See Table 11.

The results for surgical treatment indicate on a small scale a contradiction of Martzloff’s findings, since the greatest number of cures occurred in grade 111. For radium, in agreement with Cutler and Healy, there are also slightly better results in grade I11 (im- mature, anaplastic), but this is readily accounted for by the higher percentage of early cases with this type, whereas in the advanced group considered alone the more differentiated varieties led to better results. Although one is tempted to conclude that there is, therefore, no relation between histologic type and prognosis, a possible reservation must be made. Many of our cases have in the past received only small quantities of radium, and it is possible that degrees of radiosensitivj ty become evident only when irradiation is uniform arid of maximum intensity. Nevertheless, from


what data we possess and the many contradictory findings in the literature, we must align ourselves with such writers as Plaut and Doderlein, who were able to find little relation between the structure of cervicd cancer and prognosis. In further :igreement with Diiderlein it should, however, be noted that our irradiated cases of adenoc:trcinoma of the cervix are all dead.

l?IQ. 4. s Q l J A M O I J S CARCINOMA OF TllE C E R V I X . CiRADE 111

CARCINOMA OF THE CORPUS UTERI In the twenty-one years covered by the present report 145 cases

of carcinoma of the corpus have been treated, of which 137 were primary. The treatment of choice hiis uniformly been complete hysterectomy alone, although a few exceptions to this rule have occurred. A small number of cases regarded a t the time of curettage as menopausal bleeding or glandular hypcrphsia have received a preliminary dose of r:idiuIn, and this group accordingly includes rmny of the earliest cases. Several operable cases in which the patient's general condition has been regarded as pre- carious have in recent years received radium only. Postoperative x-ray therapy has not been givcn any patient in the five-year group and has been given only in occasional cases since that time.


1. Five-year Results (1910-19%): TOTAL CASES, 90

Recurrent, 5 Primary, 85

Inoperable, 15 Palliation only, 5 Radium only, 6

Radium and partial removal, 4 Results: Five-year cure, 1 ; dead, 5

Results: Dead, 3; lost, 1 Operable cases, 70

Radium only, 2

Radium and hysterectomy, 18 Results: Dead, 2

Results: Five-year cures, 5 ; three-year cures and lost, 5; opera- t,ive deaths, 3; died of recurrence, 5

Hysterectomy only, 50 Results: Five-year cures, 16; three-year cures and lost, 2; died

of intercurrent disease, 1 ; operative mortality, 3; died of recurrence, 15; lost, 13

Summary of primary cases Absolute jive-year cure rate . . . . . . . . . . . . . . 22 c 85 = 25.8 per cent With deduction of untraced.. . . . . . . . . . . . . . . . . . . . . . 34 per cent Operability. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 per cent Operative mortality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 per cent Three-year cures on traced operated cases.. . . . . . . . . 52 per cent

2. Three-year Cases (1926 and 1927): In the years 1926 and 1927, 2 recurrent and 24 primary cases were treated. I n 6 of the primary cases a combination of mdium with hysterectomy was employed and, of these, 5 are free from disease at present. Of the 15 patients treated by hysterectomy alone, 5 only are known to be well, 5 are dead (one postoperative death), the others untraceable. Three cases were inoperable. The mortality rate was 5 per cent.

3. Recent Cases (1928-1930): Of the 28 primary cases treated in the years 1928 to 1030, 4 received radium and x-rays only, 7 radium and hysterectomy, 17 hystmectomy only. There were 5 postoperative deaths, a mortality rate in these years of 21 per cent.

Summary of Results A successful five-year outcome in only 34 per cent of even the

traced cases was distinctly disappointing, for it had been cheerfully assumed on the service that the average case of cancer of the corpus enjoyed a favorable prognosis, This impression was doubtless due to the influence of other reported results which, however, were


usually based upon oper:ttive cases only or even upon traceable operative survivals. The figures on the present series, even when so calculated, remain slightly below such results as those reported by Stacy (63.8 per cent) and Zweifel (77-88 per cent,). When searching for percentages of cures based on all cases, one finds extra- ordinary differences, with figures ranging from 14.84 per cent (Crile) to about 50 per cent (v. ,Jaschke). Part of the differences in end-results may depend upon the conception of the pathologist as to where to draw the line between adenomatous hyperplasia and malignancy, a possibility also suggested by Heyman. If this is an important factor, the comparison of end-results from different, clinics will be of little value.

The primary mortality among the cases in which hysterectomy was performed was 11 per cent, a percentage to be compared with such figures as 3.37 per cent (Smit,h and Grinnell), 6 per cent (Stacy), and 9 per cent (Burnam). I t is significant that the primary mortality, when divided, becomes 7.7 per cent for patients under sixty and 19 per cent for patients over t,h:tt age.

In view of the disappointing results and high mortality, the possibility of irradiation methods its a substitute for surgery must be considered. A review of other reports on the treatment of this type of cancer leads, however, to much confusion, for the method of reporting end-results for corpus carcinoma has never been clarified as for cervical cancer, and there is constant difficulty in evaluating successes in different combinations of surgical and irradiation therapy, on account of differences of opinion on what constitutes an operable case. Yet there are a number of reports of 50 per cent or better of so-called operable ci~scs cured by irradiation treatment for periods up to five years (Voltz, Schreiner, Heyman, I3urnam). Other combinations of treatment, such as radium followed by hysterectomy (Healy and Cutler) or radium followed by a curettage and hysterectomy if cancer renxrins (Burnam), have led to encouraging results. Against the promise of these findings are certain surgical series with a very high percentage of succcsses and the testimony of certain eminent author- ities that adenocarcinoma is a radioresistant growth (Lacassagne, Doderlein).

Most writers agree that conclusive data do not exist to determine finally the best form of therapy. The results in cases trcnted by preoperative radium in this clinic, though better than those treated by operation alone, have no value in the controversy, since

FIQ. 5. ADENOCARCINOMA OF THE CORPUS, GRADE I

F I G . 6. ADENOCARCINOMA OF THE CORPUS, GRADE 11

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they represent on the average a less advanced group. On account of the uncertainty of the advantages of irradiation and the marked apprehension which its use causes an increasing number of patients who understand its relation to cancer, the treatment of carcinoma of the corpus on the Roosevelt service will continue to be, for the favorable case, surgery only. Yet, because of the high mortality in the present series, an attempt will be made to increase the group in which surgery is avoided for reasons of poor general physical

Fm. 7. ADENOCARCINOMA OF THE CORPUS, GRADE I11

condition, in particular among women over sixty years of age. In advanced cases originally regarded as inoperable and in those explored cases in which there is unremovable malignant tissue, radium and x-rays are of course essential.

Pathological Note on Carcinoma of Corpus The prognostic value of histologic types has been asserted for

carcinoma of the corpus as for carcinoma of the cervix, and the suggestion made that the anaplastic type is nearly always fatal in surgically treated cases (Mahle) but often curable by irradiation (Healy and Cutler).

When the slides of the present group of cases were classified, only three grades were used, since i t was felt that the aim of such arbitrary division is most easily accomplished by the separation of


Adcnocnrcit~ontn 1 Totnl __-__ ___ Grade1 . . . . . . . . . . . . . . . . . . . . . 12 Grade 1 1 . . j 23 . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . Grade 111. , I I 4

two extremes from the middle group, Furthermore, this had the advantage of conformity with the classification of cervical cancer, in which three groups are now a more or less accepted standard. Finally, it is to be noted that Cutler's fourth class, namely, superficial papillary carcinoma, may lead to confusion in that it brings in an apparent factor of gross extension which would be difficult to determine from a specimen obtained by curettage. Hence the classification consists of Grade I (ndenoma mnlignum), in which the glands are immensely hypertrophied but their differcntinted

Alive 3-5 Years Pcr Ceut ~ _ _ _

9 75';: 52"' 12 /o 0 ('/ 0 /O

TABLE IV Prognosis in Relation to Ilistologic T y p e i n Corpus Carcinoma Trcotcd by

Hysterectomy Only

. . . . . . . . . . . . . . . . 1 21 I 547; I 39 Total

TABLE V Prognosis iri Relation lo Histologic T y p e i n Corpus Carcirionia Treated by

Irradiation ond Hysterectomy

Aderiocnrcinoma 1 Totnl I Alive 3-3 Yews 1 I'cr Cent

form and the cylindrical shape of the cells are maintained; Grade I1 (adenocarcinoma), in which the gland form is distorted or even lost in some areas and in which the cells and nuclei have become large and irregular; Grade I11 (anaplastic carcinoma), in which the growth is diffuse with only slight, if any, indication of a ghn- dular origin.

When three-year and five-year results are considered and the operable cases divided into early with growth superficial, intermediate with partial infiltration of the uterine wall, and advanced with invasion of the cervix, tubes, ovaries, or peritoneum, the dis- tribution and results for different histologic types among 60 cases treated by hysterectomy only are as shown in Table 111.


When condensed to exclude lost cases, Table I11 becomes Table IV,

In the cases treated by irradiation followed by hysterectomy the results were as shown in Table V.

From these tables it will be seen that the prognosis improved with increasing differentiation of the tumor, whatever the form of treatment, and that in the anaplastic type there were no cures in either series. The difference in prognosis of the several grades is possibly to be explained largely by the differences in degree of gross extension in which they tended to occur at the time of institution of therapy.

CARCINOMA OF THE OVARY The end-results for the treatment of cancer of the ovary were

published in detail in 1929, but for completeness these are now brought to date.

Five-year Cases (1 91 0-1 925) : TOTAL CASES, 66

Recurrent, 8 (exploratory, 8; inoperable, 7; lost, 1) Primary, 58

Inoperable, ie., growth not all removable, 26 Exploratory celiotomy, 8

Operative mortality, 2 Colpotomy, 1 Unilateral and bilat,ernI salpingo-oophorectomy, 5 Complete hysterectomy, bilateral salpingo-oophorectomy, 12

0perat.ive mortality, 2 Operable, i . e . , all gross tumor removable

Advanced (necessity of excising extragenital parts), 8 Results: Four-year cure, 1; operative mortality, 1; death or

Borderline (adhesions, perforation of cyst, uterine or tuba1 invasion), 13

Results: Five-year cures, 2; operative deaths, 3; death or

recurrence, 6

recurrence, 5; lost, 4 Early (limited to one or both ovaries), 10

Resu1t.s: Five-year cures, 2; operative mortality, 0; deat>h or recurrence, 5 ; deat,h from intercurrent disease, 1 ; lost, 5

6.9 per cent Mortalit'y on all operations. . . . . . . . . . . . . . . . . . . . 14 per cent Cure rate on operable cases.. . . . . . . . . . . . . . . . . . 12 per cent Cure rate on traced operable cases. . . . . . . . . . . . . . . . . 19 per cent

Summary of primary cases Absolute cure ra te . . . . . . . . . . . . . . . . . . . . . . 4 + 58 =


Three-year Cases (l926-I92?) : Eighteen cases, all primary, were treated in 1926 and 1927. The status of these patients a t the end of three years was as follows: alive and well, 3; dead or living with recurrence, 13; lost, 2. There was'one postoperative fatality.

Recent Cases (1 928-1 930) : Twenty-four cases were treated in the years 1928 to 1930, of which 4 were recurrent, and 9 more inoperable. Postoperative x-ray therapy was being used system- atically for the first time in this period.

Of these, only 8 were operable.

FIQ. 8. P A P I L L A R Y C Y S T A D E N O M A OF THE O V A R Y

hlultiple peritoneal implantations. Patient well after fourteen years.

Summary of Results The prognosis in cancer of the ovary is notoriously bad, and

the results here set forth are probably close to the average. A recent report, for instance, that of Schleyer for the I University Frauenklinik in Vienna, gives an absolute cure rate of 9.52 per cent in 126 cases, with a primary mortality of 12.37 per cent. Other widely varying figures have been published, such as those of Norris and Vogt (37.5 per cent for three years), Byron and Berkoff (14.5

T H E PROGNOSIS OF GYNECOLOGICAL CANCER 2543

per cent for six months to nine years), Pvlayfield (38 per cent for “papillary cystadenoma ”), Pfannenstiel (14.6 per cent), Schaefer (13.1 per cent), and Stuebler and Brandess (24.5 per cent for three years). For comparison, the figures are of little value on account of differences in reporting inoperable and lost cases and presumable differences in pathological classificat,ion.

In the last three years at the Roosevelt Clinic postoper a t’ ive x-ray therapy has been employed in 17 cases, with little apparent improvement in results. Certainly no cures of otherwise incurable

FIG. 9. PAPILLARY CYSTADENOCARCINOMA OF THE OVARY, GRADE I Piitient died nine years after original operation.

cases can be reported, and the detection of inhibition of rate of growth too often depends upon the bias of the observer. More enthusiastic reports have been made by Strassmann, Heyman, and most recently by Ford. The latter notes a survival of 18 of 69 cases treated by operation, x-rays, and radium, for periods of four to seven years.

The present treatment at the Roosevelt Hospital for ovarian cancer consists in immediate operation for the early and borderline cases, for in these the diagnosis of a malignant tumor is usually not made before operation. In these cases postoperative x-ray therapy is invariably, and intravaginal radium frequently, given. Advanced cases are, when correctly diagnosed, treated preoper-

24


atively by x-rays and by intra-uterine and vaginal vault radium, these treatments being usually followed by exploratory celiotomy. I n cases found to be advanced after the abdomen has been opened, as much growth as possible is removed to facilitate later irradiation. A hysterectomy is likewise performed whenever possible in these cases to allow for vagind drainage, an advantage still regarded in this clinic as greater than that gained by retaining the uterus for use later as a holder for radium, as Heyman recommends.

1'1~. 10. PAPILLARY CYSTADENOCARCINOMA OF THE OVARY, GRADE I1

Pathological Note on Carcinoma o j Ocary In no type of new growth is it more necessary to draw a sharp

line between benign and malignant forms, and in few regions is it more difficult than in the ovary. I n our files are 4 cases regarded a t operation as incurable, due to multiple implantations on the peritoneum, but in which the patients have now survived from five to fifteen years following simple hysterectomy and removal of the tubes and ovaries. Although an original diagnosis of carcinoma was made, a review of the slides has indicated that the growth was of an intermediate type. The behavior of these tumors, as well as their borderline histology (Fig. S), makes it


more logical to regard them as benign and to exclude them from the present report. The inclusion of these cases with implants would have at once doubled the percentage of five year cures and the addition of other cases with an identical histology would bring the cure rate to a t least 20 per cent. The separation of these borderline growths from the truly malignant ones is the important distinction to be made in the study of the degrees of malignancy in papillomatous tumors of the ovary, for with the malignancy de-

FIG. 11. PAPILLARY CYSTADENOCARCINOMA OF THE OVARY, GRADE 111

finitely established, the histologic types (Figs. 9, 10, 11) sppar- ently make little difference in the prognosis.

CARCINOMA OF THE FALLOPIAN TUBES Two cases of probable primary tubal cancer have been observed

in the twenty-one year period, 1910-1030. In each the largest mass of growth was in the tubes, but in each there was also cancer in the ovaries, so that the primarily tubal character of the growth was not positively determined. Cases of this disease are sufficiently rare to justify abstracts of the histories.

Nov. 23, 1913. abdominal adhesions.

1. M.P., a wornan of thirty-four, married but childless, was admitted, She had been operated on four months before for

Her chief complaints at admission were scant


menses and backache. Celiotomy revealed large di1:tted tubes filled with carcinoma, with extension to the ovaries, one of which was enl:qcd and cystic. Operation consisted in coriiplete abtloniinrtl hyst erectoriiy and bilateral salpingo-oophorectomy. The pathological report was papillary adenoearcinoma (Fig. 12). Death was due to recurrence, but the date is not known.

Fro. 12. PAPILLARY ADENOCARCLNOMA ow THE FALLOPIAN Turns

2. D.D., an unmarried woman of forty-two, was admitted, July 8, 1926. Her chief complaints were the presence of :tn abdominal mass rind dysuria. The tubes were found to be greatly dilated and fillccl with ctircinomn; the ovaries were cystic, also containing csrcinom:t. ('om- plete abdornind hysterectomy and bilatcral salpingo-oophorectomy weie done. The pnthological report was p:ipillary cystadenocarcinorlln. Un- fortunately the case was subsequently lost sight of.

The unfavorable outcome in one of these and the probable similar failure in the other are characteristic of most cases of tuba1 cancer, as has been shown in Wechsler's recently compiled collection of 200 cases in which there were 6 cures. A report of Wharton and Krock is slightly more promising, with 3 patients out of 14 well after three years.


CANCER OF THE VULVA From 1910 to 1030 there have been trcated 20 cases of cancer

of the vulva. All of these have been observed either over a period of five years or have already recurred, so that relatively final results on all the cases can be tabulated. TOTAL CASFX, 20

Recurrent, 1 (treated by excision of nodes; recurred) Primary, 19

Radium only, 2. Partial vulvectomy, 4. Complete vulvectomy, 2. Partial vulvectomy with excision of nodes 1:itcr for rccurrcncc, 3.

Partial vulvectomy with unilateral excision of nodes, 1. Five-ycnr

Partial vulvectomy with uni1:itcrnl excision of nodes and later Five-

Five-year

Advanced cases, both died Five-year cure, 1; died, 3

E’ive-year cure, 0; dcnd, 2

Five-year cure, 0; dead, 2; lost, 1

cure, 1

completion of vulvcctoniy and excision of opposite nodes, 5 . year cures, 2; dead, 3

cure, 0; died operation, 1; lost, 1 Complete vulvectomy and bilateral excision of nodes, 2.

Summary of primary cases Absolute cure rate . . . . . . . . . . . . . . . . . . . . . . . 4 + 19 = 21.1 per cent Deduction of untraced. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 per cent Operative mortality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 per cent

The results do not compare very unf:tvorably with those noted in the most recent article by Tnussig, in which he reported 26.5 per cent cures in 7G cases. A scrutiny of the successful cases in this series, however, indicates that :it least three were very favorable. One of the five-year cures followed the removal of a tiny intracystic adenocarcinomn of undetermined origin diagnosed as malignant only by the pathological laboratory. Two others were slow-growing, differentiated squamous cancers developing on the basis of a senile leukoplakia. I n each cancer developed ag:tin more than five years after the original excision, probably on the basis of the same leukoplakia that had been previously incomplctely removed. The fourth was an apparently highly malignant cancer of Bartholin’s gland. This patient is now well over fourteen years after treatment.

In the list of 20 cases just summ:u.izecl there is evidence of n great dissimilarity in theory of treatmcnt. Only a few of the cases received a complete operation at the outset, and it is a striking fact that 8 of the 15 patients in whom an incomplete operation wits done came to further surgery arid of these all died except the two prcviously cited, in whom an apparently new cancer developed on

2548 HOWARD C. TAYLOR, J R ,

the basis of an incompletely excised leukoplakic vulvitis. These results speak strongly for Taussig's views on the necessity of a complete excision of all labial, perineal, and perianal skin, and a radical dissection of the inguinal and femoral lymph nodes. With the extended type of procedure, the so-called Basset operation, Taussig reports 81.8 per cent five-year cures in 11 operations without a fatality. In comparison with these improving surgicnl results, irradiation has not led to any striking advances and must

FIG. 13. CARCINOMA OF BARTHOLIN'S GLAND Patient well after fourteen years.

apparently in most cases be combined with surgery or electro- cautery excision (Schreiner, Forssell).

From the analysis of these 20 cases, it appears clearly indicated that in the future early cases should be treated in the Roosevelt clinic by a complete excision of all skin of the vulva and perineum and dissection of both groins and femoral regions. Such operations may be easily divided in two stages and should be followed by external irradiation of the lymphatic areas. In the advanced


cases interstitial irradiation by means of platinum-filtered radium needles may be attempted to reduce the size of the growth, but i t appears probable that for any cure of an even moderately advanced case surgical excision of the regional lymph nodes is a prerequisite.

Pathological Note on Carcinoma of Vulva The histology of the vulva1 lesions is rather similar to that of

the cervix, and little of interest was noted in the review of the microscopic sections. The two cases developing on the senile leukoplakia were, as noted, highly differentiated squamous epi- theliomas, whereas the Bartholin gland tumor was so highly anaplastic that the original diagnosis was round-cell sarcoma (Fig. 13). Two other cases in which tissue was available from repeated recurrence displayed an interesting tendency to become steadily less differentiated in the later specimens, a phenomenon of considerable theoretical interest, but one which appears never to have been exhaustively studied.

CANCER OF THE VAGINA Cases of primary vaginal cancer, when carefully separated

from those secondary to a small cervical lesion, are rare. Only 9 have been treated in the Roosevelt clinic in 21 years. Several of the included cases were originally classed as urethral in origin but, inasmuch as the anterior vaginal walls were in these cases completely involved by an ulcerating growth, i t is safe to classify them as probably primary in the vagina.

TOTAL CASES, 9 Recurrent, 1 Primary, 8

Radical colpectomy, 2. Radium, 6.

dead, 4

Both old cases and lost Alive and well, 1 for four years and 1 for six months;

The radical operation for vaginal cancer is technically so difficult, and its history contains so few successes (Nurnberger), that i t has few if any adherents today. On the other hand, there are an increasing nuniber of reported cures from the use of radium (Bienenfeld, Stacy, Schreiner, Heyman). The four-year case in the present series was treated by two surface applications of radium to the growth, totalling 3700 milligram hours. The more recent case, now clinically healed, was treated by a preliminary dose of


surface irr:idixtion, followed by needles into the l m e of the growth and a pelvic x-ray cycle.

CHORIONEPITHELIOM A

Only three cases of chorionepithelioma have been through the service, the smallness of the group being due perhaps to the :h- sence of an obstetrical division in the hospital. abstract of the case histories follows:

1. E.P., a married wornan of thirty-two, entered the 1iospit:il Fclx 18, ISl(i. Shc had onc child six years old and h:td had a three niont hs' miscnrringc three yc:trs before admission, for which curettagch 1i:itl been done. Hrr chicf complnint was the presence of a snnguineous discli:u.gc. On Feb. 18, 1916, :t nodule was excised from each Intern1 vaginal w:ill just above B:trtholin's gl:intl, one 2.0 cni. and the other 3.0 crn. in diameter, :mtl :L p:tt 1iologic:il diagnosis of chorioncpitliclioni~t w:ts in:tde. On h1:irch :3 :L srcond opcr:tt ion w:is pcrformctl-cornplcte hyst crcctomy and bilnter:d s:tlpingo-oophorectorny for :in enlarged uterus wit 11 muscle replaced hy n lohulntcd growth. The rntlomctrium was n o r i i d but pnthologie c.xaniin:it ion showed chorionepithelioma of the inyomct riiim. On hl:irch 22, :L third operation was andrrt:tken for cwision of :L recurrrnt growth in the v:igin:i (p i t ho1ogic:il tli:Lgnosis: chorioncpitliclioiii:i), :itid the pat icnt was given r:tclium t her:ipy, 1170 milligram hours. Ilmt h occurred in nine inont hs.

2. A.R., a imirricd womm of t wenty-nine, with four chiltlrcn from seven yc:rrs to four months, entered the hospital April 17, 1919. Onc rnorit h before :ttlniission she had iindrrgonc c u r d tage. She complnincd of bleeding beginning six weeks after the birth of hcr last child, at first intermit tent but later continuous, we:ikness, and p:tin in the b:ick. A boggy miss w:is found in the anterior v:tgin,zl w:tll, with gc'htinous 1nateri:il in the cervix. Iioentgrnogranis of the chest showctl hcalctl tuberculosis. No oper:rtion was (lone but a biopsy rcveulcd chorion- cpithelionia of the vagina. The patient died three weeks after ndniission.

3. L.P., a niarricd woin:in of thirly-two, entered the 1iospif:tl Fc~b. 2, 1926. She had one child seven years old and hnd h : ~ l one rr1isc:irringe t hrec weeks before admission, since which time she had suft'c~etl froin continuous blerding. The uterus was found to be cnlnrged, cdern:it oils, and bleeding, with a tunior in thc funclus. ('omplcte :tbdomin:il hystcr- ectorny aiitl bi1:iter:il salpingo-oophorectoriiy were done. The pat hologic diagnosis was cliorionepithelioma of the uterus; bilateral corpus Iutein cysts of ov:Lries. Tlic p:btient was discharged well but has not been followccl.

The pithological sections in these cases offered nothing re- marknble. The first case is of interest on account of the long latent period between the last pregn:tncy xiid the developnlcnt of


the tumor, as well as its apparent origin from chorionic rests in the muscular layer.

SARCOMA OF THE UTERUS Nine cases of sarcoma of the uterus have been treated in the

years from 1910 through 1930. I n view of the large number of fibromyomas passing through the clinic, this, as will be shown later, is a very low frequency.

The salient features of the nine cases follow:

FIG. 14. ~IYOSARCOMA OF THE UTERUS

1. E.S. Admitted, March 25, 1919. Age forty-four. Single. No previous operations. Chief complaint : bleeding. Gross findings: myometrium almost completely involved by a soft growth. Operation: complete hysterectomy, bilateral salpingo-oophorectomy. Pathologic diagnosis: sarcoma. Case untraced.

2. A.T. Admitted, Dec. 30, 1923. Age fifty-seven. Single. No previous operation. Chief complaint : abdominal tumor. Gross findings: two soft masses in the uterus, 10 cm. and 8 cm. in diameter, with invasion of myometrium and omentum. Operation: complete abdominal hysterectomy, bilateral salpingo-oophorectomy ; partial epiploectomy. Patho- logical diagnosis: myos:trcom:t (Fig. 14). Death on ninth day postoper :t t ' we.


3. M.M. Admitted, June 27, 1924. Age forty-seven. Married. No children. Previous operation: myomectorny t hrre and one-lidf years ago. Chirf complaint : backache, discharge, i r regihr and incrrasing menses. Gross findings: mass on posterior uterinr wall with eutrnsion to ovaries and broad ligaments. Operation: partial hysterectomy, bilateral salpingo-oophorectomy, and radium. Pat hologic diagnosis: sarcoma with metastasis. Patient free from growth after two yc:trs; thrn lost.

4. E.A. Admitted, May 4, 1927. Age thirty-four. Singlr. No previous operations. Chief complaint: nbdominnl turnor. Gross findings: a 25 cm. pedunculated fibroid with central soft area adhcrent to omentum. Operation: hysteropexy, niyomectorny, par t id epiplorctorny. Pathologic (1i:tgnosis: fibroinyoma with liquefaction necrosis. Drat h :it five months of recurrence. Slides were reviewed and diagnosis ch:ingetl to myosarcoma.

5 . 13,s. Admitted Nov. 12, 1927. Age fifty-seven. Married. No children. No previous opcrations. Chief complaint : return of mrnsrs. Gross findings: multiple fibroids of the uterus, the largest, 8.0 cm. in dinmctrr, with soft center. Operation: supravaginal hystrrrctorny, bilaternl salpingo-oophorectomy, the malignant character of t he turnor not being recognized. Pathologic diagnosis: myosarcoma. Recurrence in cervix in about a year and dcath from pulirionary metastasis.

ti. E.S. Admitted Nov. 1, 1927. Age sixty-seven. Married. One child. Previous operations: myomectomy twcnty-three years previously; rrmoval of polyps of cervix on two occasions, four yews and one year previously. Chief complaint : bleeding. Gross findings : two largr purple polyps in cervical canal, one 4 X 3 X 1.5 cm., the other 3 X 3 X 1.5 ctn. Operation: curettage and radium. Pathologic diagnosis: s:ircornx. Patient untraced.

7. M.L. Admitted, Dee. 21, 1927. Age forty-four. Married. No children. Previous operation : curettage, three years previously. Chief complaint : brownish discharge and bleeding. Gross findings: shaggy polypoid growths on upper vagina, and in cervical and entlonictri:tl canals with extension into the right broad ligament. Operation : complete abdominal hysterectomy, bilateral sftlpingo-oophorectomy. Pathologic diagnosis: myosarcoma. Death on ninth day.

8. F.B. Admittrd, Nov. 13, 1929. Age thirty-nine. Married. One child. Previous operation : partial oophorectorny, fourteen years before. Chief complaint : menorrhagia. Gross findings: a sarcomittous polyp, 5.0 cm. long in cavity of uterus with extension into broad ligamtbnts and into both ovaries, there being a snrcomatous cyst of the right ovary, 15 x 8 x 0.0 cm. Operation: complete hysterectomy, bilateral salpingo-oophorectomy, followed by radium in the vaginal vault and x-ray irradiation of pelvis. Pathologic diagnosis: myosnrcornn.

9. L.B. Admitted, Sept. 18, 1930. Age sixty-one. Married. Four children. Previous operations, ;1. curettage nnd litter n cure1 t:tge with radium for fibroids twelve years before. Chief complaint: pain in

Pelvic veins showed invasion.

Patient free of disease a t six months.


abdomen and back. Gross findings: a pedunculated tumor in the endometrial cavity, 12 X 6 X 5 cm., with some invasion of wall. Oper- ation: complete abdominal hysterectomy, bilateral salpingo-oophorectomy. Pathologic diagnosis : adenomyosarcoma. No evidence of disease a t three months.

In summary, it is to be noted that there were two postoperative deaths, two patients died of recurrence, three are well over short periods, and two are untraced.

The series illustrates a special danger in the handling of myosarcoma, namely, the clinical or pathological failure to suspect the condition on account of the relative rarity of malignancy among myomas. Such an error is illustrated by case 5 , which was treated by a supravaginal hysterectomy with death following the development of the disease in the cervical stump. Three similar occur- rences have been reported from England, in two of which the patient ultimately died (Blacker, Spencer). In a second case (number 4) the sarcoma in a tumor removed by myomectomy was not discovered for several months, until clinical evidence of recurrence directed renewed attention to the microscopic slides. Three similar cases of sarcoma in tumors removed by myomectomy, one under a centimeter in diameter, have been previously reported from the Roosevelt Hospital (Taylor), hut in each of these cases a correct pathologic diagnosis was made and the uterus removed a t once in a second operation. Boriney also reports a case treated by myomectomy in which pathologic failure to recognize the sarcoma resulted in rapid recurrence and death. Finally, in the present series a third case, fortunately already treated by complete hysterectomy, was overlooked in the laboratory until, because of the surgeon's suspicions of the gross specimen, further sections were taken.

Pathological Note on Myosarcoma The sections of the tumors in this series all give evidence of a

high degree of malignancy, a finding to be expected from the unfavorable end-results and the advanced condition in which many of the growths were found. That the percentage of cures may depend almost solely upon the type of case regarded as true sarcoma by the pathologist was excellently demonstrated by an article of Evans, published in 1920. Classifying 72 cases of myosarcoma or cellular myoma in three groups, depending upon the number of mitotic figures, Evans found that in the 13 cases of the most malignant group there were no cures, whereas in the other


groups there were no recorded deaths among the followed cases. Similarly the frequency of this tumor depends upon pathological classification, for it could be shown that among 968 myomns : k t the Mayo Clinic sarcoma was present in 0.62 per cent, 1.25 per cent, or 4.0 per cent, depending upon the strictness of qualific a t' ion for admission to the sarcoma group. In the present series, if we exclude cases 6, 7 , and 9, which were probably not derived from myomas but from the endometrium, the ratio in our clinic becomes 6 : 4000, or 0.15 per cent, a figure far lower than any previously reported among the authors listed by Evans, arid possibly indicative of further still unsuspected clinical and pathological failure to detect sarcoma in apparently benign tumors.

SARCOMA OF THE PELVIC CONNECTIVE TISSUE One case of sarcom:L of the rectovaginal septum was operated

upon.

S.B., a married woman of fifty-five, with seven children, was admitted to the hospital June 10, 1923, complaining of dysuria. A m:iss the size of an orange (8 X 8 X ci cm.) was found attached to the rectum and posterior vaginal wall. It was excised by the vnginal route and :I,

pathologic diagnosis of fibrosarcomu of the rectovaginal septum W:LS

made. The patient died eight years later of cardiac disease.

SARCOMA OF THE OVARY Eight cases of ovarian sarcoma were originally listed, but a

review of the slides c:tused the transfer of three cases to the ovarian carcinoma series with a diagnosis of round-cell carcinoma of the embryonal type. Five cases remain to be reported, of which two could not be restudied in the pathological sections, as these had been lost.

1. M.C. Admitted, June 22, 1910. Age thirty-five. Single. No previous opcrations. Chief complaint : amenorrhea, increase in size of abdomen. Gross findings: solid tumors of both ovaries, 12 x 15 ern. and 12 x 10 cm. in diameter respectively, with metastasis t o colon and parietal peritoneum. Operation : complete hystercctomy and bil:tt- era1 salpingo-oophorectomy. Pathologic diagnosis: spindle-cell sarcoma. Case untraced.

2. D.R. Admitted, June 12, 1913. Age fifty-two. Married. lCight children. Previous operations: removal of cyst of sitme size and microscopic structure from left ovary one year previously a t the Roosevelt Hospital, which was, however, not a t that time called sarcoma. Gross findings: a cyst 30 X 20 X 15 cm. in diameter in the right ovary containing masses of friable material, adhesions to the intestine. Operation:

The salient features are as follows:

FIG. 15. SARCOMA OF THE OVARY

Death after four years.

I?Ic;. 16. 1 ~ l B R O S A I X O M A OF THE OVARY

Tumor appeared in opposite ovary after one yedr.

2555


excision of tumor; enterorrhaphy. Pathologic diagnosis : spindle-cell sarcoma (Fig. 16).

3. I.W. Admitted, Sept. 25, 1913. Age forty-eight. Married. Ten children. No previous operations. Chief cornplaint : increase in size of abdomen. Gross findings: solid tumor of left ovary, 14 X 10 x 10 cm., with met,astasis throughout the abdominal cavity. Operation: complete abdominal hysterectomy, bilateral salpingo-oophorectomy. Pathologic diagnosis: sarcoma of mixed type.

4. E.D. Admitted, June 11, 1924. Age fifty-eight. Married. Eleven children. No previous operations. Chief complaint : abdomind tumor for one and one-half years. Gross findings: immense, solid and cystic turnor of left ovary, 24 X 20 X 18 cm. with mrtastases to uterus and ornentum. Operation : supravaginal hysterectomy with b ih te rd snlpingo-oophorect omy. Pat hologic diagnosis : myosarcorna (Fig. 1.5). Patient lived about four years and died with multiple peritoneal growths.

5. W.S. Admitted, Feb. 2, 1929. Age fifty-five. Married. Three children. No previous operations. Gross findings: soft solid turnor of the right ovary, 16 cm. in diameter, with capsule intact. Operation: complete abdominal hysterectomy, bilateral salpingo-oophorectomy. Pathologic diagnosis: fibrosnrcoma of right ovary. Patient alive and well, two years.

Postoperative death in twenty four hours.

Death in five months.

Pathological Note on Sarcoma of the Ovary Of the five cases, three were spindle-cell sarcoma or fibrosar-

coma. One of these patients died as a result of the excision of such a tumor from the right ovary a year after the removal of a similar growth from the left side, although in the absence of other metastasis the second tumor should probably be regarded as a coincident and not a secondary neoplasm. In neither of the other cases of spindle- cell sarcoma was metastasis present, so that these three examples bear out the views expressed by various observers (Kriimer, Stern- berg, Caylor), that the ovarian fibrosarcoma is relatively benign. Mayer’s statistics, however, indicate th:it these tumors are not entirely innocuous.

The two remaining cases were associated with extensive peritoneal metastasis, and both patients died. The tissue of one case, originally classed as a “sarcoma of mixed type,” could not be restudied. The histology of the second case had features suggestive of myosarcoma, with areas of peculiar arrangement of the tumor cells around the blood vessels, perhaps meriting its classification with tumors described by Sternberg as perivasculsr sarcoma.”

In sarcoma of the ovary, as in other of the rarer tumors whose classification is uncertain, it should be clear that the one factor which overshadows all others in determining percentages of cures

T H E PROGNOSIS OF GYNECOLOGlCAL CANCER 2557

is the pathologic classification. The spindle-cell type in particular should undoubtedly be separately reported and the possibility of a confusion with fibroma carefully weighed.

ADVANCED PERITONEAL TUMORS OF DOUBTFUL ORIGIN In every gynecological ward there are occasionally to be seen

patients with advanced growths characterized by progressive cachexia, abdominal enlargement due to ascites, intestinal dis- tension, and irregular hard palpable masses in the pelvis and scat- tered through the abdominal cavity. The propensity of gall- bladder and gastro-intestinal tract tumors to metastasize to the pelvis in both males and females is known, but in women many of these growths continue to be arbitrarily classed as ovarian cancer. The true diagnosis can in rare cases be definitely established by examination only, more often by the study of cells from n cen- trifuged specimen of the ascitic fluid, and not always by exploratory operation itself. For this reason a group of cases of uncertain origin must be reported in which the pelvic peritoneum was exten- sively involved as a part of n generalized growth. One subdivision of the group in which the possibility of ovarian cancer exists may be used to make the end-results in ovarian cancer appear still worse, if the reader desires.

TOTAL CASES, 20 Recurrent, 4 Primary, 16

Palliative treatment, 6 Exploratory celio tomy, 10

Secondary ovarian, 4 (3 with a typical Krukenberg histology and

General peritoneal, 6 (sarcoma, 2; carcinoma, 2; undetermined, 2) one with a sigmoid type of carcinoma)

CONCLUSION No spectacular successes have been reported in the present

paper. Yet it is probable that the results in the treatment of gynecological forms of cancer in the Roosevelt Gynecologic Clinic are for the most part close to a more or less general average being widely maintained for these special types in America and Europe.

Variations up to 5 or 10 per cent in the end-results in cancer of the cervix and from 10 to 25 per cent or more in the other less studied forms are probably insufficient to indicate definite variations in excellence of treatment. Other factors, such as the


character of cases coming to thk clinic, the funds available for following lost cases, and the pathologist’s personal tendencies in the classification of the case with a borderline histology, are usually sufficient to account for such differences.

Yet the present survey has led to certain conclusions: 1. Cancer of the cervix in the only two reportable years (1024-

1025) in which radium was used practically exclusively was curable for at least five years in 18 per cent of all cases. The amount of irradiation in these years was inadequate. An increase in dosage, a better method of application, and the addition of deep x-ray therapy will, it is hoped, lead to improved results for the years after 1827.

It is to be noted also, however, that in the years 1921-1923, when the plan of treatment for favorable cases was preoperative radium and later radical hysterectomy, the absolute five-year cure rate was 29.7 per cent.

2. Carcinoma of the corpus gave an absolute cure rate of 25.8 per cent, r?, disappointing figure, due in part to a large number of lost cases. Among the traced operated cases the results ap- proachcd the average reported by other institutions. The high mortality, especi:illy in women over sixty, leads to the suggestion that irradiation should be substituted for surgery at, least in this group.

3. Carcinoma of the ovary yielded only G.8 per cent of cures, a very low figure, due perhaps entirely to a review of the sections and the exclusion of all cures in cases possibly classifiable as papillary cystadenoma. The successes were all due to factors uncon- trollable by the surgeon, namely, the restriction of the growth a t the time of operation to an unruptured cyst. Roentgen therapy has not produced cures in otherwise incurable cases in the Roosevelt, clinic, but will be continued in view of favorable outside reports.

4. Carcinoma of the vulva yielded 21.1 per cent cures, but it is probable that this figure might have been better had several of the early cases not been at first treated by a too conservative operation.

5. Carcinoma of the vagina has recently been treated by radium, which has led to some preliminary encouraging results.

6. Sarcoma of the uterus and ov:iry offer difficulties in histologic diagnosis which may largely affect the reported percentage of cures. From a more practical point of view a failure 011 the part of either surgeon or pathologist to differentiate myosarcorna

T H E PROGNOSIS OF GYNECOLOGICAL CANCER 2559

from a benign fibromyoma may jeopardize the individual patient’s chances.

7. A few rarer tumors, carcinoma of the tube, chorionepithelioma, and sarcoma of the rectovaginal septum are reported. Ah apparent cure is noted in a case of the disease last cited.

8. Advanced peritoneal malignant tumors of undetermined origin, usually regarded as ovarian, have been separately considered. They form a fairly large and quite hopeless group.

A careful review of the pathological sections of cases of cancer of the cervix has led to little corroboration of the finding of several writers that histologic form bears a relation to prognosis due to variations in malignancy or in radiosensitivity. There was a very slight indication of such a relationship in carcinoma of the corpus. The correct separation of corpus adenocarcinoma from endometrial hyperplasia, of papillary cystadenocarcinoma of the ovary from papillary cystadenoma, of myosarcoma from fibromyoma, of fibrosarcoma from fibroma of the ovary is, however, of vital importance in prognosis.

This study has been made in part to meet the demands of the rapidly improving standards of cancer treatment and to answer the question raised by the existence of the cancer specializing institutions of the right of general services to continue the treatment of mdig- nant tumors. From a naturally biased point of view it is our opinion that there is little evidence at present to show that the percentage of cures in cases of gynecological cancer increases with complexity of equipment, or that for the individual case of uterine cancer more is required than a modern high-voltage x-ray apparatus and a relatively small quantity of radium.

The prestige of the cancer specializing institute is due probably in large part to its physical equipment, but its actual superiority rests in its more active interest in the general tumor problem as well as the greater care with which pathologic material and clinical records are handled. The relative deficiencies of the smaller clinic appear from our study to be chiefly those of the occasional clinical or pathological error in diagnosis due to a lack of complete attention to the tumor problem and, above all, to the absence of a systematized plan of therapy, which permits some cases to be undertreated. The mere consciousness of the defects, however, should result to a large degree in their elimination.

25


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