Routine noninvasive hysterography in the evaluation and treatment of endometrial carcinoma

GYNECOLOGIC ONCCiWGY ‘4, 354~367 (1976).

Routine Noninvasive Hysterography in the Evaluation and Treatment of Endometrial Carcinoma

BARRIE ANDERSON, M.D.,’ DOUGLAS J. MARCHANT, M.D., JOHN E. MUNZENRIDER, M.D., JEFFREY P. MOORE, M.D.,

AND GEORGE W. MITCHELL, JR., M.D. Departments of Obstetrics and Gynecology, Therapeutic Radiology, and Diagnostic

Radiology, Tufts-New England Medical Center, Boston, Massachusetts 02111

Received April 1976

Hysterography is an important aid in the diagnosis and treatment of endometrial carcinoma. Using a noninvasive technique, no significant complications have occurred in 134 patients. Important information concerning site of origin, size, and extent of the tumor and uterine deformities has been obtained and has altered the treatment in 28% of the cases studied. The importance of having a knowledgeable observer to direct and interpret the study is stressed. The significance of possible transtubal and hematogenous spread is discussed.

INTRODUCTION

In recent years much attention has been focused on refining the criteria by which endometrial carcinoma is diagnosed and treated. Such refinements include the use of endometrial washings [l], hysteroscopy [2], revision of the international staging system [3], and hysterography [4-61. Dalsace and Garcia-Calderone [7] have recommended hysterography in the work-up of patients with abnormal bleeding, particularly in the postmenopausal age group. They emphasized that the curette may miss small endometrial lesions and that coexisting cervical and endometrial carcinomas may go undetected. The largest series of cases of carcinoma of the endometrium studied with hysterography is that of Norman [8,93 who advocated its use to help determine the type of radiation therapy to be used. Wallace et al. [4] added that hysterography was useful to define the size, shape, and location of a neoplasm and thus was helpful in guiding placement of radium applicators.

In an effort to plan treatment more precisely (Table l), hysterography was first used at the New England Medical Center Hospital in the pretreatment work-up of patients with endometrial carcinoma in January 1972. It has been a part of the work-up of all patients with endometrial carcinoma since May 1972 and has provided information concerning tumor volume, uterine size, endocervical involvement, and uterine anomalies (Table 2). Much of this information might be obtained by careful uterine exploration during dilatation and curettage. However, many patients are referred after this diagnostic procedure has already been performed, often without any record having been made of such findings. Hysterog- raphy eliminates the need for a second operative procedure.

’ Send reprint requests to: Barrie Anderson, M.D., New England Medical Center Hospital, De- partment of Obstetrics and Gynecology, 171 Harrison Avenue, Boston, Massachusetts 02111.

354 Copyright @ 1976 by Academic Press, Inc. All rights of reprcduction in any form reserved.

NONINVASIVE HYSTEROGRAPHY 355

TABLE 1 POTENTIAL USES OF HYSTEROGRAPHY

Choice of appropriate radiation modality Guidance in intracavitary radium application Elimination of preoperative radiation Staging Determination of the true site of origin of the tumor

TABLE 2 USEFUL INFORMATION GAINED BY HYSTEROGRAPHY

I. Findings related to the uterus A. Uterine size B. Uterine shape C. Uterine position D. Nature of uterine enlargement

1. Elongated cervix 2. Fibroids 3. Tumor

E. Uterine anomalies

II. Findings related to the tumor A. Location of tumor B. Volume of tumor C. Configuration of tumor D. Endocervical involvement E. Site of tumor origin

By December 31, 1974, a series of 134 patients studied hysterographically had been accumulated. Contraindications to hysterography that were observed were active bleeding, vaginal obstruction by metastases and a dilatation and curettage within 1 week. The latter restriction was arbitrary, but was based on evidence suggesting that the probability of hematogenous intravasation is increased when there has already-been endometrial trauma such as dilatation and curettage during the preceding few days [15]. No major complications occurred. Most patients experienced vaginal spotting or minimal vaginal bleeding which usually stopped within 24 hr.

METHOD

The technique employed for most cases was noninvasive, using a Malmstrom- Thoren unit (Fig. 1). A vaginal examination was done to estimate the size and shape of the vagina and cervix. The vagina was cleansed with Phisohex and water. The entire instrument was prefilled with water-soluble dye (Sinografln, Squibb). Using sterile technique, the suction cup was applied to the cervix so that the acorn-tipped cannula fit into the external cervical OS. Under fluoroscopic control, dye was injected in small increments into the cervical canal and uterine cavity. Noteworthy findings were recorded on spot films. Once the cavity had been moderately filled, rotational views were obtained. The absence of an instrument in

356 ANDERSON ET AL.

FIG. 1. Cervical applicator of Malmstrom-Thoren unit.

the cervix allowed better observation of endocervical detail. Gentle cervical traction could be applied as needed to improve visualization.

Since no tenaculum was used and no dilatation of the cervical canal was necessary, patient discomfort was considerably less than with traditional techniques. No patient requested that the test be discontinued because of discomfort, although, when asked specifically, most patients admitted to minor cramps at the time of the application of the cervical cup.

In a few instances, severe vaginal atrophy or a markedly deformed cervix made the use of this instrument impossible. In these cases, one of three alternative techniques was used: (1) A tenaculum replaced the suction cup with the rest of the system remaining the same; (2) a vaginal Foley catheter with a 30-ml bag inflated in the apex of the vagina replaced the entire system; or (3) the traditional technique with a tenaculum and an intrauterine cannula was used.

When hysterography is done, it is important to have a knowledgeable observer present to direct timing of X rays and to interpret findings that may be difficult to record on spot films. In our institution, all hysterograms were performed by the gynecologic oncology fellow and a radiologist.

The total time involved in the performance of this procedure is about y2 hr for the patient, 20 min for the gynecologist, and 10 min for the radiologist.

RESULTS

In only 17 of 151 cases was hysterography impossible. Nine of these patients were very elderly, virginal, or nulliparous women who could not tolerate pelvic


examination except under anesthesia. Seven had Stage III disease with vaginal metastases. One patient had a syncopal attack during the pelvic examination preceding the study.

A hysterogram performed with this technique on a patient with a nonmalignant lesion is shown in Fig. 2. The shagginess and polypoid excrescences typical of endometrial carcinoma are seen in the hysterogram in Fig. 3. This patient had a slightly enlarged uterus that sounded to 4 in. Hysterography gave a more complete picture of the nature of the uterine enlargement and the volume of tumor.

Early films were of value in defining the location of tumor masses (Fig. 4). Once filling was more complete, this detail was lost.

Rotational views add information concerning more precise localization of tumor masses as well as uterine shape and position. Figure 5 shows the early part of a sequence on a patient with Stage I, group 1 adenoacanthoma of the endometrium. The early hysterographic films showed multiple small polypoid excrescences and shagginess in the fundus. No cervical defects were seen. Rotational views (Fig. 6) demonstrated that the uterus was anteverted and that the largest bulk of tumor was in the left posterolateral cornual region. /

A major advantage of hysterography is the ability to identify anatomical tumor and uterine variations that will affect the choice of radiation modality. Figure 7 shows the hysterogram of a patient with a bulky obstructing mass. Sounding of this patient’s uterus might be expected to give a faulty impression of cavity size. In addition, radium could not be placed in the upper right portion of the cavity.

FIG. 2. Hysterogram performed with the MalmstrowThoren unit in a patient with nonmalignant pathology. The entire cervical outline is well visualized.

358 ANDERSON ET AL.

FIG. 3. Hysterogram showing characteristic shagginess and polypoid excrescences in a patient with adenocarcinoma of the endometrium.

FIG. 4. Sequence showing loss of tumor detail by complete filling of the cavity in this patient with Stage I, group 1 endometrial carcinoma.


F %G. 5. Early films on a patient with Stage I, group 1 disease. Tumor is more prominent left cornu.

in the

FIG. 6. Rotational films on the patient in Fig. 5 showing the posterolateral location of the main tumor mass. Tubal filling is present bilaterally.

360 ANDERSON ET AL.

FIG. 7. A bulky obstructing Stage I, group 3 lesion.

This bulky lesion could not be effectively treated with brachytherapy. Such a patient should be treated with external radiation therapy rather than intracavitary radium.

Variations in uterine shape, such as.arcuate and bicornuate uterus, were seen in 11 patients (8.2%). Figure 8 shows a late film of a patient with Stage II disease. Hysterography revealed a bicornuate uterus with a left hydrosalpinx and, on the right, spillage of dye into the peritoneal cavity. In this case, hysterography made it possible to direct the application of radium properly. If the bicomuate shape of the uterus were not appreciated in advance, a proper placement of radium (Fig. 9) might be misinterpreted as uterine perforation. Conversely, an application that omitted one horn might be mistakenly considered acceptable. Uterine anomalies were suspected in none of the 11 patients prior to hysterography.

Information that would otherwise be lost can be obtained by the use of hysterography. Figure 10 shows a diagram of the pelvic findings on a 74-year-old woman with moderately well-differentiated adenocarcinoma of the endometrium involving the endocervix. She had a past history of phlebitis, hypertension, and congestive heart failure and was a very poor candidate for surgery. The uterus was irregularly enlarged, with an estimated lO-cm depth, and there was a stony hard mass arising from the left-lower uterine segment. The left-sided mass was thought to be a calcified fibroid. The rest of the pelvic mass was thought to be carcinoma with parametrial spread to the right. A pelvic X ray (Fig. 11) confirmed the presence of the fibroid but still left the impression that Stage III disease was present. The hysterogram (Fig. 12) revealed a bicornuate uterus with tumor in the


FIG. 8. Bicornuate uterus with left hydrosalpinx and endocervical involvement. Tubal spillage is present on the right side only.

right horn and the endocervix and a relatively normal left horn. This patient was then appropriately placed in Stage II, and an otherwise difficult radium application (Fig. 13) was performed properly.

Follow-up hysterography after treatment has been difficult. One problem is vaginal stenosis secondary to irradiation. Also, intrauterine adhesions could be expected to occur and to interfere both with the performance and with the accuracy of the examination.

Another potential use for hysterography is detection of cervical involvement (Figs. 8 and 12). This is difficult to detect radiologically since even normal cervices show a wide degree of hysterographic variation and irregularity [8]. All patients had an endocervical curetting. Histologic evidence of tumor in the endocervix was required to place a patient in Stage II. The correlation of positive findings on hysterogram with positive histology in endocervical curettings was 67%. This correlation was related to experience and improved steadily over the years of the study.

Finally, hysterography may provide necessary information concerning the site of origin of a malignancy. The tumor shown in Fig. 14 was felt to be a well- differentiated, predominantly papillary adenocarcinoma consistent with either an endometrial or an endocervical primary. Clinically the cervix appeared normal and findings were consistent. with an endometrial primary, Hysterography revealed the true endocervical origin of the tumor (Fig. 15). The endocervix was enlarged with a tiny but normal uterine body at the top. This patient was appro-

362 ANDERSON ET AL.

FIG. 9. Radium application in the same patient shown in Fig. 8.

FIG. 10. Findings on pelvic examination indicate Stage III disease in this


I FIG. 11. X ray of the pelvis confirms the presence of a calcified fibroid in the left pelvis in Pal ient shown in Fig. 10.

the

FIG. 12. Hysterogram on patient shown in Figs. 10 and 11 shows a bicomuate uterus and endocervical involvement.

FIG. 14. A mucin-producing papillary adenocarcinoma found in a patient who clinically was thought to have endometrial carcinoma.

364


FIG. 15. Hysterogram on the patient in Fig. 14 shows a cervix filled with tumor and a small normal fundus above it.

priately treated for her endocervical disease. Endocervical tumors were unexpec- tedly found in three patients.

Tubal spillage (Figs. 6, 8, and 15), either unilateral or bilateral, occurred in 53% of all patients studied. Obstruction was rarely related to a bulky tumor mass. The incidence of tubal patency in normal postmenopausal women is unknown. The high incidence of tubal obstruction in this group of patients may be of importance in considering the possibility of tumor spread by the tubal route.

DISCUSSION

In our series, information gained by hysterography has affected the therapeutic decision in 28% of the cases (Table 3). In some instances, this has resulted in addition of more radiation therapy, while in others the amount of radiation was decreased. The value of this change in the amount of therapy depends on its effect on complication and recurrence rates.

366 ANDERSON ET AL.

TABLE 3 REASONS FOR CHANGE IN TREATMENT PROTOCOL BECAUSE OF HYSTEROGRAPHY

Uterine anomaly (bicomuate or arcuate) No tumor seen Endocervix positive (all later confirmed histologically) Large tumor volume Endocervical primary Large uterine cavity Fibroids

Total 36 (28%)

In a future publication, survival of 91 patients treated at the New England Medical Center Hospital prior to the use of hysterography will be compared with that of 134 patients treated subsequently by the same group of physicians with the aid of hysterography. Though there is no decrease in short-term survival, follow- up data are limited and no final conclusion can yet be drawn.

The question of the effect of peritoneal spillage and possible hematogenous spread of disease due to hysterography is important. Transtubal spread of tumor during hysterectomy, dilatation and curettage, pelvic examination, and hysterography has been of great theoretical concern [ 111. However, the viability of tumor cells obtained from peritoneal washings in patients with endometrial carcinoma is unknown [ 111. Studies in autotransplantation of human tumor cells by Southam et al. [12] suggest that the initiation of autochthonous cancer cell growth at a new site usually requires the deposition of very large numbers of dispersed cells (105). Though peritoneal cytologic findings have been found to correlate well with prognosis in corpus cancer [13], intraperitoneal tumor cells may represent the presence of more advanced disease rather than its cause.

Vascular showers of tumor cells have been shown to occur at the time of dilatation and curettage and hysterectomy [14,15], but the ultimate fate of these cells is also unknown. Since nearly all patients with endometrial carcinoma undergo diagnostic curettage prior to treatment, but only 10 to 15% have distant metastases, it seems likely that the majority of the intravascular tumor cells shed are not successful in establishing metastases.

The information to be gained from a procedure must be weighed against the risk taken. Therefore, neither of the above concerns should preclude the performance of appropriate studies for work-up and staging that may lead to improved survival and decreased complications.

In summary, hysterography has been found to be a useful technique in defining tumor volume, location, and site of origin and in identifying uterine anomalies. The additional information gained has altered the treatment in a significant propor- tion of the patients studied. The ultimate value of hysterography will be deter- mined when 5-year follow-up statistics are available for comparison with pres- ently available data on patients treated without hysterography.

REFERENCES

1. Gravlee, L. C. Jet irrigation method for the diagnosis of endometrial adenocarcinoma, its principle and accuracy. Obstet. Gynecol. 34, 168-173 (1969).


2. Joelsson, I., Levine, R. U., Moberger, R., Hysteroscopy as an adjunct in determining the extent of carcinoma of the endometrium, Amer. J. Obstet. Gynecol. 111, 606-702 (1971).

3. The international classi$cation of gynecological malignancy, 1971 & 1974. 4. Wallace, S., Jing, B., and Medellin, H. Endometrial carcinoma: Radiologic assistance in diag-

nosis, staging, and management, Gynecol. Oncol. 2, 287-299 (1974). 5. Schwartz, P. E., Kohom, E. I., Knowlton, A. H., and Morris, J. M. Routine use of hysterog-

raphy in endometrial carcinoma and postmenopausal bleeding, Obstet. Gynecol. 45, 378-384 (1975).

6. Wolff, J. P., Goldfarb, E., Rumeau-Rouquette, C., and Breart, G. The value of hysterogram for the prognosis of endometrial cancer, Gynecol. 0~01. 3, 103-107 (1975).

7. Dalsace, J., and Garcia-Calderon, J. Gynecologic radiography, Medical Department, Paul B. Hooker, New York (1959).

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9. Norman, 0. Hysterography in cancer of the uterus, Semin Roentgenol. 4, 244-251 (1969). 10. Asplund, J. The uterine cervix and isthmus under normal and pathological conditions, a clinical

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Gynecol. Obstet. 103, 332-336 (1956). 12. Southam, C. M., Brunschwig, A., and Dixon, Q. in Biological interactions in normal and

neoplastic growth, Little Brown, Boston, pp. 723-738 (1962). 13. Creasman, W. T., and Rutledge, R. The prognostic value of peritoneal cytology in gynecologic

malignant disease, Amer. J. Obstet. Gynecol. 110, 773-781 (1971). 14. Roberts, S., Long, L., Jonasson, O., McGrath, R., McGrew, E., and Cole, W. H. The isolation

of cancer cells from the blood stream during uterine curettage, Surg. Gynecol. Obstet. 111, 3-11 (1960).

15. Merrill, J. A. Dissemination of cancer cells during surgical curettage, Amer. Surg. 29, 206-211 (1963).

Routine noninvasive hysterography in the evaluation and treatment of endometrial carcinoma

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