Ureteral obstruction in carcinoma of the cervix

URETERAL

OBSTRUCTION

C. W. ALDRIDGE,M.L)., (From

the Departwlents

APPLETOX,

of

Obstetrics

IN CARCINOMA

OF THE CERVIX

WIS., AND ,J. T. MASON, M.D., SEATTLE,~ASH. and

Gynecology,

and

Crology,

University

of Michigan

Hospital)

N OUR year-by-year association with patients having carcinoma of the cervix at the University of Michigan Hospital, we have been impressed with the large number who develop pathologic conditions of the urinary tract. Changes in the bladder or uret,hra secondary to irradiation or extension of the neoplasm are common. Our interest here, however, is primarily concerned with the problem of ureteral obstruction. I

The reported incidence of ureteral obstruction and subsequent death from uremia has varied considerably with different investigators. It is usually agreed, however, that ureteral obstruction and terminal uremia are a common eventuality. De Alvarez,’ in a review of the University of Michigan Hospital autopsy series, found that 40 per cent of patients with cervix carcinoma died of uremia. Herger and Schreiner’ reported that 53 per cent of their autopsy series revealed stricture of one or both ureters. Diehl and Hundley3 recently have indicated that 38 per cent of a group of 37 patients showed some degree of ureteral dilatation one year aft,er therapy. For many years there has been a difference of opinion concerning the cause of ureteral obst,ruction. Several factors may, of course, play a part in its production. l’irst,, it may be caused by extension of the neoplasm and either compression or infiltration of t,he ureter by carcinoma with resulting obstruction of the lumen. Second, it may be caused by changes secondary to irradiation. This might be manifest by edema which develops during or immediately following therapy or by fibrosis and scarring some time later. Everett4 has subscribed to this latter theory. In 1934, he reported eleven out, of eighteen patients with ureteral obstruction seconclary to irradiation for carcinoma of t,he cervix. One should also not overlook the fact that infection may be an important factor in the production of ureteral stricture. We have long considered the possibility of active early surgical management of the ureters (i.e., transplantation into bowel, nephrostomy, or cutaneous ureterostomy) when eviclence of ureteral obstruction is first demonstrated. Any procedure which might hope to prolong the life of 40 to 50 per cent of these patients now dying of uremia should be given serious consideration. In order to accumulate additional data. regarding ureteral obstruction this study of pa,tients with cervix carcinoma was planned and carried out. It, was hoped that by careful analysis of the records of a large group of patients we might, again det,etmine the incidence of obstruction. We hoped also to learn whether the incidence of obstruction before deat,h varied significantly from the inciclence observed in the autopsy series. A comparison of these two groups might itnlicat,e how many patients actually die from obstruction. Furthermore, it seemed desirable to determine the actual cause of t,he obstruction. In carrying out our work we have studied sections of ureters 1272

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taken at the time of autopsy to determine whether compression or changes due to irradiation could be discovered. We have also st,udied the records of the patients to determine whether there existed any relationship between clinical course and therapy or change in the extent of the disease. Finally, we have tried to evaluate the results of our present management of patient,s with evidence of ureteral obstruction. Have the cases which we treated by ure~eral dilatations or nephrostomy done better than the untreated group?

Material The group studied includes all cases of cer\-is (carcinoma see11in the gynecologic service from January, 1942, t,o *January, 1947. The t,otal of 45X patients were distributed according to clinical groups as outlined in Table I. The clinical groupings were determined by the following criteria : Clinicab Group I.-Very small and early, histologically proved carcinoma of the cervix, such as intraepit,helial lesions and carcinoma arising in a cervical polyp. In general use, these are t,he early commonly unrecognized eases. Clinical Group 11.-Clinically recognizable, histologically proved carcinoma of the cervix, exclusive of Clinical Group I lesions, still ent,irelj- confined to thca cervix and without evidence of parametrial thickening or vaginal infiltration. Clinical Group IIT.-Histologically proved carcinoma ot’ the cervix with questionable parametrial thickening. The cervical lesion proper map; or ma.y not be extensive, the important feature of this group being the question of parametrial involvement. Into this group are placed those patients concerning whom there might, well be a difference of opinion regarding extension into the adjacent tissues. TABLE

-

I.

TOTAL

NUMBER OF PATIEXTS WITH CARCIKOMA ok TME CERVIX FKOM JAN~RY, TO JANI:ARY, 1947, ACCORDINO TO CLINICAI, GROUP ---I-___-_____ -__~ __.._ ._.. Clinical Group I 30 II 42 III 59 IVa 1;:; IVb I53 __. .I.58 Total -

I!W!. ~..

clinical Group Il/.-All histologically proved carcinomas of the cervis rcvealing definite parametrial thickening or inva,sion of the vagina. For conrenience and statistical comparison these advanced easesare subdIvidcd as follows: IVa,: Any carcinoma of the cervix presenting definite extension beyond the cervix. This may be parametrial thickening or invasion of the vaginal wall and the involvement may be unilateral or bilateral. TVb: Advanced carcinoma of the cervix with complete fixation (frozetl pelvis) on one or both sides and/or metastasis either local or remote. The clinical grouping is based on the initial examination when the patient is first seen at our hospital. In developing our clinical grouping we have attemptetl to recognize the fact that the early lesion is t,he important, one (CYinic*al Group I). We have also recognized the questionable case in whi~~h it is difficult or impossible to determine accurately the presentaeor ;rbsrnc~ of l)aril metrial thickening (Clinical Group III). We have recently again revised our clinical grouping so that, it can be more accurately compared to the League of Nations Classification. F’or purposes of comparison as far as this study is concerned, our Clinical Groups I: II? and III

1274

ALI~RIDGE

AND

hm. .1. Obst. % Gynec. December. 1950

MASON

are all included in the League of Nations I, while our clinical Group 1Va is equivalent to League of Nations II. Clinical Group IVb includes League of Nations III and TV. In an effort to make it more convenient to convert to our classification to that of the League of Nations we now have replaced the terms IVa and IVb with IV, 2, IV, 3, and IV, 1. Of the total group of 458, there were pyelographic studies on 333. Two hundred nineteen revealed normal pyelograms. One hundred fifteen showed abnormal pyelograms. (By abnormal pyelograms is meant either hydronephrosis or nonvisualization as demonstrated by intravenous or retrograde pyelography.) Of the group having pyelograms 34 per cent showed evidence of obstruction. We have omit,ted all pyelogram interpretations including mild grades of hydronephosis which were of doubtful significance. The distribution is shown in Table II. II.

TABLE

TOTAL

CLINICAL

GROUP

NTJMBER

OF PATIENTS HAVING PYELOGRAMR,NORMAL JANUARY, 1942, 'TO JAWARY, 1947

-

TOTAL

I

7

II III IVa IVh Total

22 43 134 12.7 333

AND

NORMAL

ABXORMAL,

ABNORMAL

7(100%) SO( 91%) .16( 84961 lM( 78%) 52( 41%) 319( Sfi%,

0 2( 9%)) 7(16%/c) 30(22%) 75(59%) 144(34%)

The gross survival rate in the abnormal-pyelogram group was 16 per cent as compared to 62 per cent in the normal-pyelogram group. While the percentage survival shows a decrease in the more advanced clinical groups, the survival is decidedly less in the abnormal pyelogram group. This indicates the importance of ureteral obstruction in determining the prognosis for any one paGent. This comparison is represented graphically in Table III. TABLE

CLINICALGROIIP I

11 111 IVa. IVh Total

III.

COMPARISOX

OF SURVIVAL PYELOGRAM

NORMALPYELOGRAM 71%

75jc Ti%

61% 46% 62%

RATES GROWS

IK

NORMAL

GROSSSURVIVALALL CASES1942TO1946 97.5%

82.5;;,, 773% 64.4% 31.0% 58.6%

AND

ABXORMAL

ABKORMALPYELOGRAM --

50 % 14% 27% 12% 16%

At the autopsy table, patients dying of uremia have demonstrated thickening and nodulation of the broad ligaments. This is often extensive enough to form a solid bridge of tissue extending from one wall of the pelvis to the other in which all organs are fixed (frozen pelvis). The ureters may be visualized passing into this mass after they enter the true pelvis. Dilatation of the ureters usually begins at the margin of the tumor mass which fills the pelvis. The lumen of the ureter is relatively constricted as it courses through the mass. It is not necessary to have complete stenosis of the ureter before dilatation may develop above. Upon microscopic section of this mass one might expect to find that it contains either inflammatory tissue, neoplasm, or fibrous tissue. The sections which we have studied have usually demonstrated neoplasm. Fig. I, A shows a cross section of ureter as it passes through a mass of neoplasm. There was

URETERAL

OBSTRUCTION

IN

CERVIX

CARCINOMA

R.

Fig. 1.--A, Cross section of the left ureter as it passes through writ. It is surrounded by squamous-cell carcinoma. Above this massive pyelohydronephrosis. B. High sower showing detail of the carcinoma cells.

the base the ureter

of

was

the in

Fig. Fig. Fig. visualization

2.-&b. 3.-Mrs. I.-Mrs. on

V. M. (No. V. M. (No. V. M. (No. the left indicating

536144). Normal 536144). Intravenous 53G444). Intravenous autonephrectomy.

pyelogram on pyelogram p3’elogram

Nov. 10, on June on March

1943, at the time of initial irradiation. 10. 1944. Normal left pyelogram: 2 plus right 11, 1947. The right pyelogram is now normal:

hydronephrosis. however.

there

is non-

3 i CO $5 c 3, 7 r,

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massive pyelohydronephrosis above this level. The ureter ca,n be seen surrounded by neoplasm. No scarring or fibrosis ca.n be seen. Fig. 1. B is high power, and shows the cancer cells more clearly. Further effort to determine the cause of uret,eral obstruction was made by study of the patients’ records for specific clues. For instance, we were interested in knowing how many-times evidence of obstruction was found opposit,e the side of greatest palpable pelvic involvement. This sit,uation was noted in five cases, but on closer analysis the findings were seen to be equivocal in all but one case. In this one case, the patient developed a left pyelohydronephrosis which required nephrectomy nine months after treatment and died elsewhere six months later; yet, on repeated examination by several members of the staff, the right adnexal region consistently showed more t,hickening. We are more impressed with the number of patients consistently showing ureteral ohstzltction on the side of greatest pelvic involvement. Repeated pyelograms showed either progression or improvement in thirt? patients. Twenty-five demonstrated progression and only one of t.his gron~ remains alive. Five showed regression of the obst~ruction and four of these a.re still alive. There was no patient with progression of hydronephrosis who did not also have advanced and progressin g- neol>lnstic involvrutent of the pelvis. The findings in one case are of sufficient interest to \\rarsant repolting here. Mrs. I’. 31. t Wo. 536444) had a diagnosis of carcinoma of the cervix, Clinical Group IVa, made on Sov. 9, 1943. At t,hat time thickening was felt to be most marked on the left. She received 2.200 T to each of four pelvic ports from Nov. 9, 1943, to Dec. 5, 1943. On December 6, Wt mg. of radium were implanted for 60 hours or a total dose of 5,400 mg. hr. Pyelograms were negative at this time (Fig. 2). In tion on the left then drvelnl~~l due to extension of the neoplasm. Another case is also of interest because it demonstrates the actual clearing of uretcral obstruction following irradiation with no further treatment. Mrs. S. B. (No. 511544) was seen first on Sept. 3, 1942, and a diagnosis of carcinoma of the cervix, CXinical Group 1% was made. Pelvic examination revealed bilateral pelvic involvement with fixation. She received a full course of external irradiation beginning on September 5. On September 16, pyelograms revealed a 2 plus hydronephrosis bilaterally (Fig. 5). Because of this finding, radium therapy was omitted, Attempts at ureteral dilatation were unsuccessful on Sept. 23 and Sept. 24, 1942. On Jan. 21, 1943, the left pyelogram was negative and the right hatI almost cleared (Fig. 6). Pelvic examination at that time revealed less thickening bilxt erally and no fixation. Normal pyelograms were obtained on March 2, 1!$44 (Fig. 7 8. Thtl patient is alive on last follow-up and her condition is rrlportrd as satisfactory

Until recently it has been our policy t,o tlilatr the ureters when unilntrt*al hydronephrosis was present. Nephrost,omy is performed when bilateral ohstruction is present and the neoplasm is not progressing so far as ran be determined clinically. The patient’s general condition would, of course, have to 1~’ such as to permit operation. Nephrectom,v is caonsidered only when syni JItomatic pyelohydronephrosis is present. Certain interesting facts regarding ureter4 dilat,ation have come t,o light. Of the nine patients receiving dilatation, one remains alive. Tn the group 01

J.-Mm. nephrosis bilaterally. Fig. &--MIX. plete clearing on Fig. i.-Mrs.

Fig.

Fig.

5.

S. B. (Ko. 511544). A calcitle-I lymph S. B. (No. 511544). the right. S. B. (Xo. 511544). Piormal

Intmvenous node can Intravenous

Fig.

6.

intravenous

pyelogram

on

March

left

time

2. 1944.

pyelog~~am ofi Sept. 16. 1942. at the be seen owrlying the aacral promontory. pyelogram on Jan. 21, 1943. The

initial pyelogram

of

is now

irra~llation, normal

7.

and

in(licating

Fig.

there

is almost

a 2 plus

com-

hydra-

g$ 02 8. x-s .- 0

2r

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patients who died, the average interval between dilatation of the ureter and death was eight months. The shortest interval was one month, the longest fifteen months. Three of the five patients showing regression of obstruction had ureteral dilatations. Yet dilatation of the ureter did not appear to be of benefit,. Only one of the nineteen surviving patients in the abnormal-pyelogram group had dilatations. Our results, at least, suggested t)hat the trauma incident to dilatation might actually increase edema and stenosis and hasten the development of autonephrectomy. Three patients had nephrostomies. All of these were performed on patients with plasma nonprotein nitrogen levels ranging from 88 to 163 mg. per cent preoperatively. Except for the uremia, their general condition was satisfactory. All of them had advanced cervix carcinoma. Although the nonprot.ein nitrogen was not in any case over 43 mg. per cent postoperatively, all three patients died in one, two, and seven months, respectively. The cause of death is not known since it, occurred elsewhere. Nephrostomy performed on patients such as these (i.e., with advanced neoplasm and uremia) apparently does not materially improve prognosis. Comment This study reveals a close correlation between the incidence of ureteral obstruction as determined by pyelograms (34 per cent) and the incidence of uremia as a cause of death in our a.utopxy series (40 per cent). This tends to confirm the findings of others, that ureteral obstruction resulting in uremia is one of the important causes of death from carcinoma of t,he cervix. By taking roentgenograms with radium applied to the cervix and ureteral catheters in place, and with the vagina tightly packed in our routine manner, we have found that the ureters often pass as close a.sI to 2 cm. to the source of irradiation. During the years covered in this st,utly, OUP customary radium application consisted of a tandem tube in the uterus and cervix with 20 mg. and 30 mg. in the cervix; together with a 20 mg. capsule in each lateral fornis for a total dose of approximately 5,000 mg. hr. (0.5 mm. platinum equivalent filtration). Recently, by increasing the amount of radium implanted t,o 100 ma., the dosage has been increased to approximately 6,000 mg hr. ‘CVe feel that the ureters are subjected to a significant amount of irradiation. 111 this study, however, we have not been able to demonstrate that irradiation commonly causes strict.ure of the ureter. Actually, quite the reverse has been true. Our findings indicate that obstruction is usually due to extension of the neoplasm. We have observed regression of hydronephrosis with decrease in demonstrable pelvic neoplastic involvement after s-ray therapy in one instance. Furthermore, whenever ureteral obstruction developed there was a.11 associated clinical advancement of the neoplasm. We also not,ed that obstruction of the meter commonly develops on the side of greatest palpable pelvic involvement. While our experience does not allow us to state that irradiation never plays a part, in the etiology of ureteral obstruction, it would seemthat obstruct,ion 1smore often due to the extension of the neoplasm. Everett’s recent review of his experience” tends to indicate that ureteral ohst,rurtion due to irradiation is greatly depenclent upon the radium dosage. Until 1939 he used a large amount of radon (3.0 Gm. ) for a short exposure of one hour or a tota. dose of 3,000 mg. hr. In this series of patients he observed ureteral obst,rurtion in 48.4 per cent. However, when t,he amount. of radium administered was diminishecl even though the total close was increased (two applications of 100 mg. radium for 24 hours, two weeks apart for a total of 4,800 mg. hr.) “there were no urological lesions which could be conclusivelv at,tributed to irradiation.” External irradiation had not been changed radi-

ALDRIDGE

AND

MASON

tally. His total dose (2,500 r to each of four pelvic ports) is slightly higher than ours. Ureteral obstruction due to irradiation is unusual in our series because the dose has not been great enough t,o cause stenosis. Our treatment of uret,eral obstruction, whether it be by ureteral dilatation or nephrostomy, has not improved prognosis. Alt,hough uremia is a common cause of death in cervix carcinoma, there are those who prefer not to divert the urinary tract since they feel that. by so doing, nothing would be accomplished but the substitution of another less pleasant cause of death. We feel, in light of this study, that diversion of the urinary tract when bilateral obst.ruction is first noted would give better results than we have had with this t.ype of procedure in the past..

Conclusions 1. Our incidence of ureteral obstruction in all cases of carcinoma of the cervix is 34 per cent. This agrees closely with the reported incidence of obstruction as found at autopsy (40 per cent,). 2. Our evidence points to t,he fact, that, the cause of obskuction t,o the ureters is extension of the neoplasm. 3. From the long-range therapeutic standpoint ureteral dilatation is not indicated, and if used at all should be restrictecl to the alleviation of pain of a unilateral hydroureter hydronephrosis only (luring or shortly after x-ray t,herapy. 4. Early diversion of the urinary tract, either by ureterosigmoid transplants or cutaneous ureterostomy, would seem to be preferable to late nephrostomy drainage. 5. Nephrostomy is indicated in patients having pyelohydronephrosis.

References 1. 2. 3. 4. 5.

De Alvarez, R. R.: AM. J. OBST. & GYNEC. 54: 91, 191i. Herger, C. O., and Schreiner, B. F.: Surg., Gynee. & Obst. 43: 710, 1926. Diehl, W. K., and Hundley, J. M.: Surg., Gynec. 8; Obst. 87: 705, 1948. Everett, H. 5.: AM. J. OBST. & GYNEC. 28: 1, 1934. Everett, H. S., Brac.k, C. B., and Farber, CT. J.: Aat. J. OBST. & GYE~EC. 58: 118

EMT

COLLFXE

AVESUF:.

904, 1949.