GYNECOLOGIC
ONCOLOGY
Radical
8,
152-163 (1979)
Hysterectomy
Preceded
LEON
L. ADCOCK,
Division of Gynecologic Oncology, University of Minnesota Medical
by Pelvic Irradiation M.D.’
Department of Obstetrics und Gynecology, School, Minneapolis, Minnesota 55455
Received November 17, 1978 A total of 124 patients, who had prior pelvic irradiation, had radical hysterectomy performed at the University of Minnesota Hospitals from 1939 to 1977. The patients fall into two groups: those who had pelvic radiation and radical hysterectomy as primary therapy and those who had radical hysterectomy for postradiation persistent or recurrent cancer of the cervix. A major objective of this report is to describe the incidence, management, and long-term follow-up of patients with complications. Pelvic irradiation followed by radical hysterectomy as primary therapy for cancer of the cervix cannot be justified because of the high risk of urinary tract complications, some of which eventually result in demise of the patient. Radical hysterectomy for postradiation persistent or recurrent cancer is an acceptable procedure for early disease. It would appear from this experience that many patients with small cervical or vaginal postradiation neoplasms can be successfully managed with more conservative procedures such as simple hysterectomy and partial vaginectomy. The value of pelvic lymphadenectomy was not demonstrated. Exenterative procedures are becoming more frequently indicated for eradication of malignancies, with a reduction of long-term urinary tract complications.
At present, radical hysterectomy is indicated for primary therapy of early invasive cervical cancer and in selected patients with persistent or recurrent cervical cancer when primary pelvic irradiation fails to control the disease. Complications in the latter group of patients are significant, particularly after supravoltage external beam therapy [I]. The records of all patients who received external beam and intracavitary pelvic irradiation and subsequently underwent radical hysterectomy, with or without pelvic lymphadenectomy, at the University of Minnesota Hospitals from 1939 through 1977 were analyzed for this report. All of these patients have been followed until death or the time of this report. Radiation techniques at the University of Minnesota Hospitals were reviewed by Makowski and co-workers in 1962 [2]. These techniques were unchanged until 1971 when a IO-MeV linear accelerator became available for external beam radiation therapy and Fletcher afterloading intrauterine tandem and vaginal ovoids were utilized for intracavitary and upper vaginal radium therapy. The patients fall into two groups: those who had (a) pelvic radiation and radical ’ To whom requests for reprints should be addressed: Box 395 Mayo Memorial Building, University of Minnesota, Minneapolis, Minn. 5.5455. 152 0090-8258/79/050 152-l 2$0 1.0010 Copyright All rights
@ 1979 by Academic Press, Inc. of reproduction in any form reserved.
RADICAL
HYSTERECTOMY
PRECEDED
BY
PELVIC
153
IRRADIATION
surgery as primary therapy and those who had (b) radical surgery preceded by irradiation for persistent or recurrent cancer. Most of the patients who received combined primary therapy were treated between 1961 and 1967 for highly undifferentiated epithelial neoplasms of the cervix. These neoplasms, identical to those described by Glucksmann and Cherry, were associated in the experience of this department with a poor prognosis [3,4]. In the 38 years under examination a total of 124 patients who had prior pelvic irradiation had radical hysterectomy performed at the University of Minnesota Hospitals. Survival of patients is of the greatest significance: however, a major objective of this report is to describe the incidence, management, and long-term follow-up of patients with complications. As radiation techniques have improved, it has become apparent that most patients with persistent or recurrent cancer are not candidates for radical hysterectomy, because they usually have inoperable pelvic wall or distant metastases that also preclude exenterative procedures. RESULTS
OF COMBINED
PRIMARY
THERAPY
OF CERVICAL
CANCER
Between 1941 and 1969,43 patients were treated by pelvic irradiation followed 6 weeks later by radical hysterectomy as primary therapy for cervical cancer. Table 1 lists the histologic diagnosis of the neoplasms. Of these, 34 women survived 5 years with no evidence of disease (NED). In the surgical specimens of 30 patients there was no recognizable tumor, but 2 of these later died of metastatic cancer. Residual tumor was found in 13 operative specimens. Of these 13 patients, 7 survived 5 years without evidence of disease. However, one died of metastatic carcinoma at 94 months. Table 2 plots survival against location of tumor in the surgical specimen for these patients. Table 3 plots survival against the initial staging of the cervical cancer. Table 4 plots the initial staging against the location of the tumor in the operative specimen. Of these patients, 34 had “mixed carcinomas,” and 27 survived 5 years without evidence of disease. Bilateral pelvic lymphadenectomy was performed on 40 of 43 patients who received combined therapy. Four patients had carcinoma in one or more pelvic lymph nodes. Two survived 5 years without evidence of disease. However, one of the two patients who survived 5 years died of metastatic carcinoma 94 months after therapy. TABLE RADIATION
THERAPY
AND
TREATMENT
Histologic
diagnoses
RADICAL
1 HYSTERECTOMY
OF CERVICAL
AS PRIMARY
CANCER
No.
of patients
Undifferentiated carcinoma Adenocarcinoma Leiomyosarcoma Squamous cell carcinoma Adenosquamous carcinoma
34 6 I I I
Total
43
154
LEON L, ADCOCK TABLE
2
RADIATION THERAPY AND RADICAL HYSTERECTOMY AS PRIMARY OF CERVICAL CANCER: SURVIVAL AND OPERATIVE SPECIMEN
TREATMENT TUMOR
Operative specimen tumor
No. of patients
5 years NED
Dead of tumor
Dead of other disease
None Central Central and nodes Nodes only Total
30 9 3 1 43
27 (90%) 5 1* 1** 34 (7%)
2 3 2 0 7
1 1 0 0 2
* Dead of metastatic carcinoma at 94 months. ** No evidence of disease at 106 months. TABLE RADIATION
3
THERAPY AND RADICAL HYSTERECTOMY AS PRIMARY TREATMENT OF CERVICAL CANCER: STAGING AND PATIENT SURVIVAL
Stage
No. of patients
5 years NED
Dead of tumor
Dead of other disease
I II III Total
22 18 3 43
20 (90.9%) 13 (72.9%)* 1 34 (79.0%)
1 4 2 7
1 1 0 2
* One patient died of metastatic carcinoma at 94 months. TABLE
4
RADIATION THERAPY AND RADICAL HYSTERECTOMY AS PRIMARY TREATMENT OF CERVICAL CANCER: STAGING AND LOCATION OF OPERATIVE SPECIMEN TUMOR
Stage
No. of patients
None
Central
Central and nodes
Nodes only
I II III Total
22 18 3 43
19 10 1 30
3 4 2 9
0 3 0 3
0 1 0 1
RESULTS OF THERAPY FOR PERSISTENT OR RECURREN.T CERVICAL CANCER
Eighty-one patients were operated on for persistent or recurrent cancer following primary radiation therapy, 60 having received radiation therapy at the University of Minnesota Hospitals. Of these, 75 patients were operated on before December 31, 1972, and only 6 between January 1, 1973 and December 31, 1977, attesting to the efficacy of present techniques of pelvic radiation for treatment of the primary disease. The 75 patients followed for 5 or more years will be discussed.
RADICAL
HYSTERECTOMY
PRECEDED
BY
PELVIC
15.5
IRRADIATION
Of the 75 patients, 49 survived 5 years without evidence of disease. Table 5 plots the location of tumor in the operative specimen against patient survival. Of the 75 patients, 3 1 had radical hysterectomy for persistent cancer and 44 for recurrent cancer. Of the 31 with persistent disease, 16 survived 5 years without further evidence of disease and of the 44 with recurrent disease, 33 survived 5 years. Three patients also had resection of one distal ureter and the adjacent bladder with ureteroneocystostomy. Two of them survived 5 years without evidence of disease, and one of the two survivors had had tumor in the cervix and pelvic lymph nodes. Two patients had a radical cervicectomy for recurrent cancer of the cervical stump, and one survived 5 years without evidence of disease. Although all 75 patients had preoperative biopsies showing cancer, 26 did not have cancer found in the operative specimen. Of these 26, 3 subsequently died of cancer, one at 132 months. Noninvasive carcinoma was present in the operative specimen of 5 patients, and all were without evidence of disease after 75, 127, 128, 167, and 213 months. Table 6 plots the original stage of the disease against the interval between radiation therapy and radical hysterectomy, and Table 7 shows the histologic diagnoses. Of the 75 patients who had radical hysterectomy performed for persistent or recurrent cancer, bilateral pelvic lymphadenectomy was performed on 45. Seven patients had one or more involved lymph node, and one of these survived 5 years without evidence of disease. Five of the 75 patients had pelvic lymph node biopsy only. One of these had an obturator lymph node replaced by carcinoma and was alive at 306 months. The other 4 did not have carcinoma in the biopsied nodes. Of the 5 patients who had only pelvic lymph node biopsy, 2 survived 5 years without evidence of disease, 2 died of recurrent carcinoma in the pelvis, and the 5th accounted for the one operative death in this report. The remaining 25 patients had radical hysterectomy without either bilateral pelvic lymphadenectomy or pelvic lymph node biopsy. Of the 25, 16 survived 5 TABLE POSTRADIATION CERVICAL
RADICAL CANCER:
LOCATION TUMOR
Operative Tumor
specimen
None Central Central Nodes Total
and nodes only
5
HYSTERECTOMY
No. of patients
AND
FOR PERSISTENT OF OPERATIVE
OR RECURRENT SPECIMEN
SURVIVAL
5 years NED
Dead of tumor
Dead of other disease
26 41
23* 24**
2 14
6 2
I I
5 I
0 0
7.5
49
22
4
* One patient died of metastatic disease ** One patient died of metastatic disease *** One operative death from uncontrolled
at 132 months. at 76 months. hemorrhage and cardiac
arrest,
1 j***
1953.
156
LEON
L.
ADCOCK
TABLE
6
POSTRADIATION RADICAL HYSTERECTOMY FOR PERSISTENT OR RECURRENT CERVICAL CANCER: INTERVAL BETWEEN ORIGINAL STAGING AND RADICAL HYSTERECTOMY Hysterectomy Original stage
No. of patients
Less than 6 months
I II III Unknown
2 40 25 5 3
0 16 13 1 1
Total
75
31
0
6to 12 months 2 4 4 1 0 II
performed
12 to 24 months
24 to 60 months
5 to 10 years
Over 10 years
0 9 2 2 2
0 4 3 0 0
0 5 2 0 0
0 2 1 I 0
15
7
7
4
years without evidence of disease. Of the 45 patients who had bilateral pelvic lymphadenectomy in addition to hysterectomy, 31 survived 5 years. To determine whether bilateral pelvic lymphadenectomy played a different role for patients with persistent cancer than for those with recurrent cancer, these groups were analyzed separately. Thirteen patients with persistent cancer, diagnosed within 6 months of completion of radiation therapy, underwent radical hysterectomy. Seven were alive 5 years later, without evidence of disease. Radical hysterectomy with bilateral pelvic lymphadenectomy was performed on 16 patients with persistent cancer, and 9 were alive and free of disease 5 years later. Radical hysterectomy without either pelvic lymph node biopsy or bilateral pelvic lymphadenectomy was performed on 12 patients with recurrent cancer and 9 were free of disease 5 years later. Radical hysterectomy with bilateral pelvic lymphadenectomy was done on 29 patients with recurrent cancer, and 22 survived 5 years without evidence of disease. Table 8 shows these patients. Table 9 plots the location of the operative specimen tumor against the interval between radical hysterectomy and recurrence or metastasis. All 24 patients analyzed in this table died of cancer. Table 10 plots the site of the original operative specimen tumor against the location of subsequent cancer in 21 patients. Most had pelvic recurrences, including the 6 patients who had pelvic lymph node involvement. TABLE
7
POSTRADIATION RADICAL HYSTERECTOMY FOR PERSISTENT OR RECURRENT CERVICAL CANCER: HISTOLOGIC DIAGNOSES OF ORIGINAL NEOPLASM Histologic
diagnosis
No.
of patients
Squamous cell carcinoma Adenocarcinoma Undifferentiated carcinoma
62 10 3
Total
75
RADICAL
HYSTERECTOMY
PRECEDED
BY
PELVIC
157
IRRADIATION
TABLE 8 POSTRADIATION RADICAL HYSTERECTOMY FOR PERSWENT OR RECURRENT CERVICAL CANCER: TYPE OF PELVIC LYMPH NODE SURGERY
AND
Persistent
Total
POSTRADIATION
CERVICAL
Recurrent
cancer
No. of patients
Procedure Radical hysterectomy, alone Radical hysterectomy, pelvic lymph node biopsy Radical hysterectomy, bilateral pelvic lymphadenectomy
SURVIVAL
5 years NED
No. of patients
I
I2
9
2
0
3
2
16
9
29
22
31
16
44
33
TABLE 9 RADICAL HYSTERECTOMY FOR PERSISTENT OR RECURRENT CANCER: OPERATIVE SPECIMEN TUMOR AND SUBSEQUENT OF CANCER
Interval between and recurrence specimen
None Central Central Nodes Total
**
and nodes only
5 years NED
I3
DEVELOPMENT
Operative tumor
cancer
No. of patients
Less than 6 months
hysterectomy or metastases
6 to 24 months
24 to 60 months
Over 60 months
3 15
0 4
2 9
0 I
I” ,**
5 I
2 0
2 0
I I
0 0
24
6
13
3
2
* Squamous cell carcinoma metastatic to the left ilium Expired of metastatic carcinoma at 76 months.
COMPLICATIONS
at 132 months.
OF THERAPY
Ureteral strictures were a frequent complication of extensive ureteral dissection. Ureterovaginal, vesicovaginal, and rectovaginal fistulas were the major complications in this series, and ureteral fistulas were almost always associated with strictures. Of the 43 patients who received radiation and radical hysterectomy as primary therapy, 20 had these complications as shown in Table 1I. Six patients had fistulas, and 2 of the 6 had multiple fistulas. Fourteen patients had other complications as listed in Table 12. Of these 14 patients, 6 also had urinary tract or rectal complications. Fifteen of the 43 patients had uneventful postoperative courses. Of the 20 patients who had urinary tract or rectal complications, 16 were alive
158
LEON L. ADCOCK TABLE POSTRADIATION CERVICAL
10
RADICAL HYSTERECTOMY FOR PERSISTENT OR RECURRENT CANCER: OPERATIVE SPECIMEN TUMOR AND LOCATION OF SUBSEQUENT CANCER
Location of subsequent cancer Operative specimen tumor
Pelvis
None Central Central and nodes Nodes only Total * Total exenteration
Total
1 2 0 0 3
3 15 5 1 24
2 13* 5 1 21
was later performed on one patient who survived 18 months. TABLE
RADIATION
Distant metastasis
11
THERAPY AND RADICAL HYSTERECTOMY AS PRIMARY TREATMENT OF CERVICAL CANCER: URINARY TRACT AND RECTAL COMPLICATIONS AND OUTCOMES
Complication Ureteral stricture Unilateral, spontaneous recovery Bilateral spontaneous recovery, nephrostomy, unilateral nephrectomy, spontaneous recovery Vesicovaginal fistula Ileal diversion Vesicovaginal and rectovaginal fistulas Successful repair of vesicovaginal fistula Ureterovaginal and rectovaginal fistulas Ureteroileoneocystostomy Ureterovaginal fistulas Nephrostomy and bilateral ureteroileoneocystostomy Nephrectomy Rectovaginal fistula, colostomy
No. of patients
Survived 5 years
Dead of tumor
5
4
1
7 1 1
1 0
1
1
Dead of other disease
0
1
1
0
0
1
1*
0
0
1 1 0
0
0
0 0
0 1
* Died at 100 months of septicemia secondary to chronic pyelonephritis.
without evidence of disease after 5 years. However, one patient died 100 months later from complications of a ureteroileoneocystostomy. Of the series of 7.5 patients on whom radical hysterectomy was performed for postradiation persistent or recurrent cancer of the cervix, 31 had urinary tract or rectal complications, or both. These patients, with their complications and outcome, are analyzed in Table 13. Three died as a result of complications, from 50
RADICAL
HYSTERECTOMY
PRECEDED
TABLE RADIATION
THERAPY OF CERVICAL
AND
RADICAL CANCER:
BY
PELVIC
IRRADlATION
12
HYSTERECTOMY MISCELLANEOUS
AS PRIMARY
TREATMENT
COMPLICATIONS
No.
3 2 I 1
cellulitis
Wound infections Wound dehiscence Pelvic abscess Thrombophlebitis and bilateral leg edema Bilateral leg edema only Thrombophlebitis Lymphocyst Pneumonia Congestive heart failure
1 I I I 2 I
Total * Six of these
patients
of
patients*
Complications Pelvic
159
14 also had urinary
tract
or rectal
complications.
days to 96 months after surgery. Twelve patients had fistulas, two of them multiple. Twenty-three patients had other complications, which are listed in Table 14. Of these 23, 14 also had urinary tract or rectal complications. Thirty-five of the 75 patients had an uneventful convalescence. Twenty-one of the patients with urinary tract or rectal complications were alive without evidence of disease 5 years later. However, two patients died at 92 and 96 months of disease related to urinary tract complications. In the total series, 33 patients had ureteral strictures and 26 of these had spontaneous recovery and did not need surgical intervention. Of the 33 patients with ureteral stricture, 25 survived 5 years without evidence of disease. DISCUSSION
External beam radiation and radium therapy followed by radical hysterectomy as primary therapy for cancer of the cervix has been shown in this review to result in a satisfactory 5-year survival rate. Unfortunately, the risk of urinary tract and rectal complications seems excessive. Management of complications required major surgical procedures and prolonged hospitalization. One patient died 100 months later of septicemia secondary to chronic pyelonephritis: she had had rectovaginal and ureterovaginal fistulas and a ureteroileoneocystostomy was subsequently performed. Survival following radical hysterectomy for patients with recurrent cervical cancer was satisfactory. Early diagnosis of recurrent carcinoma is essential if radical and ultraradical procedures are to be curative. Survival following radical surgery for patients with persistent cancer of the cervix was not as satisfactory. Patients with persistent and recurrent cancer also had a high risk of significant complications, and in this series of 75, 3 died of complications of surgery. Exenterative procedures might have offered a more complication-free survival.
Total
* Died
of pyelonephritis
at 92 months.
Ureteral stricture, unilateral Spontaneous recovery Ureteroileoneocystostomy Ureteral stricture, bilateral Spontaneous recovery Nephrostomy and ureteroileoneocystostomy Nephrostomy and ureteroureterostomy Bilateral nephrostomy, nephrectomy, and pyeloileocutaneous conduit Nephrectomy and spontaneous recovery Vesicovaginal tistula Total exenteration, persistent cancer Unsuccessful repair, ileal conduit Ureterovaginal fistula, unilateral Spontaneous closure Bilateral nephrostomy and ureteroileoneocystostomy Nephrectomy Unilateral ureteroileoneocystostomy Bilateral ureterovaginal and rectovaginal tistulas Colostomy and ileal conduit Ureterovaginal fistula, bilateral l eal conduit Vesicovaginal listula, bilateral ureteral stricture Bilateral nephrostomy, nephrectomy. and coloureteral conduit Rectovaginal fistula, no treatment Vesicorectal fistula, colostomy and ileal conduit Ureterovaginal fistula, ureteroureterostomy, ureterovaginal fistula with repair
Complications
POSTRADIATION
**
Died
of septic
13
***
Died
1
0
of pyelonephritis
at 96 months.
0
2
0
0 0 1***
I 1 I
0
8
I
1
0
0
1
1
1
1 1 I 1
I 1 1 I
I
0 0
21
0 0
I I
0
0 0 0
1 0
Dead of other disease
I** 0 0
1* 0
I 1
2 0 0
2 0
Dead of tumor
CANCER:
0
7 1 I
5 years NED
9 I I
31
CERVICAL
OUTCOMES
2 I
AND
OR RECURRENT
5 I
No. of patients
COMPLICATIONS
PERSISTENT
at 50 days.
FOR
TABLE RECTAL
shock
TRACT
URINARY
AND
HYSTERECTOMY
RADICAL
RADICAL
HYSTERECTOMY
PRECEDED
BY
PELVIC
IRRADIATION
161
TABLE 14 POSTRADIATION RADICAL HYSTERECTOMY FOR PERSISTENT OR RECURRENT CERVICAL CANCER: MISCELLANEOUS COMPLICATIONS No. of patients
Complication
3 7 3 1 4 2 1 I 1
Pelvic cellulitis Pelvic abscess Thrombophlebitis Lymphocyst Wound infection Pneumonia Congestive heart failure Pelvic hematoma External iliac vein thrombosis Total * Fourteen
of these
23* patients
also
had urinary
tract
or rectal
complications.
Tumor involvement of the lymph nodes was a poor prognostic sign. The small number of survivors among the women with pelvic lymph node metastases raises the question whether lymphadenectomy in this situation is of significant value. The survival of patients who had radical hysterectomy and bilateral pelvic lymphadenectomy was not significantly greater than that of patients who had radical hysterectomy alone. However, bilateral pelvic lymphadenectomy did not increase the incidence of complications, although undoubtedly it increased operating time and blood loss. Other investigators have abandoned pelvic lymphadenectomy after pelvic irradiation as a part of primary therapy for cancer of the cervix [5,6]. Significant complications have included lymphocyst formation, leg edema, wound infection, thrombophlebitis, and hydronephrosis. Most significantly the procedure did not increase patient survival. Kelso and Funnel1 reported a low but significant incidence of complications among patients who received external beam irradiation following radical hysterectomy 171. In their series of 280 patients operated on by senior staff personnel, the low incidence of complications was not unexpected; experienced surgeons avoid potential complications and manage them more satisfactorily when they occur. Upper vaginal and intrauterine radium therapy, without external beam irradiation, followed by radical hysterectomy, has been utilized in a number of series [S-l I]. Koller reported no significant complications with this technique [lo]. The other investigators reported a significant but relatively low incidence of complications. This is particularly true in the series of Rampone and co-workers, where “modified” radical hysterectomy was performed [ 121. Radical hysterectomy, with or without pelvic lymphadenectomy, preceded by external beam and intracavitary pelvic radiation therapy is accompanied by a high risk of postoperative complications, the most significant being urinary tract and intestinal fistulas and ureteral stenosis [ 13-171. It is difficult to justify combined therapy, as results in the present series show. Complications associated with
162
LEON
L. ADCOCK
radical hysterectomy preceded by pelvic irradiation vary with the amount of preoperative radiation and the extent of the surgical procedure. Improvement of operative techniques has decreased the previously high incidence of ureteral complications associated with radical hysterectomy [ 18-221. The surgical procedures initially performed at the University of Minnesota Hospitals were of the Class IV type, as described by Piver rf al. [23]. With appreciation of the ureteral complications, Class III type procedures have been performed more frequently in recent years. Exploratory laparotomy is essential for most patients with persistent or recurrent cancer of the cervix who have disease apparently localized to the pelvis. Exenterative procedures are now preferred for persistent or recurrent cancer because of radiation damage to the rectum and distal urinary tract. However, radical hysterectomy with or without pelvic lymphadenectomy is a procedure more acceptable to patients; because urinary tract or intestinal continuity are not sacrificed, a varying amount of the vagina may at times be preserved. Unfortunately, persistent or recurrent cancer frequently is not recognized until the disease is advanced and radical or ultraradical surgery, which initially might have been possible, is not feasible. CONCLUSION
Selected patients with persistent or recurrent cancer of the cervix can survive when treated by radical hysterectomy. Full pelvic irradiation followed by radical hysterectomy as primary therapy cannot be justified because of the high risk of complications. Radical hysterectomy for persistent or recurrent cancer following pelvic irradiation is an acceptable procedure for early disease. Thirty-one patients undergoing radical hysterectomy for persistent or recurrent cancer of the cervix had noninvasive carcinoma or no tumor found in the operative specimen. The 5-year survival rate in patients with no evidence of disease was 90.3%. It would appear from this experience that many patients with small cervical or vaginal postradiation neoplasms can be successfully managed with more conservative procedures such as a simple hysterectomy and partial vaginectomy. The value of bilateral pelvic lymphadenectomy was not demonstrated. Of the 24 patients who had radical hysterectomy for persistent or recurrent cancer and subsequently died of cancer, 2 1 had pelvic recurrences. Exenterative procedures might have been more successful in eradicating the malignancy. Meticulous follow-up examinations are essential after radiation therapy, and all abnormal finding must be evaluated without a period of observation. Unfortunately, at this institution, with the present highly effective radiation therapy techniques, most patients with persistent or recurrent disease have pelvic cancer or distant metastases that are not amenable to surgery. REFERENCES 1. Greiss, F. C., Blake, D. B., and Lock, F. B. Complications of intensive radiation cervical carcinoma, Ohst~r. Gynecol. IS, 417-429 (1961). 2. Makowski, E. L., McKelvey, J. L., Flight, G. W., rr ul. The results of irradiation carcinoma of the cervix, /. Amer. Med. Ass. 182, 637-642 (1962).
therapy therapy
for of
RADICAL
HYSTERECTOMY
PRECEDED
BY
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IRRADIATION
163
3. Clucksmann, A.. and Cherry, C. P. Incidence, histology, and response to radiation of mixed carcinomas (adenoacanthomas) of the uterine cervix, Con(~r 9, 971-979 (1956). 4. Glucksmann, A. Relationship between hormonal changes in pregnancy and the development of “mixed carcinomas” of the uterine cervix, Conwr 10, 831-837 (1957). 5. Gray, M. J., Gusberg, S. B., and Guttmann, R. Pelvic lymph node dissection following radiotherapy. Amer. J. Ohstrt. Gynerol. 76, 629-633 (1958). 6. Rutledge, R. N., Fletcher, G. H., and MacDonald, E. J. Pelvic lymphadenectomy as an adjunct to radiation therapy in treatment of cancer of the cervix, Amer. J. Roentgend. 93,607-614 (1965). 7. Kelso, J. W., and Funnell, J. D. Combined surgical and radiation treatment of invasive carcinoma of the cervix, Amer. J. Obster. Gynucol. 116, 205-212 (1973). 8. Burch, J. C., and Chalfant, R. L. Preoperative radium irradiation and radical hysterectomy in the treatment of cancer of the cervix, Amer. J. Obster. Gynecd. 106, 1054-1064 (1970). 9. Churches, C. K.. Kurrle, G. R., and Johnson, B. Treatment of carcinoma of the cervix by combination of irradiation and operation, Amer. J. Ohsrrt. Gy/?ecw/. 118, 1033-1040 (1974). 10. Koller, 0. A comparison between the results of irradiation therapy alone and individualized radiological and surgical treatment of cervical carcinoma stage I. Acttr Ohstrt. Gyntwd. &~c~nd. SUP/J/. 7, 68-74 (1964). 11. Villasanta. U. Radium and external irradiation versus radium and operation for early invasive carcinoma of the uterine cervix, Amer. J. Obsr~r. Gynrcd. 106, 498-505 (1970). 12. Rampone, J. F., Valborg, K., and Kolstad, P. Combined treatment of stage 1-B carcinoma of the cervix, Oh.st~t. Gynecol. 41, 163-167 (1973). 13. Crawford, E. J., Jr.. Robinson, L. S.. 111, and Vaught. J. Carcinoma of the cervix, Amer. J. Obster. Gynewl. 91, 480-485 ( 1965). 14. London, D. L., and Dunn, L. J. Radical hysterectomy and pelvic lymphadenectomy following pelvic irradiation, Amer. J. Obstet. Gynecol. 93, 1128-I 132 (1965). 15. Parker, R. T., Wilbanks. G. D.. Yowell, R. K., and Carter, F. B. Radical hysterectomy and pelvic lymphadenectomy with and without preoperative radiotherapy for cervical cancer, Amer. J. Obstrt. Gynecol. 99, 933-942 (1967). 16. Stage, A. H., Crawford, E. J., Robinson. L. S., and Brooks, G. G. Combined radiologic/operative therapy in the treatment ofcervical malignancy, Amu. J. Ohsf~r. Gynccd. 120, 960-968 (1974). 17. Sweeney. W. J.. III, and Douglas, R. G. Treatment of carcinoma of the cervix with combination radiation and extensive surgery. Amer. J. Ohsrc,~. G~nccol. 84, 981-991 (1962). 18. Burch, J. C., Chalfant. R. C., and Johnson, J. W. Technique for prevention of uretero-vaginal fistula following radical abdominal hysterectomy. Atln. Surg. 161, 832-837 (1965). 19. Green, T. H., Jr. Ureteral suspension for prevention of ureteral complications following radical Wertheim hysterectomy, Obsrc,r. G.wrec,ol. 28, l-l 1 (1966). 20. Lash, A. F. Ureteral protection in radical abdominal and vaginal hysterectomy as surgical treatment of cervical carcinoma, Inr. Surg. 58, 352-354 (1973). 21. Macasaet, M. A., Lu. T.. and Nelson, J. H., Jr. Ureterovaginal fistulaas acomplication ofradical pelvic surgery, Amer. J. Ohxtc~t. G~n~co/. 124, 757-760 (1976). 22. Novak, F. Procedure for the reduction of the number of ureterovaginal tistulas after Wertheim’s operation, Amer. J. Obstc,r. Gynccd. 72, 506-510 (19.56). 23. Piver, M. S., Rutledge, F. N., and Smith, J. P. Five classes of extended hysterectomy for women with cervical cancer. Oh.crc,r. G~/tec~o/. 44, 265-272 (1974).