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The effect of radical hysterectomy on bladder physiology
The effect of radical hysterectomy on bladder physiology J. PETER FORNEY, M.D. Dallas, Texas Voiding dysfunction and vesical sensation and continence problems were serially evaluated by history and C02 cystourethroscopy in 22 women who had undergone a radical hysterectomy. In 11 of these women, the cardinal ligaments had been divided completely, and in the other 11, the inferior 1 to 2 em of these ligaments had been spared. Satisfactory voiding occurred significantly earlier (20 versus 51 days) in women who had had an incomplete transection. Vesical sensation was diminished in all subjects, but the magnitude of the sensory deficit was no greater in those who had had a complete transection. Stress incontinence occurred more frequently in those who had had a complete transection. Hypertonic cystometric measurements and decreased intraurethral pressure were common postoperative findings, and it is postulated that sympathetic denervation is responsible for both of these alterations. (AM. J. OesTET. GYNECOL. 138:374, 1980.)
in operative technique, anesthesia, antimicrobials, and the clinical laboratory, combined with restrictive use of radical hysterectomy to heaithier women with clinically localized cervical cancer, have markedly decreased the frequency of operative death, serious infection, and urinary fistulas. However, the frequency of bladder dysfunction after radical hysterectomy has not been similarly reduced and is now recognized as the most common complication of radical hysterectomy. For years, patients have a diminished awareness of vesical distention and may void "by the clock" rather than by urge. Months may pass before patients can initiate and/or successfully complete micturition. Manual suprapubic pressure and vigorous straining are often the ultimate solution to nearly complete evacuation of the bladder, and a small percentage of wonten must even resort to periodic selfcatheterization. Postoperative urinary stress incontinence seems also to occur in a disproportiortately high percentage of patients. The incidence, sev~rity, and pathogenesis of these alterations in bladder function have been the subject of IMPROVEMENTS
From the Cecil H. and Ida Green Center for Reproductive Biology Sciences, and the Department of Obstetrics and Gynecology, The University of Texas Health Science Center at Dallas. Received for publication February 15, 1980. Accepted june 11, 1980. Reprint requests:]. Peter Forney, M.D., Department of Obstetrics and Gynecology, The University of Texas Health Scimce Center at Dallas, 5323 Harry Hines Blvd., Dallas, Texas 75235.
374
past repons. 1- 10 This article readdresses these issues; however, the method of evaluation, results, and conclusions are, in some respects, unique.
Materia! and method Between June I, I976, and May 30, I979, I performed radical hysterectomy and pelvic lymphadenectomy on 37 women. Twenty-two underwent preoperative and serial postoperative C0 2 cystourethroscopy with simultaneous evaluation of the urethral and bladder pressure profile (Cu-UBPP). A Robertson 18guage urethroscope and a Browne C0 2 Cystometry Moniter, Model CR-2, were used to inspect the lower urinary tract and record urethral and vesical pressures. A complete urinary history was taken and intravenous pyelography, urine culture, and residual urine measurement were routinely performed preoperatively. Relevant clinical characteristics of the study group are detailed in Table I. Tvvo vvornen had a preoperative history compatible with mild stress urinary incontinence, and one \.voman related a history of longstanding urinary urgency and frequency. No patient had a positive preoperative urine culture, a residual urine greater than lO ml, or an abnormal intravenous pyelogram. A pelvic lymphadenectomy with radical hysterectomy similar to that described by Meigs'' was performed in II of the 22 women studied. In these I1 women, the cardinal ligaments were exposed by dissection of the pararectal and paravesical spaces and were divided to the pelvic diaphragm (Fig. I). In the other II women, the inferior l to 2 ern of each cardinalliga0002-93i8/80/2003i4+09$00.90/0
©
1980 The C. V. Mosby Co
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Effect of radical hysterectomy on bladder
375
Table I. Clinical characteristics
H. C.
B. E. J. C. D. G. B. T. L.L.
P.M. A. D. E. R. D
.u.
n
1 .
R.N. M.G. N.H. F. G.
w.c.
K. M. D.P. u JI .... F. T.
M.S. L. B. R.J.
Hzstory of Incontinence
Diagnosis
Patients
33 29 49 :~2
25
40 24 37 32 q 1
.n
34 65 :16 38 37 36 25 31
43 33 20 18
5
I 53 I23 II6 I70 II8 I38 I8I II2 I 57
3
172
2 2 0 5 I
5 3
4 0 2
3 2 3 0 2 4
3 I
1
I89 II4 106 I35 I44 II9 I35 !49 I28 I04 205
Stage IB (Occ) squamous cell carcinoma of cervix Stage IB (Occ) squamous cell carcinaoma of cervix Stage IB (Occ) squamous cell carcinoma of cervix Stage IB squamous cell carcinoma of cervix Stage IIA adenocarcinoma of vagina Stage IB adenocarcinoma of cervix Stage IB squamous cell carcinoma of cervix Stage IB squamous cell carcinoma of cervix Stage IB squamous cell carcinoma of cervix Stage IB squamous eel! carcinoma of cervix Stage IB (Occ) squamous cell carcinoma of cervix Stage IB (Occ) squamous cell carcinoma of cervix Stage iB adenocarcinoma of cervix Stage IB adenocarcinoma of cervix Stage IB squamous cell carcinoma of cervix Stage IB squamous cell carcinoma of cervix Stage IB squamous cell carcinoma of cervix Stage IB squamous cell carcinoma of cervix Stage IB squamous cell carcinoma of cervix Stage IB (Occ) squamous cell carcinoma of cervix Stage IB (Occ) squamous cell carcinoma of cervix Stage IB squamous cell carcinoma of cervix
"Stress" None 'Urge" None None "'one "'one None None None None None "'one '"Stress" "'one "'one "'one None
None None None None
Table II. Preoperative Cu-UBBP Maximum intraurethral Pressure (em H 20)
Volume at first urge (cc of C02)
Volume at painful urge (cc of C02)
H. C. B. E. J.C.
90 I35 IOO
I50 I20 50
220 230 I80
D. G. B. T.
K. M. D.P. J. R. F. T. M.S. L. B.
IOO I20 95 90 IOO 65 I20 IOO 75 I40 75 90 II 0 I20 I20 II5 90 I25
I75 IOO I80 I 50 IIO IIO I20 I25 I50 I80 I20 IIO I60 IIO I40 I40 I25 I30
3IO I 50 270 200 170 I90 200 200 250 220 ISO 260 250 I75 250 200 2IO 225
n
1'}(\
1 1/\
C}Q(\
Patient
L.L.
P.M. A. D.
E. R. B. P. R.N. M.G. N.H. F. G. W.C.
!'..
T
J·
lJU
uv
ment was left intact (Fig. 2). In all cases the uterosacral and vesicouterine ligaments were divided lateral to the rectum and bladder as deeply as necessary to equate with the level of transection of the cardinal ligaments. In no case was the superior vesical artery ligated, and in each case the ureter was entirely freed from the cardinal and vesicouterine ligaments. The excised vaginal cuff was approximately l em longer in those patients
4JV
Pressure profile No pressure rise No pressure rise No pressure nse Uninhibited contraction at 140 cc of C0 2 No pressure rise No pressure rise No pressure rise No pressure rise :'1/o pressure rise No pressure nse No pressure rise No pressure rise No pressure rise No pressure rise No pressure rist" No pressure rise No pressurt" rise No pressure rise No pressure rise No pressure rise No pressure 1 ise No pressure rise No pressure rise
who had complete transection of the t.:ardinal ligaments. Nonbulky adenocarcinomas confined to the endocervix and Stage IB squamous cell carnnomas of less than l em in maximum diameter were chosen for less radical resection of the cardinal ligaments and vagina. A No. 16 Foley catheter with a 5 cc balloon was inserted suprapubicaiiy in aii patients prim to ciosure of the abdominal wall. There were no serious postopera-
376
Forney Am.
Fig. I. The cardinal ligament has been divided at the pelvic wall and to the fascia overlying the levator muscle. The paravesical and pararectal spaces are in communication. The ureter has been mobilized from the cardinal ligament and is retracted laterally. tive infections, or urinary fistulas. One patient, A. D., died 5 months postoperatively, but her death was unrelated to malignancy or the operative procedure. No patient has been lost to follow-up, and all are clinically free of recurrent disease. Cu-UBPP was performed preoperatively, 10 to 14 days postoperatively, and every I to 2 weeks thereafter until the patient was capable of voiding with less than a 50 ml urinary residual. Cu-UBPP was then repeated at 3-month intervals for the first year, and every 6 months thereafter. Follow-up has ranged from 6 to 43 months, with from five to 12 examinations per patient. I performed all examinations and recorded urinary histories at each visit. The examination routine was as follows: Preoperatively and postoperatively, patients without a catheter were instructed to void; whereupon they were placed in the lithotomy position and the periurethral area was cleansed. After the urethral meatus had been topically anesthetized, the urethroscope , with C0 2 for obturation, was passed through the urethra and into the bladder. The urinary· residual was measured and cultured. With the urethroscope held at the vesical neck, the bladder was filled retrogradely with C0 2 at a rate of 120 cc/minute. The volume at first urge and that at
J.
Onober IS, 1!-!i!O Obstel. Gvnecol.
Fig. 2. The inferior segment of the cardinal ligament has been spared and can be seen bridging between the pelvic wall and vagina. The ureter is retracted laterally. painful urge to urinate were recorded. To check for the normal sphincteric action of the vesical neck and proximal urethra, the endoscope was withdrawn into the upper urethra and the patient was instructed to perform a forceful Valsalva maneuver. Patients with a suprapubic catheter in situ were examined as outlined above, with the following exceptions : ( 1) They were not asked to void prior to the examination. (2) If painful urge did not occur before 500 cc of C02 had been instilled into the bladder, the procedure was terminated for fear of vesical overdistention. (3) After Cu-UBPP, saline solution was placed into the bladder through the suprapubic catheter, and the patient was given the opportunity to urinate. The volume of instilled saline solution varied with individual differences in bladder capacity, but generally ranged from 150 to 250 mi. Five to ten minutes were allowed for voiding and then the residual volume was measured. If the patient was capable of emptying the bladder to all but 50 ml or less of the instilled saline solution, the catheter was clamped and she was allowed to void on her own. Patients were retested within 48 hours to ensure consistently adequate vesical emptying before the catheler was removed. Urobiotics were administered prophylactically for 24 hours after cystourethroscopy, and documented infections were treated for 10 days with appropriate antibiotics.
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Effect of radical hysterectomy on bladder 377
Table III. Days to spontaneous and satisfactory vesical emptying Complete transection of cardinal ligaments
Patintl
32 120 84 20 47 80 30 26 63 20 35 51
D.(;. B. !'. LL
A. D. E. R. B. P.
w.c. K. M. J. R.
R.J
F. T.
Mean
= p
Incomplete transection of cardinal ligament.\
Patient
14 28 21
H. C. B. E.
J. c.
P.M. R.N. M.G.
21
Hi
21
~.H.
14
F. G. D.P. M.S. L. B.
21
18 25 21
20
< 0.01.
Table IV. Comparison of preoperative volume at first urge and postoperative "olume at first urge on day of catheter removal Complete transection of cardinal ligaments Patient D. G. B. T. L.L. A. D. E. R. B. P. W.C. K. M. .J. R.
R.J. F. ·r.
Preop. vol. (cc of C02)
175 100 180 110 110 120 110 160 140 110 140
Postop. val. (cc of C02)
250 >500 320 130 ' 150 250 300 >500 380 380 190
Results Preoperative Cu-UBPP. Table II details the preoperative measurements of maximum intra urethral pressure, volume at first urge, and volume at painful urge for each patient. All volumes were within the range of reported values for normal women. 12 Filling pressure was low and did not rise, even at painful urge, in any subject. One patient, J. C., had a history of urinary urgency and frequency and demonstrated an uninhibited detrusor contraction during the early filling phase of the cystometrogram. Her symptoms and the graphic findings suggested that she suffered from the "unstable bladder syndrome." Time from operation until consistently satisfactory emptying of bladder. The 22 patients were divided into two groups: II who had complete transection of the cardinal ligaments, and II who had incomplete transection. The mean number of postoperative days before a patient could consistently void with less than a :JO ml urinary residual was fewer, 20 versus 51, in patients who had incomplete transection of the cardinal
Incomplete transection of cardinal ligament\ Patient H. C. B. E. J. C. P.M. R.N. M.G. N.H. F. G. D.P. M.S. L. B.
Preop. vol. (cc of C02)
150 120 50 150 125 150 180 120 110 125 130
Postop. vol. (a of C02)
220 225 100 200 275 380 320 300 300
>500
220
ligaments (Table Ill). With the Mann-Whitney test for comparison of nonparametric means, this difference was statistically significant (p < 0.01). Additionally, 7 of 11 women in the group with complete transection of the cardinal ligaments reported, when last examined, that they used accessory somatic muscles to initiate and sustain voiding. This was in contrast to 3 of II patients who had the less radical operation. Bladder sensation. Table IV reflects the magnitude of postoperative vesical sensory change for each patient. In every instance, there was an imrease in the volume required to elicit the urge sensation. The mean increase in C0 2 :required to elicit the first urge sensation on the day that the catheter was removed was 160 cc among the II women who had complete transection of the cardinal ligaments, as compared to 140 cc in the 11 patients who had incomplete transection. This difference was insignificant. In addition to a quantitative loss of sensation, there was also a qualita.tive change. All 22 women reported a postoperative alteration in the perception of vesical dis-
378
October lcl, 1\180 Am. J. Obstet. Gvnecol.
Forney
Table V. Comparison of preoperative and mean postoperative maximum intraurethral pressures Incomplete cardinal ligament transection
Complete cardinal ligament transection Patient D. G. B. T. L.L. A. D. E. R. B. P.
w.c.
K. M. J. R. R.J. F. T.
Preoperative
Mean postoperative
(em H 20)
(em H~)*
100 120 95 100 120 120 90 l!O 120 120 115
45 60 40 90 90 60 60 75 90 105 95
Preoperative Patient H. C. B. E.
J. c.
P.M. R.N. M.G. N.H. F. B. D.P. M.S. L. B.
(em H~)
150 135 100 90 120 120 140 75 120 90 125
Mean postoperative (em
H~)t
70 115 90 80 90 60 120 45 70 50 120
*Mean decrease 35. tMean decrease= 32.
tention. Typically, bloating and a vague feeling of fullness in the lower abdomen replaced the normal urge to void. Most volunteered that, once they became aware of bladder fullness, severe cramps would shortly follow if they did not soon void. Interestingly, J. C., who had both a history and a cystometrogram compatible with the "unstable bladder syndrome," reported complete resolution of her problem postoperatively. Four women (B. E., B. T., K. M., and M.S.) when last tested were 36, 26, 11, and 5 months removed from the time of their operations and could not appreciate a voiding urge at 500 cc of C0 2• Once a patient was capable of emptying the bladder, neither the volume at voiding urge nor the volume at painful urge varied more than 50 cc of C0 2 throughout the period of follow-up, except in two instances. B. E., at her 18-month examination, and M. G., at her 6-month examination, were found to have lost the voiding urge entirely. Despite the admonition to "void by the clock," these patients had not voided at regular intervals. M. G. regained the voiding urge 20 months postoperatively, but B. E. at her 36 month's visit could not appreciate urinary urgency at 500 cc of C0 2 • Residual urine. Except in two patients, the values of residual urine decreased progressively in the postoperative period. B. E. and M.G., mentioned previously, demonstrated an increase in residual urine coincident with the discovery of a high-capacity, sensationless bladder. Stress incontinence and urethral pressure changes. Five women with a negative preoperative history developed urinary stress incontinence postoperatively. Four of the five had undergone the more radical operation. One of two patients with preexisting stress incontinence became considerably more symptomatic, and the other was symptomatically unchanged. Postop-
erative urethroscopy demonstrated a proximal urethral opening with the Valsalva maneuver in each symptomatic patient and in two other patients withom a history of incontinence. In all 22 patients, intraurethral pressure maxima were consistently lower postoperatively and did not vary more than 15 em of H 20 from one postoperative examination to another. TaWe V depicts preoperative and mean postoperative maximum intraurethral pressure measurements on each patient. The mean pressuredecreases among the two operative groups were similar. Postoperative bladder pressure profiles (Table VI). In the immediate postoperative weeks, all patients who underwent complete transection of the cardinal ligaments, and 4 of ll who had incomplete transection, demonstrated a progressive rise in vesical pressure upon filling. Fig. 3 displays preoperative and serial postoperative bladder pressure profiles on a single patient, E. R. All 15 women who developed this unique cystometric pattern had strikingly similar records. Despite the progressive rise in bladder pressure, no patient who had this pattern sensed any painful urge to void until the intravesical pressure exceeded maximum intraurethral pressure, whereupon C0 2 began to escape around the urethroscope. Ten of fifteen patients who had an abnormal rise in pressure during vesical filling were capable of voiding to less than a 50 ml urinary residual. Bladder pressure profiles eventually returned to normal in all subjects. Hypertonic cystometric findings persisted for 14 to 210 days, with a mean of 46 days. No patient redeveloped bladder hypertonus. To determine whether the parasympathetic nervous system was responsible for detrusor hypertonia, Pro· Banthine was administered to three patients and cystometric evaluation was repeated. In each instance, the
Effect of radical hysterectomy on bladder
Volume l:l8 ~umber
379
·l
a.li.••••Preop
•1 st Urge
•A- 2wks Postop
A Painful Urge
ct.'"" 4wks Postop
:.:."• 6 wks Postop Fig. 3. Preoperative and serial postoperative urethral and vesical pressure studies on patient E. R. Note the postoperative diminution of intraurethral pressure, the uniformly low initial intravesical pressure. and the progressive rise in intravesical pressure that occurred postoperatively.
Table VI. Bladder pressure profiles at lO to 14 days postoperatively
I Patient D.
c:.
B. T. L.L.
A. D.
E. R. B. P. W.C.
K. 1\1.
J.
R.
R.J. F. T.
I
Comblete cardinal ligam'ent transection Normal filling pressure, progressive rise beginning at 200 cc C02 Normal filling pressure, progressive rise beginning at 110 cc C02 Normal filling pressure, progressive rise beginning at 110 cc C0 2 Normal filling pressure, progressive rise beginning at 120 cc C0 2 Normal filling pressure, progressive rise beginning at 125 cc C0 2 Normal filling pressure, progressive rise beginning at iOO cc C02 Normal filling pressure, progressive rise beginning at 130 cc C0 2 Normal filling pressure, progressive rise beginning at 250 cc C02 Normal filling pressure, progressive rise beginning at 225 cc C02 Normal filling pressure, progressive rise beginning at 150 cc C0 2 Normal filling pressure, progressive rise beginning at 225 cc C02
bladder pressure profile was unaffected by this parasympatholytic agent. Urinary infection. At t.he time of removal of the suprapubic catheter, the urine culture was positive in only one patient. Six patients had one or two positive postoperative urine cultures. Infection was asymptomatic in four patients, and the other two had symptoms compatible with cystitis. The culture obtained at the most recent postoperative examination in each subject was sterile.
I j
I ncomblete cardinal ligam;nt transection
Patient H. C.
Normal filling pressure, no rise
B. E.
Normal filling pressure, no rise
]. C.
Normal filling pressure, no rise
P.M.
Normal filling pressure, progressive rise beginning at 160 cc C02 Normal filling pressure, no rise
R.N.
N.H.
Normal filling pressure-:. progressive r-ise beginning at i 10 cc C()2 ~ormal filling pressure, no rise
F. G.
~ormal
D.P.
:"iormal filling pressure, no rise
M.S.
Normal filling pressure, progressive rise beginning at 200 cc C02 Normal filling pressure, progressive rise beginning at 130 cc C02
M.G.
L. B.
filling pressure, no rise
----
Comment The findings of this study are in agreement with previously described alterations in bladder function that followed radical hysterectomy, e.g., (I) decreased and altered awareness of vesical distention, (2) prolonged postoperative urinary retention, (3) stress incontinence, and ( 4} hypertonic cystometric findings. In view of these findings and those of other investigators, the etioiogy as wen as the practicai significance of these four derangements will be discussed.
380 Forney
Onober L!,
i'IKII
Am . .J. Obstet. Gvm·c<>l.
Sensory deficit. Autonomic afferent nerves traverse the cardinal, uterosacral, and pubovesicocervical ligaments, and, of necessity, many are transected during the performance of radical hysterectomy. 2 • 13 This undoubtedly explains vesical sensory loss after radical hysterectomy. In this study the degree of sensory impairment did not markedly differ between the radical and less radically treated groups of patients. This finding suggests that afferent nerves are concentrated proximally in the cardinal, uterosacral, and pubovesicocervical ligaments, so that leaving the inferior portion of these ligaments adds little to sensory integrity. With loss of physiologic cortical sensory input, patients should become aware of secondary, less sensitive indicators of vesical distention, such as peritoneal stretching and pressure on adjacent abdominal viscera. The substitute sensations of bloating and vague pelvic heaviness were present in the patients of this study, as well as in patients reported on by other investigators. 3 • 7• 8 Postoperative urinary retention. Normal micturition requires a prolonged, forceful, and coordinated detrusor muscle contraction. Such a contraction is dependent upon a complex interplay of sensory impulses from the bladder, cortical and brain stem modulation of the sacral micturition center, and parasympathetic neurons innervating the bladder detrusor. Since sensory afferent and autonomic efferent nerves are divided at the time of radical hysterectomy, a less than physiologic detrusor contraction that results in the inability to void and a high urinary residual is a predictable, well-recognized, and herein reaffirmed sequel of radical hysterectomy. Using the denervation supersensitivity test of Lapides and associates, i 4 Glahn 7 and Seski and Diokno 10 independently demonstrated parasympathetic denervation in patients who had undergone radical hysterectomy. This test remains positive for months to years after radical hysterectomy, and indicates that regeneration of preganglionic parasympathetic nerves may never occur. Aithough such regeneration is possible, the likelihood of regrowth across the void created by radical excision of paravaginal tissue seems to be remote. The present study demonstrates that voiding to low residual occurs sooner in the postoperative period if transection of the cardinal ligaments is incomplete, and I assume that partial transection spares more preganglionic parasympathetic neurons and allows for earlier accommodation of the nervous system and
ments appears to hasten and facilitate postoperatin· voiding, the surgeon should consider this operative modification in patients with small, Stage I nulignancies. From a practical standpoint, the knowledge that bladder contractions will be unphysiologic after a complete or partial parasympathetic denervation makes it imperative that the bladder detrusor be functionally normal preoperatively, and that it not be subjected to mechanical injury postoperatively. An exception to this may be in the patient who has an "unstable bladder syndrome." One accepted treatment for this disorder is partial denervation of the bladder, and the single patient in this series who had an "unstable bladder" experienced improvement of the condition as a consequence of radical hysterectomy. To avoid the mechanical damage to the detrusor muscle that may result from urinary retention, longterm decompression of the bladder is advised. I believe that the intraoperative placement of a suprapubic catheter, combined with instruction of the patient in regard to management of the catheter, offers the best prophylaxis against injury to the bladder muscle, the lowest incidence of urinary infection, and the highest degree of acceptance by the patient. Few patients after radical hysterectomy rely solely upon a detrusor contraction to empty the bladder. Most patients in this study initiated and completed micturition by using accessory somatic muscles-the rectus and diaphragm. For this reason, before attempted removal of the catheter, all patients should be educated in these mechanisms of voiding and should have sufficient strength and mobility to successfully use them. Stress incontinence. Five women developed stress incontinence postoperatively, and the problem worsened in one of two patients who had preexisting incontinence. Urethral pressure profile data revealed that in 17 of 22 patients there was a 20 em H 2 0 or greater decrease in maximum intraurethral pressure in the postoperative period. This does not reflect a lack of estrogen, since all women who underwent oophorectomy were given estrogen prophylactically. It has been conjectured that the basis of postoperative stress incontinence is radical resection of the cervix and upper vagina that results in decreased vesical neck support. I. 3 • 4 • 6 • 7 Such was the urethroscopically demonstrated finding in seven women in this study. However, neurogenic factors may play a role and will be discussed below in conjunction with an explanation of
adaptation of the patient to their numerical loss ...A:w.l~
postoperative detrusor hypertonia.
though the intent of radical hysterectomy is to obtain a wide cancer-free margin, the inferior segments of the cardinal ligaments are far removed from small cancers confined to the cervix, and because sparing these seg-
Hypertonic cystometric findings. When cystometry is performed at a time remote from radical hysterec-
tomy, investigators have often discovered that patients have a high-capacitv bladder with a low filling pressure
Effect of radical hysterectomy on bladder
Volume 13H Number 4
and a large urinary residual.!."' It was once assumed that hypotonia was characteristic of the detrusor muscle after radical hysterectomy, and that this finding was entirely due to parasympathetic denervation. Postoperative hypotonia, however, does not fit all investig-ators' observed cystometric findings after radical hvsterectomy. Those who have performed serial cystometn, beginning in the period immediately after radical hysterectomy, have discovered that the bladder had a high filling pressure and a reduced capacitv.'· 10 • 16 • 17 With the passage of time, the filling pressure returned to normal, and only those patients who had histories compatible with overdistention developed a hypotonic cystometrogram. Serial cystometric data on the patients presented herein corroborate both findings, i.e .. hypertonus proximal to the operative site and hypotonia with chronic vesical overdistention. There have been two explanations for the detrusor hypertonia observed immediately after operation: ( 1) parasympathetic dominance, 17 • 18 and (2) a decrease in the musculoelastic properties of the detrusor muscle and the paravesical soft tissue as a consequence of postoperative edema, hematoma, and cicatricial changes. 7 • 10 This study and that of Seski and Diokno 10 suggest that the first theory is improbable because detrusor hypertonia is not abolished by parasympatholytic drugs. The second theory, favored by Glahn 7 and Seski and Diokno. 10 fails to explain why many, but not all, patients in this study had a hypertonic cystometrogram postoperativelv. It is also striking that subjects who had a complete division of the cardinal ligaments had a I 00% incidence of hypertonia, as compared to 30% in the group which underwent the less radical operation. The findings in this study and a rewview of currently held theories in regard to vesical neurophysiology lead me to propose sympathetic denervation as an alternate reason for postoperative detrusor hypertonia. Previous explanations for all aspects of bladder dysfunction after radical hysterectomy have been based upon the assumption that transection of sympathic autonomic nerves, which also traverse the cardinal, uterosacral, and pubovesicocervical ligaments, is without physiologic significance. 2 • '· ». 111 However, in view of studies which show a highly important functional role for the sympathetic nervous system in the physiology of vesical filling, 111 - 2 ;; it seems unlikely that the division of a major portion of the vesical svmpathetic nerve supply could
REFERENCES I. Thornton, W. N., Jr.: Late urinary system complications following radical hysterectomy for carcinoma of the cer.
"--
\'IX, AM.
r
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~-----
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381
be inconsequential. The bladder detrusor and vesical neck are richly endowed with sympathetic nerves, and it has been unequivocally demonstrated that the bladder and upper urethra are under dual svmpathetic and parasympathetic innervation. Additionally, many short, intrinsic neurons interconnect these two divisions of the autonomic nervous system. These interconnections occur at the level of parasympathetic ganglia and depress parasympathetic condwtion, thus favoring continence during vesical filling.~ 6 It is also recognized that sympathetic postganglionir nerves terminate upon both alpha and beta adrennreceptors, and that alpha and beta receptors are distributed unevenly throughout the detrusor muscle. vc·sical neck, and urethra. 27 - 29 When stimulated. the beta-adrenergic receptors which are diffusely present throughout the bladder muscle cause relaxation of the detrusor muscle, and the alpha-adrenergic receptors which are concentrated in the vesical neck and upper un·thra cause contraction of smooth muscle. On the basis of studies which suggest that, under normal conditions, vesical filling without a rise in pressure is partly due to sympathetic beta-adren<·rgic stimulation,29· 30 and not solely to the intrinsic pmperties of the detrusor muscle and perivesical comlt'ctive tissue bed, 31 I postulate that sympathetic denervation contributes to bladder hypertonus after radical hysterectomy. Additionally, I postulate that the luss of alpha stimulation to the vesical neck partially explains the postoperative decrease in intraurethral pressure and contributes to the observed incidence of p(lstoperative stress incontinence. This hypothesis is compatible with the observed cystometric findings. It is also compatible with the lower incidence of vesical hypertonia which occurred in patients who had incomplete transection of the cardinal ligaments. The return to a normal bladder pressure profile did not occur in some patients until several months after radical hysterectomy. and an explanation of hypertonus based solely upon perivesical edema and hematoma forma ilion could not explain thts duration of hypertonic change. However, regeneration of injured nerves and autonomic adaptation could explain temporary hypertonia, with ultimate return to normaL To test this hypothesis in future studies, 1 plan to measure the effect of sympathomimetic and >} mpatholytic agents on postoperative urethral and vesu al tone.
2. Twombly, G. H., and Landers, D.: The innervation of the bladder with reference to radical hysterectomy. AM. J 0BSTET. GYNECOL. 71:1291, 1956 . 3. Lewington, Vl.: Disturbances of micturition following
382 Forney
4.
5. 6. 7.
8. 9.
10.
II.
12. 13. 14. 15. 16. 17.
Wertheim hysterectomy,]. Obstet. Gynaecol. Br. 63:861, 1956. Green, T. H., Jr., Meigs, J. V., Ulfelder, H., et al.: Urologic complications of radical Wertheim hysterectomy: Incidence, etiology, management, and prevention, Obstet. Gynecol. 20:293, 1962. Symmonds, R. E.: rvforbidi~y and complications of radical hysterectomy with pelvic lymph node dissection, AM. J. 0BSTET. GYNECOL. 94:663, 1966. Fraser, A. C.: The late effects of Wertheim's hysterectomy on the urinary tract, J. Obstet. Gynaecol. Br. Commonw. 73:1002, 1966. Glahn, B. E.: The neurogenic factor in vesical dysfunction following radical hysterectomy for carcinoma of the cervix, Scand. J. Urol. Nephrol. 4:107, 1970. Palm, L., and Folke, R.: Bladder function following either radiotherapy or radical operation ad modum Okabayashi for cervical cancer, Dan. Med. Bull. 17:113, 1970. Barclay, D. L., and Roman-Lopez,]. J.: Bladder dysfunction after Schauta hysterectomy, AM. J. 0BSTET. GYNECOL. 123:519, 1975. Seski,J. C., and Diokno, A. C.: Bladder dysfunction after radical abdominal hysterectomy, AM. J. 0BSTET. GYNECOL. 128:643, 1977. Meigs, J. V.: Radical hysterectomy with bilateral dissection of the pelvic lymph nodes. 2. The method of Joe V. Meigs, M.D., in Meigs,]. V., editor: Surgical treatment of cancer of the cervix, New York, 1954, Grune & Stratton, Inc., pp. 149-196. Robertson, J. R.: Gas cystometrogram with urethral pressure profile, Obstet. Gyneco!. 44:72, !974. Smith, P. H., and Ballantyne, B.: The neuroanatomical basis for denervation of the urinary bladder following major pelvic surgery, Br. J. Surg. 55:62, 1968. Lapides,]., Friend, C. R., Ajemian, E. P., et al.: Denervation supersensitivity as a test for neurogenic bladder, Surg. Gynecol. Obstet. 114:241, 1962. Fraser, A. C.: Cystometry after Wertheim's hysterectomy, J. Obstet. Gynaecol. Br. Commonw. 74:746, 1967. Richter, K., and Albrich, W.: Zur Frage der postoperativen Harnverhaltung nach erweiterter total extirpation wegen carcinoma co IIi uteri, Zbl. Gyniikol. 73: 1103, 1951. Roman-Lopez, J. J. and Barclay, D. L.: Bladder dysfunction following Schauta hysterectomy, AM. ]. 0BSTET. GYNECOL. 115:81, 1973.
Am.
J.
October I:,, I '!KO Obstet (;""'col.
18. Yousseff, A. F.: Cystometric studies in gynemlo)!;Y ;md obstetrics, Obstet. Gynecol. 8:81. 1956. 19. El-Badawi, A., and Schenk, E. A.: Dual innervation of the mammalian urinary b!addeL A histochemical study o! the distribution of cholinergic and adrenergic nt>rves. ;\ m . .J. Anat. 119:405, 1966. 20. El-Badawi, A., and Schenk, E. A .. A new theurv ui the innervation of bladder musculature. Part I. Morplwlog' of the intrinsic vesical innervation apparatus, J l'rol. 99:585, 1968. 21. Boyarsky, S., Labay, P., Gregg. R., et al.: Pharmacologic studies of the nature of the sympathetic nerves of the urinary bladder, Paraplegia 6:136, 1968. 22. Malin, J. M., Jr., and Boyarsky, S.: The eHects of cholinergic and adrenergic drug stimulation of detrmor muscle, Invest. Urol. 8:286, 1970. 23. El-Badawi, A., and Schenk, E. A.: A new theory of the innervation of bladder musculature. Part 4. Innervation of the vesicourethral junction and external nrt>thral sphincter,]. Urol. 111:613, 1974. 24. Bradley, W. E., and Timm, G. W.: Physiology of micturition, Vet. Clin. North Am. 4:487, 1974. 25. Khanna, 0. P.: Disorders of micturition. ~~europhanna cologic basis and results of drug therapv. Urologv 8::) 16, 1976. 26. Ostergard, D. R.: The neurological control of micturition and integral voiding reflexes, Obstet. Gynecol. Surv. 34:417, 1979. 27. Edvardsen, P., and Setekleiv, J.: Distribution of adrenergic receptors in the urinary bladder of cats, rabbits and guinea pigs, A.cta Pharmacol. Toxico!. 26:437, 1968. 28. Gregg, R. A., Boyarsky, S., Labay, P .. et al.: Presence of beta-adrenergic receptors in urinary bladder of dog and cat: Response to isoproterenol, Arch. Phys. Med. Rehabil. 51:88, 1970. 29. Nergardh, A.: Autonomic receptor functions in lower urinary tract. Survey of recent experimental results, .J. Urol. 113:180, 1975. 30. Rohner, T. J., Raezer, D. M., Weiss, A. J., et al.: Contractile responses of dog bladder neck muscle to adrenergic drugs,]. Ural. 105:657, 1971. 31. Tang, P. C., and Ruch, T. C.: Non-neurogenic basis of bladder tonus, Am. J. Physiol. 181:249, 1955.
in operative technique, anesthesia, antimicrobials, and the clinical laboratory, combined with restrictive use of radical hysterectomy to heaithier women with clinically localized cervical cancer, have markedly decreased the frequency of operative death, serious infection, and urinary fistulas. However, the frequency of bladder dysfunction after radical hysterectomy has not been similarly reduced and is now recognized as the most common complication of radical hysterectomy. For years, patients have a diminished awareness of vesical distention and may void "by the clock" rather than by urge. Months may pass before patients can initiate and/or successfully complete micturition. Manual suprapubic pressure and vigorous straining are often the ultimate solution to nearly complete evacuation of the bladder, and a small percentage of wonten must even resort to periodic selfcatheterization. Postoperative urinary stress incontinence seems also to occur in a disproportiortately high percentage of patients. The incidence, sev~rity, and pathogenesis of these alterations in bladder function have been the subject of IMPROVEMENTS
From the Cecil H. and Ida Green Center for Reproductive Biology Sciences, and the Department of Obstetrics and Gynecology, The University of Texas Health Science Center at Dallas. Received for publication February 15, 1980. Accepted june 11, 1980. Reprint requests:]. Peter Forney, M.D., Department of Obstetrics and Gynecology, The University of Texas Health Scimce Center at Dallas, 5323 Harry Hines Blvd., Dallas, Texas 75235.
374
past repons. 1- 10 This article readdresses these issues; however, the method of evaluation, results, and conclusions are, in some respects, unique.
Materia! and method Between June I, I976, and May 30, I979, I performed radical hysterectomy and pelvic lymphadenectomy on 37 women. Twenty-two underwent preoperative and serial postoperative C0 2 cystourethroscopy with simultaneous evaluation of the urethral and bladder pressure profile (Cu-UBPP). A Robertson 18guage urethroscope and a Browne C0 2 Cystometry Moniter, Model CR-2, were used to inspect the lower urinary tract and record urethral and vesical pressures. A complete urinary history was taken and intravenous pyelography, urine culture, and residual urine measurement were routinely performed preoperatively. Relevant clinical characteristics of the study group are detailed in Table I. Tvvo vvornen had a preoperative history compatible with mild stress urinary incontinence, and one \.voman related a history of longstanding urinary urgency and frequency. No patient had a positive preoperative urine culture, a residual urine greater than lO ml, or an abnormal intravenous pyelogram. A pelvic lymphadenectomy with radical hysterectomy similar to that described by Meigs'' was performed in II of the 22 women studied. In these I1 women, the cardinal ligaments were exposed by dissection of the pararectal and paravesical spaces and were divided to the pelvic diaphragm (Fig. I). In the other II women, the inferior l to 2 ern of each cardinalliga0002-93i8/80/2003i4+09$00.90/0
©
1980 The C. V. Mosby Co
Volume 13H Number 4
Effect of radical hysterectomy on bladder
375
Table I. Clinical characteristics
H. C.
B. E. J. C. D. G. B. T. L.L.
P.M. A. D. E. R. D
.u.
n
1 .
R.N. M.G. N.H. F. G.
w.c.
K. M. D.P. u JI .... F. T.
M.S. L. B. R.J.
Hzstory of Incontinence
Diagnosis
Patients
33 29 49 :~2
25
40 24 37 32 q 1
.n
34 65 :16 38 37 36 25 31
43 33 20 18
5
I 53 I23 II6 I70 II8 I38 I8I II2 I 57
3
172
2 2 0 5 I
5 3
4 0 2
3 2 3 0 2 4
3 I
1
I89 II4 106 I35 I44 II9 I35 !49 I28 I04 205
Stage IB (Occ) squamous cell carcinoma of cervix Stage IB (Occ) squamous cell carcinaoma of cervix Stage IB (Occ) squamous cell carcinoma of cervix Stage IB squamous cell carcinoma of cervix Stage IIA adenocarcinoma of vagina Stage IB adenocarcinoma of cervix Stage IB squamous cell carcinoma of cervix Stage IB squamous cell carcinoma of cervix Stage IB squamous cell carcinoma of cervix Stage IB squamous eel! carcinoma of cervix Stage IB (Occ) squamous cell carcinoma of cervix Stage IB (Occ) squamous cell carcinoma of cervix Stage iB adenocarcinoma of cervix Stage IB adenocarcinoma of cervix Stage IB squamous cell carcinoma of cervix Stage IB squamous cell carcinoma of cervix Stage IB squamous cell carcinoma of cervix Stage IB squamous cell carcinoma of cervix Stage IB squamous cell carcinoma of cervix Stage IB (Occ) squamous cell carcinoma of cervix Stage IB (Occ) squamous cell carcinoma of cervix Stage IB squamous cell carcinoma of cervix
"Stress" None 'Urge" None None "'one "'one None None None None None "'one '"Stress" "'one "'one "'one None
None None None None
Table II. Preoperative Cu-UBBP Maximum intraurethral Pressure (em H 20)
Volume at first urge (cc of C02)
Volume at painful urge (cc of C02)
H. C. B. E. J.C.
90 I35 IOO
I50 I20 50
220 230 I80
D. G. B. T.
K. M. D.P. J. R. F. T. M.S. L. B.
IOO I20 95 90 IOO 65 I20 IOO 75 I40 75 90 II 0 I20 I20 II5 90 I25
I75 IOO I80 I 50 IIO IIO I20 I25 I50 I80 I20 IIO I60 IIO I40 I40 I25 I30
3IO I 50 270 200 170 I90 200 200 250 220 ISO 260 250 I75 250 200 2IO 225
n
1'}(\
1 1/\
C}Q(\
Patient
L.L.
P.M. A. D.
E. R. B. P. R.N. M.G. N.H. F. G. W.C.
!'..
T
J·
lJU
uv
ment was left intact (Fig. 2). In all cases the uterosacral and vesicouterine ligaments were divided lateral to the rectum and bladder as deeply as necessary to equate with the level of transection of the cardinal ligaments. In no case was the superior vesical artery ligated, and in each case the ureter was entirely freed from the cardinal and vesicouterine ligaments. The excised vaginal cuff was approximately l em longer in those patients
4JV
Pressure profile No pressure rise No pressure rise No pressure nse Uninhibited contraction at 140 cc of C0 2 No pressure rise No pressure rise No pressure rise No pressure rise :'1/o pressure rise No pressure nse No pressure rise No pressure rise No pressure rise No pressure rise No pressure rist" No pressure rise No pressurt" rise No pressure rise No pressure rise No pressure rise No pressure 1 ise No pressure rise No pressure rise
who had complete transection of the t.:ardinal ligaments. Nonbulky adenocarcinomas confined to the endocervix and Stage IB squamous cell carnnomas of less than l em in maximum diameter were chosen for less radical resection of the cardinal ligaments and vagina. A No. 16 Foley catheter with a 5 cc balloon was inserted suprapubicaiiy in aii patients prim to ciosure of the abdominal wall. There were no serious postopera-
376
Forney Am.
Fig. I. The cardinal ligament has been divided at the pelvic wall and to the fascia overlying the levator muscle. The paravesical and pararectal spaces are in communication. The ureter has been mobilized from the cardinal ligament and is retracted laterally. tive infections, or urinary fistulas. One patient, A. D., died 5 months postoperatively, but her death was unrelated to malignancy or the operative procedure. No patient has been lost to follow-up, and all are clinically free of recurrent disease. Cu-UBPP was performed preoperatively, 10 to 14 days postoperatively, and every I to 2 weeks thereafter until the patient was capable of voiding with less than a 50 ml urinary residual. Cu-UBPP was then repeated at 3-month intervals for the first year, and every 6 months thereafter. Follow-up has ranged from 6 to 43 months, with from five to 12 examinations per patient. I performed all examinations and recorded urinary histories at each visit. The examination routine was as follows: Preoperatively and postoperatively, patients without a catheter were instructed to void; whereupon they were placed in the lithotomy position and the periurethral area was cleansed. After the urethral meatus had been topically anesthetized, the urethroscope , with C0 2 for obturation, was passed through the urethra and into the bladder. The urinary· residual was measured and cultured. With the urethroscope held at the vesical neck, the bladder was filled retrogradely with C0 2 at a rate of 120 cc/minute. The volume at first urge and that at
J.
Onober IS, 1!-!i!O Obstel. Gvnecol.
Fig. 2. The inferior segment of the cardinal ligament has been spared and can be seen bridging between the pelvic wall and vagina. The ureter is retracted laterally. painful urge to urinate were recorded. To check for the normal sphincteric action of the vesical neck and proximal urethra, the endoscope was withdrawn into the upper urethra and the patient was instructed to perform a forceful Valsalva maneuver. Patients with a suprapubic catheter in situ were examined as outlined above, with the following exceptions : ( 1) They were not asked to void prior to the examination. (2) If painful urge did not occur before 500 cc of C02 had been instilled into the bladder, the procedure was terminated for fear of vesical overdistention. (3) After Cu-UBPP, saline solution was placed into the bladder through the suprapubic catheter, and the patient was given the opportunity to urinate. The volume of instilled saline solution varied with individual differences in bladder capacity, but generally ranged from 150 to 250 mi. Five to ten minutes were allowed for voiding and then the residual volume was measured. If the patient was capable of emptying the bladder to all but 50 ml or less of the instilled saline solution, the catheter was clamped and she was allowed to void on her own. Patients were retested within 48 hours to ensure consistently adequate vesical emptying before the catheler was removed. Urobiotics were administered prophylactically for 24 hours after cystourethroscopy, and documented infections were treated for 10 days with appropriate antibiotics.
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Effect of radical hysterectomy on bladder 377
Table III. Days to spontaneous and satisfactory vesical emptying Complete transection of cardinal ligaments
Patintl
32 120 84 20 47 80 30 26 63 20 35 51
D.(;. B. !'. LL
A. D. E. R. B. P.
w.c. K. M. J. R.
R.J
F. T.
Mean
= p
Incomplete transection of cardinal ligament.\
Patient
14 28 21
H. C. B. E.
J. c.
P.M. R.N. M.G.
21
Hi
21
~.H.
14
F. G. D.P. M.S. L. B.
21
18 25 21
20
< 0.01.
Table IV. Comparison of preoperative volume at first urge and postoperative "olume at first urge on day of catheter removal Complete transection of cardinal ligaments Patient D. G. B. T. L.L. A. D. E. R. B. P. W.C. K. M. .J. R.
R.J. F. ·r.
Preop. vol. (cc of C02)
175 100 180 110 110 120 110 160 140 110 140
Postop. val. (cc of C02)
250 >500 320 130 ' 150 250 300 >500 380 380 190
Results Preoperative Cu-UBPP. Table II details the preoperative measurements of maximum intra urethral pressure, volume at first urge, and volume at painful urge for each patient. All volumes were within the range of reported values for normal women. 12 Filling pressure was low and did not rise, even at painful urge, in any subject. One patient, J. C., had a history of urinary urgency and frequency and demonstrated an uninhibited detrusor contraction during the early filling phase of the cystometrogram. Her symptoms and the graphic findings suggested that she suffered from the "unstable bladder syndrome." Time from operation until consistently satisfactory emptying of bladder. The 22 patients were divided into two groups: II who had complete transection of the cardinal ligaments, and II who had incomplete transection. The mean number of postoperative days before a patient could consistently void with less than a :JO ml urinary residual was fewer, 20 versus 51, in patients who had incomplete transection of the cardinal
Incomplete transection of cardinal ligament\ Patient H. C. B. E. J. C. P.M. R.N. M.G. N.H. F. G. D.P. M.S. L. B.
Preop. vol. (cc of C02)
150 120 50 150 125 150 180 120 110 125 130
Postop. vol. (a of C02)
220 225 100 200 275 380 320 300 300
>500
220
ligaments (Table Ill). With the Mann-Whitney test for comparison of nonparametric means, this difference was statistically significant (p < 0.01). Additionally, 7 of 11 women in the group with complete transection of the cardinal ligaments reported, when last examined, that they used accessory somatic muscles to initiate and sustain voiding. This was in contrast to 3 of II patients who had the less radical operation. Bladder sensation. Table IV reflects the magnitude of postoperative vesical sensory change for each patient. In every instance, there was an imrease in the volume required to elicit the urge sensation. The mean increase in C0 2 :required to elicit the first urge sensation on the day that the catheter was removed was 160 cc among the II women who had complete transection of the cardinal ligaments, as compared to 140 cc in the 11 patients who had incomplete transection. This difference was insignificant. In addition to a quantitative loss of sensation, there was also a qualita.tive change. All 22 women reported a postoperative alteration in the perception of vesical dis-
378
October lcl, 1\180 Am. J. Obstet. Gvnecol.
Forney
Table V. Comparison of preoperative and mean postoperative maximum intraurethral pressures Incomplete cardinal ligament transection
Complete cardinal ligament transection Patient D. G. B. T. L.L. A. D. E. R. B. P.
w.c.
K. M. J. R. R.J. F. T.
Preoperative
Mean postoperative
(em H 20)
(em H~)*
100 120 95 100 120 120 90 l!O 120 120 115
45 60 40 90 90 60 60 75 90 105 95
Preoperative Patient H. C. B. E.
J. c.
P.M. R.N. M.G. N.H. F. B. D.P. M.S. L. B.
(em H~)
150 135 100 90 120 120 140 75 120 90 125
Mean postoperative (em
H~)t
70 115 90 80 90 60 120 45 70 50 120
*Mean decrease 35. tMean decrease= 32.
tention. Typically, bloating and a vague feeling of fullness in the lower abdomen replaced the normal urge to void. Most volunteered that, once they became aware of bladder fullness, severe cramps would shortly follow if they did not soon void. Interestingly, J. C., who had both a history and a cystometrogram compatible with the "unstable bladder syndrome," reported complete resolution of her problem postoperatively. Four women (B. E., B. T., K. M., and M.S.) when last tested were 36, 26, 11, and 5 months removed from the time of their operations and could not appreciate a voiding urge at 500 cc of C0 2• Once a patient was capable of emptying the bladder, neither the volume at voiding urge nor the volume at painful urge varied more than 50 cc of C0 2 throughout the period of follow-up, except in two instances. B. E., at her 18-month examination, and M. G., at her 6-month examination, were found to have lost the voiding urge entirely. Despite the admonition to "void by the clock," these patients had not voided at regular intervals. M. G. regained the voiding urge 20 months postoperatively, but B. E. at her 36 month's visit could not appreciate urinary urgency at 500 cc of C0 2 • Residual urine. Except in two patients, the values of residual urine decreased progressively in the postoperative period. B. E. and M.G., mentioned previously, demonstrated an increase in residual urine coincident with the discovery of a high-capacity, sensationless bladder. Stress incontinence and urethral pressure changes. Five women with a negative preoperative history developed urinary stress incontinence postoperatively. Four of the five had undergone the more radical operation. One of two patients with preexisting stress incontinence became considerably more symptomatic, and the other was symptomatically unchanged. Postop-
erative urethroscopy demonstrated a proximal urethral opening with the Valsalva maneuver in each symptomatic patient and in two other patients withom a history of incontinence. In all 22 patients, intraurethral pressure maxima were consistently lower postoperatively and did not vary more than 15 em of H 20 from one postoperative examination to another. TaWe V depicts preoperative and mean postoperative maximum intraurethral pressure measurements on each patient. The mean pressuredecreases among the two operative groups were similar. Postoperative bladder pressure profiles (Table VI). In the immediate postoperative weeks, all patients who underwent complete transection of the cardinal ligaments, and 4 of ll who had incomplete transection, demonstrated a progressive rise in vesical pressure upon filling. Fig. 3 displays preoperative and serial postoperative bladder pressure profiles on a single patient, E. R. All 15 women who developed this unique cystometric pattern had strikingly similar records. Despite the progressive rise in bladder pressure, no patient who had this pattern sensed any painful urge to void until the intravesical pressure exceeded maximum intraurethral pressure, whereupon C0 2 began to escape around the urethroscope. Ten of fifteen patients who had an abnormal rise in pressure during vesical filling were capable of voiding to less than a 50 ml urinary residual. Bladder pressure profiles eventually returned to normal in all subjects. Hypertonic cystometric findings persisted for 14 to 210 days, with a mean of 46 days. No patient redeveloped bladder hypertonus. To determine whether the parasympathetic nervous system was responsible for detrusor hypertonia, Pro· Banthine was administered to three patients and cystometric evaluation was repeated. In each instance, the
Effect of radical hysterectomy on bladder
Volume l:l8 ~umber
379
·l
a.li.••••Preop
•1 st Urge
•A- 2wks Postop
A Painful Urge
ct.'"" 4wks Postop
:.:."• 6 wks Postop Fig. 3. Preoperative and serial postoperative urethral and vesical pressure studies on patient E. R. Note the postoperative diminution of intraurethral pressure, the uniformly low initial intravesical pressure. and the progressive rise in intravesical pressure that occurred postoperatively.
Table VI. Bladder pressure profiles at lO to 14 days postoperatively
I Patient D.
c:.
B. T. L.L.
A. D.
E. R. B. P. W.C.
K. 1\1.
J.
R.
R.J. F. T.
I
Comblete cardinal ligam'ent transection Normal filling pressure, progressive rise beginning at 200 cc C02 Normal filling pressure, progressive rise beginning at 110 cc C02 Normal filling pressure, progressive rise beginning at 110 cc C0 2 Normal filling pressure, progressive rise beginning at 120 cc C0 2 Normal filling pressure, progressive rise beginning at 125 cc C0 2 Normal filling pressure, progressive rise beginning at iOO cc C02 Normal filling pressure, progressive rise beginning at 130 cc C0 2 Normal filling pressure, progressive rise beginning at 250 cc C02 Normal filling pressure, progressive rise beginning at 225 cc C02 Normal filling pressure, progressive rise beginning at 150 cc C0 2 Normal filling pressure, progressive rise beginning at 225 cc C02
bladder pressure profile was unaffected by this parasympatholytic agent. Urinary infection. At t.he time of removal of the suprapubic catheter, the urine culture was positive in only one patient. Six patients had one or two positive postoperative urine cultures. Infection was asymptomatic in four patients, and the other two had symptoms compatible with cystitis. The culture obtained at the most recent postoperative examination in each subject was sterile.
I j
I ncomblete cardinal ligam;nt transection
Patient H. C.
Normal filling pressure, no rise
B. E.
Normal filling pressure, no rise
]. C.
Normal filling pressure, no rise
P.M.
Normal filling pressure, progressive rise beginning at 160 cc C02 Normal filling pressure, no rise
R.N.
N.H.
Normal filling pressure-:. progressive r-ise beginning at i 10 cc C()2 ~ormal filling pressure, no rise
F. G.
~ormal
D.P.
:"iormal filling pressure, no rise
M.S.
Normal filling pressure, progressive rise beginning at 200 cc C02 Normal filling pressure, progressive rise beginning at 130 cc C02
M.G.
L. B.
filling pressure, no rise
----
Comment The findings of this study are in agreement with previously described alterations in bladder function that followed radical hysterectomy, e.g., (I) decreased and altered awareness of vesical distention, (2) prolonged postoperative urinary retention, (3) stress incontinence, and ( 4} hypertonic cystometric findings. In view of these findings and those of other investigators, the etioiogy as wen as the practicai significance of these four derangements will be discussed.
380 Forney
Onober L!,
i'IKII
Am . .J. Obstet. Gvm·c<>l.
Sensory deficit. Autonomic afferent nerves traverse the cardinal, uterosacral, and pubovesicocervical ligaments, and, of necessity, many are transected during the performance of radical hysterectomy. 2 • 13 This undoubtedly explains vesical sensory loss after radical hysterectomy. In this study the degree of sensory impairment did not markedly differ between the radical and less radically treated groups of patients. This finding suggests that afferent nerves are concentrated proximally in the cardinal, uterosacral, and pubovesicocervical ligaments, so that leaving the inferior portion of these ligaments adds little to sensory integrity. With loss of physiologic cortical sensory input, patients should become aware of secondary, less sensitive indicators of vesical distention, such as peritoneal stretching and pressure on adjacent abdominal viscera. The substitute sensations of bloating and vague pelvic heaviness were present in the patients of this study, as well as in patients reported on by other investigators. 3 • 7• 8 Postoperative urinary retention. Normal micturition requires a prolonged, forceful, and coordinated detrusor muscle contraction. Such a contraction is dependent upon a complex interplay of sensory impulses from the bladder, cortical and brain stem modulation of the sacral micturition center, and parasympathetic neurons innervating the bladder detrusor. Since sensory afferent and autonomic efferent nerves are divided at the time of radical hysterectomy, a less than physiologic detrusor contraction that results in the inability to void and a high urinary residual is a predictable, well-recognized, and herein reaffirmed sequel of radical hysterectomy. Using the denervation supersensitivity test of Lapides and associates, i 4 Glahn 7 and Seski and Diokno 10 independently demonstrated parasympathetic denervation in patients who had undergone radical hysterectomy. This test remains positive for months to years after radical hysterectomy, and indicates that regeneration of preganglionic parasympathetic nerves may never occur. Aithough such regeneration is possible, the likelihood of regrowth across the void created by radical excision of paravaginal tissue seems to be remote. The present study demonstrates that voiding to low residual occurs sooner in the postoperative period if transection of the cardinal ligaments is incomplete, and I assume that partial transection spares more preganglionic parasympathetic neurons and allows for earlier accommodation of the nervous system and
ments appears to hasten and facilitate postoperatin· voiding, the surgeon should consider this operative modification in patients with small, Stage I nulignancies. From a practical standpoint, the knowledge that bladder contractions will be unphysiologic after a complete or partial parasympathetic denervation makes it imperative that the bladder detrusor be functionally normal preoperatively, and that it not be subjected to mechanical injury postoperatively. An exception to this may be in the patient who has an "unstable bladder syndrome." One accepted treatment for this disorder is partial denervation of the bladder, and the single patient in this series who had an "unstable bladder" experienced improvement of the condition as a consequence of radical hysterectomy. To avoid the mechanical damage to the detrusor muscle that may result from urinary retention, longterm decompression of the bladder is advised. I believe that the intraoperative placement of a suprapubic catheter, combined with instruction of the patient in regard to management of the catheter, offers the best prophylaxis against injury to the bladder muscle, the lowest incidence of urinary infection, and the highest degree of acceptance by the patient. Few patients after radical hysterectomy rely solely upon a detrusor contraction to empty the bladder. Most patients in this study initiated and completed micturition by using accessory somatic muscles-the rectus and diaphragm. For this reason, before attempted removal of the catheter, all patients should be educated in these mechanisms of voiding and should have sufficient strength and mobility to successfully use them. Stress incontinence. Five women developed stress incontinence postoperatively, and the problem worsened in one of two patients who had preexisting incontinence. Urethral pressure profile data revealed that in 17 of 22 patients there was a 20 em H 2 0 or greater decrease in maximum intraurethral pressure in the postoperative period. This does not reflect a lack of estrogen, since all women who underwent oophorectomy were given estrogen prophylactically. It has been conjectured that the basis of postoperative stress incontinence is radical resection of the cervix and upper vagina that results in decreased vesical neck support. I. 3 • 4 • 6 • 7 Such was the urethroscopically demonstrated finding in seven women in this study. However, neurogenic factors may play a role and will be discussed below in conjunction with an explanation of
adaptation of the patient to their numerical loss ...A:w.l~
postoperative detrusor hypertonia.
though the intent of radical hysterectomy is to obtain a wide cancer-free margin, the inferior segments of the cardinal ligaments are far removed from small cancers confined to the cervix, and because sparing these seg-
Hypertonic cystometric findings. When cystometry is performed at a time remote from radical hysterec-
tomy, investigators have often discovered that patients have a high-capacitv bladder with a low filling pressure
Effect of radical hysterectomy on bladder
Volume 13H Number 4
and a large urinary residual.!."' It was once assumed that hypotonia was characteristic of the detrusor muscle after radical hysterectomy, and that this finding was entirely due to parasympathetic denervation. Postoperative hypotonia, however, does not fit all investig-ators' observed cystometric findings after radical hvsterectomy. Those who have performed serial cystometn, beginning in the period immediately after radical hysterectomy, have discovered that the bladder had a high filling pressure and a reduced capacitv.'· 10 • 16 • 17 With the passage of time, the filling pressure returned to normal, and only those patients who had histories compatible with overdistention developed a hypotonic cystometrogram. Serial cystometric data on the patients presented herein corroborate both findings, i.e .. hypertonus proximal to the operative site and hypotonia with chronic vesical overdistention. There have been two explanations for the detrusor hypertonia observed immediately after operation: ( 1) parasympathetic dominance, 17 • 18 and (2) a decrease in the musculoelastic properties of the detrusor muscle and the paravesical soft tissue as a consequence of postoperative edema, hematoma, and cicatricial changes. 7 • 10 This study and that of Seski and Diokno 10 suggest that the first theory is improbable because detrusor hypertonia is not abolished by parasympatholytic drugs. The second theory, favored by Glahn 7 and Seski and Diokno. 10 fails to explain why many, but not all, patients in this study had a hypertonic cystometrogram postoperativelv. It is also striking that subjects who had a complete division of the cardinal ligaments had a I 00% incidence of hypertonia, as compared to 30% in the group which underwent the less radical operation. The findings in this study and a rewview of currently held theories in regard to vesical neurophysiology lead me to propose sympathetic denervation as an alternate reason for postoperative detrusor hypertonia. Previous explanations for all aspects of bladder dysfunction after radical hysterectomy have been based upon the assumption that transection of sympathic autonomic nerves, which also traverse the cardinal, uterosacral, and pubovesicocervical ligaments, is without physiologic significance. 2 • '· ». 111 However, in view of studies which show a highly important functional role for the sympathetic nervous system in the physiology of vesical filling, 111 - 2 ;; it seems unlikely that the division of a major portion of the vesical svmpathetic nerve supply could
REFERENCES I. Thornton, W. N., Jr.: Late urinary system complications following radical hysterectomy for carcinoma of the cer.
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be inconsequential. The bladder detrusor and vesical neck are richly endowed with sympathetic nerves, and it has been unequivocally demonstrated that the bladder and upper urethra are under dual svmpathetic and parasympathetic innervation. Additionally, many short, intrinsic neurons interconnect these two divisions of the autonomic nervous system. These interconnections occur at the level of parasympathetic ganglia and depress parasympathetic condwtion, thus favoring continence during vesical filling.~ 6 It is also recognized that sympathetic postganglionir nerves terminate upon both alpha and beta adrennreceptors, and that alpha and beta receptors are distributed unevenly throughout the detrusor muscle. vc·sical neck, and urethra. 27 - 29 When stimulated. the beta-adrenergic receptors which are diffusely present throughout the bladder muscle cause relaxation of the detrusor muscle, and the alpha-adrenergic receptors which are concentrated in the vesical neck and upper un·thra cause contraction of smooth muscle. On the basis of studies which suggest that, under normal conditions, vesical filling without a rise in pressure is partly due to sympathetic beta-adren<·rgic stimulation,29· 30 and not solely to the intrinsic pmperties of the detrusor muscle and perivesical comlt'ctive tissue bed, 31 I postulate that sympathetic denervation contributes to bladder hypertonus after radical hysterectomy. Additionally, I postulate that the luss of alpha stimulation to the vesical neck partially explains the postoperative decrease in intraurethral pressure and contributes to the observed incidence of p(lstoperative stress incontinence. This hypothesis is compatible with the observed cystometric findings. It is also compatible with the lower incidence of vesical hypertonia which occurred in patients who had incomplete transection of the cardinal ligaments. The return to a normal bladder pressure profile did not occur in some patients until several months after radical hysterectomy. and an explanation of hypertonus based solely upon perivesical edema and hematoma forma ilion could not explain thts duration of hypertonic change. However, regeneration of injured nerves and autonomic adaptation could explain temporary hypertonia, with ultimate return to normaL To test this hypothesis in future studies, 1 plan to measure the effect of sympathomimetic and >} mpatholytic agents on postoperative urethral and vesu al tone.
2. Twombly, G. H., and Landers, D.: The innervation of the bladder with reference to radical hysterectomy. AM. J 0BSTET. GYNECOL. 71:1291, 1956 . 3. Lewington, Vl.: Disturbances of micturition following
382 Forney
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Wertheim hysterectomy,]. Obstet. Gynaecol. Br. 63:861, 1956. Green, T. H., Jr., Meigs, J. V., Ulfelder, H., et al.: Urologic complications of radical Wertheim hysterectomy: Incidence, etiology, management, and prevention, Obstet. Gynecol. 20:293, 1962. Symmonds, R. E.: rvforbidi~y and complications of radical hysterectomy with pelvic lymph node dissection, AM. J. 0BSTET. GYNECOL. 94:663, 1966. Fraser, A. C.: The late effects of Wertheim's hysterectomy on the urinary tract, J. Obstet. Gynaecol. Br. Commonw. 73:1002, 1966. Glahn, B. E.: The neurogenic factor in vesical dysfunction following radical hysterectomy for carcinoma of the cervix, Scand. J. Urol. Nephrol. 4:107, 1970. Palm, L., and Folke, R.: Bladder function following either radiotherapy or radical operation ad modum Okabayashi for cervical cancer, Dan. Med. Bull. 17:113, 1970. Barclay, D. L., and Roman-Lopez,]. J.: Bladder dysfunction after Schauta hysterectomy, AM. J. 0BSTET. GYNECOL. 123:519, 1975. Seski,J. C., and Diokno, A. C.: Bladder dysfunction after radical abdominal hysterectomy, AM. J. 0BSTET. GYNECOL. 128:643, 1977. Meigs, J. V.: Radical hysterectomy with bilateral dissection of the pelvic lymph nodes. 2. The method of Joe V. Meigs, M.D., in Meigs,]. V., editor: Surgical treatment of cancer of the cervix, New York, 1954, Grune & Stratton, Inc., pp. 149-196. Robertson, J. R.: Gas cystometrogram with urethral pressure profile, Obstet. Gyneco!. 44:72, !974. Smith, P. H., and Ballantyne, B.: The neuroanatomical basis for denervation of the urinary bladder following major pelvic surgery, Br. J. Surg. 55:62, 1968. Lapides,]., Friend, C. R., Ajemian, E. P., et al.: Denervation supersensitivity as a test for neurogenic bladder, Surg. Gynecol. Obstet. 114:241, 1962. Fraser, A. C.: Cystometry after Wertheim's hysterectomy, J. Obstet. Gynaecol. Br. Commonw. 74:746, 1967. Richter, K., and Albrich, W.: Zur Frage der postoperativen Harnverhaltung nach erweiterter total extirpation wegen carcinoma co IIi uteri, Zbl. Gyniikol. 73: 1103, 1951. Roman-Lopez, J. J. and Barclay, D. L.: Bladder dysfunction following Schauta hysterectomy, AM. ]. 0BSTET. GYNECOL. 115:81, 1973.
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18. Yousseff, A. F.: Cystometric studies in gynemlo)!;Y ;md obstetrics, Obstet. Gynecol. 8:81. 1956. 19. El-Badawi, A., and Schenk, E. A.: Dual innervation of the mammalian urinary b!addeL A histochemical study o! the distribution of cholinergic and adrenergic nt>rves. ;\ m . .J. Anat. 119:405, 1966. 20. El-Badawi, A., and Schenk, E. A .. A new theurv ui the innervation of bladder musculature. Part I. Morplwlog' of the intrinsic vesical innervation apparatus, J l'rol. 99:585, 1968. 21. Boyarsky, S., Labay, P., Gregg. R., et al.: Pharmacologic studies of the nature of the sympathetic nerves of the urinary bladder, Paraplegia 6:136, 1968. 22. Malin, J. M., Jr., and Boyarsky, S.: The eHects of cholinergic and adrenergic drug stimulation of detrmor muscle, Invest. Urol. 8:286, 1970. 23. El-Badawi, A., and Schenk, E. A.: A new theory of the innervation of bladder musculature. Part 4. Innervation of the vesicourethral junction and external nrt>thral sphincter,]. Urol. 111:613, 1974. 24. Bradley, W. E., and Timm, G. W.: Physiology of micturition, Vet. Clin. North Am. 4:487, 1974. 25. Khanna, 0. P.: Disorders of micturition. ~~europhanna cologic basis and results of drug therapv. Urologv 8::) 16, 1976. 26. Ostergard, D. R.: The neurological control of micturition and integral voiding reflexes, Obstet. Gynecol. Surv. 34:417, 1979. 27. Edvardsen, P., and Setekleiv, J.: Distribution of adrenergic receptors in the urinary bladder of cats, rabbits and guinea pigs, A.cta Pharmacol. Toxico!. 26:437, 1968. 28. Gregg, R. A., Boyarsky, S., Labay, P .. et al.: Presence of beta-adrenergic receptors in urinary bladder of dog and cat: Response to isoproterenol, Arch. Phys. Med. Rehabil. 51:88, 1970. 29. Nergardh, A.: Autonomic receptor functions in lower urinary tract. Survey of recent experimental results, .J. Urol. 113:180, 1975. 30. Rohner, T. J., Raezer, D. M., Weiss, A. J., et al.: Contractile responses of dog bladder neck muscle to adrenergic drugs,]. Ural. 105:657, 1971. 31. Tang, P. C., and Ruch, T. C.: Non-neurogenic basis of bladder tonus, Am. J. Physiol. 181:249, 1955.