Subtotal versus total abdominal hysterectomy

Transcription

Research
ajog.org
GYNECOLOGY
Subtotal versus total abdominal hysterectomy:
randomized clinical trial with 14-year
questionnaire follow-up
Lea Laird Andersen, MD; Bent Ottesen, MD, DMSc; Lars Mikael Alling Møller, MD, PhD;
Christian Gluud, MD, DMSc; Ann Tabor, MD, DMSc; Vibeke Zobbe, MD; Elise Hoffmann, MD;
Helga Margrethe Gimbel, MD, DMSc; for the Danish Hysterectomy Trial Group
OBJECTIVE: The objective of the study was to compare long-term
results of subtotal vs total abdominal hysterectomy for benign uterine diseases 14 years after hysterectomy, with urinary incontinence as
the primary outcome measure.
STUDY DESIGN: This was a long-term follow-up of a multicenter,
randomized clinical trial without blinding. Eleven gynecological
departments in Denmark contributed participants to the trial.
Women referred for benign uterine diseases who did not have
contraindications to subtotal abdominal hysterectomy were
randomized to subtotal (n ¼ 161) vs total (n ¼ 158) abdominal
hysterectomy. All women enrolled in the trial from 1996 to
2000 who were still alive and living in Denmark (n ¼ 304)
were invited to answer the validated questionnaire used in prior
1 and 5 year follow-ups. Hospital contacts possibly related to
hysterectomy from 5 to 14 years postoperatively were registered from discharge summaries from all public hospitals in
Denmark. The results were analyzed as intention to treat and
per protocol. Possible bias caused by missing data was
handled by multiple imputation. The primary outcome
was urinary incontinence; the secondary outcomes were pelvic
organ prolapse, constipation, pain, sexuality, quality of life
(Short Form-36 questionnaire), hospital contacts, and vaginal
bleeding.
RESULTS: The questionnaire was answered by 197 of 304 women
(64.8%) (subtotal hysterectomy [n ¼ 97] [63.4%]; total hysterectomy
[n ¼ 100] [66.2%]). Mean follow-up time was 14 years and mean age
at follow-up was 60.1 years. After subtotal abdominal hysterectomy,
32 of 97 women (33%) complained of urinary incontinence compared
with 20 of 100 women (20%) after total abdominal hysterectomy 14
years after hysterectomy (relative risk, 1.67; 95% confidence interval,
1.02e2.70; P ¼ .035). After a multiple imputation analysis, this
difference disappeared (relative risk, 1.36; 95% confidence interval,
0.86e2.13; P ¼ .19). No differences were seen in any of the secondary outcomes.
CONCLUSION: Subtotal abdominal hysterectomy was not superior to
total abdominal hysterectomy on any outcomes. More women seem to
have subjective urinary incontinence 14 years after subtotal abdominal
hysterectomy. This result was not confirmed by multiple imputation
analysis and should be interpreted cautiously.
Key words: hysterectomy, long-term follow-up, pelvic organ prolapse,
quality of life, urinary incontinence
Cite this article as: Andersen LL, Ottesen B, Alling Møller LM, et al. Subtotal versus total abdominal hysterectomy: randomized clinical trial with 14-year questionnaire
follow-up. Am J Obstet Gynecol 2015;212:758.e1-54.
From the Department of Obstetrics and Gynecology, Nykøbing Falster Hospital, Nykøbing Falster in
association with the University of Southern Denmark (Drs Andersen and Gimbel); Juliane Marie
Center (Dr Ottesen), Department of Obstetrics and Gynecology (Drs Zobbe and Tabor), and
Copenhagen Trial Unit, Center for Clinical Intervention Research (Dr Gluud), Rigshospitalet,
Copenhagen University Hospital, Copenhagen; and Department of Obstetrics and Gynecology,
Roskilde Hospital, Roskilde (Drs Alling Møller and Hoffmann), Denmark.
Received Sept. 9, 2014; revised Nov. 14, 2014; accepted Dec. 17, 2014.
This long-term follow-up study was supported by the research foundation of Region Sjælland,
University of Southern Denmark, and the Department of Gynecology, Nykøbing Falster Hospital,
Rigshospitalet (Copenhagen University Hospital), and Roskilde Hospital, Denmark.
B.O. and H.M.G. are members of the board of the Danish Hysterectomy and Hysteroscopy
Database. The other authors report no conflict of interest.
Presented in oral format at the 39th biannual meeting of the Nordic Federation of Societies of
Obstetrics and Gynecology, Stockholm, Sweden, June 10-12, 2014, and as a poster at the 7th
annual congress of Leading Lights in Urogynecology, European Urogynecological Association,
Athens, Greece, Oct. 2-4, 2014.
Corresponding author: L. L. Andersen, MD. [email protected]
0002-9378/$36.00 ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2014.12.039
758.e1 American Journal of Obstetrics & Gynecology JUNE 2015
A
pproximately 4500 benign hysterectomies are performed yearly in
Denmark.1 Although the use of the less
invasive laparoscopic mode of hysterectomy
is rising, 32% of Danish hysterectomies
in 2012 were abdominal,2 and more than
50% of hysterectomies in the United
States were abdominal in 2010.3
Of abdominal hysterectomies, 10%
were subtotal, and of laparoscopic hysterectomies, 20% were subtotal in
Denmark in 2011.1 In some hospitals in
Germany, subtotal laparoscopic hysterectomy is the standard and accounts for
more than 80% of laparoscopic hysterectomies.4 The background for preferring subtotal hysterectomy is that it is
simpler and quicker and may result in
Gynecology
ajog.org
fewer complications.5 However, morcellation is part of this mode of hysterectomy, and because leiomyosarcomas
are sometimes mistaken for fibromas,
morcellation is no longer recommended
by the Food and Drug Administration6;
consequently, one may assume, in the
future, large uteri will more often be
removed by abdominal hysterectomy.
Studies in the 1980s7-9 suggested that
subtotal abdominal hysterectomy (SAH)
was superior to total abdominal hysterectomy (TAH) regarding sexual function. This finding was not reproduced in
randomized clinical trials (RCTs).10-12
The risk of cervical cancer in the
remaining cervix is another important
issue. Nevertheless, if a Papanicolaou
smear is normal prior to surgery and the
woman continues to participate in cervical cancer screening, the risk of cervical
cancer is only approximately 0.03%.14,15
Three RCTs comparable with our
Danish trial15,16 comparing SAH with
TAH16-18 have performed long-term
follow-up and found no significant differences between SAH and TAH on
clinical outcomes. Few data on longterm outcomes after subtotal vs total
laparoscopic hysterectomy are available.19 Although open abdominal and
laparoscopic surgery differ in many
ways, the most recent Cochrane systematic review20 on the topic included
both methods and stated that there was
no evidence to support the shift toward
subtotal hysterectomy seen in laparoscopy. The authors of the review conclude
that more long-term follow-up is needed
because urogenital problems may occur
years after surgery, especially in postmenopausal women.20
We aimed to compare 14-year outcomes after SAH vs TAH in women
included in a randomized clinical trial
for benign uterine diseases.14,15 The
primary outcome is urinary incontinence (UI) 14 years after hysterectomy.
M ATERIALS
AND
M ETHODS
In 1996e2000, 319 women from 11 gynecological departments in Denmark
were randomized to SAH vs TAH.14
Details about eligibility criteria, consent, inclusion, randomization, and surgical procedures have been published.14
The sample size of the original trial
was calculated based on an assumed
prevalence of the primary outcome,
UI, 1 year after TAH of approximately
23%.21,22 With a power of 0.80, a
type I error of 5%, and a 15% absolute difference in UI between the
surgical groups, 160 participants had
to be included in each intervention
group.14
Results from 1 year of follow-up14
showed that significantly more women
in the SAH group were urinary incontinent compared with the TAH group. A
decrease in UI after hysterectomy was
seen in both surgical groups. The secondary outcomes postoperative complications, quality of life (Short Form-36
[SF-36]), constipation, pelvic organ
prolapse, satisfaction with sexual life,
and pelvic pain did not show any difference between surgical groups. Neither
did the further analyses of lower urinary
tract symptoms23 and sexuality.13 At 1
year, 20% of the SAH group still experienced vaginal bleeding. At 5 years,15
the significant difference between SAH
and TAH regarding UI was reproduced.
The number of incontinent women was
higher than at 1 year. In the SAH group,
11% still experienced vaginal bleeding.
All participants still alive and living in
Denmark in September 2012 were contacted by letter, and it contained the
validated questionnaire24 (Appendix;
Supplemental Material) used in prior
follow-ups.14,15 The questionnaire
assessed primary and secondary outcomes (presented in the following text).
Reminders were sent 2 and 7 months
later to nonresponders. Participants
were encouraged to return the questionnaire unanswered if they did not
wish to participate, thus avoiding reminders. Age at follow-up and follow-up
time was calculated with January 2013 as
the cutoff point.
The primary outcome, UI, was
defined as a subjective complaint of
involuntary loss of urine often or
always (question 35 in the questionnaire). Because this result could reflect a difference in treatment-seeking
behavior between surgical groups
rather than in the occurrence of UI,
we also analyzed the number of
Research
women who reported UI at any time
since hysterectomy including prior
follow-ups.14,15
Secondary outcomes were hospital
contacts, pelvic organ prolapse (POP),
pelvic pain, satisfaction with sex life,
constipation, quality of life (QoL), and
vaginal bleeding after SAH. All outcomes, except QoL, were dichotomized,
and the SAH and TAH groups were
compared using a c2 test. Analyses were
conducted as intention to treat as well as
per protocol excluding participants that
did not receive the allocated intervention
(Figure 1). As in prior follow-ups,14,15
the conclusions are based on the
intention-to-treat analyses. Additionally,
satisfaction with sex life was analyzed
separately for those stating they had a
partner and those who did not.
QoL was assessed by the validated SF36 questionnaire25 included in our
questionnaire (Supplemental Material).
SF-36 was scored according to the specifications by Quality Metric using the
official scoring software. For each
participant a physical component score
(PCS) and a mental component score
(MCS) were calculated. These scores are
validated and a norms based mean of 50
is interpreted as average QoL. Means
were compared between surgical groups
using the Wilcoxon rank sum test
because the scores were not normally
distributed.
Some women did not answer all
questions resulting in different totals for
each analysis. The number in each group
for the particular analysis is stated in
Table 1. To account for possible bias
caused by missing data because of the
loss to follow-up and incomplete questionnaires, multiple imputation (MI)
was carried out using the FCS method in
SAS (version 9.3; SAS Institute, Cary,
NC) using the PROC MI and MIANALYZE functions. The 14-year outcomes
imputed were UI, pelvic pain, POP,
satisfaction with sex life, QoL, and
constipation.
The following variables were included
in the imputation model because they
were associated with (P < .1) one or
more of the outcomes in the multivariate
logistic regression: baseline variables included type of surgery, number of
JUNE 2015 American Journal of Obstetrics & Gynecology
758.e2
Research
Gynecology
ajog.org
FIGURE 1
Flowchart of participants
The figure shows participants at each stage of the trial from randomization through all follow-ups and
reasons for dropouts.
SAH, subtotal abdominal hysterectomy; TAH, total abdominal hysterectomy.
Andersen. SAH vs TAH, RCT with 14 year follow-up. Am J Obstet Gynecol 2015.
deliveries, largest baby greater than 4000
g, smoking more than 5 cigarettes per
day, alcohol consumption greater than
14 units per week (1 unit ¼ 12 g of
alcohol), UI, pain, and constipation.
Follow-up variables included were as
follows: UI, pelvic pain, POP, constipation, satisfaction with sex life at 1
and 5 years, and physical (PCS) and
mental (MCS) QoL scores at 1 year.
One hundred imputed datasets were
created using a maximum of 100 iterations. This was chosen to obtain high
precision in the analyses. The MI
method assumes that missingness is
missing at random, meaning that
missing data are related to other
observed variables but not to unobserved variables or to the missing
items.26 The imputed datasets were
analyzed by a c2 test, and the pooled
analyses were carried out using the
MIANALYZE function (SAS Institute).
Relative risks were logarithmically
transformed before pooling to comply
with Rubin’s rules for pooling imputed
results.27 The QoL scores were not normally distributed, and despite using the
transformations of inverse, log, squared,
gamma, exponential, box cox, and beta,
we could not approximate the normality.
We entered the untransformed scores in
the MI model and analyzed them using
the Wilcoxon rank sum test. Because a
normal distribution is assumed in MI,
this could potentially skew other outcomes. However, we ran the MI with and
without QoL included, and it had no
impact on other outcomes.
Hospital contacts were registered for
all randomized women by looking up all
discharge summaries from Danish public hospitals from 5 years postoperatively
until July 2013 in the central registry of
discharge summaries. Any hospital
contact regarding abdominal, gynecological, urological (including UI), plastic
surgical, or dermatological complaints
were scrutinized. If the contact might be
related to the prior hysterectomy, it was
registered. Hospital contacts from the
time of surgery until 5 years postoperatively have been published elsewhere.14,15 Hospital contacts were
divided into the following categories:
recurrent urinary tract infection
(including pyelonephritis), pain, UI,
POP, cervical problems (bleeding or
dysplasia), other urogenital, skin problems/hernias, and others.
All data were handled and analyzed
using SASjmp version 10 statistical
software (SAS Institute) except for MI,
which was carried out in SAS version 9.3
(SAS Institute).
The original trial as well as this followup was accepted by the regional ethics
committee journal number, SJ-268, as
well as the Danish Data Protection
Agency journal number 2012-41-0286.
R ESULTS
We contacted 304 women (95.3%)
(SAH: 153; TAH: 151); 10 (3.1%) had
died, from causes unrelated to hysterectomy, and 5 (1.6%) had left Denmark.
Two hundred forty-nine women (82%)
returned the questionnaire; however, 52
(17.1%) returned it blank stating that
they did not wish to participate. A total
of 197 (64.8%) answered the questionnaire (Figure 1).
Gynecology
ajog.org
Research
TABLE 1
Primary and secondary outcome measures at 14 year follow-up intention-to-treat
Outcome
(n [ SAH/TAH)
Observed data
SAH
TAH
RR
95% CI
Multiple imputation
P value RR
95% CI
P value
UI, % (n ¼ 96/100)
32 (33.3)
20 (20)
1.67 1.02e2.70 .035
1.36
0.86e2.13
.19
Constipation, %
(n ¼ 97/100)
14 (14.4)
7 (7)
2.06 0.87e4.89 .091
1.77
0.83e3.77
.14
Pelvic organ prolapse,
% (n ¼ 93/97)
12 (12.9)
11 (11.3)
1.14 0.53e2.45 .74
0.97
0.50e1.86
.92
Satisfied with
sexual life, %
(n ¼ 75/78)
48 (64)
53 (67.9)
0.94 0.75e1.18 .61
1.09
0.76e1.58
.64
Pelvic pain, %
(n ¼ 96/100)
14 (14.6)
10 (10)
1.46 0.68e3.12 .33
1.33
0.69e2.55
.40
Vaginal bleeding, %
(SAH only, n ¼ 97)
a
0
QoLb
Mean (95% CI)
SAH
Mean (95% CI)
TAH
PCS mean (95% CI)
50.4 (48.5e52.4) 51.3 (49.4e53.2)
.54
50.05 (48.5e51.6) 50.9 (49.1e52.8) .67
MCS mean (95% CI)
54.8 (52.9e56.7) 53.2 (51.4e55.1)
.39
54.4 (52.5e56.1)
52.2 (50.7e54.2) .87
CI, confidence interval; MCS, mental component score; PCS, physical component score; QoL, quality of life; RR, relative risk; SAH, subtotal abdominal hysterectomy; TAH, total abdominal hysterectomy; UI, urinary incontinence.
a
Statistically significant; b Wilcoxon rank sum test.
The number of participants in the
groups was similar: 97 of 153 (63.4%) in
the SAH group and 100 of 151 (66.2%)
in the TAH group. Characteristics of the
participants and nonparticipants in this
follow-up (Table 2) did not differ according to baseline variables from time
of surgery except that fewer of the participants were smokers at the time of
surgery and more participants had an
alcohol consumption greater than 14
units per week at time of surgery than
the nonparticipants. The 2 surgical
groups of responders were comparable
(Table 2). Mean age at follow-up was
60.1 years; mean follow-up time was 14.1
years.
More women in the SAH group (32 of
97, 33.3%) than in the TAH group (20 of
100, 20%) reported UI often or always
(P ¼ .035) (Table 1). The difference was
also significant in the per-protocol
analysis (P ¼ .024) (Table 3). Table 3
also shows the other analyses of UI as
described in the Materials and Methods
section.
Analysis of multiple imputed data
showed no significant differences between surgical groups regarding UI
(P ¼ .19) (Table 1).
Neither the physical (PCS) nor the
mental (MCS) score of the SF-36 QoL
questionnaire differed between the surgical groups, and the means were
consistent with the expected mean of 50
(Table 1). None of the participants
experienced vaginal bleeding at 14 years.
Twenty-one women (11.5%) stated
they did not have a partner. Of these, 9
(42.9%) stated that they did not know
whether they were satisfied with their sex
life. Six (28.6%) stated they were satisfied and 6 (28.6%) stated they were not.
Among those with a partner (n ¼ 162,
88.5%), 22 (13.6%) did not know
whether they were satisfied with their sex
life, 94 (58%) were satisfied, and 46
(28.4%) were not. Those who stated they
did not know whether they were satisfied
were excluded from the analysis of
satisfaction with sex life in the 2 surgical
groups (Table 1). There was no
difference in satisfaction with sex life
between SAH and TAH overall (Table 1)
or when subdivided according to partner
status (data not shown). The other secondary outcomes are shown in Table 1.
None of them showed significant differences between surgical groups in the
analysis of observed data or in multiple
imputation.
Hospital contacts from 5 to 14 years
after hysterectomy are shown in Figure 2.
There was no significant difference in the
total number of hospital contacts (SAH,
29 [17.7%] vs TAH, 18 [11.3%]; relative
risk, 1.57; 95% confidence interval,
0.91e2.71; P ¼ .10).
C OMMENT
On observed data, we found that more
women had UI after SAH than after
TAH 14 years after surgery. This is
consistent with prior results from our
trial.14,15 At 14 years, the percentage of
UI in the TAH group has reached
approximately the prehysterectomy
level, whereas the percentage in the SAH
758.e4
Research
Gynecology
ajog.org
TABLE 2
Characteristics for responders and nonresponders as well as the responders divided into surgical groups
Participants
(n [ 197)
Characteristic
Nonparticipants
(n [ 122)
P value
SAH participants
(n [ 97)
TAH participants
(n [ 100)
Age, y (SD)
60.1 (5.8)
60.5 (6.6)
.58
60.7 (5.9)
59.6 (5.6)
Follow-up time, y (range)
14.1 (12e16)
14.04 (12e16)
.77
14.2 (12e16)
14.03 (12e16)
1.8 (0e5)
1.74 (0e5)
.58
1.85 (0e5)
1.76 (0e4)
Parity (range)
2
BMI, kg/m (SD)
a
26.1 (6.7)
25.5 (4.6)
.38
26.45 (7.1)
25.71 (6.3)
115 (58.4)
70 (57.4)
.86
58 (59.8)
57 (57.0)
63 (31.9)
42 (34.7)
.59
29 (29.9)
34 (33.6)
Dysmenorrhea
8 (4.1)
4 (3.31)
.74
3 (3.1)
5 (4.9)
Pelvic pain
9 (4.6)
4 (3.31)
.58
6 (6.2)
3 (2.9)
Endometriosis
0
1 (0.83)
.16
0
Other
2 (1.02)
1 (0.83)
.87
1 (1.03)
1 (0.99)
SAH
97 (49.2)
64 (52.5)
.58
TAH
100 (50.8)
58 (47.5)
.58
Smoking >5 cigarettes
per day, %b
46 (23.4)
57 (46.7)
< .0001
18 (18.6)
28 (28.0)
Alcohol >14 units
per week , %b,c
22 (11.2)
6 (4.9)
.047
13 (13.4)
9 (9.0)
Chronic disease, %d
97 (49.2)
25 (29.4)
.0018
49 (50.5)
48 (48.5)
Preoperative UI, %
48 (25.0%) (n ¼ 192)
20 (17.4%) (n ¼ 115)
.110
26 (27.7%) (n ¼ 94)
22 (22.2%) (n ¼ 99)
Indication for hysterectomy, %
Fibroids
Abnormal uterine bleeding
0
Type of surgery, %
BMI, body mass index; SAH, subtotal abdominal hysterectomy; TAH, total abdominal hysterectomy; UI, urinary incontinence.
a
BMI at follow-up for participants but baseline for nonparticipants; b At time of surgery; c A unit of alcohol, in Denmark, is defined as 12 g of alcohol, which is the approximate content of a normal
beer or a glass of wine; d At 14 year follow-up for participants and at 1 year for nonparticipants.
group is now higher.14 However, the MI
analysis did not show a significant difference. No significant differences were
found between SAH and TAH on the
secondary outcomes.
The strengths of the present results are
that they represent the largest randomized clinical trial on the topic and have
the longest follow-up time. The Danish
social security number enabled us to
locate all participants and look up hospital contacts for everyone.
One limitation of this follow-up is the
low response, which might compromise
the external validity of the trial. Nonresponders might differ in a systematic
way from responders, meaning that our
sample at follow-up is less representative
of the population than the original trial
sample. Other than smoking and alcohol
consumption at the time of surgery, our
baseline data do not suggest systematic
differences. The internal validity could
be compromised if an imbalance was
seen in responders between intervention
groups. However, the responders in the 2
surgical groups are comparable according to baseline characteristics.
None of the reasons given for not
participating were related to the hysterectomy method. Explanations of our low
response could be the loss of interest
because of the long follow-up, older age,
or medical conditions making it overwhelming to be asked to participate. In
addition, according to the ethics committee, we were allowed to contact participants by letter only. Contact by
telephone was allowed in earlier followups14,15 as well as in a comparable trial.16
We used MI to handle missing data.
This analysis showed no significant
difference regarding UI or any other
outcomes. This might reflect that there
truly is no difference, and our observed
finding may be caused by attrition bias.
Alternatively, the uncertainty incorporated in MI (within imputation variance
and between imputation variance)26 increases with the percentage of missing
data and yields wider confidence intervals
leading to nonsignificant results. A third
explanation of the difference between our
observed and MI results could be an
unknown confounding factor related to
missingness as well as UI, meaning that
our assumption of missing at random is
incorrect, and the data are truly missing
not at random. In this case, the MI
analysis is not valid.26 Our observed
findings correspond well with prior
follow-ups of this trial with higher
response proportions.14,15 The relative
Gynecology
ajog.org
FIGURE 2
TABLE 3
Hospital contacts from 5 to 14
years after hysterectomy
Analyses of urinary incontinence
Urinary incontinence
(n [ SAH/TAH)
SAH (%)
TAH (%)
RR
95% CI
P value
Questionnaire only (n ¼ 97/100)
32 (33.3)
20 (20)
1.67
1.02e2.70
.035a
Questionnaire or prior treatment
for UI according to discharge
summaries (n ¼ 97/100)
34 (35.4%)
23 (23%)
1.54
0.98e2.41
.056
Questionnaire at any time point
(all participants in RCT)
(n ¼ 161/158)
67 (41.6%)
49 (31%)
1.34
1.0e1.80
.049a
Questionnaire at any time point
(only those who answered 14 year
follow-up) (n ¼ 96/100)
45 (46.9%)
31 (31%)
1.51
1.05e2.17
.023a
Per protocol (n ¼ 84/88)
29 (34.5)
17 (19.3)
1.78
1.06e3.00
.024a
CI, confidence interval; RCT, randomized controlled trial; RR, relative risk; SAH, subtotal abdominal hysterectomy; TAH, total
abdominal hysterectomy; UI, urinary incontinence.
a
Research
Statistically significant.
Bar chart of hospital contacts possibly related to
the prior hysterectomy. Contacts are divided into
categories and are shown for each hysterectomy
group separately.
UTI, urinary tract infection.
Andersen. SAH vs TAH, RCT with 14 year follow-up. Am J
Obstet Gynecol 2015.
risk found in MI for UI is the same as it
was in the 5 year follow-up15; however, in
that analysis the value was P ¼.052, much
closer to a statistically significant result.
This could reflect the increased uncertainty because of the higher percentage of
missing data as explained above.
Another limitation of the trial is the
lack of blinding. This has been discussed
in prior follow-ups.14,15
Long-term follow-up of SAH vs TAH
has been completed in 3 other RCTs.16-18
The longest follow-up was 11.3 years,18
with a mean age of 57 years. These trials
found no significant differences in the
outcomes studied. Persson et al18 saw a
tendency toward worse outcomes after
SAH than after TAH and concluded that
this might have been significant if the
study had sufficient power or longer
follow-up. Our trial is larger and has
longer follow-up, and we found a significant difference in UI. We also looked at
the number of incontinent women at any
time point to see whether the difference
found at 14 years was a difference in
occurrence of UI or a difference in
treatment-seeking behavior between surgical groups. This analysis also showed
significantly more women with UI in the
SAH group than the TAH group.
The comparable trials also had
missing data. Thakar et al17 had a
response of 65% (n ¼ 181), Persson
et al18 a response of 82% (n ¼ 151), and
Greer et al16 a response of 27.4% (n ¼
37). Our response of 64.8% (n ¼ 197) is
comparable with these. None of the other
long-term follow-ups16-18 included MI
or other ways of handling missing data,
meaning that possible attrition bias was
not elucidated in these trials. A metaanalysis including all long-term RCTs
and taking attrition bias into account
would be of great interest.
Our trial included white women only,
and therefore, our results cannot be
readily transferred to populations of
mixed ethnicity. The prevalence of UI
differs between ethnic groups; stress UI
is less common in women of African
descent.28,29 This could explain the difference between our results and those of
Thakar et al17; their population was
mixed and one third of the population
was of African descent.
One theory to explain our finding of
more UI in the SAH group is that the
method of suspension of the vagina used
in SAH and TAH might differ; no instructions regarding suspension were
given to the surgeons. The suspension
performed in TAH might yield more
support than the woman’s own connective
tissue, spared in SAH, which might lead to
stress UI in the SAH group. A further
investigation of how suspension is performed might elucidate this.
Like comparable trials,16-18 we found
no difference in QoL between surgical
groups. QoL scores were similar to our 1
year follow-up.14 QoL is important when
treating benign diseases, and a stable
score after 14 years is a good outcome for
the participants.
Up to 14 years after hysterectomy, we
still saw hospital contacts possibly
related to hysterectomy. We found a
nonsignificant tendency toward more
hospital contacts in the SAH group. No
other long-term follow-ups16-18 have
looked at this outcome.
None of the women had vaginal
bleeding at 14 years. At 5 years,15 11% of
the women in the SAH group experienced vaginal bleeding. Natural menopause is the main reason for the
difference in results from 5 to 14 years.
Only one woman had her cervix
removed since last follow-up, and this is
included in the cervical problems category in Figure 2.
Other outcomes might be important
after laparoscopic hysterectomy such as
vaginal dehiscence in total laparoscopic
hysterectomy and leiomyosarcomas and
other complications to morcellation after subtotal laparoscopic hysterectomy.
RCTs with long-term follow-up are
needed to compare subtotal vs total
758.e6
Research
Gynecology
laparoscopic hysterectomy to shed light
on these outcomes unless the subtotal
approach is stopped because of morcellation issues.6 The percentage of hysterectomies performed abdominally has
been declining.1,2 The recent discussion
of morcellation6 could mean a return to
abdominal hysterectomy for large uteri
and an increase in vaginal hysterectomy
for smaller uteri.
In conclusion, on observed data, more
women were urinary incontinent after
SAH compared with TAH; however, this
result must be interpreted cautiously
because of a high loss to follow-up. A
metaanalysis of all long-term follow-ups
might elucidate this topic. The shift toward subtotal hysterectomy in laparoscopy might not be of long-term benefit
to the patients, if the results from
abdominal hysterectomy can be directly
transferred to laparoscopy.
ACKNOWLEDGMENTS
We thank Jakob Hjort for his generation of the
allocation sequence and excellent management
of the randomization procedure and program;
Kasper Munck (SAS Institute) for statistical
advice and help with the multiple imputation; and
Per Winkel (Copenhagen Trial Unit) for advice
about multiple imputation. The remaining members of the Danish Hysterectomy Trial Group are
provided with the full-length article at ajog.org.
This study was registered at ClinicalTrials.gov
with the identifier number of NCT01880710.
The trial is registered on clinicaltrials.gov under
Nykoebing Falster County Hospital Record
sj-268: Total versus subtotal hysterectomy: http://
clinicaltrials.gov/ct2/show/NCT01880710?term¼
hysterectomy&rank¼27. The Hysterectomy Trial
Group consists of the authors and of the
following members: Kristian Jakobsen, MD,
Helle Christina Sørensen, MD, Kim ToftagerLarsen, MD, DMSc, Nini Møller, MD, Department
of Obstetrics and Gynecology, Nordsjællands
Hospital, Hillerød, Denmark; Ellen Merete Madsen, MD, Mogens Vejtorp, MD, DMSc, Helle
Clausen, MD, PhD, Department of Obstetrics
and Gynecology, Herlev University Hospital,
Herlev, Denmark. The authors’ contribution
included the following: H.M.G. designed and
was the principal investigator of the original trial,
created and validated the questionnaire,
recruited and randomized participants, and sent
out questionnaires for the prior follow-ups.
L.L.A. is responsible for sending out the 14
year questionnaires, handling the data and statistical analysis, and drafting and revising the
article. L.L.A. is the corresponding author. B.O.,
C.G., A.T., and V.Z. participated in the design
and conduct of the original trial as well as this
follow-up. L.M.A.M. and E.H. participated in the
ajog.org
design of the long-term follow-up with L.L.A. and
H.M.G. All of the authors critically revised the
article and approved the final manuscript. The
Danish Hysterectomy Trial Group participated in
recruiting and randomizing the participants. The
local ethics committees of the participating
centers (Bornholm, Frederiksborg, Roskilde,
Storstrøms, and Vestsjællands Counties, journal
number 1995-1-65) and the Danish Data Protection Agency had accepted the design of the
randomized clinical trial before the recruitment of
patients as well as the current follow-up. The
regional ethics committee in Region Sjaelland
accepted the design of the long-term follow-up
(journal number SJ-268).
REFERENCES
1. Dansk Hysterektomi Database. Danish hysterectomy database yearly report, 2011. Dansk
Hysterektomi Database; Oct. 1, 2012.
2. Danish Hysterectomy and Hysteroscopy
Database. National yearly report, 2012. 2013.
3. Wright JD, Herzog TJ, Tsui J, et al. Nationwide trends in the performance of inpatient
hysterectomy in the United States. Obstet
Gynecol 2013;122:233-41.
4. Wallwiener M, Taran FA, Rothmund R, et al.
Laparoscopic supracervical hysterectomy (LSH)
versus total laparoscopic hysterectomy (TLH):
an implementation study in 1,952 patients with
an analysis of risk factors for conversion to laparotomy and complications, and of procedurespecific re-operations. Arch Gynecol Obstet
2013;288:1329-39.
5. Sutton C. Past, present, and future of hysterectomy. J Minim Invasive Gynecol 2010;17:421-35.
6. Food and Drug Administration. Laparoscopic
uterine power morcellation in hysterectomy and
myomectomy. Silver Spring, MD: Food and
Drug Administration Safety Communication;
2014.
7. Kilkku P, Gronroos M, Hirvonen T,
Rauramo L. Supravaginal uterine amputation vs.
hysterectomy. Effects on libido and orgasm.
Acta Obstet Gynecol Scand 1983;62:147-52.
8. Kilkku P. Supravaginal uterine amputation vs.
hysterectomy. Effects on coital frequency and
dyspareunia. Acta Obstet Gynecol Scand
1983;62:141-5.
9. Kilkku P, Lehtinen V, Hirvonen T, Gronroos M.
Abdominal hysterectomy versus supravaginal
uterine amputation: psychic factors. Ann Chir
Gynaecol Suppl 1987;202:62-7.
10. Thakar R, Ayers S, Clarkson P, Stanton S,
Manyonda I. Outcomes after total versus subtotal abdominal hysterectomy. N Engl J Med
2002;347:1318-25.
11. Persson P, Brynhildsen J, Kjolhede P.
A 1-year follow up of psychological well-being
after subtotal and total hysterectomy—a randomised study. BJOG 2010;117:479-87.
12. Zobbe V, Gimbel H, Andersen BM, et al.
Sexuality after total vs. subtotal hysterectomy.
13. Jacoby VL. Hysterectomy controversies:
ovarian and cervical preservation. Clin Obstet
Gynecol 2014;57:95-105.
14. Gimbel H, Zobbe V, Andersen BM,
Filtenborg T, Gluud C, Tabor A. Randomised
controlled trial of total compared with subtotal
hysterectomy with one-year follow up results.
BJOG 2003;110:1088-98.
15. Andersen L, Zobbe V, Ottesen B, Gluud C,
Tabor A, Gimbel H. Five-year follow up of a
randomised controlled trial comparing subtotal
with total abdominal hysterectomy. BJOG 2014
[Epub ahead of print].
16. Greer WJ, Richter HE, Wheeler TL, et al.
Long-term outcomes of the Total or Supracervical Hysterectomy (TOSH) Trial. Female
Pelvic Med Reconstr Surg 2010;16:49-57.
17. Thakar R, Ayers S, Srivastava R,
Manyonda I. Removing the cervix at hysterectomy: an unnecessary intervention? Obstet
Gynecol 2008;112:1262-9.
18. Persson P, Brynhildsen J, Kjolhede P. Pelvic
organ prolapse after subtotal and total hysterectomy: a long-term follow-up of an open
randomised controlled multicentre study. BJOG
2013;120:1556-65.
19. Nesbitt-Hawes EM, Maley PE, Won HR,
et al. Laparoscopic subtotal hysterectomy: evidence and techniques. J Minim Invasive Gynecol
2013;20:424-34.
20. Lethaby A, Mukhopadhyay A, Naik R. Total
versus subtotal hysterectomy for benign
gynaecological conditions. Cochrane Database
Syst Rev 2012:CD004993.
21. Iosif CS, Bekassy Z, Rydhstrom H. Prevalence of urinary incontinence in middle-aged
women. Int J Gynaecol Obstet 1988;26:255-9.
22. Milsom I, Ekelund P, Molander U,
Arvidsson L, Areskoug B. The influence of age,
parity, oral contraception, hysterectomy and
menopause on the prevalence of urinary incontinence in women. J Urol 1993;149:1459-62.
23. Gimbel H, Zobbe V, Andersen BJ, et al.
Lower urinary tract symptoms after total and
subtotal hysterectomy: results of a randomized
controlled trial. Int Urogynecol J Pelvic Floor
Dysfunct 2005;16:257-62.
24. Gimbel H, Zobbe V, Ottesen BS, Tabor A.
Randomized clinical trial of total vs. subtotal
hysterectomy: validity of the trial questionnaire.
25. Bjorner JB, Thunedborg K, Kristensen TS,
Modvig J, Bech P. The Danish SF-36 Health
Survey: translation and preliminary validity
studies. J Clin Epidemiol 1998;51:991-9.
26. Schafer JL, Graham JW. Missing data: our
view of the state of the art. Psychol Methods
2002;7:147-77.
27. Ratitch B, Lipkovich I, O’Kelly M. Combining
analysis results from multiply imputed categorical data. PharmaSUG 2013;2013.
28. Graham CA, Mallett VT. Race as a predictor
of urinary incontinence and pelvic organ prolapse. Am J Obstet Gynecol 2001;185:116-20.
29. Thom DH, van den Eeden SK, Ragins AI, et al.
Differences in prevalence of urinary incontinence
by race/ethnicity. J Urol 2006;175:259-64.
ajog.org
Gynecology
Research
APPENDIX
Supplemental materials
758.e8
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e10
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e12
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e14
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e16
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e18
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e20
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e22
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e24
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e26
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e28
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e30
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e32
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e34
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e36
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e38
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e40
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e42
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e44
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e46
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e48
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e50
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e52
Research
Gynecology
ajog.org
ajog.org
Gynecology
Research
758.e54

Subtotal versus total abdominal hysterectomy

Transcription

Similar documents

Center for Women`s Health - University of Illinois College of Medicine

Center for Women`s Health - University of Illinois College of Medicine

AUGUST 6-8,2o1o FoNTAINEBLEAU HoTEL MIAMI BEACH, FLoRIDA

mcgraw-hillresidents.com

Los Olivos brochure - Los Olivos Women`s Medical Group

OBGYN Issue 9

Seija Grenman - The Nordic Federation of Societies of Obstetrics

Plisic, Ljiljana

informational flyer - Tufts University School of Medicine

a Copy of the Event Brochure