A. Pelvic floor dysfunction and its impact on quality of life in gynecological
1. Comparison of pelvic floor symptom with reference group
Table 2 displays the pelvic floor symptoms in gynecological cancer group and reference group. In the urinary symptoms, gynecological cancer patients showed significantly higher rate of urinary frequency, nocturia and stress incontinence. In bowel symptoms, gynecological cancer group showed significantly higher rate of straining, urgency and incomplete emptying stool than the reference group.
Gynecological cancer survivors were less likely to be sexually active than the reference group (38.2% vs 93.7%). The sexual symptom questions were provided individually to find the difference between the groups; the data are summarized in Table 3. Gynecological cancer survivors reported less sexual desire (libido), less vaginal lubrication during intercourse and more pain with intercourse.
Table 2-1. Pelvic floor dysfunction in gynecological cancer group and reference
Difficulty emptying bladder 12 (35.3) 3 (18.7) 0.068 Bowel function
Table 3. Sexual questionnaire item analysis
How would you describe your level of sexual interest during the past month (libido)?
None 13 2 How often do you have an orgasm?
3 Seldom 1 0.215
Do you have sufficient natural vaginal lubrication during intercourse?
0 Yes 4 13 0.022
1 No 9 2
Do you experience pain with intercourse?
0 Never 2 10 0.008
1 Occasionally 3 5
2 Frequently 5
3 Always 3
Is sexual intercourse enjoyable for you?
3 Not at all 5 3 0.09
2 Occasionally 8 5
1 Frequently 6
0 Always 1
2. Relation of pelvic floor symptoms with pelvic floor muscle strength and MEP Subsequently, we divided the gynecological cancer survivors in two subgroups according to whether the urinary incontinence or not: incontinence group and continence group and compared the pelvic floor strength and MEP. In incontinence group, pelvic floor muscle strength is significantly weaker than that in continence group (4.21 vs 19.53, P = 0.04). We obtained motor evoked responses in only five patients of incontinence group, but in twelve patients of continence gorup with all the stimulations (cord, cortical and sacral plexus, respectively). Two in incontinence group and six in continence group showed motor evoked potential with stimulation on only one side of sacral plexus and the potential could evoked with cortical stimulation at the same cases. The latency with cortical stimulation with facilitation in incontinence group was more delayed compared to that in the continence group, but not significantly (p=0.07) (Table 4). One in incontinence group showed no motor evoked potential by sacral stimulation and cortical stimulation at rest, but by cortical stimulation with facilitation, the potential was evoked (latency 19.60 ms, amplitude 0.50 mV, CET 100%). Interestingly, five of them had lymphedema at the same side where the potentials were not provoked. Other participants we could not evoked motor responses at any stimulation.
Table 4. Comparison of pelvic muscle strength between incontinence and continence group in gynecological cancer survivors
Incontinence group
(n=16)
Continence group
(n=18) P value
Pelvic muscle strength
Peak pressure (cmH2O) 4.21 ± 3.12 19.53 ± 14.32 0.04
Sacral stimulation
Latency 3.80 (2.95-4.35) 3.35 (2.80-3.70) 0.21
Amplitude 0.20 (0.10-0.30) 0.25(0.10-0.35) 0.53
Cortical stimulation at rest
Latency 22.05 (19.80-28.05) 21.20(18.00-24.20) 0.26
Amplitude 0.30 (0.10-0.40) 0.25 (0.10-0.40) 0.52
Threshold 85.00 (65.00-97.00) 80.00 (60.00-95.00) 0.42 Cortical stimulation at facilitation
Latency 20.15 (17.15-25.00) 18.00(16.80-20.25) 0.07
Amplitude 0.55 (0.20-0.75) 0.60 (0.20-0.80) 0.46
Threshold 75.00 (67.00-85.00) 70.00 (65.00-76.00) 0.24
0
3. Comparison of HRQOL outcomes with reference group
Clinically meaningful differences (10 points) were observed between gynecological
cancer patients and healthy controls in terms of physical functioning (71.7 vs 84.6), social functioning (79.2 vs 95.8) and global health status (52.6 vs 75.7) (Fig 2).
Fig 2. Mean functional scores of patients with gynecological cancer compared with reference group. A higher score represents a higher level of functioning or global health status/QOL. *Differences in health-related quality of life scores between groups were considered clinically relevant if 10 points
0
Fatigue Nausea/vomitting Pain Dyspnea Insomnia Appetite loss Constipation Diarrhea Financial difficulties As for symptom-related showed remarkably worse outcomes in terms of constipation (38.8 vs 8.3), diarrhea (33.3 vs 18.7) and financial difficulties (24.2 vs 4.2) (fig 3).
Fig 3. Mean symptom scores of patients with gynecological cancer compared with reference group. A higher score represents a higher perception of the symptom. *Differences in health-related quality of life scores between groups were considered clinically relevant if 10 points
4. Impact of pelvic floor dysfunction on cancer generic HRQOL outcomes (EORTC QLQ-C30)
There was a strong association between functional scales and bladder and bowel function-related covariates. Urinary urgency negatively affected physical functioning (p=0.003), role functioning (p=0.005) and social functioning (0=0.007) and urinary incontinence negatively associated with the global health status/QOL (p=0.021) and physical functioning (p=0.024). Difficulty emptying negatively affected the global health status/QOL (p=0.019) and social functioning (p=0.034). Incomplete evacuation was negatively associated with the physical functioning (p=0.007). Sexual inactivity negatively affected the global health status/QOL (p=0.021) (Table 5). No variables were associated with emotional functioning (data no shown).
Table 5. Relationship among generic (EORTC QLQ-C30) HRQOL outcomes and pelvic
EORTC European Organisation for Research and Treatment of Cancer, QOL Quality of life, HRQOL health-related quality of life
*Statistically significant difference (p<0.05)
B. Effectiveness of Pelvic Floor Rehabilitation Program for gynecological cancer survivor
There were no significant differences between exercise and control groups in any of the baseline characteristics (Table 6). No significant difference in the participants‟ ages was found between the intervention and control groups at baseline. The proportions of marriage, education level and employment status were not significantly different between the groups. A diagnosis of stage 1 disease had been made in 20% and 18.1%, and 10%
and 9.1% had undergone surgery without additional treatments respectively. Before beginning the exercise programs, pelvic floor strength measured by perineometer were 12.8 ±16.6 and 11.3 ± 9.9, No differences were found in the baseline latencies and amplitudes of pudendal motor nerve stimulating at cortical area, cord and sacral plexus among groups. We only obtained motor evoked responses in eight patients in exercise group and nine patients in control group at baseline assessment. Other participants we could not evoked motor responses with magnetic stimulation.
Table 6-1. Baseline comparative characteristics between the two groups in gynecological
Table 6-2. Baseline comparative pelvic floor function between the two groups in
Threshold 70.0 (65.0-77.5) 78.0 (71.3-100.0) 0.25
Cranial stimulation with facilitation
Latency 19.2 (18.3-22.2) 20.9 (20.1-24.8) 0.13
Amplitude 0.5 (0.2-0.7) 0.3 (0.1-0.4) 0.32
Threshold 65.0 (35.0-77.5) 70.0 (70.0-80.0) 0.22
Table 6-3. Baseline comparative quality of life between the two groups in gynecological
Emotional functioning 72.22 ± 14.43 65.15 ± 20.69 0.46
Cognitive functioning 79.63 ± 11.11 75.76 ± 15.57 0.71
Social functioning 87.04 ± 16.20 72.73 ± 23.89 0.21
Thirty-four participants who underwent the initial evaluation were randomly allocated into 2 groups: 17 subjects were assigned to the exercise group, and 17 to the control group. Before they began to do exercises, three women from exercise group and three women from control group failed to appear in the program session for personal reasons.
Two patients from the each group were dropped out during the intervention. Finally, 12 and 12 participants in the exercise and control groups, respectively, completed the interventions and the follow-up evaluations (Fig 4).
Gynecological cancer met
Fig 4 Flow chart of participants through the randomized controlled trial of the exercise program and analysis.
1. Changes in frequency of pelvic floor dysfunction
Stress incontinence was decreased from 64.3% to 33.3% after the intervention in the exercise group (p=0.036). Urinary urgency was decreased from 57.1% to 33.3% after the intervention in the exercise group (p=0.042). Flatus incontinence was decreased from 57.1 % at the baseline to 25.0 % after the intervention in the exercise group (p=0.033) and defecation urgency was decreased from 42.9% to 16.7% after the intervention in the exercise group (p=0.027). But these variables revealed no statistically changes between before and after the intervention in control group. The comparison of changes in prevalence of stress incontinence and flatus incontinence revealed significantly difference between the exercise and control group, but the changes of urinary and defecation urgency were not significantly different between the groups. (Table 7). The proportion of sexually active women increased from 41.7 % at the baseline to 75.0 % after intervention in the exercise group, whereas the change was not significant in the control group. The comparison of changes in prevalence of sexually active women revealed significantly difference between the exercise and control group.
Table 7. Difference of prevalence in pelvic floor dysfunction between exercise and
* P<0.05 between baseline and follow-up data in exercise group
2. Changes in pelvic muscle strength and MEP
Pelvic floor muscle strength significantly increased after the exercise programs (from 12.8 cmH2O to 31.5 cmH2O; p = .02). Compared with the control group, exercise group resulted in significantly increase in pelvic floor muscle strength (p=0.028) (Table 8)
The amplitude of pudendal nerve motor evoked potentials (MEPs) to sacral stimulation increased slightly (From 0.12 mV to 0.32 mV) and the excitability threshold to sacral stimulation significantly decreased after exercise program (From 93% to 67%), but these variables were not significantly changed in the control group. The comparison of changes in amplitude and threshold to sacral stimulation revealed significantly difference between the exercise and control group.
The resting excitability threshold at rest (RET) and contraction (CET) significantly decreased after the exercise program. The reductions in RET were 14.6% and 2.1% in the exercise and control group, respectively. CET decreased by 16.7% in the exercise group, which reflected statistically significant changes between before and after the intervention, but the change was not significantly different in the control group. The latency of MEPs to cortical stimulation with contraction of pelvic floor muscle in the exercise group decreased significantly after exercise (20.25 ms to 18.58 ms, P = 0.04). The changes of the latencies of MEP after muscle contraction from that at rest became significantly larger after exercise in the exercise group. The amplitude of MEPs to cortical stimulation with contraction of pelvic floor muscle in the exercise group increased significantly
(from 0.38 mV to 0.59 mV, P = 0.04), but the comparison of changes revealed no difference between the exercise and control group.
Table 8. Comparison of pelvic floor strength and motor evoked potential between exercise and control groups at baseline and after
Amplitude 0.32(0.12-0.67) 0.47(0.39-1.24) 0.41 0.25(0.11-0.52) 0.32 (0.21-0.68) 0.87 0.29 (-0.30-1.15) 0.10(-0.02-0.35) 0.25 Sacral stimulation
Latency 3.36(3.11-3.73) 3.43(3.18-3.49) 0.08 3.31(3.01-3.64) 3.43(3.31-3.62) 0.47 -0.63(-1.30-0.05) -0.63 (-7.35-0.10) 0.56 Amplitude 0.12(0.11-.0.18) 0.32(0.26-0.61) 0.02 0.11(0.12-0.21) 0.12(0.11-0.53) 0.66 0.25(0.15-0.55) 0.01(-0.10-0.12) 0.01
Threshold 93.03(86.00-97.00) 67.52(47.52-80) 0.03 85.00(75.0-100) 84.04(63.52-100) 0.29
Amplitude 0.21(0.14-0.57) 0.24(0.12-0.42) 0.12 0.22(0.14-0.32) 0.24(0.16-0.35) 0.79 0.03(-0.20-0.30) 0.02(-0.12-0.21) 0.88 Threshold 76.64(65.02-77.53) 59.71(50.02- 0.03 78.01(71.28-100.00) 76.12(53.02- 0.86 -14.57(-36.50- -2.02(-35.02- 0.03
65.02) 100.00) 25.00) 20.02) Cortical stimulation with facilitation
Latency 20.25(18.33-23.42)
18.58(17.15-21.03)
0.04 20.89(20.13-24.82)
20.00(17.72-22.11)
0.25
-1.73(-0.95~19.82)
-0.67(-20.45-1.95) 0.04
Amplitude 0.38(0.17-0.59) 0.59(0.52-1.01) 0.04 0.33(0.12-0.42) 0.42(0.13-0.45) 0.34 0.19(-0.30~0.70) 0.11(0.02-0.21) 0.47
Threshold 65.02(35.01-77.53)
50.02(40.02-67.52)
0.04 70.00(70.02-80.02) 65.02(50.51-92.45)
0.92 -16.67(-3.85-45.01)
-5.18(-70.02-3.02) 0.03
3. Changes in HRQOL outcomes
Clinical meaningful differences (10 points) (Salvatore P et al., 2009) were observed
between before and after intervention in the exercise group in terms of physical functioning, sexual worry, sexual activity and sexual/vaginal functioning (66.9 vs 80.3. P = 0.03; 42.3 vs 20.7 P = 0.04; 19.1 vs 30.5 P = 0.02; and 12.5 vs 27.1, P = 0.04 respectively). The comparison changes of these variables revealed significant difference between the exercise and control group. Improvements were found in QOL functional domains especially roll function and social function but difference to baseline did not reach significance (Fig 5 & 6).
0
Fig 5. Comparison changes of mean functional scores of exercise group compared with control group in EORTC QLQ C-30. A higher score represents a higher level of functioning or global health status/QOL *Differences in health-related quality of life scores between groups were considered clinically relevant if 10 points
0
Body Image Sexual worry Sexual activity Sexual/vaginal functioning
Body Image Sexual worry Sexual activity Sexual/vaginal functioning compared with control group in EORTC QLQ CX-24. A higher score represents a higher level of functioning or global health status/QOL (A and B) and higher symptom score represents a higher perception of the symptom (C and D) *Differences in health-related quality of life scores between groups were considered clinically relevant if 10 points
Ⅳ. DISCUSSION
This research examined the pelvic floor dysfunction and QoL issues in gynecological cancer survivors. The results of this study demonstrate that women with treatment of gynecological cancer have more pelvic floor dysfunction compared to the reference group. Nocturia and urinary incontinence in bladder function and straining, urgency and incomplete emptying stool in bowel function are most pronounced and have a relevant impact on HRQOL especially physical functioning. Patients receiving pelvic floor rehabilitation program have higher their pelvic muscle strength, better pelvic floor function and more enhanced excitatory motor pathway compared to the control group.
After exercise, participants reported less sexual worry and better physical functioning and sexual activities
In our study, stress incontinence and nocturia were significantly higher in gynecological cancer survivors. Urinary incontinence, chiefly, stress incontinence, is a common problem after radical hysterectomy and it‟s reported in 19-81% of patients with gynecological cancers.(Jackson and Naik 2006) The etiology of genuine stress incontinence after radical surgery is uncertain, but it may be the result of disruption to the anatomic support of the bladder and urethrovesical junction following resection of the upper vagina and parametrium or related to pudendal and pelvic nerve damage and loss of periurethral tone.(Jackson and Naik 2006). In a cross-sectional matched cohort study(Hazewinkel, Sprangers et al.), the gynecological cancer survivors had a
significantly higher risk of stress incontinence than the reference group. According to Hsu et al., (Hsu, Chung et al. 2009) pelvic neural dysfunction was higher in surgery patients. They suggested that the direct injury of traction during surgery{Carlson, 1997
#319}, pelvic anatomic dislocation after surgical manipulation{Lin, 1998 #322}, and excision of tissues around vagina (Ercoli, Delmas et al. 2003; Raspagliesi, Ditto et al.
2007) may have caused damage on pelvic nerves (especially on bladder and urethra) during radical hysterectomy. Brooks and co-workers (Brooks et al.2009) recently reported that urinary incontinence is common late side effects after radical hysterectomy.
They detected bothersome urge and stress incontinence in, respectively, 17% and 27% of 66 patients treated with radical hysterectomy. In that respect, the 47.5% of our patients with urinary incontinence is more prevalent than the proportions mentioned by Brooks et al.
We found incontinence group patients had weaker pelvic floor muscle strength and impaired pudendal nerve. Revealing neurogenicity in a patient with pelvic floor dysfunction may alter the choice of therapy. It is known that pudendal nerve innervates the levator ani muscles which have key role of continence. Continence and coordinated micturition, as well as defecation, sexual arousal, and orgasm, are dependent on the integrity of the central and peripheral nervous pathways to the sacral region. Nerve damage is more frequent in incontinence patients than in continent controls. In our pilot study, one participant in the intervention group showed delayed onset of latency produced with sacral stimulation (6.0msec) in left side. She had leg lymphedema left side
and urinary symptom such as urinary urgency. Our study comprised only very few participants, so the further study is needed to replicate our findings.
We could appraise the excitability of the intracortical motor circuitry corresponding to the anal sphincter. With muscle contraction, the latencies of motor evoked potential were reduced and amplitudes were increased. In one case, the potential which was not recorded to the cortical stimulation at rest was evoked after facilitation. The latency to the cortical stimulation with facilitation in the incontinence group was larger than that in the continence group. In the incontinence group with intact sacral function, they may contract the pelvic floor muscle less than 10% of maximal contraction at baseline. There is a correlation between the increase in voluntary contraction of the target muscle and the reduction in latency, until a certain level of around 10-15% of maximal contraction (Ravnborg, 1996). However, pelvic floor contraction is difficult to verify and quantify, and the ability to voluntarily contract the pelvic floor is not present in many women (Bump et al., 1991). That is the one of the reason in the development of PFRP to improve the pelvic floor function in gynecological cancer survivors.
Transcranial magnetic stimulation (TMS) is one potential approach in the assessment of the corticospinal pathways and sacral plexus function. Gunnarsson et al.
studied 18 women with genuine stress urinary incontinence are found that the women who responded well to pelvic floor exercises also produced shorter latencies to cortical stimulation with facilitation. Even though the role played by the motor cortex in anorectal pathophysiology is not completely understood (Vodusek 2004), Lefaucheur
(Lefaucher 2005) assessed the excitability of the external anal sphincter with the rest motor threshold and the duration of the cortical silent period with single TMS pulses. In our study, participants received PFRP showed increased amplitude and decreased the motor threshold of pudendal nerve stimulating cortical area with facilitation. These finding could be interpreted as the enhanced excitability of the motor cortical representing the external anal sphincter.
Bowel function was impaired especially in straining and urgency for defecation.
Hazewinkel et al (Hazewinkel et al., 2010) also reported that the prevalence of urgency for defecation and distress from constipation and obstructive defecation was significantly more after radical hysterectomy than in the reference group. Hsu et al. reported that radiotherapy patients exhibited greater intestinal dysfunction (Hsu et al.2009). Many studies have indicated that radiotherapy to the pelvic cavity has easily caused diarrhea and abdominal pain (Haboubi et al 1988; Classen et al., 1998;Danielsson et al.,1991;
Lantz et al., 1984). Pieterse et al. did not find increased prevalence bowel symptoms at 24 months after treatment of early-stage cervical cancer (Pieterse et al.,2006). However, they used a non-validated questionnaire with only two questions about bowel function.
Sexual inactivity has been reported in almost two of third patients in gynecological cancer survivors. Sexual dysfunction in this study is mainly caused by dyspareunia and viginal dryness. It is known that sexual dysfunction from surgery is caused by a shortened vagina (Jensen et al., 2004), vaginal dryness (Jensen et al. 2004; Schover et al.
1989; Bukovic et al.2003; Burns et al.,2007), and decreased libido (Herzog et al.,2007;
Bukovic et al.2003;Jensen et al., 2003; Seibel et al., 1982; Cull et al., 1993). In contrast, the sexual dysfunction from radiotherapy are caused by vaginal stenosis which yields dyspareunia, difficulty in orgasm, decrease in sexual satisfaction, and change in body image. A cross-sectional study of 860 survivors of cervical cancer found that survivors of cancer also experienced worse body image, impaired sexual/vaginal function, and more sexual worry when compared with 494 control subjects with no history of cancer (Wenzel et al.,2005).
In addition, there was a strong association between pelvic floor dysfunction and several HRQOL aspects. “Physical functioning” is the most severely impaired functioning as expected, and the present study confirms that “social functioning” is also important limitation in these patients. Interestingly, as compared to reference group, clinically meaningful worse outcomes were found for constipation and diarrhea, indicating that these aspects are greatly impaired after the treatment in gynecological cancer survivors.
PFRP has been found especially valuable in case of stress incontinence, which is a major component of pelvic floor dysfunction in gynecological cancer survivors.
Moreover, they have a beneficial effect on HRQOL measurements. In our study, significantly greater post-exercise changes in the scale of peak vaginal pressure. The prevalence of stress incontinence was decreased from 64.3% to 33.3% after the intervention in the exercise group. Burgio et al (Burgio et al., 1998 Behavioral vs drug treatment for urge urinary incontinence in older women) reported a mean 80.7%
reduction in incontinence episodes in women with incontinence using anorectal biofeedback to help train their pelvic muscles.
The mechanism behind this effect is not yet defined but with the results of our study, we suggested several hypotheses. We assessed the excitability of the motor cortical representation of the external anal sphincter by using transmagnetic stimulation (TMS).
After exercise, the latency to the cortical stimulation with facilitation was significantly shorter than that at baseline in exercise group. In both group, the latencies after muscle contraction became shorter, however the comparison of difference of latency showed significance between the groups. To achieve minimal latency of MEPs, a contraction more than 10% of maximal voluntary contraction (MVC) is needed. It is difficult to contract pelvic floor muscle maximally, but after PFRP, a degree of voluntary activation increased. It has been reported that the facilitative role of central nervous system was dependent on a degree of voluntary activation (Hanptmann et al., 1996; Mill and Kimiskidis,1996).
We found that exercise group reported significantly higher QoL than that of control group. Moreover, the differences in QoL scores meet the previously identified minimally important differences on the EORTC QLQ C-30 and CX-24. In follow-up analysis of subscales, physical functioning were most strongly associated with exercise group. We found that physical functional aspect of QoL was significantly improved in the exercise group. Physical function are important in activities of daily living for cancer survivors and have been shown to be the most important but also the most compromised aspect of
QoL for gynecological cancer survivors. Many researches in other groups of cancer survivors also has demonstrated that exercise interventions can increase muscular strength and endurance, physical functioning, and cardiovascular fitness. These results
QoL for gynecological cancer survivors. Many researches in other groups of cancer survivors also has demonstrated that exercise interventions can increase muscular strength and endurance, physical functioning, and cardiovascular fitness. These results