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 indicate that exercise is an important and effective intervention for improving and maintaining physical functional aspect of QoL in gynecological cancer survivors. In addition, we developed cancer specific exercise program.

This study has several limitations. The cross-sectional evaluation of pelvic floor dysfunction in gynecological cancer survivors did not allow us to adjust the analysis for baseline data before treatment. In addition, the inclusion criteria and the sample size of the study might have reduced the generalisability of the study and limited the power of the analysis, respectively. A further limitation of the study is related to the characteristics of the reference group. Because of the lack of Korean normative data for the EORTC QLQ-C30 and CX-24, this study used age-matched reference group this not fully taking into account the characteristics of general population.

The duration of the exercise program (4 weeks) was unlikely to be long enough to verify the effects of exercise. Our program may not be of sufficient intensity to change in a short period. More extended duration and frequency of the intervention, longer-term follow-up, and larger sample size are needed to evaluate the effectiveness of PFRP in the gynecologic cancer survivors.

Despite these limitations, our results provide a preliminary indication that a pelvic floor rehabilitation program may be efficacious with regard to urinary incontinence and

quality of life. Considering the effect sizes for the rate of urinary incontinence between groups, the sample size required at 5% significance level and 80% power was 250 survivors of gynecological cancer per group.