1. BACKGROUND:
1.8. Sexual function
As with any form of pelvic surgery there is a risk of altering sexual function. The impact of IPAA on sexual function is probably multifactorial. With all pelvic surgery, there is a risk of pelvic nerve damage, resulting in retrograde ejaculation and impotence in men and vaginal dryness in women, leading to reduced sexual function. Furthermore, anatomical changes as a result of the surgery can lead to vaginal adhesions in women resulting in dyspareunia. In addition, it is reasonable to hypothesize that bowel function also affects sexual function and that poor pouch function may be a contributing factor in patients with a poor sexual function postoperatively. Whereas several studies have evaluated sexual function after IPAA on a
general level, only one has looked at the impact of pouch function on sexual function. This particular study only included women, and found no association between pouch function and sexual function, but a trend towards significant association between impaired sexual function and interference of stool leakage during intercourse 124.
The literature is conflicting regarding sexual function after IPAA. Several studies find that sexual function in both men and women remains relatively unchanged
postoperatively14,68,88,110,125-130, and may even improve after surgery 78,125,127. The most common indication for IPAA is ulcerative colitis. Patients with inflammatory bowel disease (IBD) with colon and rectum in situ are more likely than the average population to have reduced sexual function131-133, and the tendency is stronger in patients with active disease than patients in remission132-134. The reason why some studies report an improvement in sexual function after surgery is probably found in an improvement in the patients’ general health and may be due to better stool control postoperatively. This would also suggest a correlation between bowel/pouch function and sexual function. 64
Others again find reduced sexual function with increased risk of vaginal dryness and dyspareunia in women, and impotence, and retrograde ejaculation in men124,135,136
2. AIMS OF THE STUDY
Restorative proctocolectomy is the treatment of choice for most patients with ulcerative colitis and familial adenomatous polyposis, and is often performed on relatively young patients who will live with the results of the operation for many years. The functional outcome is therefore of great importance. However there is a considerable variation in functional outcome, and the reasons are to a large extent unexplained. The objective of this thesis was to undertake a thorough investigation of patients having undergone IPAA surgery at our unit the past decade to increase the understanding of contributors to functional outcome. Our specific aims were:
1. To investigate surgical results, and the effect of septic pelvic complications on functional outcome.
2. To determine whether there are differences in function and quality of life among patients undergoing IPAA having two different pouch designs (J and K pouch).
3. To investigate the effect of functional outcome on quality of life.
4. To correlate postoperative bowel function with sexual function in male and female patients.
5. To perform physiological tests and endoscopic examination on IPAA-patients with well and poorly functioning pouches and two different pouch designs to determine factors contributing to functional outcome.
6. To evaluate the morphology and emptying patterns of the ileal pouch with a pelvic MRI in well and poorly functioning pouches, comparing the results with findings from
manovolumetric analysis and pouch endoscopy.
7. To establish a reference of normal MRI findings in pelvic pouch patients, as this is the first study published on MRI-findings of pouch patients with a well functioning control group.
3. METHODS:
3.1 Patients
All patients undergoing IPAA between 2000 and 2013 were identified from hospital medical records (N=103). Preoperative, perioperative, and postoperative information was gathered retrospectively by an independent investigator, and quality of life, sexual functioning and pouch function was assessed using questionnaires. The best and worst functioning patients were identified, and invited to undergo examination with manovolumetric testing, pouch endoscopy and MRI. Figure 2 illustrates how the patients were included in each study. To ensure the well and poorly functioning groups were comparable, the groups were stratified by pouch design.
3.2 Surgical technique and follow up:
The majority were operated on in a three-stage procedure having undergone an initial subtotal colectomy before pouch formation. Most of these were performed laparoscopically, many in
Figure 2:
Inclusion of patients for Study 1-4. The arrows indicate that some of the patients were included in several studies.
other hospitals before undergoing IPAA in our unit. IPAA was performed through a low midline incision in all patients. Four consultant surgeons were part of the “pouch team”
during the study period, and at least two were present at every operation. All patients were diverted with a loop ileostomy. Patients operated on before 2008 were given a stapled J-pouch.
All patients operated on in 2008 and onwards had a hand-sewn, double folded K-pouch according to the technique of continent ileostomy (Kock pouch) (Figure 3). Both pouch types were constructed from two 15 cm segments of terminal ileum. The pouch anal anastomosis was created within a maximum of two centimetres above the dentate line, and stapled in the majority of the patients.
3.3 Questionnaires
All patients were sent questionnaires regarding their quality of life (Short Form Health Survey 36; SF-36137), and sexual function (International Index of Erectile Function 5; IIEF 5138 for male, Pelvic organ prolapse/urinary Incontinence Sexual Function Questionnaire 12; PISQ 12139 for female). The questionnaires regarding sexual function and quality of life are given as
J-Pouch K-Pouch
Figure 3:
Formation of a J-pouch and a K-pouch. For each reconstruction the distal 30 cm of the ileum is folded into two loops. These are then sutured longitudinally to form a J-pouch. In the case of a K-pouch, the apex of the two loops is folded as in the figure and the pouch is completed by a transverse suture as shown. The drawings are printed with the permission of Prof. Leif Hulten.
appendixes. The results were compared to the average Norwegian population (SF-361, male sexual function140 and female sexual function141). All patients were also interviewed
regarding their pouch function using a pouch functioning score (PFS) according to Oresland et al106. (Table 1).
During the telephone interview, the patients were asked about all complications, including those treated at other hospitals or by their general practitioner, and specifically about pouchitis and reoperations. Previous episodes of pouchitis were defined as an episode with increased frequency of defecation and/or bloody stool, responding on with antibiotics88.
Table 1: Oresland pouch function score (PFS)
Score
0 1 2
Daytime ≤ 4 5 ≥6
No. of bowel movements
At night 0 > 1/week ≥ 2/night Urgency
(inability to defer evacuation > 30 min)
No Yes
Evacuation difficulties
(>15 min spent in toilet on any occasion during the week)
No Yes
Daytime No >1/week
Soiling or seepage
At night No >1/week
Inability to release flatus safely No Yes
Perianal soreness No Occasional Permanent
Daytime No >1/week
Protective pad
At night No >1/week Dietary restrictions
(avoid certain items that interfere with pouch function)
No Yes
Medication
(continuous or occasional)
No Yes
Social handicap
(not able to resume full-time occupation or participate in social life)
No Yes
*Score range 0-16: Overall good function scores 0 points, overall poor function scores 16 points.
3.4 Barostat
The manovolumetric tests were conducted using a barostat (G&J Electronics Inc, Toronto, Canada) simultaneously measuring volume (V) of the pouch at present pressures (P1), and pressure (P2) of the anal canal. The barostat was connected to a non-distensible plastic tube (Ch 18) with a thin-walled, disposable, flaccid, noncompliant plastic bag hermetically tied to the end of the tube and placed in the pouch, measuring pouch volume (V). A tracheal tube (7 mm Mallinckrodt®) was placed over the Ch18 tube, and the cuff was connected to the barostat, measuring anal pressure (P2). The distensions of the bag were started at increasing pressures (P1), measuring V and P2 at each distension. P1 was lowered to zero after each distension.
There was no bowel preparation, but patients were asked to empty the pouch and bladder before examination. Patients were lying in a left lateral position.
The following parameters were investigated: resting anal pressure (RAP), maximum squeeze pressure, pouch sensibility (first sensation, urge to defecate and discomfort), pouch
compliance (Delta V/ Delta P), rectoanal inhibitory reflex and pouch motility patterns during the distensions. Motility fell into four subtypes; initial pouch contraction, initial and
unchanged volume readings, gradual adaption to increased volumes, and motility waves throughout the distension period. (Figure 4).
Figure 4:
Pouch motility was categorised in as one of four motility patterns;
initial pouch contraction, initial and unchanged volume readings, gradual adaption to increased volumes, and motility waves throughout the distension period.
3.4. Pouch Endoscopy:
The patients were invited back to the outpatient clinic within six months for a pouch endoscopy, performed by an independent gastroenterologist. The endoscopy findings were scored after the pouchitis disease activity index (PDAI)142. In addition the following was noted; presence of pre-pouch ileitis and the level of the anastomosis (distance from the
anstomosis to linea dentate). Biopsies were taken from the lower posterior and anterior part of the pouch for histological analysis. The biopsies where investigated by pathologists at the hospital describing the presence of inflammation (no, mild, moderate or severe acute inflammation).
3.5 Biomarkers:
Patients also delivered faecal samples to test for enteric pathogens and calprotectin
(Calprotectin ELISA; Buhlmann Laboratories AG, Basel, Switzerland), and they had general blood tests taken (Hb, LPK and CRP).
3.6 MRI:
The MRIs were undertaken the same day as the endoscopies and performed prior to the endoscopy to avoid any irritation of the pouch. There was no bowel preparation before the MRI scans, but the patients were asked to empty the pouch before imaging. Before the examination started, the patients were instructed how to perform squeezing, straining and evacuation. The first part of the examination consisted of morphological MRI sequences, after which contrast (methylcellulose) was installed in the pouch from the anal canal through a continent ileostomy catheter. The amount of gel was individualised, installing the volume at which the patients reported an urge to defecate. Finally, the dynamic sequences were done while the patients were squeezing, straining and emptying the pouch. Two independent radiologist consultants assessed the MRI scans separately to validate the findings; both were blinded for the patient histories. The different parameters evaluated are given in Table 13 (see section 4.4.2).
The pelvic volume was calculated from standardised pelvimetric measurements of the bony pelvis143-145 (Figure 5-8). The measurements were used to calculate the pelvic inlet (π X anatomical transverse distance X the distance from the promontory to the upper border of the pubic symphysis), pelvic outlet (π X the intertuberous distance) and height (distance from superioposterior pubis to the posterior anorectal junction, at the level of tuber). The volume was then calculated using a formula for frustrum 143,144.
3.7 Ethical approval:
All studies have been approved by the Regional Ethics Committee (REK no. 2012/363 and 2014/2206).
Figure 5: The anatomical limitations in the axial plane used to measure the Interischial distance (IS).
Figure 6: The anatomical limitations in the axial plane used to measure the intertuberous distance (IT).
Figure 7: The anatomical limitations in the coronal plane used to measure the transverse distance of the pelvis (IP; the cranial line) and the interacetabular distance (IA; the caudal line).
Figure 8: The anatomical limitations in the sagital plane used to measure the distance between the promontory (Pr) and the upper border of the pubic symphysis (SyU), the line distance is referred to as PrSyU, and the angle between PrSyU and a line drawn along the upper border of the pubic symphysis.
Figure 6 Figure 5
Figure 7 Figure 8
4 RESULTS 4.1 Study 1
4.1.1 Main findings:
1 RPC is a safe procedure with few complications
2 Our patients have good functional outcome with no significant difference between J and K pouches, although with a tendency towards better function in K patients.
3 Septic pelvic complications were negatively correlated with pouch function.
4 A PFS of ≥ 8 was the best cut-off to predict when functional outcome significantly impairs quality of life.
5 Our patients have good life quality with a tendency towards better function in K patients. Compared to the average Norwegian population the IPAA patients score slightly worse in general health.
4.1.2 Surgical outcome:
There was no postoperative death. Short-term complications are given in Table 2, and long-term complications are given in Table 3.
Table 2: Complications within 30 days of stoma closure (N=103)
After RPC After stoma closure
Reoperations Total: 9
Anastomotic leakage: 1 Small bowel obstruction: 6 Possible peritonitisa: 2
Total: 3
Small bowel perforation: 2 Intraabdominal bleeding: 1 Abdominal
complications
Other: Intraabdominal abscessb: 1 Pelvic abscessb: 1
Intraabdominal abscessb: 2
Infection
(Non-pouch related include pneumonia, urinary tract infection, wound infections etc)
Total: 20
Excessive drainage from the pouch: 9 Ileitis: 1
Non-pouch related: 10
Total: 7 Perianal abscess: 2
Non-pouch related: 5
Small bowel obstruction 12 5
Readmission due to dehydration 36 3
Anastomotic stricture requiring dilatation
9 2
Venous thrombosis 6 1
Other Complications not requiring surgery
Other 13 8
a: Both patients were operated on with no finding of peritonitis. b: Drained percutaneously.
No patient had the pouch removed or the intestine diverted. One patient had the pouch excised owing to local recurrence of cancer, and two died from metastatic disease from colonic cancer. The remaining 100 patients are alive with anal function.
4.1.3 Functional outcome Eighty-eight patients agreed to being interviewed regarding their function, the results given in Table 4. Of the 88 patients 97.3% would have had the surgery again.
In a multivariate analysis of the PFS with age at surgery, gender, duration of
Table 3: Long-term complications (N=103)
J
Table 4: Function of patients with a J- and K-pouch PFS=pouch functional score Antidiarrhoeal medication 38 (43.1%) 21 (47.7%) 17 (38.6%) 0.390 Social handicap 18 (20.5%) 5 (11.4%) 13 (29.5%) 0.041
4.1.4 Quality of life
Seventy-eight patients answered the questionnaire regarding quality of life. There were no significant differences in SF 36 - scores, although there was a tendency towards better function in K
patients (Table 5). The results are compared to those reported for the average Norwegian population1 (Figure 9).
Table 5: SF-36 score (mean)
Total (78) K (40) J (38 ) p-value
General Health 64.7 69.0 60.2 0.069
Physical function 91.9 92.3 91.4 0.794
Role Physical 71.4 73.1 69.7 0.868
Bodily pain 75.5 77.4 73.6 0.518
Role Emotional 81.4 88.9 73.7 0.113
Social Function 78.5 80.1 76.8 0.570
Vitality 56.3 59.9 52.6 0.205
Mental Health 79.1 79.9 78.4 0.730
Figure 9:
Quality of life of patients in the present study and of the average Norwegian population assessed by SF-361.
RPC = Restorative proctocolectomy.
4.1.5 Quality of life and functional outcome:
Figure 10 illustrates the correlation between quality and pouch function in the 77 patients responding to both the SF-36 and PFS forms. The patients were divided into three groups according to their PFS as performed by Berndtsson et al in a previous study107. Patients with impaired pouch function had poorer QoL scores in all eight SF-36 domains. We found a PFS of ≥8 to be the best cut-off point in the scoring system where function was poor enough to impair quality of life.
Figure 10:
SF-36: correlation between pouch function and quality of life in each domain. PFS, pouch functioning score.
4.2 Study 2:
4.2.1 Main findings:
1 Patients report good sexual function after IPAA surgery, and the sexual function is also good compared to the average Norwegian population.
2 In women there was a significant relationship between poor pouch function and impaired sexual function. This was not true for men.
3 In both men and women increasing age was correlated with impaired sexual function.
4.2.2 Sexual function:
The postoperative sexual function in men evaluated by IIEF-5 and compared to the average Norwegian population is given in Table 6.
The postoperative sexual function in women is given in Table 7, and compared to the normal Norwegian population141 in Table 8. The five answering alternatives in PISQ were grouped into the three categories used to assess female sexual function in the comparing study of the average Norwegian population.
Table 6: Sexual function in men divided by age and compared to the Norwegian average population
Table 8: Sexual function in women compared to the Norwegian average population
Norwegian study: PISQ answer IPAA patients
N=24
Normal population
No Always/ usually climax during intercourse 13 (54.2 %) 26 %
Mild Climax sometimes during intercourse 6 (25%) 50 %
Orgasm problems
Manifest Seldom/never climax during intercourse 4 (16.7 %) 24 %
No Always/usually feel sexual desire 6 (25 %) 10 %
Mild Seldom/sometimes during sexual intercourse 14 (58.3 %) 36 %
Genital pain
Manifest Always/usually during sexual intercourse 3 (12.5 %) 9 %
In PISQ there are 5 alternative answers (always, usually, sometimes, seldom, never), in the Norwegian study there are 3 (no, mild, manifest problem). This table shows how we have grouped the PISQ answers to fit the answering alternatives in the Norwegian study to be able to compare the results.
Table 7; Postoperative sexual function in women, evaluated by PISQ (N=24)
Always Usually Sometimes Seldom Never
How frequently do you feel sexual desire 1 5 14 3 1
Do you climax when having sexual intercourse with your partner 8 5 6 3 1
Do you feel sexually excited when having sexually activity with your partner
8 9 4 1 1
How satisfied are you with the variety of sexual activities in your current sex life
5 8 6 2 1
Do you feel pain during sexual intercourse 2 1 4 10 7
Are you incontinent of urine with sexual activity 0 0 2 2 19
Does fear of incontinence (stool or urine) restrict your sexual activity
1 2 6 4 11
Do you avoid sexual intercourse because of bulging of the vagina 1 1 1 1 18
When you have sex with your partner, do you have negative emotional reactions such as fear, disgust, shame or guilt
0 0 3 1 19
Much less intense
Less intense Same intensity More intense
Much more intense Compared to orgasms you have had in the past, how intense are
the orgasms you have had in the past six months.
0 6 15 2 0
4.2.3 Pouch function versus sexual function:
In women there was a significant relationship between poor pouch function and impaired sexual function (Figure 11). The same was not true for men (Figure 12). In both men and women, increasing age was significantly correlated to poor pouch function (p =0.006 and 0.038 respectively).
Figure 12:
Correlation between pouch function and sexual function in men (N=44).
Figure 11:
Correlation between pouch function and sexual function in women (N=24).
4.3 Study 3:
4.3.1 Main findings:
1 Well functioning pouches had a significantly larger volume, with volume at urge counting for 38% of functional outcome.
2 Sensibility thresholds seemed to be triggered only by pressure and not by volume.
3 Compliance was better in the good functioning group at lower distension pressures 4 More patients with a poorly functioning pouch had histological inflammation 5 Patients with hand-sewn anastomosis had worse pouch function.
6 Patients with a well functioning pouch had shorter rectal cuff.
4.3.2 Patients:
Of the 60 patients eligible for Study 3, 47 agreed to join (22 well functioning and 25 poorly functioning). The patients complications and demographics can be seen in Table 9.
Table 9: Demographics and complications in patients with good and poor functioning pouches.
Good n=22
Poor n=25
P-value (Mann-Whitney U test)
J pouch 11 15 0.496
Female 6 11 0.239
Age (median, range) 52 [28,70] 52 [14,72] 0.814 Follow-up in years
(median, range)
9 [4,16] 11 [3,16] 0.723
PFS (median, range) 3 [1,5] 9 [6,15] < 0.001
Hand-sewn anastomosis 1 7 0.035
Septic pelvic complications 0 2 0.180
Perianal fistula/abscess 0 3 0.097
Septic pelvic complications and perianal disease
0 5 0.064
≥ 1 pouchitis episode 4 11 0.061
4.3.3 Barostat:
the pressures triggering the sensations were the same in all groups. Using binary regression with the pouch function as dependant variable and volume at urge as independent variable, Nagelkerke R square is 0.380 indicating the urge volume explains 38% of pouch function.
Table 10: Manovolumetric findings in patients with good and poor functioning pouches.
Good
Figure 16 illustrates the pouch volume at different disension pressures.
Pouch compliance is illustrated in Figure 17. Using linear regression there was no correlation between compliance and septic pelvic complications.
0 at any other pressures.
There were no differences in motility pattern in the well and poorly functioning pouch groups (p=0.657), and pouch motility was not correlated to pouchitis, septic pelvic complications, urge or emptying difficulties.
Sphincter function in the well and poorly function groups are illustrated in Table 10. None of the patients had a pouch anal inhibitory reflex. There were no significant differences in resting anal pressure (p=0.321), maximum squeeze pressure (p=0.953) or pressure at urge (p=0.903) in patients with or without leakage.
4.3.4 Pouch endoscopy and biomarkers:
In total 46 of the 47 patients underwent pouch endoscopy. The findings from the pouch endoscopy and biomarkers are displayed in Table 11. Neither histological nor endoscopic PDAI scores were correlated to urge volume or compliance. Calprotectin was not correlated
In total 46 of the 47 patients underwent pouch endoscopy. The findings from the pouch endoscopy and biomarkers are displayed in Table 11. Neither histological nor endoscopic PDAI scores were correlated to urge volume or compliance. Calprotectin was not correlated