3. METHODS
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 to PFS (p=0.263), but to PDAI score (p<0.001) and histological inflammation (p=0.003).
Table 11; Endoscopic findings and lab results in patients with good and poor functioning pouches Good
Histological inflammation Total: 14
Mild: 11
Distance from the anastomosis to the dentate line in cm (median)
0.5 [0.5, 1.0] 0.5 [0.5, 2,5] 0.053
4.4 Study 4:
4.4.1 Main Findings:
1 Total pelvic volume measured by MRI was not correlated to pouch volume at urge.
Some transverse bony limitations were correlated to urge volume.
2 There were no differences in morphological MRI findings between the well and poorly functioning pouches. Morphological findings of inflammation on MRI seems to be a normal finding, also in well functioning pouches, and was not correlated to histological findings of acute inflammation. Increased pouch wall thickness was correlated to PDAI scores. Endoscopy remains the golden standard to diagnose pouchitis.
3 There were no differences in functional MRI results between the groups, and none of the radiological findings correlated to emptying difficulties, urge or soiling.
4 Endoscopy remains the golden standard for diagnosing of pouchitis.
4.4.2 MRI
There was no correlation between pelvic volume and volume at urge (Figure 18).
Figure 18:
Correlation between pouch volume at urge and the pelvic pouch volume calculated from bony limitations on MRI.
The bony limitations of the pelvis correlated against urge volume are given in Table 12.
The findings from the MRI examinations are given in Table 13.
There were no
differences between the
well and poorly functioning groups. The majority of patients had one or more signs of
inflammation (14 in the well functioning and 22 in the poorly functioning group). In Table 14 radiological signs of inflammation is correlated against biopsies, endoscopic PDAI scores and a history of pouchitis.
Table 12: Pelvimetric measurements of the bony pelvis:
N=43
IP; anatomical transverse distance, IA; interacetabular distance. IS; interischial distance. IT:
intertuberous distance. C: Sagittal image. Pr (promontory), SyU; upper border of the pubic symphysis. APrSyU: Angle between a line drawn from the promontory to the upper border of the pubic symphysis and a line drawn along the upper border of the pubic symphysis.
Table 14: Morphological findings of inflammation on MRI correlated against biopsies, endoscopy and a history of pouchitis.
Acute inflammation on pouch biopsies
PDAI score History of ≥ 1 episodes of pouchitis
Pouch wall thickness 0.270 0.017 0.253
Pouch wall edema 0.292 0.549 0.196
Enlarged lymph nodes 0.341 0.116 0.552
Peripouch free fluid 0.276 0.278 0.913
Radiologist conclude on pouchitis*:
0.481 0.458 0.287
*When increased pouch wall thickness (>3 mm) and pouch wall oedema was present, the rasiologists concluded on pouchitis based on morphological findings on MRI.
(Statistical analyses were not calculated on the following inflammation parameters, as they were displayed in few patients; peripouch edema (n=1) peripouch fatty proliferation (n=2), presacral sinus/abscesses (n=1) or peripouch or perianal sinuses (n=3)).
Table 13: MRI findings from the morphological and dynamic MRI in well and poorly functioning pouches
Largest diameter of small bowel loops before emptying (mm) Median [Range]
Pouch wall thickness (mm)
Measured on distended pouch mm (3DT2FS). The wall thickness is measured in a well-distended nondependent portion of the pouch to avoid falsely elevated measurements from factors such as dependent fecal material and inadequate distensions. > 3 mm was considered pathological
Outlet stricture of ileoanal anastomosis N 0 0 0.143
Median Pelvic floor descent* before dynamic imaging (mm)
N ≥ 30 mm 0 0 1.000 Pelvic floor descent* during valalva (mm)
N ≥ 30 mm 6 5 0.664 Pelvic floor descent* during emptying (mm)
N ≥ 30 mm 12 15 0.459
Atrophic sphincter N 1 0 0.306
Atrophic levator N 2 1 0.962
Dysfunction of external sphincter (Failure to open during emptying) N 3 5 0.668 Obstructive intussusception (Pouch infolding in anal canal during
emptying)
N 1 1 1.000
*Descens was defined as a downward movement of the anorectal junction on straining of more than 2 cm below the pubooccygeal line. ≥30 mm was considered pathological.
5. METHODOLOGICAL CONSIDERATIONS 5.1 Study 1:
A limitation with study 1, is that bowel function was assessed at varying intervals from the original pouch operation. However, several studies have shown that pouch function stabilises around a year after surgery, and remains stable for many years until it declines slightly s after 10-15 years62,65,103. The study population included all patients undergoing IPAA, not only patients with UC. As the purpose of the study was to investigate functional outcome and quality of life of patients undergoing IPAA, we chose to include all patients regardless of indication for surgery. This is consistent with most other studies reporting functional outcome after IPAA surgery. There were only 4 patients with other diagnoses, and it is unlikely this skewed the results. Another limitation with the study is the difference in the duration of follow-up between patients with J and K pouches. In the UK multi-centre report of 2491 patients, function (particularly continence in the form of minor leakage) deteriorated slightly after 15 to 20 years65. This finding had also been observed in a previous study by Bengtsson et al104. As our patients had a shorter duration of follow up being 11 years for patients with a J-pouch and three years for a K-pouch, it is unlikely a difference in follow up time alone can explain the differences between J and K pouches. There was also a significant difference in mean age (50 years in patients with a J-pouch and 43 years for those with a K-pouch). Several studies have shown a marginal worsening in function in patients over 50 years of age78,113,114. In the multivariate analysis in the present study, age was not significant as a predictor of a poorer outcome, but the number of patients was small.
The K-pouch construction is somewhat more complicated, which could affect perioperative conditions. However, the only difference in the procedures is that K pouches require hand
suturing rather than stapling, and we found little difference in operating time. As the
complexity of IPAA requires a specialized unit with experienced surgeons, the slightly more complex construction of the K pouch should be of minor concern, especially as the outcome of this operation is meant to last for the rest of the patient’s life. As this is a young patient group most will have their pouch for decades.
The assessment of pouch function was conducted through a telephone interview; this was to make sure the questionnaire was answered in the same way by all patients. One limitation with this is that patients may report a better function than what they actually have. As the interviews were done by an independent interviewer who did not operate the patients, and whom the patients did not know, we believe the possible report bias is reduced.
5.2 Study 2:
This study was designed as a retrospective study assessing patients’ postoperative sexual function. The patients’ sexual function before undergoing pouch surgery had not been
assessed, and we therefore decided to compare with a control group of the average Norwegian population rather than asking the patients about their function prior to surgery. As the mean follow up time was seven years, we would expect a recall bias if the patients were to report their preoperative function. There are some limitations with the comparing studies. Firstly, they were done on a cross section of the Norwegian population in total, not on a healthy population. The patients having undergone pouch surgery are otherwise quite healthy. This might explain why our patients in some cases have a better sexual function than what is reported in the average population. It is not likely to assume that patients having undergone pouch surgery have a better function than their healthy peers. Secondly, we chose to use
PISQ to evaluate female sexual function as this is the only questionnaire validated in
Scandinavia139. There was no study on the average Norwegian female population using PISQ,
Scandinavia139. There was no study on the average Norwegian female population using PISQ,