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, which makes comparison more challenging. However, PISQ is divided into different domains of function enabling us to compare with studies having evaluated female sexual functions within the same domains. Thirdly, the comparing study on sexual function in men is done in 2001, and on men above 40 years of age. This is a limitation as 42% of our male patients are below 40 years. However, very few of our patients under 40 have an erectile dysfunction, so the comparison is more relevant for patients above 40. It is likely to assume that the sexual function in the Norwegian population is the same as a decade ago. Our main goal of this study was to look at the correlation between pouch function and sexual function. In addition we have compared IPAA patient’s sexual function with the sexual function of the average
Norwegian population. Having considered the limitations of the comparing studies, it does not seem that our patients have a worse sexual function than the average population. Further comparison would require more comparable studies.
When evaluating sexual function and pouch function for women we chose to include an outlier with a severe sexual dysfunction, as she specifically stated her sexual function was reduced after surgery. If she is excluded, the correlation would still be significant with a p-value of 0.041 and a correlation coefficient (R) of 0.43.
Lastly, the number of included patients is not very high. However, the response rate is high and our data is consistent. We have the impression that the variability in sexual and pouch function is captured in a representative manner. The reported results correspond well with findings of other studies.
5.3 Study 3:
In this study we compared the well and poorly functioning pouch patients to look for predictors of function. To ensure the well and poorly functioning groups were comparable, the groups were stratified by pouch design. As a result, the well and poorly functioning groups contained the same amount of J and K patients with similar PFS and hence it did not make sense to analyse whether pouch design is correlated with functional outcome in this study. It might have been a better study design to select well and poorly functioning pouches without stratifying for design. Another limitation with the comparison of pouch volume in J and K patients is the differences in follow up time (median 14 years for J and 5 years for K, p
= < 0.001). As mentioned in section 5.1, studies find that pouch function only deteriorate slightly with follow up time, and this happens after 15-20 years65,104. Therefore, it is not likely that difference in follow-up time alone explains the difference.
In Study 1 we found septic pelvic complications to be significantly correlated to impaired function, but we found no correlation between septic pelvic complications and function in Study 3. However, the small study population and low number of complications are obvious limitations with the comparisons in study 3. In studies including more patients, septic pelvic complications and pouchitis are known to impair pouch function64,65,67,69,71,77,146-148.
In this study many tests are undertaken. Yet we chose not to Bonferroni correct the significant p-value as the most important comparisons were those of the manovolumetric tests, where the difference in volume had a value < 0.001 and would have been significant at any chosen p-value. The other significant findings are merely a confirmation of what is already known.
A final limitation in the third paper is the fact that the patient cohort is somewhat unselected.
Four patients with other diagnoses than UC are included, and a patient with PSC (known to increase the risk of severe pouchitis) is also included. To exclude confounders these patients could have been excluded.
5.4 Study 4:
In this study we examined the well and poorly functioning patients with morphological and dynamic MRI scans to look for differences between the groups and contributors to functional outcome. We measured bony limitations to calculate a total pelvic volume to correlate pelvic volume with urge volume. A limitation with this comparison is the difficulty to calculate the total pelvic volume due to the geometric form of the bony pelvis. Another limitation with the volume comparison is that soft-tissue structures and organs in the pelvis taking up space in addition to the pouch, have not been considered in this correlation. We did not find any significant differences in morphological MRI findings between the well and poorly functioning groups, and we did not find MRI signs of pouchitis to be correlated to PDAI scores or histological acute inflammation. A limitation with the correlations is that intravenous MRI contrast was not given, as this probably would have improved the MRI evaluation of inflammation. We found no difference in functional MRI results between the well and poorly functioning pouches, and we did not find any radiological findings correlated to emptying difficulties, urge or soiling. However a limitation with the comparisons is the small number of patients suffering from the mentioned symptoms. There might be correlations which the present study was underpowered to find. A limitation with the functional MRI series is that the patients were laying down in the MRI machine while emptying the pouch, as this is both an uncomfortable and none-physiological position for
emptying. Finally we were unable to quantify the evacuation fraction, as we did not have a reliable measure of the amount of emptied gel.