Female sex and increasing age were strong risk factors for inadequate sigmoidoscopy, as was unknown provider type and, to a lesser extent, examinations performed by non-gastroenterologist physicians. An increase in the number of examinations limited by pain, stool, or angulation only partially accounted for these increased risks; models that either adjusted for limitations or were restricted to those with no limitations showed some attenuations in the risk estimates, but age, sex, and unknown provider type remained strongly associated with inadequate sigmoidoscopy. There was an increased risk of distal CRC among those who had a sigmoidoscopic examination that reached a depth of insertion of less than 40 cm. The presence of limitations of the examination, including spasm/pain, stool, and angulation, did not predict future distal CRC, apart from their association with depth of insertion.
This study has several strengths, most notably the large sample size and availability of follow up data to allow us to quantitate the subsequent risk of distal CRC post-sigmoidoscopy. However, there were several limitations that should be mentioned. Firstly, depth of insertion is only a crude measure of the amount of the colorectum that has been examined. Even among patients with examinations that reach similar depths, the anatomical segment of the colon that is visualised varies. Prior studies have estimated that about 50–75% of sigmoidoscopies view the entire sigmoid colon, while only a minority of examinations (10–40%) visualise the entire descending colon.13–15
Furthermore, when the CoCaP programme began in 1994, endoscopists were instructed to measure insertion depth based on a straightened sigmoidoscope, with all loops removed. However, no specific quality control measures were instituted to ensure that endoscopists were adhering to this protocol, so it is not known to what degree endoscopists recorded depth of insertion while loops remained. Thus a number of examinations coded as “adequate” may truly have been inadequate according to the actual amount of colon visualised. The net effect of this misclassification however would likely have been to weaken the strength of our observed association, rather than to strengthen it.
Secondly, the possibility of additional misclassification exists in the data, especially because the data were primarily collected for clinical rather than research purposes by multiple endoscopists. For example, underreporting may have occurred in the collection of data regarding limitations of the examination if clinicians failed to note this on the sigmoidoscopy report. Nevertheless, a standardised form was used for all sigmoidoscopies, with items such as limitations in “checkbox” format, to allow clinicians to record data in a consistent and efficient way.
Thirdly, some sigmoidoscopies may have been terminated at the time when a polyp that was not suitable for immediate removal was discovered; these patients would likely have been referred for colonoscopy, making continuation of the sigmoidoscopy unnecessary. Our data support this assertion. Although the prevalence of polyps tended to be greater with increasing depth of sigmoidoscope insertion, those with examinations to less than 30 cm actually had a higher prevalence of polyps (and especially of advanced adenomas). Thus it seems likely that some small fraction of these shorter examinations was terminated prior to the maximal possible depth of insertion. We attempted to reduce this problem by excluding those sigmoidoscopies that resulted in the diagnosis of cancer. Furthermore, this problem did not result in a large bias; the risk of inadequate examination according to age and sex was almost identical if we restricted to those study subjects who had no polyps identified by sigmoidoscopy, and adjustment for the baseline findings had no impact on the rate ratios for distal CRC according to sigmoidoscopy depth.
Finally, the analyses that examined the risk of distal CRC according to depth of insertion were based on a relatively small number of cases (n
45). Thus our estimate of 40 cm as the most appropriate cut point in defining “inadequate” examinations may have been affected by the limited precision of our risk estimates. Our data are consistent with more modest elevations in cancer risk in those with examinations reaching between 40 and 59 cm insertion. None the less, this study is, to our knowledge, the first to attempt to quantify the risk of subsequent cancer according to depth of endoscopic insertion.
Our results are largely consistent with those of prior studies examining age5–7
as risk factors for incomplete sigmoidoscopy. In another recent analysis from the Clinical Outcomes Research Initiative (CORI), Walter et al
used data from over 15 000 examinations in asymptomatic persons performed in multiple sites throughout the USA to assess the risk of inadequate sigmoidoscopy (less than 50 cm) by age and sex.5
In this population, the proportion of inadequate examinations ranged from 10% in men aged 50–59 years to 32% in women aged 80 years and older. Other recent analyses have had similar findings,6,7
although several other small studies failed to find an association with age9,16
These results for sigmoidoscopy are also similar to those of several studies that found that older age and female sex were predictive of incomplete or difficult colonoscopy.17–20
Our results are also consistent with a those of Schoen and colleagues21
who found an increased risk of subsequent advanced colorectal pathology following an inadequate baseline sigmoidoscopy, defined as an examination to less than 50 cm and/or an examination in which less than 90% of the colorectal mucosa was visualised due to inadequate preparation (odds ratio 2.7 (95% CI 1.4–5.4)). This study, conducted among participants in the ongoing PLCO screening trial in the USA,22
was based on 72 advanced adenomas; six cases of invasive cancer were also included.
What then accounts for this decreased depth of insertion of the sigmoidoscope in women and older individuals? As suggested in our data, pain, suboptimal bowel preparation, and angulation of the colon account for some, but not all, of these associations. There is other evidence to support these findings; women are more likely to have tortuous colons17,23
and to experience pain during sigmoidoscopy,24,25
while older individuals are more likely to have suboptimal bowel preparation.5,8,26
However, other variables are also clearly important predictors. Previous pelvic or abdominal surgery,6–9
experience of the endoscopist,9,27
and body weight7
have all been reported to be associated with inadequate sigmoidoscopies. We were unable to directly assess these variables with the possible exception of endoscopist experience. Unknown provider type may have provided an estimate of limited endoscopist experience, as those with a lower procedure volume may be more likely to fail to enter a provider identification number on the sigmoidoscopy form or to enter an untraceable number. As certain potentially relevant variables were unavailable to us, it remains possible that at least part of the observed association with age and sex is due to uncontrolled confounding. However, other studies that have controlled for the variables above still found associations with age and sex,5–8
although admittedly no study has controlled for all of the above variables. Additionally, it is possible that underreporting of examination limitations by clinicians (as discussed above) could lead to residual confounding when this variable is included in the multivariate models, resulting in risk estimates that are too high.
Despite this, the large magnitude of the associations observed, the precision with which we were able to estimate these associations, and the agreement with prior studies provides strong support for an association of age and sex with inadequate screening flexible sigmoidoscopy. Clinicians should be aware of the potential for limited examinations in older and female individuals, and should consider steps to maximise the potential for an adequate screening examination. For example, several small randomised controlled trials have reported reductions in pain during sigmoidoscopy associated with the use of smaller diameter endoscopes in women,28
or with the use of medications29,30
or audiovisual stimulation31
to minimise pain and/or anxiety; in the case of examinations limited by stool, an alternate preparation strategy, such as oral sodium phosphate, could be used.32
Alternatively, if an adequate sigmoidoscopy proves difficult, other screening tests can be considered. Because spasm/pain, angulation, and stool cannot fully explain the association between age/sex and inadequate sigmoidoscopy, additional research is needed to better characterise the reasons for inadequate examinations. However, regardless of the reasons, a sigmoidoscopy examination to less than 40 cm is a cause for concern, due to the increased risk of subsequent CRC.