This study has demonstrated that the colonic transit measured by WMC significantly correlated with the widely used comparator, ROM. Categorization of constipated subjects into slow or normal colonic transit based on WMC studies matched closely with ROM studies. Specifically, WMC estimate of colonic transit fulfills the expected concordance of at least 65% with ROM, validating WMC to determine whether colonic transit profile is normal or delayed.
There are numerical differences in the actual colonic transit estimates by the WMC and ROM techniques. This is not unexpected given the evidence that particle size influences the transit of solid particles in the small bowel and colon. For example, Stivland et al. observed differences between transit of 1 mm diameter pellets and ~4mm radiopaque markers (20
). Van der Sijp et al. (21
) documented faster transit of ROM relative to smaller radioisotopically labeled particles. Similarly, indigestible capsules travel more quickly through the colon than ROM, and capsule transit is faster than small dispersed particles (22
ROM assesses whole gut transit as it assesses the location of the markers relative to the time of marker ingestion rather than the time of onset of colonic transit. Inclusion of gastric emptying and small bowel transit time to the transit estimate could account for 6 to 10 h difference between the colon transit time by ROM and the WMC technique. The absolute number estimate for colonic transit time is therefore less relevant than the correct classification of subjects having a normal or delayed transit and the sensitivity and specificity of the test.
The patients in this study represent the spectrum of colonic transit profiles usually encountered in clinical practice, with ~40% having objectively delayed colonic transit by the standard ROM method. This multicenter cohort of patients with constipation reflects the experience of documented slow transit in 38–80% of patients with constipation in other studies (3
) adding to the generalizability of the data in this study to clinical practice.
The pH change as the capsule traverses from the ileum to the colon determines the time of onset of colon transit with WMC,. The pH in the cecum is more acidic than that of the ileum because of the fermentation of digestive residue by colonic anerobic flora and the nature and concentration of the colonic flora (25
). This pH drop at the ileocecal junction is well documented in the medical literature (26
) with the use of ingestible radiotelemetry capsules initially in healthy volunteers and subsequently in patients with a variety of diseases including inflammatory bowel disease (29
) and adenomas in the colon, and even in children (26
). Overall, pH profiles in the GI tract are characterized by an abrupt rise in pH between the stomach and duodenum, a slow continued rise in pH through the small bowel until reaching the cecum where pH decreases about 1 unit, and subsequently, there is a slow rise in pH through the colon. In general, these changes in pH differed slightly in health and disease, for example, pH decrease was greater in the healthy subjects (7.4 to 5.8) than in the Crohn’s disease patients [7.3 to 6.7 (29
)], but the observed decrease in both populations was sufficient to identify transition from ileum to cecum. A recent scintigraphic study has validated this pH change at the ileocolonic junction and has shown that the fall in pH observed with WMC corresponds to the time of arrival of the WMC (labeled with a radioisotope) into the cecum or ascending colon [the anatomy having been outlined with use of a different radioisotope (30
)]. In this validation study, we did not assess the effect of different amounts or types of fiber intake, the effect of vigorous exercise, or the potential influence of significant sigmoid diverticulosis and hypertrophy of the muscularis propria. These conditions might alter the pH profile at the ileocecal region or the propulsion or retention of the capsule through the distal colon. Formal prospective studies will be required to address these questions.
Occasionally, the pH drop at the ileocecal junction is not clearly discernible, as occurred in 1 participant in the current study. Reasons for the lack of the pH drop are not understood but may be related to the bacteria in the cecum, and previous food intake. In 4 participants, we could not clearly identify the rise in pH between the stomach and duodenum and this compromised assessment of the SLBTT. Therefore, there might be difficulty in interpreting the test in <1% for CTT and 3–4% for SLBTT, consistent with previous studies (12
The study also showed the relationship between CTT and SLBTT measured by the WMC and stool consistency measured by Bristol stool form scale, rather than stool frequency, confirming a prior study (31
). This is consistent with the significant relationship between colonic transit by scintigraphy and stool form in pharmacodynamic studies of renzapride or linaclotide (32
). In 10 healthy volunteers, there was significant correlation between overall, gastric and colonic transit measured by scintigraphy and by WMC (34
This study has therefore provided validation of the WMC to estimate colonic transit, by showing good agreement between the WMC and ROM method. The agreement and correlation in this study are higher than the study of Rao et al. that used a simplified ROM method to assess colonic transit with a single abdominal radiograph taken five days after marker ingestion (12
). It is relevant to note that relative to ROM, the WMC provides a 20% misdiagnosis in slow transit constipation and a false positive rate of 9% in normal transit constipation. However, this assumes that ROM is a “gold standard”; whereas, it should be termed a non-reference standard. The WMC is able to characterize pressure activity in the colon in health and disease states (35
). Studies are now under way to determine whether additional information of clinical relevance is provided by measurement of colonic contractile functions. The ability to measure transit and pressures has the potential to enhance the ability of gastroenterologists and surgeons in practice to assess patients with suspected motility disorders such as gastroparesis and slow transit constipation. This general availability of a technique with standardized and automated analysis contrasts with the lack of general applicability or availability of whole gut scintigraphy and intubated intraluminal manometry available at tertiary referral centers (36
). Capsule based methods do not expose patients to radiation, in contrast to radioscintigraphy and radiopaque marker methods, the latter requiring multiple fluoroscopic or radiologic images (39
Other capsule techniques are reported to measure gastrointestinal motility noninvasively, without radiation exposure, using very different techniques and measuring different dimensions of motor function. A magnet tracking analyses the origin, direction, amplitude and velocity of movements of a magnetic capsule relative to space-time plots detected through a detection matrix (4 × 4 magnetic field sensors) and dedicated software implanted in a laptop computer (40
). At present, this is a research technique in non-ambulant subjects. Image analysis with capsule endoscopy detects contractile patterns (phasic luminal closure and radial wrinkles by wall texture analysis), non-contractile patterns, intestinal content, and endoluminal motion (41
). It was used in patients with small intestinal motility disorders and in healthy volunteers exposed to glucagon (42
There are potential pitfalls with using all capsules to measure gut transit including technical failures, inability to swallow the capsule, the potential for non-passage of or intestinal obstruction by the capsule in stenosing gut disorders, and greater cost relative to the radiopaque marker transit method. Application of the WMC is contraindicated in patients with known esophageal or intestinal strictures, and children under 18 years of age, in whom validation studies have not yet been completed.
In conclusion, the WMC provides a clinically relevant estimate of colonic transit that is able to differentiate slow from normal transit constipation. Wireless motility capsule technology has the potential to bring valid, noninvasive motility measurements to the practice of gastroenterology in the community.