Introduction
Since the first report of successful terminal ileum (TI) intubation by Nagasako in 1971,1 there have been several reports describing the technical aspects, success rates, diagnostic yield, and biopsy outcomes in diseases involving the TI. TI intubation occurs during colonoscopy by many clinicians,2–4 and it plays an important role in diagnosing diseases. The TI hosts many toxic substances and is lined by specialized lymphoid tissue of the immune system; thus, ileoscopy is usually performed to assess the state of the ileum or to diagnose or exclude diseases such as inflammatory bowel disease (IBD), infectious diseases, and parasitic diseases,5–7 especially in the post-COVID-19 period, where the expanding gastrointestinal manifestations of COVID-19 infection are difficult to distinguish.8–10 Furthermore, histological examination of the ileal mucosa acquired during TI intubation may facilitate accurate and definitive diagnoses, and some small bowel inflammatory diseases can only be diagnosed by ileoscopy.11,12 All of these factors make TI intubation an appealing diagnostic technique during colonoscopy.
However, there is no absolute consensus on when ileoscopy should be attempted. Some physicians believe that this approach is an important adjunct to colonoscopy and should be used in all cases if the circumstances allow it.13 This may necessitate a change in management. Others believe that this treatment option is optional, depending on the indications and after considering the discomfort, time, yield, special techniques, and unnecessary risks.14,15 It also remains controversial whether an ileal biopsy should be attempted in patients undergoing TI intubation. As a result, evaluation and biopsy of the TI are left to the discretion of endoscopists according to their clinical experiences, after considering the indications, patient tolerance, operating techniques, and other difficulties during the examination.
This study was designed to ascertain whether TI intubation is a useful procedure for all patients who undergo a colonoscopy. We also aimed to further evaluate which clinical indication is more warranted with a higher diagnostic yield. Third, we evaluated whether TI biopsy should be performed in every patient despite a normal endoscopic appearance.
Materials and methods
A systematic search was performed in PubMed from January 1, 1971, to October 1, 2025, using the search terms “terminal ileums OR terminal ileum intubation OR ileum”, “intubations OR intubating OR catheterization OR intubate OR intubated OR intubation”, “ileoscopy OR ileoscopies OR ileocolonoscopy”, “yield OR diagnosis OR diagnose OR diagnosed OR diagnoses”, and “biopsies OR pathology OR biopsy”. Reference lists from the identified papers were further hand-searched to identify relevant studies. The EMBASE, Cochrane Library, and Science Citation Index were also searched for these topics.
The searches were restricted to English-language results. Articles were selected if the abstract contained a yield or biopsy of the TI in the form of published trials, other controlled or comparative studies, or case series. Three reviewers (SW, ZH, and XH) independently retrieved the data. If there were any disagreements, the three reviewers referred to the relevant data, discussed the data, and finally reached a consensus. Some of these data were analyzed using chi-square analyses. This review was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. While not prospectively registered, we have documented the search strategy and inclusion criteria transparently.
Inclusion and exclusion criteria: The studies included in this systematic review were those performed on TI intubation during colonoscopy and were not randomized controlled trials. Case reports, letters, systematic reviews, and studies on animals or cell lines were excluded. When there were duplicate studies, the study with the largest sample size was included.
Qualitative analysis and data extraction
Two authors extracted the data separately, and the results were compared. If there was any disagreement, the authors discussed the study with a third author and reached a final conclusion. We used Review Manager 5.0.16 (Cochrane Collaboration, Oxford, UK) to summarize the details of the studies. The extracted data included the first author, publication year, country, inclusion criteria, age and sex of the patients, study design, indication for colonoscopy, and outcomes. The outcomes included the TI intubation rate, yield of TI intubation, yield of TI biopsy, diagnostic yield, and rate of necessitating a change in management.
The TI intubation rate was defined as the proportion of TI intubations relative to the total number of colonoscopies. The yield of TI intubation was defined as the ratio of the number of patients with abnormal TI findings after TI intubation to the total number of TI intubations. The yield of TI biopsy was defined as the ratio of the number of patients with TI histopathological findings through TI biopsy to the total number of TI biopsies. The diagnostic yield was defined as the ratio of the number of patients with endoscopic or histopathological findings that led to clinical intervention through TI intubation to the total number of TI intubations. The rate of need for a change in management was defined as the ratio of the number of patients who received a new diagnosis or one we believed would lead to specific investigations or management, such as therapy initiation, further imaging, or surgical intervention, through TI intubation to the total number of TI intubations. Patients with diarrhea, abdominal pain, weight loss, high C-reactive protein level, and hypoalbuminemia, along with previous negative stool testing for infection, were defined as having a high pretest probability of Crohn’s disease.16 Significant ileum histology was defined as histopathological findings from biopsy specimens of endoscopically normal-appearing ileal mucosa that necessitate a clinical intervention.
It was inappropriate to perform a meta-analysis due to the significant clinical heterogeneity of the studies. Based on their design, the studies were categorized into randomized crossover trials, randomized parallel-group trials, and non-randomized controlled trials. In addition, the methods of TI intubation and main outcome assessments varied.
Statistical analysis
Descriptive statistics were used to summarize study characteristics. Categorical variables are presented as percentages, and continuous variables are presented as mean ± standard deviation or mean as appropriate. Categorical variables were evaluated with a chi-square test or Fisher’s exact test. A P-value of <0.05 was considered to indicate statistical significance, and all tests were two-sided.
Patient and public involvement statement
Patients or the public were not involved in the design, conduct, reporting, or dissemination plans of our research.
Results
We included 975 studies, and the process of identifying relevant studies is shown in Figure 1. Of the 975 initially potentially relevant studies, 24 were duplicates, and 923 were case reports, letters, systematic reviews, or irrelevant studies. Thus, 28 studies were included, and eight were acquired by manually searching the reference lists. Finally, 36 studies were included.3,5–7,14,17–47 Of these, 15 were prospective studies, and the remaining 21 were retrospective. We defined “selected research” as TI intubation performed to investigate the etiology of a certain group of patients with symptoms of underlying digestive diseases, while “unselected research” refers to TI intubation performed on all unscreened patients undergoing colonoscopy, without prior selection based on specific digestive symptoms under investigation.
The basic characteristics and diagnostic yield of the included studies are summarized in Table 1.3,5–7,14,17–47 Eleven studies were from Europe, ten from the USA, eleven from Asia, two from Brazil, one from Australia, and one from Nigeria. The median number of TI-treated patients was 358. The success rate of TI intubation ranged from 30.9% to 100% among the prospective studies. The yield of TI intubation varied from 0.4% to 41%. The lowest incidence was reported in the study by Harewood et al.,22 where only 17 abnormalities were found in 3,858 unselected patients who underwent TI assessment; the highest incidence was reported in the study by Geboes et al.,5 where endoscopic lesions of the TI were found in 123 of 300 patients.
Table 1Basic characteristics of included studies in systematic review
| Study (year) | Country | Sex (women, men) | Average years | Study design | Case selection | Patients (n) | Patients of TI intubation (n) | TI intubation rate |
|---|
| Borsch et al., 198417 | Germany | | 53.9 | Prospective | Unselected | 555 | 400 | 72.0% |
| Kundrotas et al., 199414 | USA | 106, 164 | Women 59, Men 61 | Prospective | Unselected | 270 | 213 | 78.9% |
| Zwas et al., 19956 | UK | – | – | Prospective | Unselected | 144 | 138 | 95.8% |
| Geboes et al., 19985 | Belgium | Diarrhea (119, 138) Control (21, 22) | Diarrhea 35.8 (11–71) Control 47.6 (39–75) | Prospective | Diarrhea versus polyp surveillance (control) | 300 | Diarrhea 257, Control 43 | 100.0% |
| Bhasin et al., 20007 | India | – | – | Prospective | Unselected | 66 | 57 | 86.4% |
| Shah et al., 200118 | USA | 114, 54 | 51 | Retrospective | Diarrhea | 168 | 142 | – |
| Yusoff IF, 200219 | Australia | 621, 509 | 45 | Retrospective | Diarrhea | 1,131 | 508 | – |
| Ansari et al., 200320 | UK | – | – | Prospective | Unselected | 120 | 117 | 97.5% |
| Morini et al., 200321 | Italy | CNBD (56, 82) Control (56, 82) | – | Prospective | CNBD versus control | CNBD 156, Control 138 | CNBD 138, Control 138 | 93.9% |
| Cherian et al., 20043 | UK | 971, 733 | 60 | Retrospective | Unselected | 2,537 | IBD 120, without IBD 1,584 | – |
| Harewood et al., 200522 | USA | 2,401, 1,457 | – | Retrospective | Unselected | 21,638 | 3,858 | – |
| Yoong et al., 200623 | UK | – | – | Retrospective | Unselected | 346 | 346 | – |
| Iacopini et al., 200624 | Italy | 336, 264 | 65 | Prospective | Unselected | 600 | 272 | – |
| Powell et al., 200725 | UK | 131, 101 | 52 | Prospective | Unselected | 232 | 232 | – |
| McHugh et al., 200726 | USA | 249, 165 | 37.6 | Retrospective | Unselected | 414 | 414 | – |
| Kennedy et al., 200827 | USA | 2,812, 3,596 | 63 | Retrospective | Unselected | 6,408 | 6,408 | – |
| Jeong et al., 200828 | South Korea | 1,782, 2,139 | 45 | Prospective | Unselected | 3,921 | 3,417 | 87.1% |
| Melo et al., 200929 | Brazil | 47, 64 | 51.6 | Prospective | Macroscopically normal terminal ileum mucosa | 111 | 111 | – |
| Emami et al., 200930 | Iran | 73, 55 | 63 | Prospective | Unselected | 128 | 93 | 72.7% |
| Melton et al., 201131 | USA | 6,009, 3,776 | 46 | Retrospective | Unselected | 9,785 | 9,785 | – |
| Sayilir et al., 201132 | Turkey | – | – | Retrospective | CNBD versus others | 295 | CNBD 135, others 160 | – |
| Makkar et al., 201333 | USA | 464, 225 | 48.3 | Retrospective | CNBD | 689 | 370 | – |
| Wijewantha et al., 201434 | Sri Lanka | – | – | Retrospective | Unselected | 764 | 764 | – |
| Koksal et al., 201435 | Turkey | 142, 155 | 42 | Retrospective | Normal-appearing TI and with <5 aphthous ulcers | 297 | 297 | – |
| Velidedeoğlu et al., 201536 | Turkey | 24, 33 | 44.12 ± 11.42 | Retrospective | Unselected | 57 | 57 | – |
| Akere et al., 201737 | Nigeria | – | – | Prospective | Unselected | 272 | 84 | 30.9% |
| Meral et al., 201838 | Turkey | 726, 584 | 55.79 ± 14.29 | Prospective | Unselected | 1,310 | 1,032 | 78.8% |
| Borsotti et al., 201939 | Italy | – | – | Prospective | CNBD | 504 | 492 | 97.6% |
| Mari et al., 202040 | Israel | 878, 922 | – | Retrospective | Unselected | 1,800 | 1,800 | – |
| Leiman et al., 202041 | USA | 4,411, 3,388 | 58 (52–64) | Retrospective | Unselected | 7,799 | 3,356 | – |
| Wang et al., 202042 | China | 774, 901 | 49 | Retrospective | Unselected | 1,675 | 994 | – |
| Rosevics et al., 202143 | Brazil | 2,181, 1,201 | 56.9 ± 13.1 | Retrospective | Unselected | 3,382 | 3,382 | – |
| Alkhatib et al., 202244 | USA | 461, 547 | 51.7 | Retrospective | Unselected | 1,008 | 1,008 | – |
| Vora et al., 202445 | USA | 185, 114 | 52 | Retrospective | Macroscopically normal terminal ileum mucosa | 299 | 299 | – |
| Shu et al., 202446 | China | 4,004, 3,595 | 53 | Retrospective | Unselected | 7,599 | 7,599 | – |
| Dąbkowski et al., 202547 | Poland | 169, 128 | 55.2 | Retrospective | Unselected | 297 | 297 | – |
| TOTAL | – | – | – | – | – | 7,884 | 6,619 | 84.0% (6,619/7,884) |
| Study (year) | Yield of TI intubation (%) | Yield of TI biopsy, by indication where available (%)
| All cases (%) | Diagnostic yield† | Rate of necessitating a change in management‡ | §Note |
|---|
| Endoscopically normal TI (%) | Endoscopically abnormal TI (%) |
|---|
| Borsch et al., 198417 | – | – | – | 5.0% | 5.0% | – | 1 |
| Kundrotas et al., 199414 | 2.0% | Not biopsy | 25.0% | – | 0.5% | 0.5% | 2 |
| Zwas et al., 19956 | – | – | – | Asymptomatic 2.7%, Diarrhea 29% | Overall 7.2%, Asymptomatic 2.7%, Diarrhea 29% | 2.9% | 3 |
| Geboes et al., 19985 | Overall 41%, Diarrhea/ CD 47.8%, Control 0% | 1.10% | – | Diarrhea/ CD 48.6%, Control 0 | – | – | 3 |
| Bhasin et al., 20007 | 22.8% | – | – | – | 22.8% | 8.8% | 1 |
| Shah et al., 200118 | – | 2.4% | – | – | 3.5% | 1.4% | 2 |
| Yusoff et al., 200219 | 5.1% | 0 | – | – | 5.1% | 2.6% | 1 |
| Ansari et al., 200320 | 17.9% | – | – | 2.6% | 20.5% | – | 3 |
| Morini et al., 200321 | CNBD 34.0%, Control 10.8% | CNBD 2.2 % Control 2.4% | CNBD 46.8% Control 13.3 % | – | CNBD 17.4%, Control 3.6% | – | 2 |
| Cherian et al., 20043 | IBD 16.7%, without IBD 2.59% | Overall 1.5%, IBD 0, without IBD 1.7% | – | IBD 19%, without IBD 7.4% | 4.1% | – | 2 |
| Harewood et al., 200522 | 0.4% | – | – | – | 0.4% | – | 1 |
| Yoong et al., 200623 | Abdominal mass 33.3%, Diarrhea 9.2^ | – | – | 4.6% | 4.6% | 2.3% | 2 |
| Iacopini G, 200624 | 5.5% | – | – | 2.2% | 2.2% | 2.2% | 2 |
| Powell et al., 200725 | – | 2.3% | – | – | 2.2% | 0.0% | 2 |
| McHugh et al., 200726 | 19.3% | 5.1%, significant histologic chronic inflammation 4.2% | 73.8%, significant histologic chronic inflammation 67.5% | 18.4% | 18.4% | – | 2 |
| Kennedy et al., 200827 | 1.0% | Not biopsy | 32% | 0.3% | 0.3% | 0.04% | 2 |
| Jeong et al., 200828 | Overall 3.7% | Not biopsy | Overall 8.8%, Right lower quadrant pain 1.8%, Diarrhea 0.4 | – | 0.3% | 0.1% | 2 |
| Melo et al., 200929 | – | 0.9% | – | – | – | – | 2 |
| Emami et al., 200930 | 4.3% | – | – | – | 4.3% | 2.2% | 1 |
| Melton et al., 201131 | Overall 24.9% | Total 5.0%, CD 10.9% | Total 47.7%, CD 75.0% | – | – | – | – |
| Sayilir et al., 201132 | – | Overall 4.4 %, CNBD 5.9%, Other 3.1% | – | – | Overall 4.4 %, CNBD 5.9%, Other 3.1% | 0.0% | 2 |
| Makkar et al., 201333 | – | – | – | 5.1% | 5.1% | 1.6% | 2 |
| Wijewantha et al., 201434 | 7.1% | 3.8% | 37.0% | 6.2% | 10.6% | 6.2% | 2 |
| Koksal et al. 201435 | 33.0% | 8.5% | Overall 59.8% | 25.3% | 25.3% | – | 2 |
| Velidedeoğlu et al., 201536 | – | – | 14% | 14% | 14% | 1.8% | 2 |
| Akere et al., 201737 | 2.4% | – | – | 17.9% | 17.9% | – | 2 |
| Meral et al., 201838 | Overall 6%, IBD 14.1% chronic diarrhea 12.1% | Not biopsy | 62.9% | – | 3.8% | – | 2 |
| Borsotti et al., 201939 | 11.4% | – | – | 10% | 3% | 3% | 2 |
| Mari et al., 202040 | 12% | – | – | 12% | 12% | – | 2 |
| Leiman et al., 202041 | 1.1% | – | 50% | 0.1% | 0.1% | – | 2 |
| Wang et al., 202042 | – | – | – | 0.8% | 0.8% | – | 2 |
| Rosevics et al., 202143 | 5.3% | – | 50.84% | 2.7% | 2.7% | 0.9% | 2 |
| Alkhatib et al., 202244 | 3.7% | Not biopsy | 48.6% | – | 1.8% | 1.8% | 2 |
| Vora et al., 202445 | – | 4.3% | – | 4.3% | 1.3% | 1.3% | 2 |
| Shu et al., 202446 | 2% | – | – | 2.0% | 0.1% | 0.1% | 2 |
| Dąbkowski et al., 202547 | 1.7% | – | – | 1.7% | – | – | 1 |
The yields of the TI biopsies were separated into three parts: biopsies obtained from endoscopically normal TIs, biopsies acquired from endoscopically abnormal TIs, and biopsies of unknown origin. Generally, routine biopsy of a normal macroscopic TI has a low diagnostic yield, ranging from 0% to 8.5%, while the yield of endoscopically abnormal TIs varies from 8.8% to 73.8%.
The diagnostic yield and rate of necessitating a change in management are summarized in Table 2.3,5–7,14,17–28,30,32–46 A total of 33 studies reported the diagnostic yield of ileoscopy; 26 studies included patients who were unselected, and seven studies focused on patients with diarrhea. The diagnostic yield in all patients was 2.6% (995 abnormalities were found in 37,722 patients); 0.5% of patients changed their management. The percentage of patients with a total diagnostic yield was much greater among the selected patients than among the unselected patients (5.1% vs. 2.5%) (χ2 = 61.01, P < 0.0001). The percentage of patients necessitating a change in management among the selected patients was twice as high as that among the unselected patients (1.5% vs. 0.4%) (χ2 = 60.36, P < 0.0001).
Table 2Diagnostic yield of terminal ileum intubation with or without biopsy
| Study (year) | Patients of TI intubation (n) | Case selection | Diagnostic yield (%) | Necessitate a change in management (%) | Diagnostic yield (n) | Necessitate a change in management (n) | Note† |
|---|
| UNSELECTED | | | | | | | |
| Borsch et al., 198417 | 400 | Unselected | 5.0% | – | 20 | – | 1 |
| Kundrotas et al., 199414 | 213 | Unselected | 0.5% | 0.5% | 1 | 1 | |
| Zwas et al., 19956 | 138 | Unselected | 7.2% | 2.9% | 10 | 4 | |
| Bhasin et al., 20007 | 57 | Unselected | 22.8% | 8.8% | 13 | 5 | |
| Ansari et al., 200320 | 117 | Unselected | 20.5% | – | 24 | – | |
| Cherian et al., 20043 | 1,704 | Unselected | 4.1% | – | 70 | – | |
| Harewood et al., 200522 | 3,858 | Unselected | 0.4% | – | 17 | – | |
| Yoong et al., 200623 | 346 | Unselected | 4.6% | 2.3% | 16 | 8 | |
| Iacopini et al., 200624 | 272 | Unselected | 2.2% | 2.2% | 6 | 6 | |
| Powell et al., 200725 | 232 | Unselected | 2.2% | 0 | 5 | 0 | |
| McHugh et al., 200726 | 414 | Unselected | 18.4% | – | 76 | – | |
| Kennedy et al., 200827 | 6,408 | Unselected | 0.3% | 0.04% | 22 | 3 | |
| Jeong et al., 200828 | 3,417 | Unselected | 0.3% | 0.1% | 11 | 3 | |
| Emami et al., 200930 | 93 | Unselected | 4.3% | 2.2% | 4 | 2 | 2 |
| Wijewantha et al., 201434 | 764 | Unselected | 10.6% | 6.2% | 81 | 47 | |
| Koksal et al., 201435 | 297 | Normal-appearing TI and with <5 aphthous ulcers | 25.3% | – | 75 | – | |
| Velidedeoğlu et al., 201536 | 57 | Unselected | 14% | 1.8% | 8 | 1 | |
| Akere et al., 201737 | 84 | Unselected | 17.9% | – | 15 | – | |
| Meral et al., 201838 | 1,032 | Unselected | 5.2% | – | 54 | – | |
| Mari et al., 202040 | 1,800 | Unselected | 12% | – | 216 | | |
| Leiman et al., 202041 | 354 | Unselected | 0.6% | – | 2 | | |
| Wang et al., 202042 | 994 | Unselected | 0.8% | – | 8 | – | |
| Rosevics et al., 202143 | 3,382 | Unselected | 2.7% | 0.9% | 90 | 30 | |
| Alkhatib et al., 202244 | 1,008 | Unselected | 1.8% | 1.8% | 18 | 18 | |
| Vora et al., 202445 | 299 | Macroscopically normal terminal ileum mucosa | 1.3% | 1.3% | 4 | 4 | |
| Shu et al., 202446 | 7,599 | Unselected | 0.1% | 0.1% | 7 | 7 | |
| SUBTOTAL | 35,339 | – | 2.5% (873/35,339) | 0.4% (139/35,339) | 873 | 139 | |
| SELECTED | | | | | | | |
| Geboes et al., 19985 | 300 | Diarrhea/ CD versus polyp surveillance | 5.0% | – | 15 | 0 | |
| Shah et al., 200118 | 142 | Diarrhea | 3.5% | 1.4% | 5 | 2 | |
| Yusoff et al., 200219 | 508 | Diarrhea | 5.1% | 2.6% | 26 | 13 | |
| Morini et al., 200321 | 276 | CNBD versus control | CNBD 17.4%, Control 3.6% | – | 24, 5 | – | |
| Sayilir et al., 201132 | 295 | CNBD versus others | Overall 4.4 %, CNBD 5.9%, Other 3.1% | 0.0% | Overall 13, CNBD 8, others 5 | 0 | |
| Makkar et al., 201333 | 370 | CNBD | 5.1% | 1.6% | 19 | 6 | |
| Borsotti et al., 201939 | 492 | CNBD | 3.0% | 3.0% | 15 | 15 | |
| SUBTOTAL | 2,383 | – | 5.1% (122/2,383) | 1.5% (36/2,383) | 122 | 36 | |
| TOTAL | 37,722 | – | 2.6% (995/37,722) | 0.5% (175/37,722) | 995 | 175 | |
The indications for colonoscopies in patients with successful TI intubation are documented in Table 3,3,5,6,19,21,23,24,26,28,31,32,35,36,38,40,43 with a total of 24,077 patients in 16 studies, 22,698 unselected patients in 12 studies, and 1,379 selected patients in four studies. The most common indications for unselected patients were IBD, anemia, abdominal pain, and diarrhea. Compared with all other indications, diagnostic yield was more common for known IBD, anemia, abdominal pain, and chronic diarrhea. These values were 26.7%, 16.1%, 14.9%, and 12.4%, respectively.
Table 3Clinical indications for colonoscopy
| Study (year) | Diarrhea
| Abdominal pain
| IBD
| Anemia
| Others
| Note† |
|---|
| n | Diagnostic yield | n | Diagnostic yield | n | Diagnostic yield | n | Diagnostic yield | n | Diagnostic yield |
|---|
| UNSELECTED | | | | | | | | | | | |
| Zwas et al., 19956 | 28 | 8 (28.6%) | 7 | 0 | – | – | 7 | 0 | 96 | 2 (2.1%) | 1 |
| Cherian et al., 20043 | – | – | – | – | 120 | 20 (16.7%) | – | – | 1,584 | 41 (2.6%) | 1 |
| Yoong et al., 200623 | 119 | 11 (9.2%) | 74 | 2 (2.7%) | 33 | 5 (15.2%) | 36 | 4 (11.1%) | 65 | 6 (9.2%) | 1 |
| Iacopini et al., 200624 | – | – | 31 | 0.0% | – | – | 45 | 2 (4.4%) | 196 | 4 (2.0%) | 2 |
| McHugh et al., 200726 | 135 | 14 (10.4%) | 23 | 1 (4.3%) | 157 | 45 (28.7%) | 62 | 9 (14.5%) | 37 | 7 (18.9%) | 2 |
| Jeong et al., 200828 | 1,058 | 58 (5.5%) | 1,254 | 48 (3.8%) | – | – | 82 | 2 (2.4%) | 1,522 | 17 (1.1%) | 1 |
| Melton et al., 201131 | 5,108 | 735 (14.4%) | 3,629 | 758 (20.9%) | 1,644 | 460 (27.9%) | 502 | 156 (31.1%) | – | – | 1 |
| Koksal et al., 201435 | – | – | – | – | 23 | 8 (34.8%) | 44 | 17 (38.6%) | – | – | 2 |
| Velidedeoğlu et al.,201536 | 19 | 6 (31.6%) | 14 | 0.0% | – | – | – | – | 24 | 2 (8.3%) | |
| Meral et al., 201838 | 74 | 9 (12.2%) | 89 | 4 (4.5%) | 85 | 12 (14.1%) | 252 | 8 (3.2%) | 532 | 29 (5.5%) | 1 |
| Mari et al., 202040 | – | – | – | – | 72 | 32 (44.4%) | 161 | 25 (15.5%) | – | – | |
| Rosevics et al., 202143 | 421 | 27 (6.4%) | 486 | 21 (4.3%) | 273 | 61 (22.3%) | 278 | 13 (4.7%) | 2,197 | 85 (3.9%) | |
| SUBTOTAL | 6,962 | 868 (12.5%) | 5,607 | 834 (14.9%) | 2,407 | 643 (26.7%) | 1,469 | 236 (16.1%) | 6,253 | 193 (3.1%) | |
| Range | – | 5.5–31.6% | – | 0.0–20.9% | – | 14.1–44.4% | – | 3.2–38.6% | – | 1.1–18.9% | |
| SELECTED | | | | | | | | | | | |
| Geboes et al., 19985 | 257 | 44 (17.1%) | – | – | – | – | – | – | 43 | 0 (0.0%) | 1 |
| Yusoff et al., 200219 | 508 | 26 (5.1%) | – | – | – | – | – | – | – | – | 1 |
| Morini et al., 200321 | 138 | 47 (34.1%) | – | – | – | – | – | – | 138 | 15 (10.9%) | 1 |
| Sayilir et al., 201132 | 135 | 8 (5.9%) | – | – | – | – | – | – | 160 | 5 (3.1%) | 2 |
| SUBTOTAL | 1,038 | 125 (12.0%) | – | – | – | – | – | – | 341 | 20 (5.9%) | |
| Range | – | 5.1–17.1% | – | – | – | – | – | – | – | 0.0–10.9% | |
| TOTAL | 8,000 | 993 (12.4%) | 5,607 | 834 (14.9%) | 2,407 | 643 (26.7%) | 1,469 | 236 (16.1%) | 6,594 | 213 (3.2%) | |
Melton et al.31 screened asymptomatic patients for cancer—the “Other” group had the greatest proportion of abnormal ileoscopy findings (63%), but this did not explain the specific screening outcomes to be excluded. Table 3 shows that the most common clinical indication was IBD (26.7%), which was more common during TI intubation. According to the four selected studies, patients with diarrhea had a diagnostic yield of 12.0%, which was similar to that of diarrhea patients in the previous 12 studies (χ2 = 0.15, P = 0.69). However, the diagnostic value of the diarrhea group was significantly greater than that of the “Others” group for both the unselected and selected patients (χ2 = 392.62, P < 0.0001; χ2 = 10.41, P < 0.01).
It remains controversial whether biopsy via normal ileoscopy is suitable for clinical intervention, especially for patients with diarrhea. We assessed the yield of ileal histopathology with a normal endoscopic appearance, and the results are presented in Table 4.3,5,18,19,21,25,26,29,32,34,35,45 Twelve studies were included; these consisted of seven studies involving unselected patients, and five studies involving patients with diarrhea. Of the 2,587 unselected patients who underwent ileoscopy, new information was added to 91 patients (3.5%) despite having normal endoscopic TI findings. In addition, histological assessment of biopsies from selected patients revealed abnormal findings in 22 of the 927 patients (2.4%), which was consistent with previous data from unselected patients (χ2 = 2.87, P = 0.09).
Table 4Yield of ileum histopathology with normal endoscopic appearance
| Study (year) | Patients of TI intubation (n) | Case selection | Endoscopically normal (n) | Histopathology with normal ileum (n) | Significant ileum histology (%) |
|---|
| UNSELECTED† | | | | | |
| Cherian et al., 20043 | IBD 120, without IBD 1,584 | Unselected | Overall 717, IBD 85, without IBD 632 | Overall 11, IBD 0, without IBD 11 | Overall 1.5%, IBD 0, without IBD 1.7% |
| Powell et al., 200725 | 232 | Unselected | 216 | 5 | 2.3% |
| McHugh et al., 200726 | 414 | Unselected | 334 | 17 | 5.1% |
| Melo et al., 200929 | 111 | Macroscopically normal terminal ileum mucosa | 111 | 1 | 0.9% |
| Wijewantha et al., 201434 | 764 | Unselected | 710 | 27 | 3.8% |
| Koksal et al., 201435 | 297 | Normal-appearing TI and with <5 aphthous ulcers | 200 | 17 | 8.5% |
| Vora et al., 202445 | 299 | Macroscopically normal terminal ileum mucosa | 299 | 13 | 4.3% |
| SUBTOTAL | 3,821 | – | 2,587 | 91 | 3.5% (91/2,587) |
| SELECTED† | | | | | |
| Geboes et al., 19985 | 300 (Diarrhea/ CD 257, Control 43) | Diarrhea /CD versus polyp surveillance (control) | 177 | 2 | 1.1% |
| Shah et al., 200118 | 142 | Diarrhea | 83 | 2 | 2.4% |
| Yusoff et al., 200219 | 508 | Diarrhea | 158 | 0 | 0.0% |
| Morini et al., 200321 | CNBD138, Control138 | CNBD versus control | 214 | 5 | 2.3% |
| Sayilir et al., 201132 | 295 (CNBD135, others160) | CNBD versus others | 295 | 13 | 4.4% |
| SUBTOTAL | 1,521 | – | 927 | 22 | 2.4% (22/927) |
| TOTAL | 5,342 | – | 3,514 | 113 | 3.2% (113/3,514) |
Discussion
TI intubation is the gold standard for the completion of colonoscopy and is vital to the diagnostic process. Usually, colonoscopy documentation includes endoscopic visualization, photography, video of cecal landmarks, and TI intubation.44 Unfortunately, photographs of the cecum often fail to convincingly demonstrate classical cecal landmarks, and the use of video is inconvenient. This approach results in better assurance of completion during terminal ileoscopy.48 In addition, several studies have shown that failure to detect tumors during screening colonoscopy might result from an incomplete procedure.22,30 A recent study reported a case of a small bowel neuroendocrine tumor in the TI detected through colonoscopy with TI intubation during screening. Although the overall diagnostic yield for malignant tumors remains low, TI evaluation continues to be a valuable tool in cancer screening.49 Additionally, some small bowel inflammatory diseases can be established only by ileoscopy, and such diseases include Crohn’s disease, which preferentially affects the small intestine—especially the TI.50,51 In conclusion, TI endoscopy and biopsy are generally considered the gold standards for the differential diagnosis of infectious, inflammatory, and noninflammatory disorders that mimic IBD according to symptomatic and endoscopic findings.35
There have been no randomized controlled trials focusing on the role of ileoscopy or biopsy, and the evidence in our report mainly consists of retrospective/prospective observational studies and a case-control series. Studies have reported that the success rate of TI intubation varies from 72% to 97% when attempted,18,19 with patients treated for no more than 3–4 m on average.14 The reasons for unsuccessful intubation include technical difficulties, discomfort, obstructive lesions, retained blood, poor bowel preparation,28 redundancy of the colon,14 TI stricture, and inability to identify ileal openings.7 While there are few complications,7 a 79-year-old man was reported with a colonic perforation of the sigmoid diverticulum.35 This was not associated with the performance technique. These features make TI intubation an appealing and applicable diagnostic method for colonoscopy.
Although several studies have described the yield of ileoscopy, it is still unclear whether TI intubation should be performed routinely in all patients. Some researchers believe that TI intubation should be a standard practice.30 In several studies, ileoscopic findings revealing normal TI mucosa may also help to diagnose, differentiate, and rule out some mimicking diseases. In these cases, a normal TI or biopsy specimen helps to avoid further diagnostic studies and aids in making wise decisions for the next step of management.14,30,35 Therefore, although the number of positive findings in unselected patients was low, normal TI intubation was also very helpful in clinical intervention. However, other researchers have suggested that TI intubation should not be performed for every patient due to the low yield.5,23 In our analysis, ileoscopy rarely revealed pathological findings in unselected patients, while TI intubation might offer much more diagnostic information among selected patients, especially those with diarrhea.5,18,19,21,32,33
TI intubation has a high diagnostic yield when applied to specific clinical conditions, such as chronic nonbloody diarrhea and IBD.5,6,18,21,39 It also plays an important role in the diagnosis of colonic tuberculosis, intestinal stricture, ileitis, and lymphoma.52 We recommend considering TI intubation even when the procedural indication is related to the “upper gastrointestinal” tract or presents with nonspecific symptoms. A representative case reported by Amadu et al.53 well illustrates this point: a 53-year-old woman presented with epigastric pain and showed no improvement after a course of proton pump inhibitors. Subsequent upper gastrointestinal endoscopy revealed persistent duodenal lesions. Ileoscopy performed concurrently demonstrated aphthous ulcers in the TI, and magnetic resonance imaging further indicated mild inflammation in the same region, ultimately leading to a diagnosis of duodenal Crohn’s disease.53 This case highlights that TI examination can provide critical clinical and endoscopic evidence when proximal gastrointestinal findings remain inconclusive.
Our findings in Table 2 demonstrated that routine TI intubation seldom provided diagnostic information, while its additional time cost significantly increased the workload on a national scale, impacted histopathological services,23 and exacerbated patient discomfort. However, against the backdrop of the rising global prevalence of IBD and the clinically non-negligible incidence of incidental ileitis—including aphthous ulcers, erosions, nonsteroidal anti-inflammatory drug-induced enteropathy, and early Crohn’s disease—we must also recognize the practical importance of establishing terminal ileal intubation as a standard step in most colonoscopies. This is based on two key considerations: first, early Crohn’s disease frequently localizes to the TI, and missed diagnosis may lead to delayed treatment and disease progression; second, attempting intubation only in cases with strong indications may hinder the maintenance and improvement of endoscopists’ technical proficiency. Therefore, incorporating the terminal ileal intubation rate as a quality key performance indicator will not only enhance the detection of pathological findings but also serve as an essential measure to ensure the quality of endoscopic practice.
For patients undergoing TI intubation, routine mucosal biopsy when the endoscopic appearance is normal is controversial. Yusoff et al.19 verified that microscopic findings from normal ileoscopy in patients with chronic diarrhea did not contribute to their diagnosis. Nonetheless, Sayilir showed no significant difference in the yield of TI biopsies between patients who presented with chronic nonbloody diarrhea and those with other indications.32 This finding is similar to our data—the yield of TI biopsy in unselected patients was 3.5%, and the percentage ranged from 0.9% to 8.5% in patients with a normal ileoscopy. The selected patients complaining of diarrhea had a subtotal yield of ileal histopathology with a normal endoscopic appearance of 2.4% (ranging from 0% to 4.4%). The low yield suggested little value in undertaking a biopsy in macroscopically normal TIs. However, some experts believe that a normal-appearing ileal mucosa may sometimes reveal significant pathological findings. Misra et al.54 reported the diagnostic role of TI biopsies in patients with suspected intestinal tuberculosis. There have been cases of cytomegalovirus colitis and microsporidiosis diagnosed by biopsy of normal-appearing TIs.5,6,32,54 Harewood and McHugh maintained that biopsies from normal-appearing mucosa in patients suspected of having Crohn’s disease may yield histological abnormalities due to TI ‘skipping’ or intramural disease.22,26 The results of a study by Samuel et al.55 found that 10 of 24 (41.7%) patients with clinically active Crohn’s disease who were assessed endoscopically demonstrated microscopic evidence of chronic inflammation. This finding suggests that TI biopsies may be useful in patients with Crohn’s disease with a high pretest probability. It can also be argued that a normal TI biopsy result is useful in some cases to avoid subsequent or repeat ileoscopies. In light of this, adopting a targeted biopsy strategy in clinical practice may be the preferable approach. This strategy emphasizes precise sampling of suspicious lesions, thereby maintaining diagnostic accuracy while avoiding extensive random biopsies, ultimately improving efficiency, shortening procedure time, and reducing patient risk.
Beyond its diagnostic role, ileoscopy plays a crucial role in the postoperative management of Crohn’s disease. For patients who have undergone ileocecal resection, endoscopic monitoring of the TI within six to twelve months after surgery is an essential process for assessing and preventing recurrence.56 The degree of endoscopic recurrence is standardized using the Rutgeerts score, which directly guides subsequent treatment strategies: a score ≥ i2 indicates moderate to severe recurrence, necessitating step-up intensification of therapy and timely adjustment or escalation of medication regimens to achieve endoscopic remission.57 However, the timing of such monitoring endoscopy requires careful consideration. If patients experience postoperative infectious complications (such as surgical site infection, anastomotic leakage, or pneumonia) or have related high-risk factors (such as corticosteroid use, malnutrition, or perioperative blood transfusion),58 endoscopic examination should be appropriately postponed until acute complications have fully resolved, nutritional status has improved, and immunosuppressive risks have been mitigated. The algorithm for deciding whether to obtain a terminal ileal biopsy is presented in Figure 2.
There are several limitations to our review. First, the included studies were predominantly observational in nature, exhibiting significant clinical and methodological heterogeneity. Second, the substantial heterogeneity observed among the included studies—such as the varying definitions of “diagnostic yield” and “need for a change in management” across different studies—precluded us from performing a formal meta-analysis or conducting a quantitative assessment of publication bias. Nevertheless, by providing weighted pooled estimates, number needed to test, and detailed outcome ranges, we have maximized the transparency and interpretability of the results. Third, our review was not prospectively registered (e.g., in PROSPERO), which may introduce reporting bias.
In summary, high-quality colonoscopy is essential for the screening and management of conditions such as colorectal tumors and inflammatory diseases, and terminal ileal intubation represents a key component of this procedure. To standardize this practice, it is recommended to document ileal landmarks—such as the ileocecal valve, plicae, and lymphoid follicles—with photographic records after intubation, while also monitoring and reporting TI intubation rates at the institutional level. Although the overall safety of colonoscopy is closely linked to sedation management, the risk of perforation during TI intubation itself is extremely low, particularly when performed by experienced operators. For beginners, mastering certain techniques can effectively shorten the learning curve. Methods such as applying retroflexion in the cecum, adhering to gentle suction and insufflation sequences, and utilizing the water exchange technique can significantly improve intubation success rates and enhance the patient experience.
Conclusions
Terminal ileal intubation is the gold standard for completing colonoscopy. It has a vital role in the diagnostic process. We recommend that TI intubation be adopted as standard practice and attempted in all patients with photo documentation. In cases with abnormal mucosal findings or red-flag symptoms—particularly diarrhea, suspected IBD, abdominal pain, or anemia—biopsy should be obtained.
Declarations
Acknowledgement
We extend our sincerest appreciation and gratitude to our esteemed colleagues Shuling Wang et al. in our team for their invaluable contributions to our research endeavors. The conference abstract they published, presented at the 18th Congress of Gastroenterology in China, proved to be a pivotal resource for our work.59
Funding
This work was supported by the National Natural Science Foundation of China (82170567, 82100587, and 82300641), the Shanghai Sailing Program (No. 23YF1458700), the Chenguang Program of the Shanghai Education Development Foundation, and the Shanghai Municipal Education Commission (Grant No. 23CGA44).
Conflict of interest
None.
Authors’ contributions
Study conception and design (JQ, JG, XH, YB, ZL), acquisition of data (LG, TW), analysis and interpretation of data (JQ, JG, XH, LG, TW), drafting of the manuscript (JQ, JG), critical revision of the manuscript for important intellectual content (YS, ZH, YB, SW, ZL), study supervision (YB, ZL). All authors have made substantial contributions to this work and have approved the final manuscript.