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 ileal mucosa obtained during TI intubation may facilitate diagnosis in selected patients, and ileoscopy with biopsy can provide important diagnostic information for suspected small bowel inflammatory diseases, particularly Crohn’s disease.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.2,13 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. All four database searches were conducted on October 1, 2025. Database-specific search strings for EMBASE, the Cochrane Library, and the Science Citation Index and source-level retrieval counts were not retained. Manual searching covered reference lists of included studies and relevant reviews; the source article for each of the eight additional studies was not recorded.
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 screened titles, abstracts, and full texts. Screening disagreements were resolved through discussion and consensus among the three reviewers. The review was not prospectively registered. Available study-selection counts are presented in Figure 1; database-specific retrieval counts and granular full-text exclusion reasons were not retained.
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
LG and TW independently extracted the data using a standardized extraction form. Discrepancies were resolved through discussion; if agreement could not be reached, YB adjudicated. LG, TW, and YS cross-verified the extracted data. No formal quality or risk-of-bias assessment was conducted. 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 extracted as reported in each source study and was defined as the proportion of TI intubations leading to a new diagnosis, additional investigation, treatment initiation, imaging, or surgery. Outcomes not reported by a source study were treated as missing rather than zero. 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. All included studies were prospective or retrospective observational studies; no randomized controlled trials were included. In addition, the methods of TI intubation and main outcome assessments varied.
Statistical analysis
Descriptive statistics were used to summarize study characteristics and crude aggregate proportions. Categorical variables are presented as percentages, and continuous variables are presented as reported by the source studies. Because of substantial clinical heterogeneity and overlapping indication categories, no inferential comparisons were performed across studies or indication groups.
Patient and public involvement statement
Patients or the public were not involved in the design, conduct, reporting, or dissemination plans of our research.
Results
The database searches identified 975 records in aggregate, and the available study-selection counts are shown in Figure 1. After 24 duplicates were removed, 951 records were screened. A total of 923 records were excluded and were collectively categorized in the retained records as case reports, letters, systematic reviews, or irrelevant studies; stage-specific exclusion reasons were not recorded. Twenty-eight studies were included from the database searches, and eight additional studies were identified by searching reference lists of included studies and relevant reviews. 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 | Republic of 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 (crude) | – | – | – | – | – | 77,215 | 50,917 | 65.9% (50,917/77,215) |
| 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% | – | 5.2% | – | 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% | 0.0% (0/354) | – | 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 diagnostic yield: 26 involved unselected samples and seven involved selected samples. The crude aggregate diagnostic-yield proportion was 2.6% (993/37,722), comprising 2.5% (871/35,339) in unselected samples and 5.1% (122/2,383) in selected samples. Management-change data were reported for 26,092 TI intubations; the crude descriptive proportions were 0.7% overall (175/26,092), 0.6% in unselected samples (139/24,285), and 2.0% in selected samples (36/1,807). Because the included studies were heterogeneous, no cross-study hypothesis testing was performed.
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 | 0.0% | – | 0 | – | |
| 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% (871/35,339) | 0.6% (139/24,285) | 871 | 139 | |
| SELECTED | | | | | | | |
| Geboes et al., 19985 | 300 | Diarrhea/ CD versus polyp surveillance | 5.0% | – | 15 | – | |
| 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) | 2.0% (36/1,807) | 122 | 36 | |
| TOTAL | 37,722 | – | 2.6% (993/37,722) | 0.7% (175/26,092) | 993 | 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 24,077 indication occurrences in 16 studies, including 22,698 occurrences from 12 unselected-sample studies and 1,379 occurrences from four selected-sample studies. Individual patients could contribute to more than one indication. The crude diagnostic-yield proportions were 26.7% for known IBD, 16.1% for anemia, 14.9% for abdominal pain, 12.4% for chronic diarrhea, and 3.2% for other indications; these overlapping categories were not compared inferentially.
Table 3Clinical indication occurrences and diagnostic yield
| 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 descriptively shows the highest crude diagnostic-yield proportion for IBD (26.7%), followed by anemia (16.1%), abdominal pain (14.9%), diarrhea (12.4%), and other indications (3.2%). Because indication groups overlapped and patient-level de-duplication was not possible, no statistical comparisons were performed between indication groups or between selected and unselected samples.
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. Histological assessment of biopsies from selected samples revealed abnormal findings in 22 of 927 patients (2.4%), compared descriptively with 91 of 2,587 patients (3.5%) in unselected samples; no cross-study inferential comparison was performed.
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
Cecal intubation, documented by visualization of cecal landmarks, is the standard marker of complete colonoscopy; TI intubation may provide additional information in selected cases. Colonoscopy completion is usually documented by endoscopic visualization and photography of cecal landmarks, with TI intubation serving as an optional adjunct.44 Unfortunately, photographs of the cecum often fail to convincingly demonstrate classical cecal landmarks, and the use of video is inconvenient. TI intubation can provide additional confirmation of examination extent when cecal landmarks are difficult to document.48 Incomplete colonoscopy can contribute to missed lesions, but this does not establish TI intubation as a routine requirement.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 diagnostic yield for malignant tumors is low, this case illustrates a possible role for TI evaluation in selected patients.49 For suspected small-bowel inflammatory disease, including Crohn’s disease, ileoscopy and biopsy may contribute to diagnosis alongside clinical assessment and cross-sectional imaging.50,51 TI endoscopy and biopsy may contribute to the differential diagnosis of disorders that mimic IBD but should be interpreted within the broader clinical context.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 variable success rates of TI intubation when attempted,18,19 with a mean intubation time of approximately 3.4 minutes reported in one prospective study.14 The reasons for unsuccessful intubation include technical difficulties, discomfort during the procedure, obstructive lesions, retained blood, poor bowel preparation, colonic redundancy, TI stricture, and inability to identify the ileal openings.7,28 While there are few complications,7 potential adverse events such as biopsy-associated bleeding and perforation should still be considered.35 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 descriptive summary, diagnostic-yield proportions were higher in selected than in unselected samples, particularly in studies of diarrhea, although no cross-study inferential comparison was performed.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 Evidence from a single case is insufficient to recommend TI intubation broadly for upper gastrointestinal or 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 illustrates a possible complementary role for TI examination when proximal gastrointestinal findings are inconclusive but cannot establish routine practice.
Our findings in Table 2 demonstrated that routine TI intubation seldom provided diagnostic information, while its additional time cost substantially increased the workload on a national scale, impacted histopathological services,23 and exacerbated patient discomfort. Taken together, these data support selective rather than routine TI intubation pending higher-quality comparative evidence.
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.35 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. These findings support a targeted biopsy approach, particularly for abnormal mucosa or a high pretest probability of ileal disease, while effects on diagnostic accuracy, procedure time, and risk require further study.
Beyond its diagnostic role, ileoscopy may be useful 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 established approach for assessing postoperative recurrence.56 Endoscopic recurrence is commonly graded using the Rutgeerts score, which informs subsequent treatment decisions.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 the timing of endoscopy should be individualized according to clinical stability and treatment-related risks.
There are several limitations to our review. First, all included studies were observational and showed substantial clinical and methodological heterogeneity, including inconsistent definitions of diagnostic yield and management change. Second, no formal quality or risk-of-bias assessment was conducted. Third, database-specific search strings for three databases, source-level retrieval counts, granular full-text exclusion reasons, and the specific sources of the eight manually identified studies were not retained, limiting reproducibility and complete PRISMA reporting. Fourth, management-change outcomes were missing from many studies, and indication categories overlapped without patient-level de-duplication. Consequently, aggregate proportions are presented only as crude descriptive summaries; no meta-analysis, number-needed-to-test calculation, cross-study hypothesis testing, or quantitative publication-bias assessment was performed. Finally, the review was not prospectively registered, which may introduce reporting bias.
In summary, cecal intubation remains the standard marker of complete colonoscopy. TI intubation can be considered when clinically indicated or when additional documentation of examination extent is needed. The observational evidence summarized here does not support routine TI intubation in all patients or its use as a standalone quality indicator. Reported complications are uncommon, but TI-specific adverse-event evidence is limited. Targeted biopsy is most appropriate for abnormal terminal ileal mucosa or a high pretest probability of ileal disease, whereas routine biopsy of normal-appearing mucosa has a low diagnostic yield.
Conclusions
Cecal intubation is the standard marker of complete colonoscopy. TI intubation may be considered selectively when clinically indicated or when additional documentation of examination extent is needed; the current evidence does not support routine TI intubation in all patients or its use as a standalone quality indicator. Biopsy should be considered when terminal ileal mucosa is abnormal or when clinical findings indicate a high pretest probability of ileal disease.
Declarations
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
Prof. Zhaoshen Li serves as Honorary Editor-in-Chief and Prof. Yu Bai serves as an Editorial Board Member of Cancer Screening and Prevention. Prof. Li and Prof. Bai were not involved in the editorial review or decision-making process for this article. The authors declare no other conflicts of interest.
Authors’ contributions
Study conception and design (JQ, JG, XH, YB, ZL); literature search and study screening (SW, ZH, XH); data extraction (LG, TW); data verification (LG, TW, YS); resolution of screening disagreements by consensus (SW, ZH, XH); adjudication of unresolved data-extraction disagreements (YB); statistical analysis (JQ, JG, XH); 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.