Histological Diagnostic Yield and Clinical Significance of the First Biopsy in Device-Assisted Enteroscopy in Patients with Small Bowel Diseases: A KASID Multicenter Study
by
, , and
Hyeon Jeong Goong
1, 
Tae Joon Kim
2,
Kwangwoo Nam
3,
Jihye Park
4,
Jin-Oh Kim
5,
Hyun Gun Kim
5,
Bong Min Ko
1,
Seong Ran Jeon
5,* and
Small Intestine Research Group of the Korean Association for the Study of Intestinal Diseases (KASID)
† 1
Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon 14584, Korea
2
Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
3
Department of Internal Medicine, Dankook University Hospital, Dankook University College of Medicine, Cheonan 31116, Korea
4
Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
5
Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul 04401, Korea
*
Author to whom correspondence should be addressed.
†
Membership of the Group Names are provided in the Acknowledgments.
Diagnostics 2022, 12(4), 964; https://doi.org/10.3390/diagnostics12040964
Submission received: 10 March 2022
/
Revised: 6 April 2022
/
Accepted: 10 April 2022
/
Published: 12 April 2022
(This article belongs to the Special Issue Device-Assisted Enteroscopy: An Update on Diagnostic and Therapeutic Approaches)
Abstract
:Device-assisted enteroscopy (DAE) enables the direct visualization of small bowel lesions with histological diagnosis; however, few studies have described the diagnostic performance of enteroscopic biopsy. We investigated the diagnostic performance of enteroscopic biopsy. We used a nationwide multicenter enteroscopy database to identify patients who underwent DAE with biopsy for small bowel diseases. The patients were classified into the tumor and non-tumor groups according to the final diagnosis. They were also divided into diagnostic and non-diagnostic groups based on the enteroscopic biopsy results. The clinical significance of the first biopsy and histological diagnostic yield of DAE were analyzed. Among the 112 procedures investigated, 32 (28.9%) were diagnosed with tumors, and 80 (71.7%) were diagnosed with non-tumor diseases. The overall histological diagnostic yield of DAE was 43.7%. The histological diagnostic yield was significantly higher in the tumor than in the non-tumor group (81.2% vs. 28.8%, p < 0.001). The mean number of biopsies was significantly higher in the diagnostic than in the non-diagnostic group (5.6 ± 3.3 vs. 3.7 ± 2.1, p = 0.001). In the diagnostic group, 87.7% of the cases were histologically confirmed at the first biopsy. Therefore, the first biopsy should be performed carefully.
1. Introduction
The development of capsule endoscopy (CE) and device-assisted enteroscopy (DAE) has increased the diagnostic yield (DY) for small bowel disease. Accordingly, histological diagnosis using DAE is becoming important. DAE enables endoscopic procedures (e.g., biopsy, polypectomy, and hemostasis) and direct visualization of lesions. The DY of DAE for small bowel diseases has been reported to range from 47% to 90% [1,2,3,4,5,6,7]. However, previous data on the DY of DAE included both endoscopic and histological diagnoses. In addition, as the most common indication for DAE in those studies was suspected to be small bowel bleeding (SSBB), the DY was mainly evaluated on the basis of endoscopic diagnosis rather than histological diagnosis. Therefore, studies on the diagnostic performance of enteroscopic biopsy are limited. The optimal biopsy strategies in conventional endoscopy have been investigated. Theoretically, the diagnostic accuracy is expected to improve as the number of biopsy specimens increases. However, Choi et al. reported that 78.1–81.3% of histological diagnoses were confirmed at the first biopsy in patients with advanced gastric and colon cancers. Additionally, the DY increased to 93.8–98.3% until the fourth biopsy but did not significantly increase further with more biopsies [8]. Therefore, the quality of the first biopsy is important for diagnosis. In addition, the effect of changes in the lesion surface (e.g., bleeding) on subsequent biopsies might limit the improvement in DY with increasing number of biopsies. Although DAE is relatively safe with a low rate of procedure-related complications, it is technically difficult and more invasive than conventional endoscopy. Therefore, the technical difficulties associated with DAE may affect the diagnostic efficacy of biopsy. However, the histological performance of enteroscopic biopsy and the role of the first biopsy have not been thoroughly investigated. Therefore, in this study, we aimed to evaluate the histological DY of DAE, the factors affecting the DY of enteroscopic biopsy, and the clinical significance of the first biopsy.
2. Materials and Methods
2.1. Study Design and Patients
Using a nationwide multicenter enteroscopy database, we retrospectively analyzed the clinical data and medical records of patients who underwent DAE with biopsy for the evaluation of small bowel diseases between March 2004 and August 2021. We excluded cases in which the final diagnosis could not be confirmed by histopathology or in which the details of biopsy profiles were not assessable. This study was performed in accordance with the ethical principles of the Declaration of Helsinki and was approved by the institutional review board of each participating institution. The requirement for informed consent was waived by the institutional review boards owing to the retrospective nature of this study.
2.2. Device Assisted Enteroscopy
To identify the location and characteristics of small-bowel lesions, capsule endoscopy, computed tomography (CT)/CT enterography (CTE), magnetic resonance enterography (MRE), or small-bowel follow-through was performed before DAE. The route of entry (antegrade or retrograde insertion) was determined by each endoscopist according to the suspected lesion location, as assessed on prior imaging studies. All patients were instructed to fast for at least 8 h before the procedure. For the retrograde approach, the patients underwent bowel preparation with 2 L polyethylene glycol electrolyte lavage solution before the procedure. Most patients underwent DAE under moderate conscious sedation with midazolam, pethidine, or propofol. DAE was performed using a single-balloon enteroscopy (SBE) system (SIF-Q180; Olympus Medical Inc., Tokyo, Japan) or a double-balloon enteroscopy (DBE) system (EN-450P5/20, T5/20; Fujinon Inc., Saitama, Japan), depending on the available equipment at each institution. Enteroscopic biopsy was performed using the biopsy forceps available for enteroscopy at each facility.
2.3. Data Collection and Outcome Measures
Patient-related variables, including age, sex, and history of abdominal surgery, were reviewed. The indications for DAE included SSBB, imaging abnormalities detected before DAE, symptoms or signs of suspected small-bowel disease, and suspected/established Crohn’s disease (CD). Lesion-related variables, including location and histopathological results, were reviewed using endoscopic images and histopathological reports. The final diagnosis was confirmed by histopathological examination of enteroscopic biopsy, conventional endoscopic biopsy, or surgical specimens. The histopathological diagnosis was confirmed by expert pathologists at each hospital. The final diagnosis of CD and vasculitis was confirmed using a combination of clinical, endoscopic, radiologic, laboratory, and histological findings. The patients were classified into two groups according to the final diagnosis: tumor and non-tumor groups. We also divided the patients into the diagnostic and non-diagnostic groups based on the result of enteroscopic biopsy relative to the final diagnosis. The diagnostic group was defined as patients in whom the enteroscopic biopsy result was concordant with the final diagnosis. With respect to procedure-related factors, the DAE system, insertion route, number of biopsies, and post-procedural complications (e.g., perforation, bleeding, and pancreatitis) were documented.
The primary outcome of this study was the clinical significance of the first biopsy for the diagnosis of small bowel diseases. The secondary outcomes were the histological DY of DAE and the factors affecting the diagnostic performance of enteroscopic biopsy.
2.4. Statistical Analysis
Categorical variables are presented as frequencies and percentages. Continuous variables are presented as mean ± standard deviation values. All categorical and continuous variables were compared using the chi-square test and Student’s t-test, respectively. Fisher’s exact test was used when the expected value in any of the cells of a contingency table was <5. A logistic regression model with odds ratios (ORs) and 95% confidential intervals (CIs) was used to evaluate the factors associated with the DY of enteroscopic biopsy. A two-sided p value of <0.05 was considered statistically significant. Statistical analysis was performed using SPSS (version 22.0; SPSS Inc., Chicago, IL, USA).
3. Results
3.1. Baseline Characteristics of Patients and Small Bowel Lesions
Among the 244 procedures performed in 239 patients, histological confirmation of the final diagnosis was not obtained in 89 patients. These patients had a clinical diagnosis of ischemic enteritis, non-steroidal anti-inflammatory drug-associated enteropathy, or non-specific enteritis with non-specific inflammation on enteroscopic biopsy. Additionally, detailed biopsy profiles were not assessable in 43 patients. Therefore, 112 procedures in 107 patients were included in the final analysis (Figure 1). The baseline characteristics of the patients and lesions are summarized in Table 1. The most common indications for DAE were imaging abnormalities detected before DAE (28.6%), gastrointestinal symptoms or signs (27.7%), and suspected/established CD (25.9%). In terms of the final diagnosis, tumors were diagnosed in 32 patients (28.9%), and non-tumor diseases were diagnosed in 80 patients (71.4%). Imaging studies of the location and characteristics of the lesions were mostly performed using CT/CTE or MRE (87.5%) before enteroscopy. Of the patients, 70.5% were treated with medical therapy, 25.9% underwent surgery, and 1.8% underwent endoscopic treatment. Two patients diagnosed with CD underwent endoscopic balloon dilatation.
3.2. DAE and Enteroscopic Biopsy in the Tumor and Non-Tumor Groups
The procedure profiles of DAE and enteroscopic biopsy according to the final diagnosis are shown in Table 2. No significant difference in enteroscopy methods was observed between the tumor and non-tumor groups, and DBE was the most frequently used method (96.4%). The proportion of lesions located in the ileum was significantly higher in the non-tumor group than in the tumor group (p < 0.001). In this regard, the proportion of retrograde insertions was significantly higher in the non-tumor group (p < 0.001). Lesions detected in two or more segments of the small intestine were diagnosed as B-cell lymphoma in the tumor group (n = 1) and CD (n = 5) and vasculitis (n = 1) in the non-tumor group. The total number of biopsies was higher in the tumor group than in the non-tumor group, although the difference was not significant (5.2 ± 3.4 vs. 4.3 ± 2.6, p = 0.118). The total procedure time was significantly shorter in the tumor group than in the non-tumor group (49.0 ± 29.2 vs. 75.1 ± 43.0 min, p = 0.003). Procedure-related complications such as bleeding, pancreatitis, and perforation did not occur in any of the cases.
3.3. Clinical Significance of the First Biopsy
Figure 2 shows the cumulative DYs at the first and second or more biopsies. The overall DY of the first biopsy was 38.3%. After two or more biopsies, the cumulative DY increased to 43.7%, without statistical significance (p = 0.415). Among patients in whom diagnosis was made by enteroscopic biopsy, histological confirmation was obtained at the first biopsy in 87.7% and at the second or further biopsies in 12.3%. In subgroup analysis, the DY increased after two or more biopsies, although the difference was not statistically significant in both the non-tumor (from 25% to 28.8%, p = 0.593) and tumor (from 71.9% to 81.2%, p = 0.376) groups.
3.4. Histological DY of DAE and Factors Affecting the DY
The overall DY of enteroscopic biopsy was 43.7% (49/112). The DYs according to enteroscopic procedures and lesion characteristics are shown in Table 3. The patients were classified into the diagnostic (n = 49) and non-diagnostic (n = 63) groups. No significant associations were found between the enteroscopy methods, history of abdominal surgery, or diagnostic information obtained on prior imaging studies and the DY of enteroscopic biopsy. However, in the diagnostic group, the proportion of lesions in the duodenum or jejunum was higher than that of lesions in the ileum or in multiple sites of the small bowel (65.2% vs. 28.8%, p < 0.001). In terms of the insertion route, the proportion of anterograde insertion was significantly higher than that of retrograde insertion in the diagnostic group (55.7% vs. 29.4%, p = 0.005). The mean number of biopsies was significantly higher in the diagnostic group than in the non-diagnostic group (5.6 ± 3.3 vs. 3.7 ± 2.1, p = 0.001). The DY was significantly higher in the tumor group than in the non-tumor group (81.2% vs. 28.8%, p < 0.001). In the non-tumor group, no significant difference in DY was observed between CD and non-CD cases (27.1% vs. 33.3%, p = 0.589). The DYs for all diseases are shown in Supplementary Table S1. In univariate and multivariable logistic regression analyses, tumors (OR, 6.21; 95% CI, 1.80–21.43) and a higher number of biopsies (OR, 1.36; 95% CI, 1.13–1.65) were significant factors for a positive DY (Table 4).
4. Discussion
As the DY and therapeutic yield of enteroscopy have improved with advances in endoscopic technology, the diagnostic accuracy of enteroscopic biopsy is expected to not significantly differ from that of conventional endoscopy. In addition, we considered that the biopsy-targeting technique during DAE may be comparable to that during conventional endoscopy. Therefore, we hypothesized that the significance of the first biopsy during DAE would be similar to that previously reported for conventional endoscopy. However, whether the technical difficulty of DAE causes a difference in biopsy performance compared with conventional endoscopy has not yet been investigated.
In this study, although the number of biopsies was a significant factor for DY, 87.7% of the cases histologically diagnosed by DAE were confirmed at the first biopsy in both the tumor and non-tumor groups. The quality of the first biopsy is important because post-biopsy bleeding interferes with the endoscopic visual field during the subsequent biopsies. In tumors, optical investigation of the surface pattern before biopsy is necessary to avoid sampling of the necrotic surface or of the precancerous mucosa near the cancer-altered mucosa. In inflammatory diseases, exudate, debris, or necrosis-covered mucosa usually interferes with biopsy targeting. In addition, endoscopists might hesitate about performing further biopsy of ulcerative or erosive surfaces because of concerns about bleeding or perforation. The significance of an adequate first biopsy has been shown in previous studies on optimal biopsy strategies for diagnosing tumors during conventional endoscopy. Choi et al. analyzed the diagnostic accuracy of endoscopic biopsy in 59 patients with advanced gastric cancer and 32 patients with advanced colon cancer [8]. The histological DY of the first biopsy was 81.3% for gastric cancer and 78.1% for colon cancer. Although the second to fourth biopsies showed improved diagnostic accuracy of up to 98.3%, further biopsies did not significantly affect the DY. In addition, a retrospective study of 858 cases of early gastric cancer demonstrated that the diagnostic sensitivity of one endoscopically obtained biopsy specimen was 83.9% [9]. With advances in endoscopic imaging resolution and instrumentation, accurate biopsy targeting has become possible, resulting in appropriate tissue acquisition with fewer biopsies than in the past. The histological DY of the first biopsy in our study was similar to that in previous reports. Therefore, the quality of the first biopsy is also important in DAE.
Studies on the diagnostic accuracy of enteroscopic biopsy are limited. In a multicenter study that analyzed 877 DAE procedures, among 294 patients who underwent enteroscopic biopsy, the histological DY was 59.5% for overall small bowel diseases, 72.9% for tumors, and 54.5% for ulcer/inflammatory/stricture diseases [10]. In our study, the overall histological DY was 43.7%. The DY according to the two disease groups was 81.2% in the tumor group and 28.8% in the non-tumor group (p < 0.001). This difference in DY between the tumor and non-tumor groups was similar to that of biopsy during conventional endoscopy. For tumors, the histological diagnosis rate was reported to be 80–90% in conventional enteroscopy [11,12,13,14,15]. Therefore, in this study, enteroscopic biopsy showed comparable diagnostic effectiveness to conventional endoscopic biopsy in patients with tumors. With respect to non-tumor diseases, the histological diagnosis rate in our study was lower than that for tumors. Previous reports have shown a poor correlation between endoscopic appearance and histological results in inflammatory disease in small bowel [16,17]. Tun et al. reported that histology was diagnostic in 8–15% of patients with suspected small bowel CD. In addition, 58% of the cases with a macroscopically positive appearance on DAE showed histologically normal or non-specific findings [18]. In addition, histological confirmation is difficult in other inflammatory diseases because of the discontinuous involvement of inflammation. The histological diagnosis rate was 20–38% for intestinal tuberculosis and 5% for vasculitis [19,20]. The histological detection rate of eosinophilic gastroenteritis was estimated to be up to 80% [21]. Similar to the results of previous studies, CD, intestinal tuberculosis, and vasculitis showed a lower histological diagnosis rate (<50%) than eosinophilic gastroenteritis (60%) in the current study.
In this study, we found that an increase in the number of biopsies improved the histological DY in logistic regression analysis (OR, 1.36; p = 0.001). The mean number of biopsies in the tumor group was higher than that in the non-tumor group, although the difference was not statistically significant (p = 0.118). Current guidelines recommend an adequate number of biopsies for tumors (four to six biopsies) during conventional endoscopy [22,23,24,25,26]. However, more biopsies are required to diagnose inflammatory diseases. The histological diagnosis of CD requires serial biopsy of multiple segments of normal and abnormal mucosa [27]. At least eight biopsies are recommended for diagnosing intestinal tuberculosis [20]. Even for eosinophilic gastroenteritis, which has a relatively higher histological diagnosis rate than other inflammatory diseases, more than five to six biopsies are recommended [21]. Therefore, considering the current recommendations, the number of biopsies in the non-tumor group in this study was relatively low. Moreover, we could not determine whether the number of biopsies was significantly different between the diagnostic and non-diagnostic groups among patients with non-tumor diseases (5.3 ± 3.2 vs. 3.9 ± 2.2, p = 0.053). Unlike in conventional endoscopy, no recommendation on the optimal number of biopsies during DAE has been proposed. In this study, the mean number of biopsies in the tumor group was similar, and the DY was comparable, to that in conventional endoscopy. However, in the case of inflammatory diseases, the DY might have been underestimated because the mean number of biopsies was lower than the current recommendations for conventional endoscopy. As enteroscopy is more invasive and technically difficult than conventional endoscopy, further studies on the optimal number of enteroscopic biopsies for each small bowel disease are necessary.
This study had a few limitations. First, owing to the retrospective study design, the procedural protocols were inconsistent. Differences in the biopsy forceps, sedation protocols, endoscopists’ experiences, and skills in each participating institution might have affected the DY. However, we were unable to evaluate these factors in our study. Second, as discussed earlier, the number of biopsies for inflammatory diseases was lower than the current recommendations. The number of biopsies for inflammatory diseases was mostly fewer than five to six. In this regard, the DY was relatively lower than previously published data. Third, the DYs of SBE and DBE could not be compared because DBE was performed in 96.4% of the procedures. However, the technical success rate, DY, and therapeutic yield of SBE and DBE were not different in recent studies [28,29,30]. Despite these limitations, this study is valuable because data on biopsy protocols in DAE are lacking, compared with conventional endoscopy. Enteroscopic biopsy is technically challenging, and the anatomy of the small intestine is different from that of the stomach or colon. Therefore, a further large-scale prospective study investigating the diagnostic performance of enteroscopic biopsy is needed to develop adequate biopsy protocols according to disease type.
5. Conclusions
The histological DY of enteroscopic biopsy was comparable to that of conventional endoscopy. The DY was higher for tumors than for non-tumor diseases. In addition, the DY improved as the number of biopsies increased. However, most of the cases diagnosed by enteroscopic biopsy were histologically confirmed at the first biopsy. Therefore, care should be taken when performing the first biopsy.
Supplementary Materials
The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/diagnostics12040964/s1. Yields in the tumor and non-tumor group/s1, Supplementary Table S1.
Author Contributions
S.R.J. planned and designed the study. T.J.K., K.N. and J.P. carried out data collection. Data analysis was performed by H.J.G. under the supervision of J.-O.K. and B.M.K. H.G.K. supervised the writing of the manuscript. All authors have read and agreed to the published version of the manuscript.
Funding
This study was supported by the Soonchunhyang University Research Fund.
Institutional Review Board Statement
This study was performed in accordance with the ethical principles of the Declaration of Helsinki. The study protocol was approved by the Institutional Review Board and the Hospital Research Ethics Committee of Soonchunhyang University Hospital (IRB No: SCHBC 2022-01-007, 20 January 2022).
Informed Consent Statement
Not applicable.
Data Availability Statement
The datasets generated or analyzed during the current study are available from the corresponding author on reasonable request.
Acknowledgments
This study was supported by the Soonchunhyang University Research Fund and Small Intestine Research Group of the Korean Association for the Study of Intestinal Disease (KASID).
Conflicts of Interest
S.R.J. was supported by a grant from Soonchunhyang University Research Fund. Other authors have no conflicts to declare. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
References
- Ramchandani, M.; Reddy, D.N.; Gupta, R.; Lakhtakia, S.; Tandan, M.; Rao, G.V.; Darisetty, S. Diagnostic yield and therapeutic impact of single-balloon enteroscopy: Series of 106 cases. J. Gastroenterol. Hepatol. 2009, 24, 1631–1638. [Google Scholar] [CrossRef]
- Upchurch, B.R.; Sanaka, M.R.; Lopez, A.R.; Vargo, J.J. The clinical utility of single-balloon enteroscopy: A single-center experience of 172 procedures. Gastrointest. Endosc. 2010, 71, 1218–1223. [Google Scholar] [CrossRef]
- Xin, L.; Liao, Z.; Jiang, Y.-P.; Li, Z.-S. Indications, detectability, positive findings, total enteroscopy, and complications of diagnostic double-balloon endoscopy: A systematic review of data over the first decade of use. Gastrointest. Endosc. 2011, 74, 563–570. [Google Scholar] [CrossRef] [PubMed]
- Jeon, S.R.; Kim, J.O.; Byeon, J.S.; Yang, D.H.; Ko, B.M.; Goong, H.J.; Jang, H.J.; Park, S.J.; Kim, E.R.; Hong, S.N.; et al. Enteroscopy in Crohn’s Disease: Are There Any Changes in Role or Outcomes Over Time? A KASID Multicenter Study. Gut Liver 2021, 15, 375–382. [Google Scholar] [CrossRef] [PubMed]
- Estevinho, M.M.; Pinho, R.; Fernandes, C.; Rodrigues, A.; Ponte, A.; Gomes, A.C.; Afecto, E.; Correia, J.; Carvalho, J. Diagnostic and therapeutic yields of early capsule endoscopy and device-assisted enteroscopy in the setting of overt GI bleeding: A systematic review with meta-analysis. Gastrointest. Endosc. 2021, 95, 610–625.e9. [Google Scholar] [CrossRef] [PubMed]
- Rahman, A.; Ross, A.; Leighton, J.A.; Schembre, D.; Gerson, L.; Lo, S.K.; Waxman, I.; Dye, C.; Semrad, C. Double-balloon enteroscopy in Crohn’s disease: Findings and impact on management in a multicenter retrospective study. Gastrointest. Endosc. 2015, 82, 102–107. [Google Scholar] [CrossRef] [PubMed]
- Wang, P.; Wang, Y.; Dong, Y.; Guo, J.; Fu, H.; Li, Z.; Du, Y. Outcomes and safety of double-balloon enteroscopy in small bowel diseases: A single-center experience of 1531 procedures. Surg. Endosc. 2021, 35, 576–583. [Google Scholar] [CrossRef] [PubMed]
- Choi, Y.; Choi, H.S.; Jeon, W.K.; Kim, B.I.; Park, D.I.; Cho, Y.K.; Kim, H.J.; Park, J.H.; Sohn, C.I. Optimal number of endoscopic biopsies in diagnosis of advanced gastric and colorectal cancer. J. Korean Med. Sci. 2012, 27, 36–39. [Google Scholar] [CrossRef]
- Nishitani, M.; Yoshida, N.; Tsuji, S.; Masunaga, T.; Hirai, H.; Miyajima, S.; Dejima, A.; Nakashima, T.; Wakita, S.; Takemura, K.; et al. Optimal number of endoscopic biopsies for diagnosis of early gastric cancer. Endosc. Int. Open 2019, 7, E1683–E1690. [Google Scholar] [CrossRef] [Green Version]
- Lee, B.I.; Choi, H.; Choi, K.Y.; Byeon, J.S.; Jang, H.J.; Eun, C.S.; Cheon, J.H.; Shin, S.J.; Kim, J.O.; Lee, M.S.; et al. Clinical characteristics of small bowel tumors diagnosed by double-balloon endoscopy: KASID multi-center study. Dig. Dis. Sci. 2011, 56, 2920–2927. [Google Scholar] [CrossRef] [Green Version]
- Marshall, J.B.; Diaz-Arias, A.A.; Barthel, J.S.; King, P.D.; Butt, J.H. Prospective evaluation of optimal number of biopsy specimens and brush cytology in the diagnosis of cancer of the colorectum. Am. J. Gastroenterol. 1993, 88, 1352–1354. [Google Scholar] [PubMed]
- Yalamarthi, S.; Witherspoon, P.; McCole, D.; Auld, C.D. Missed diagnoses in patients with upper gastrointestinal cancers. Endoscopy 2004, 36, 874–879. [Google Scholar] [CrossRef] [PubMed]
- Gado, A.; Ebeid, B.; Abdelmohsen, A.; Axon, A. Improving the Yield of Histological Sampling in Patients with Suspected Colorectal Cancer During Colonoscopy by Introducing a Colonoscopy Quality Assurance Program. Gastroenterol. Res. 2011, 4, 157–161. [Google Scholar] [CrossRef] [PubMed]
- Kwack, W.G.; Ho, W.J.; Kim, J.H.; Lee, J.H.; Kim, E.J.; Kang, H.W.; Lee, J.K. Understanding the diagnostic yield of current endoscopic biopsy for gastric neoplasm: A prospective single-center analysis based on tumor characteristics stratified by biopsy number and site. Medicine 2016, 95, e4196. [Google Scholar] [CrossRef]
- Zhang, M.; Liu, S.; Hu, Y.; Bao, H.B.; Meng, L.N.; Wang, X.T.; Xu, Y.; Zhao, J.; Lu, B. Biopsy strategies for endoscopic screening of pre-malignant gastric lesions. Sci. Rep. 2019, 9, 14909. [Google Scholar] [CrossRef] [Green Version]
- Jeong, S.H.; Lee, K.J.; Kim, Y.B.; Kwon, H.C.; Sin, S.J.; Chung, J.Y. Diagnostic value of terminal ileum intubation during colonoscopy. J. Gastroenterol. Hepatol. 2008, 23, 51–55. [Google Scholar] [CrossRef]
- Zhong, Q.; Zhang, A.; Huang, J.; Yan, W.; Lin, J.; Huang, Q.; Huang, X.; Yu, T.; Zhu, L.; Xu, C. Analysis and Follow up of Endoscopy Results in 1099 Patients with Terminal Ileum Lesions. Can. J. Gastroenterol. Hepatol. 2020, 2020, 8838613. [Google Scholar] [CrossRef]
- Tun, G.S.; Rattehalli, D.; Sanders, D.S.; McAlindon, M.E.; Drew, K.; Sidhu, R. Clinical utility of double-balloon enteroscopy in suspected Crohn’s disease: A single-centre experience. Eur. J. Gastroenterol. Hepatol. 2016, 28, 820–825. [Google Scholar] [CrossRef]
- Gong, E.J.; Kim, H.D.; Chun, J.H.; Ahn, J.Y.; Choi, K.S.; Jung, K.W.; Lee, J.H.; Choi, K.D.; Song, H.J.; Lee, G.H.; et al. Endoscopic Findings of Upper Gastrointestinal Involvement in Primary Vasculitis. Gut Liver 2016, 10, 542–548. [Google Scholar] [CrossRef] [Green Version]
- Mehta, V.; Desai, D.; Abraham, P.; Rodrigues, C. Making a Positive Diagnosis of Intestinal Tuberculosis with the Aid of New Biologic and Histologic Features: How Far Have We Reached? Inflamm. Intestig. Dis. 2019, 3, 155–160. [Google Scholar] [CrossRef]
- Abou Rached, A.; El Hajj, W. Eosinophilic gastroenteritis: Approach to diagnosis and management. World J. Gastrointest. Pharmacol. Ther. 2016, 7, 513–523. [Google Scholar] [CrossRef] [PubMed]
- Beg, S.; Ragunath, K.; Wyman, A.; Banks, M.; Trudgill, N.; Pritchard, D.M.; Riley, S.; Anderson, J.; Griffiths, H.; Bhandari, P.; et al. Quality standards in upper gastrointestinal endoscopy: A position statement of the British Society of Gastroenterology (BSG) and Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS). Gut 2017, 66, 1886–1899. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Davila, R.E.; Rajan, E.; Adler, D.; Hirota, W.K.; Jacobson, B.C.; Leighton, J.A.; Qureshi, W.; Zuckerman, M.J.; Fanelli, R.; Hambrick, D.; et al. ASGE guideline: The role of endoscopy in the diagnosis, staging, and management of colorectal cancer. Gastrointest. Endosc. 2005, 61, 1–7. [Google Scholar] [CrossRef]
- Loughrey, M.B.; Shepherd, N.A. The indications for biopsy in routine upper gastrointestinal endoscopy. Histopathology 2021, 78, 215–227. [Google Scholar] [CrossRef] [PubMed]
- Pouw, R.E.; Barret, M.; Biermann, K.; Bisschops, R.; Czako, L.; Gecse, K.B.; de Hertogh, G.; Hucl, T.; Iacucci, M.; Jansen, M.; et al. Endoscopic tissue sampling—Part 1: Upper gastrointestinal and hepatopancreatobiliary tracts. European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2021, 53, 1174–1188. [Google Scholar] [CrossRef]
- Pouw, R.E.; Bisschops, R.; Gecse, K.B.; de Hertogh, G.; Iacucci, M.; Rutter, M.; Barret, M.; Biermann, K.; Czako, L.; Hucl, T.; et al. Endoscopic tissue sampling—Part 2: Lower gastrointestinal tract. European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2021, 53, 1261–1273. [Google Scholar] [CrossRef]
- Maaser, C.; Sturm, A.; Vavricka, S.R.; Kucharzik, T.; Fiorino, G.; Annese, V.; Calabrese, E.; Baumgart, D.C.; Bettenworth, D.; Nunes, P.B.; et al. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications. J. Crohn’s Colitis 2018, 13, 144–164K. [Google Scholar] [CrossRef] [Green Version]
- Domagk, D.; Mensink, P.; Aktas, H.; Lenz, P.; Meister, T.; Luegering, A.; Ullerich, H.; Aabakken, L.; Heinecke, A.; Domschke, W.; et al. Single- vs. double-balloon enteroscopy in small-bowel diagnostics: A randomized multicenter trial. Endoscopy 2011, 43, 472–476. [Google Scholar] [CrossRef]
- Lipka, S.; Rabbanifard, R.; Kumar, A.; Brady, P. Single versus double balloon enteroscopy for small bowel diagnostics: A systematic review and meta-analysis. J. Clin. Gastroenterol. 2015, 49, 177–184. [Google Scholar] [CrossRef]
- Kim, T.J.; Kim, E.R.; Chang, D.K.; Kim, Y.H.; Hong, S.N. Comparison of the Efficacy and Safety of Single- versus Double-Balloon Enteroscopy Performed by Endoscopist Experts in Single-Balloon Enteroscopy: A Single-Center Experience and Meta-Analysis. Gut Liver 2017, 11, 520–527. [Google Scholar] [CrossRef] [Green Version]
Figure 1.
Flow diagram for selection the screening-eligible case.
Figure 2.
Cumulative diagnostic yields according to the number of serial enteroscopic biopsies.
Table 1.
Baseline characteristics of the cases and final diagnosis.
| N = 112 | |
|---|---|
| Age, year, mean ± SD 1 | 43.4 ± 16.4 |
| Male, n (%) | 82 (73.2) |
| History of abdominal surgery, n (%) | 18 (16.1) |
| Indications for DAE 2, n (%) | |
| Suspected small bowel bleeding | 29 (25.9) |
| Imaging abnormalities | 32 (28.6) |
| Gastrointestinal symptoms and signs | 31 (27.7) |
| Evaluation of suspected/established Crohn’s disease | 14 (12.5) |
| Others (anemia, treatment, surveillance) | 6 (5.3) |
| Prior diagnostic modalities, n (%) | |
| Capsule endoscopy | 25 (22.3) |
| CT/CTE or MRE | 98 (87.5) |
| SBFT 3 | 29 (25.9) |
| Final diagnosis, n (%) | |
| Tumor disease | 32 (28.6) |
| Adenocarcinoma | 15 (13.4) |
| Lymphoma | 11 (9.8) |
| Malignant GIST 4 | 2 (1.8) |
| Leiomyosarcoma | 2 (1.8) |
| Inflammatory polyp | 1 (0.9) |
| Lipoma | 1 (0.9) |
| Non-Tumor disease | 80 (71.4) |
| Crohn’s disease | 59 (52.7) |
| Intestinal tuberculosis | 10 (8.9) |
| Eosinophilic enteritis | 3 (2.7) |
| Behcet’s disease | 3 (2.7) |
| Vasculitis | 3 (2.7) |
| Meckel diverticulum | 2 (1.8) |
| Treatment, n (%) | |
| Medical treatment | 79 (70.5) |
| Endoscopic treatment | 2 (1.8) |
| Surgical treatment | 29 (25.9) |
| Observation | 2 (1.8) |
1 SD, standardized deviation; 2 DAE, device-assisted enteroscopy; 3 SBFT, small bowel follows through; 4 GIST, gastrointestinal stromal tumor.
Table 2.
Technical characteristics of device-assisted enteroscopy and biopsy in tumor and non- tumor groups.
Table 2.
Technical characteristics of device-assisted enteroscopy and biopsy in tumor and non- tumor groups.
| Tumor (N = 32) | Non-tumor (N = 80) | p Value | |
|---|---|---|---|
| Lesion location, n (%) | <0.001 | ||
| Duodenum | 3 (100) | 0 | |
| Jejunum | 25 (58.1) | 18 (41.9) | |
| Ileum | 3 (5.1) | 56 (94.9) | |
| Multiple | 1 (14.3) | 6 (85.7) | |
| Enteroscopy methods | 0.556 | ||
| SBE 1 | 0 (0) | 3 (100) | |
| DBE 2 | 32 (29.4) | 77 (70.6) | |
| Insertion route | <0.001 | ||
| Anterograde | 28 (45.9) | 33 (54.1) | |
| Retrograde | 4 (7.8) | 47 (92.2) | |
| Total number of biopsy, mean ± SD 3 | 5.2 ± 3.4 | 4.3 ± 2.6 | 0.118 |
| Total procedure time, minutes, mean ± SD | 49.0 ± 29.2 | 75.1 ± 43.0 | 0.003 |
| Complications, n (%) | 0 | 0 | NA 4 |
1 SBE, single balloon enteroscopy; 2 DBE, double balloon enteroscopy; 3 SD, standardized deviation; 4 NA, not applicable.
Table 3.
Diagnostic yields of enteroscopic biopsy according to the technical characteristics of device assisted enteroscopy and final diagnosis.
Table 3.
Diagnostic yields of enteroscopic biopsy according to the technical characteristics of device assisted enteroscopy and final diagnosis.
| Diagnostic (N = 49) | Non-Diagnostic (N = 63) | p-Value | |
|---|---|---|---|
| Lesion location, n (%) | <0.001 | ||
| Duodenum/jejunum | 30 (65.2) | 16 (34.8) | |
| Ileum/multiple | 19 (28.8) | 47 (71.2) | |
| Matched diagnosis on prior imaging study, n (%) | |||
| Capsule endoscopy | 8 (36.4) | 14 (63.6) | 0.436 |
| CT or MRI | 34 (45.9) | 40 (54.1) | 0.513 |
| History of abdominal surgery, n (%) | 0.948 | ||
| Yes | 8 (44.4) | 10 (55.6) | |
| No | 41 (43.6) | 53 (56.4) | |
| Enteroscopy methods, n (%) | 0.99< | ||
| DBE | 48 (44.0) | 61 (56.0) | |
| SBE | 1 (33.3) | 2 (66.7) | |
| Insertion route, n (%) | 0.005 | ||
| Anterograde | 34 (55.7) | 27 (44.3) | |
| Retrograde | 15 (29.4) | 36 (70.6) | |
| Biopsy number, mean ± SD | 5.6 ± 3.3 | 3.7 ± 2.1 | 0.001 |
| Non-Tumor | 5.3 ± 3.2 | 3.9 ± 2.2 | 0.053 |
| Tumor | 5.9 ± 3.4 | 2.5 ± 1.6 | 0.025 |
| Final diagnosis, n (%) | <0.001 | ||
| Non-tumor | 23 (28.8) | 57 (71.2) | |
| Crohn’s disease | 16 (27.1) | 43 (72.9) | |
| Non-Crohn’s disease | 7 (33.3) | 14 (66.7) | |
| Tumor | 26 (81.2) | 6 (18.8) |
Table 4.
Logistic regression analysis of factors for diagnostic yields of enteroscopic biopsy.
| Variables | Univariate Analysis | Multivariate Analysis | ||
|---|---|---|---|---|
| OR 1 (95% CI 2) | p-Value | OR (95% CI) | p-Value | |
| Insertion route | ||||
| 0.005 | 0.838 | |||
| Retrograde | 0.33 (0.15–0.72) | 1.13 (0.33–3.87) | ||
| History of abdominal surgery | ||||
| 0.948 | ||||
| No | 0.96 (0.35–2.66) | |||
| Final diagnosis | ||||
| <0.001 | 0.004 | |||
| Tumor disease | 10.73 (3.90–29.51) | 6.21 (1.80–21.43) | ||
| Biopsy location | ||||
| <0.001 | 0.138 | |||
| Ileum/Multiple | 0.21 (0.09–0.48) | 0.34 (0.08–1.40) | ||
| Biopsy number | 1.36 (1.13–1.65) | 0.001 | ||
1 OR, odds ratio; 2 CI, confidential interval.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
MDPI and ACS Style
Goong, H.J.; Kim, T.J.; Nam, K.; Park, J.; Kim, J.-O.; Kim, H.G.; Ko, B.M.; Jeon, S.R.; Small Intestine Research Group of the Korean Association for the Study of Intestinal Diseases (KASID). Histological Diagnostic Yield and Clinical Significance of the First Biopsy in Device-Assisted Enteroscopy in Patients with Small Bowel Diseases: A KASID Multicenter Study. Diagnostics 2022, 12, 964. https://doi.org/10.3390/diagnostics12040964
AMA Style
Goong HJ, Kim TJ, Nam K, Park J, Kim J-O, Kim HG, Ko BM, Jeon SR, Small Intestine Research Group of the Korean Association for the Study of Intestinal Diseases (KASID). Histological Diagnostic Yield and Clinical Significance of the First Biopsy in Device-Assisted Enteroscopy in Patients with Small Bowel Diseases: A KASID Multicenter Study. Diagnostics. 2022; 12(4):964. https://doi.org/10.3390/diagnostics12040964
Chicago/Turabian StyleGoong, Hyeon Jeong, Tae Joon Kim, Kwangwoo Nam, Jihye Park, Jin-Oh Kim, Hyun Gun Kim, Bong Min Ko, Seong Ran Jeon, and Small Intestine Research Group of the Korean Association for the Study of Intestinal Diseases (KASID). 2022. "Histological Diagnostic Yield and Clinical Significance of the First Biopsy in Device-Assisted Enteroscopy in Patients with Small Bowel Diseases: A KASID Multicenter Study" Diagnostics 12, no. 4: 964. https://doi.org/10.3390/diagnostics12040964
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.
