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Abstract
Objective Recent studies have shown that motorised spiral enteroscopy (MSE) enables deeper and total small bowel evaluation compared with single-balloon enteroscopy (SBE) in suspected Crohn’s disease (CD) when analysed per procedure. However, no randomised controlled study has compared bidirectional MSE with bidirectional SBE in suspected CD.
Design Patients with suspected CD requiring small bowel enteroscopy were randomly assigned to either SBE or MSE between May 2022 and September 2022 in a high volume tertiary centre. Bidirectional enteroscopy was done if intended lesion could not be reached on unidirectional study. Comparison was made with regard to technical success (ability to reach lesion), diagnostic yield, depth of maximal insertion (DMI), procedure time and total enteroscopy rates. Depth:time ratio was calculated to avoid confounding for the location of lesion.
Results Among 125 suspected patients with CD (28% female, 18–65 years, median 41 years), 62 and 63 underwent MSE and SBE, respectively. The overall technical success (98.4 %: MSE, 90.5 %: SBE; p=0.11), diagnostic yield (95.2%: MSE; 87.3%: SBE, p=0.2) and procedure time were not significantly different. However, MSE appeared to have higher technical success (96.8% vs 80.7%, p=0.08) in deeper small bowel (distal jejunum/proximal ileum) with higher DMI, higher depth:time ratio and total enteroscopy rates when attempted (77.8% vs 11.1%, p=0.0007). Both the modalities were safe although minor adverse events were more common with MSE.
Conclusion MSE and SBE have comparable technical success and diagnostic yield for small bowel evaluation in suspected CD. MSE scores over SBE with regard to deeper small bowel evaluation with complete small bowel coverage and higher depth of insertion in a shorter time.
Trial registration number NCT05363930.
- crohn's disease
- enteroscopy
- inflammatory bowel disease
- small bowel enteroscopy
Data availability statement
All data relevant to the study are included in the article or uploaded as online supplemental information.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Recent uncontrolled studies have shown that the technical performance and diagnostic yield of motorised spiral enteroscopy (MSE) is comparable to balloon-assisted enteroscopy (BAE) when analysed per procedure. No controlled trials have ever compared bidirectional MSE with bidirectional BAE for suspected small bowel Crohn’s disease (CD).
WHAT THIS STUDY ADDS
The technical performance and diagnostic yield of bidirectional MSE was similar to bidirectional single balloon enteroscopy in suspected small bowel CD. However, there was a trend towards higher technical success with MSE for mid small bowel (distal jejunum/proximal ileal) lesions. MSE had significantly higher depth of insertion in a shorter time and higher total enteroscopy rates.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
With the advent of MSE, this results will help to guide the clinician in choosing the optimal mode of deep enteroscopy in suspected small bowel CD based on localisation (ie, MSE may be preferable for deeper small bowel lesions) and need for total enteroscopy. Higher depth of insertion in a shorter time can potentially reduce endoscopist fatigue.
Introduction
Revolution in deep enteroscopy began with the invention of the double-balloon enteroscopy (DBE) (Fujifilm, Tokyo, Japan) in 2001 by Yamamoto and Sugano, followed by the introduction of single-balloon enteroscopy (SBE) in 2006.1 2 Later, manual spiral enteroscopy (SE) was introduced in 2008 by Akerman et al, which depends on the principle of ‘rotation’ rather than ‘push and pull’ with balloon enteroscopy.3 The motorised SE (MSE) (Olympus Medical, Tokyo, Japan) introduced in 2015 addressed the prior technical challenges in SE.4
Device-assisted enteroscopy (DAE) is indicated for suspected small bowel Crohn’s disease (CD) on cross-sectional imaging or capsule endoscopy and may not require total enteroscopy once anatomical lesion of interest is reached in contrast to suspected small bowel, vascular disorders. It helps in diagnosing CD, excluding CD, diagnosing other small bowel pathologies and taking a surgical decision if a tight stenosis is found.5 Earlier studies on balloon enteroscopy have shown a high diagnostic yield ranging from 44% to 100% in suspected CD.6–11 MSE had higher diagnostic yield (65%), greater depth of insertion and higher total enteroscopy rates in an earlier retrospective study although the diagnostic yield in inflammatory lesions (41%) was not separately reported.12 A recent prospective, non-randomised study has shown that MSE and SBE have comparable technical success and diagnostic yield in suspected isolated small bowel CD when analysed per-procedure with the MSE group exhibiting a significantly higher depth of insertion in a shorter time.13 Another recent case-matched study comparing DBE with MSE (DBE: MSE=2:1), which included suspected CD, showed comparable technical success and diagnostic yield.14 However, the true technical efficacy of these two principles of enteroscopy needs to be compared by bidirectional approach in contrast to the aforementioned studies.13 14 Given the advent of MSE, the preferred mode of enteroscopy for investigation of suspected small bowel CD is not known. Hence, we aimed to compare bidirectional SBE with bidirectional MSE in suspected CD with respect to technical success, diagnostic yield, procedure time, depth of insertion and adverse events in a randomised controlled manner (NCT05363930).
Methods
Study design
The study was a prospective, randomised, open-label, comparative trial conducted at Asian Institute of Gastroenterology (AIG), Hyderabad, India between May 2022 and September 2022. AIG is a high volume tertiary GI centre performing more than 500 MSE/SBE procedures per year with a well-established inflammatory bowel disease (IBD) registry with more than 8500 patients with IBD under follow-up.
Consecutive patients with suspected CD requiring small bowel endoscopy based on clinical history, abnormal imaging (CT enterography/enteroclysis: CTE or MR enterography/enteroclysis: MRE) and/or video capsule endoscopy (VCE) were prospectively enrolled and underwent randomisation to either MSE or SBE for endoscopic examination and tissue sampling. Given the different nature of two interventions, blinding was not feasible. Patients were not involved in the design or conduct the study.
Patients screening and eligibility criteria
Consecutive patients aged between 18 and 65 years with suspected, isolated small bowel CD not reachable by oesophagogastroduodenoscopy or ileocolonoscopy were screened for possible inclusion in the MOTOR-CD trial. The inclusion criteria were as follows: (1) patients with suspected small bowel CD requiring small bowel endoscopy based on cross-sectional imaging and/or VCE with normal ileocolonoscopy, (2) ability to give a signed informed consent and (3) age ≥18 years to 65 years. Patients not fit for general anaesthesia (GA)/sedation, pregnant/lactating mother, history of major abdominal surgery/bowel resection, altered anatomy, uncorrectable coagulopathy or thrombocytopaenia, normal cross-sectional imaging/VCE and those not willing to participate were excluded prior to randomisation. Moreover, general contraindications of MSE such as those with large oesophageal varices, foregut strictures, eosinophilic oesophagitis and those on antiplatelets (other than aspirin) or ongoing anticoagulation were also excluded. The details of exclusion can be found in figure 1 (Consolidated Standards Of Reporting Trials (CONSORT) diagram).
The CONSORT flow diagram showing enrolment, allocation, analysis and results of MOTOR-CD trial. CD, Crohn’s disease; MSE, motorised spiral enteroscopy; SBE, single-balloon enteroscopy.
Randomisation and intervention
The included patients were allocated to either MSE or SBE in a ratio of 1:1 using block randomisation. Each block consisted of eight patients. The randomisation sequence was generated and each investigator received block randomisation sequence as eight sealed opaque envelope labelled as block identifier and sequence within block. Participants were enrolled for study after screening for inclusion and exclusion criteria and the study protocol was narrated to the patients at the time of written informed consent conforming to the Declaration of Helsinki ethical guidelines (2013). Assignment of the patient was sealed in an opaque envelope that was opened after obtaining written informed consent. MSE (Olympus Medical Systems Corporation, Tokyo, Japan) was usually under GA with nasotracheal intubation under fluoroscopic guidance. Fluoroscopy with or without contrast injection was useful to check position of enteroscope in case of non-progression specially when acute angulations were encountered. Patients who underwent only retrograde MSE received deep sedation with propofol. SBE (XSIF-Q260Y; Olympus Medical Systems, Tokyo, Japan) was done under monitored anaesthesia (deep sedation with propofol).13 The route of enteroscopy was based on location on prior CTE/MRE or VCE.15 For SBE, antegrade or retrograde routes were selected if the lesion was in proximal and distal half of small bowel, respectively. For MSE, antegrade route was mostly preferred unless the lesion was definitely in distal ileum due to higher yield and higher likelihood of total enteroscopy with antegrade route. All cross-sectional imaging was discussed with an expert GI radiologist (JS) and small bowel was traced from duodena-jejunal flexure (DJ) or ileocecal junction (ICJ) to determine the location of the anatomic region of interest and distance from DJ/ICJ. JS manually measured the distance from DJ flexure or IC valve by tracing and measuring loops of intestine from DJ flexure/IC junction based on whichever was closer to the lesion and finally added them to get estimated distance from DJ/IC valve.13 Small bowel was divided into three parts: upper small bowel (proximal and mid-jejunum), mid or deep small bowel (distal jejunum to proximal ileum) and lower small bowel (mid and distal ileum) for the purpose of analysing outcomes region wise. For diffuse small bowel lesions affecting more than one region, the part closest to ICJ/DJ flexure was considered for analysis. Four litres of polyethylene glycol was given to all patients with at least 8 hours of fasting to facilitate bidirectional enteroscopy in the same session. Water immersion technique with intermittent carbon dioxide insufflation was used along with with abdominal compressions to facilitate enteroscopy. Bidirectional enteroscopy was performed if unidirectional approach failed to reach the anatomical location of interest by initial route after putting haemoclips or tattooing with Indian ink to mark the depth of maximal insertion (DMI). After antegrade/bidirectional MSE requiring GA, patients were observed in high-dependency unit for 4–6 hours until recovery from GA. SBE procedures were done usually in the day care settings unless patients were admitted for any other reason than enteroscopy. After SBE procedures, patients were discharged after 4–6 hours if there are no adverse events. In cases of suspected perforation postenteroscopy, CT with water soluble oral contrast was carried out. The patients were followed up telephonically between 1 and 2 weeks of discharge to rule out delayed adverse events. All the patients were given a point of contact (SK) to report any adverse events.
Study endpoints and definitions
The primary outcome was technical success defined as the ability to reach the anatomical location of interest predefined on cross-sectional imaging (CTE/MRE) or VCE based on unidirectional or bidirectional approach in a given patient.13
All the enteroscopy procedures were performed by five small bowel endoscopists (PP, APS, RP, HR and MR) all of whom have performed at least 200 SBE and 20 MSE procedures.
Secondary outcomes were diagnostic yield, DMI, procedure time, total enteroscopy rates and adverse events.
Diagnostic yield was defined as the percentage of procedures with a definitive endoscopic diagnosis. This endoscopic diagnosis either confirmed/excluded lesions found on prior cross-sectional imaging/VCE or found new/alternate diagnosis explaining the clinical condition.13 At least eight biopsies were taken from area of interest and sent for histopathological analysis by a expert GI pathologist (AS). The histopathological diagnosis of CD was confirmed if non-caseating microgranulomas were found along with chronic inflammation and architectural distortion. The presence of one or two of these three aforementioned histological features along with active inflammation was suggestive of CD.16 Additional biopsy samples were taken for Xpert MTB/RIF (MTB-mycobacterium tuberculosis, RIF-resistance to rifampin) (Cepheid, Sunnyvale, California, USA) assay in cases of diagnostic dilemma between intestinal TB (ITB) and CD. Architectural abnormality in the non-affected area and non-caseating microgranuloma favoured CD whereas caseous necrosis and submucosal macrogranuloma favoured ITB.17 In cases where histological differentiation was not possible, ITB was excluded based on clinical, endoscopic, radiologic and other relevant findings (eg, Xpert MTB/RIF assay). Prior history of failure to antitubercular therapy favoured CD. Enteroscopic pictures of aphthous ulcers, linear ulcers, longitudinal ulcers with skip areas favoured CD whereas localised, transverse ulcers favoured ITB. More than three small intestinal segments involvement, long segment stricture, mesenteric vascularity and fatty proliferation in CTE/MRE favoured CD whereas ITB was favoured by necrotic lymph nodes and ascites.18 In cases with CD/ITB dilemma and prior to starting immunosuppressives in CD, latent TB infection screening was done using tuberculin skin test, interferon gamma assay, CT chest and history of TB infection/contact.19 All newly diagnosed cases were followed up after initial diagnosis for at least 3 months via physical visit or telephonic communication.
The DMI was calculated by push and pull technique in SBE by counting net advancement of the enteroscope during insertion phase and finally adding them at the end of examination and confirming during withdrawal.20–22 The DMI in MSE was calculated using sequential withdrawal technique. A landmark like a circumferential fold was identified which is followed on release of bowel from the overtube on withdrawal until a estimated 10 cm of small bowel was examined. Then another fold was identified and enteroscope was sequentially withdrawn until IC valve or DJ flexure.12 13 22 23 The time of procedure was calculated from insertion of enteroscope to its withdrawal. DMI was calculated beyond pylorus and ileocecal valve for antegrade and retrograde enteroscopy respectively. Both DMI and time were calculated per patient (adding the value of antegrade and retrograde if bidirectional approach was performed) rather than per procedure. The time for therapeutic procedures like endoscopic balloon dilation (EBD) was subtracted from total procedure time to calculate total enteroscopy time.
Total enteroscopy was defined as examination of small bowel from DJ flexure to ileocecal valve either by unidirectional (antegrade or retrograde route) or bidirectional enteroscopy (using both antegrade and retrograde route).12 13 24
Adverse events were reported as per American Society of Gastrointestinal Endoscopy (ASGE) lexicon for reporting endoscopic adverse events.25
Statistical analysis
A survey administration software (Goggle forms, Google, India) was used to collect the patient data (demographics, details of enteroscopy, histological findings, hospital stay). All the data were exported from ‘Google form’ to Microsoft Excel. Continuous variables are expressed as median (range) and categorical variables are expressed as number (n) and percentage (%). χ2/Fisher’s exact test was used to compare categorical variables and Mann-Whitney test was used to compare continuous variables between the two groups. A p<0.05 was considered statistically significant. Statistical package for social sciences (SPSS V.26, IBM) was used for statistical analysis.
Sample size
The sample size was calculated based on prior prospective study comparing MSE and SBE.13 Technical success per patient was chosen to use for power and sample size calculation instead of per procedure as we aimed to compare unidirectional or bidirectional approach in a given patient.13 In the aforementioned study, out of 46 patients undergoing 55 MSE procedures, lesion was reached/panenteroscopy was achieved (technical success) in 97.8% (45/46). Similarly, in 131 patients undergoing 146 SBE procedures, technical success (ability to reach anatomical location) was achieved in 83.2% (109/131).13 To show significant difference in technical success of two interventions with 5% type I error and 80% power, 62 patients per group (total 124) were required.
Results
Total 156 patients were screened. Twenty-eight patients were excluded based on eligibility criteria. Finally, 128 patients were randomised and 63 and 65 patients were allocated to MSE and SBE group, respectively. Three patients (two SBE, one MSE) were excluded from analysis. One patient in each group had lesion within the reach of ileoscopy with standard colonoscope in the terminal or distal ileum. These patients were initially recruited based on ileocolonoscopy done elsewhere which were reported as normal. One patient in SBE group withdrew consent after unidirectional enteroscopy. Recruitment was stopped once estimated analysable cases were recruited in each arm (n=62). Finally, 125 patients were analysed (62 MSE and 63 SBE) (median age 41 years, range 18–65 years, 36% female). The baseline characteristics are summarised in table 1.
Baseline characteristics of the comparative study between motorised spiral enteroscopy (MSE) and single balloon enteroscopy (SBE)
Primary outcome: technical success
Enteroscopy passage beyond duodenojejunal flexure or ileocecal valve was feasible in all procedures. The overall technical success with MSE and SBE were not significantly different (MSE: 98.4%; SBE: 90.5%, p=0.11).
Subgroup analysis
While analysing based on preprocedure localisation, the technical success did not significantly differ between MSE and SBE (see table 2, figure 2A for details) except for mid small bowel lesions (distal jejunum and proximal ileum)(technical success: MSE: 96.8%; SBE: 80.7%) where there was a trend towards significance (p=0.08).
Main findings of MOTOR-CD trial. (A) Bar diagrams showing percentage of technical success between bidirectional motorised spiral enteroscopy (MSE) and bidirectional single-balloon enteroscopy (SBE) in suspected Crohn’s disease (CD) based on preprocedure localisation along with p value. (B) Bar diagrams showing percentage of diagnostic yield between bidirectional MSE and bidirectional SBE in suspected CD based on preprocedure localisation along with p value. (C) Comparison of depth of maximal insertion between MSE and SBE in suspected CD represented as Box and Whisker plot. (D) Comparison of depth:time ratio between MSE and SBE in suspected CD represented as Box and Whisker plot.
Comparison of technical success of bidirectional motorised spiral enteroscopy (MSE) and single balloon enteroscopy (SBE) based on preprocedure localisation
Secondary outcomes
Diagnostic yield
There was no significant difference in the diagnostic yield (95.2%: MSE; 87.3%: SBE and p=0.2) between the 2 modalities when analysing as a whole or based on preprocedure localisation (see table 3, figure 2B for details). Newly diagnosed CD was the most common finding on enteroscopy (60%, 75/125). Details of final diagnosis and impact of enteroscopy on further management of the patients are summarised in online supplemental tables 1 and 2.
Supplemental material
Detailed breakdown diagnostic yield with bidirectional motorised spiral enteroscopy (MSE) and single balloon enteroscopy (SBE) based on preprocedure localisation
Depth of insertion, procedure time and total enteroscopy rates
Overall DMI per patient was higher with MSE (DMI (cm): median (range): MSE: 500 (80–600), SBE: 180 (50–600), p<0.0001) (figure 2C). Procedure time was similar between MSE and SBE (duration (min): median (range): MSE: 40 (7–145), SBE: 45 (13–260), p=0.32)). The depth:time ratio was significantly higher for MSE compared with SBE (Depth:time (cm/min): median (range): SBE: 3.33 (1–13.64), MSE: 11.5 (2.67–27.5), p<0.0001) (figure 2D).
Total enteroscopy was attempted in total 36 patients (28.8%). An attempt of total enteroscopy was only made when definite pathology could not be identified in the anticipated location and thus requiring complete small bowel evaluation. Total enteroscopy was not attempted once a satisfactory endoscopic diagnosis could be made which explained the clinical scenario and adequate histological samples were obtained. The routes of attempted and successful total enteroscopy with MSE and SBE are mentioned in table 4. Successful total enteroscopy was achieved in 77.8% with MSE (21/27) and 11.1% with SBE (1/9) (p=0.0007).
Comparison of motorised spiral enteroscopy (MSE) and single balloon enteroscopy (SBE) in suspected small bowel Crohn’s disease
Therapeutic procedures
Nine patients (three SBE, six MSE) underwent EBD of strictures. To prevent small bowel injury, after dilation and biopsy of non-passable strictures, the overtube of the balloon or MSE was not usually passed beyond. In a case of capsule retention, after EBD the proximally retained capsule was retrieved.
Adverse events and safety
All adverse events were mild according to ASGE lexicon. In SBE arm, 3/63 (4.8%) patients had adverse events: 1 had mucosal injury and self-limiting intraprocedural bleeding, 1 had postprocedure pain requiring hospitalisation for a day and 1 had impaction of controlled radial expansion (CRE) balloon in the operating channel after EBD, which required removal of the scope and re-enteroscopy on the same day to take biopsy. In the MSE arm, 13/62 (21%) had adverse events (SBE: 4.8%, p=0.008). Overall, 10 (16%) patients had superficial mucosal injury, 1 had postprocedure mild pain which subsided in a day, 1 had deep mucosal injury in the oesophagus resulting in throat discomfort and dysphagia and 1 had haematoma in upper oesophagus. However, all of these adverse events were self-limited and did not prolong hospital stay for more than 2 days.
Histological findings in CD
Detailed histological findings in newly diagnosed CD are summarised in table 5. Histology was confirmatory for CD in 5.3% (4/75) and suggestive of CD in 80% (60/75). In the rest (n=10, SBE-3, MSE-7), the biopsy was not confirmatory. In cases with suggestive and non-specific features, a diagnosis of CD was made based on enteroscopic/radiologic/clinical picture and are being treated successfully with steroids/immunomodulators/biologics (follow-up 6–11 months). A diagnosis of ITB was made in seven cases with MSE and eight cases with SBE. These patients are treated successfully with anti tubercular therapy. A patient had deterioration of symptoms after 2 months of anti-TB therapy with development of localised perforation. However, he was managed successfully with conservative measures along with anti-TB therapy at 9 months follow-up.
Histopathology findings of newly diagnosed Crohn’s disease on motorised spiral enteroscopy (MSE) and single balloon enteroscopy (SBE)
Discussion
The current randomised, open-label study has compared MSE and SBE in suspected, isolated small bowel CD. Among 125 patients with suspected CD (MSE-62, SBE-63), technical success was comparable between bidirectional MSE (98.4%) and bidirectional SBE (90.5%) (p=0.11). However, there was a trend towards higher technical success in mid small bowel lesions for bidirectional MSE (96.8%) compared with bidirectional SBE (80.7%) (p=0.08) (see online supplemental graphical abstract). The overall diagnostic yield between MSE (95.2%) and SBE (87.3%) were not significantly different (p=0.2) which did not differ by location. The DMI was significantly higher with MSE compared with SBE although procedure times were similar. More importantly, the length/time ratio was significantly higher with MSE compared with SBE given that time is dependent on DMI. Significantly high total enteroscopy rates were achieved with MSE (77.8%) compared with SBE (11.1%) considering where total enteroscopy was attempted (in one fourth). All adverse events were mild in both the groups .
Supplemental material
The technical success with MSE and SBE were very high (>90%). This could be explained by the specific population studied (suspected CD), stringent inclusion criteria (positive imaging), bidirectional enteroscopy, location of more than half of the lesions in upper and lower small bowel, exclusion of postoperative cases and highly experienced enteroscopists performing the procedures. Earlier prospective study on MSE in suspected CD showed a technical success of 87.3% which included postoperative cases.13The reported diagnostic yield of balloon enteroscopy in suspected CD is between 44% and 100%.6–11 In our study, new diagnosis of CD was seen in 60% cases. In patients with suspected CD, new diagnosis of CD varies from 25% to 75%.6–11 13 An earlier retrospective study showed high diagnostic yield of MSE (nearly 70%) in which majority of the lesions (41%) were inflammatory (CD/ITB/cryptogenic multifocal ulcerous stenosing enteritis).12 Recent meta-analysis of MSE showed 78% overall diagnostic yield.26 High technical and diagnostic success could be explained by positive cross-sectional imaging in 96%. Higher use of cross-sectional imaging rather than VCE helped to differentiate CD from ITB (prevalent in South Asia). Moreover, longer diagnostic delay leading to obstructive symptoms in many can also explain higher use of cross-sectional imaging rather than VCE.27 Chronic abdominal pain with or without features of small bowel obstruction was the most common presenting symptom, followed by chronic diarrhoea, weight loss and anaemia (table 1).
The technical success appeared to be higher with MSE for mid small bowel lesions compared with SBE. These did not achieve statistical significance due to small sample size in each group. This could be explained by the higher DMI with MSE compared with SBE as shown in a previous prospective study.13 Although we followed European Society of Gastrointestinal Endoscopy guidelines to of calculate DMI for MSE and SBE, it should be noted that these methods are approximate unless total enteroscopy is achieved.20–22 Although retrograde MSE is technically feasible (as compared with earlier manual SE), antegrade MSE was mostly preferred in our study due to higher DMI and higher likelihood of total enteroscopy compared with retrograde MSE (table 1).23 DMI in both arms should be interpreted with caution as it is dependent on the location of the lesion and the route of enteroscopy. A higher number of antegrade MSE could have influenced the results. Hence, to adjust for variable depth, we have used depth:time ratio to compare efficiency of the two modalities.
The current study did not show shorter procedure time with MSE. However, the depth:time ratio was significantly higher with MSE showing efficiency and rapidity of the procedure compared with SBE. A working length 168 cm with a short spiral overtube, which increases DMI with higher likelihood of of total enteroscopy with MSE. On the other hand, the effective length of manual SE was only 90–95 cm after exclusion of overtube length making it difficult to perform total enteroscopy even by the most experienced endoscopist.13 Apart from longer working length, integrated water jet, wider working channel diameter and user controlled spiral motor unit are additional advantages which allow faster, efficient and simplified enteroscopy with MSE reducing fatigue in the performing endoscopist.13 The importance of larger working channel can be understood from the case in which CRE balloon was stuck in SBE working channel which is unlikely to occur with MSE due to wider channel diameter. For meaningful comparison, we only analysed total enteroscopy rates in those in whom it was genuinely attempted until it can be achieved or failed due to non-progression inspite of repeated attempts bidirectionally. Most of the total enteroscopies in MSE arm could be achieved in unidirectional (antegrade) manner, whereas the only successful total enteroscopy with SBE was achieved bidirectionally (table 4) highlighting superior efficiency of MSE over SBE.
Although the adverse events rates were higher (21%) in MSE arm, all were minor and corroborates with recent meta-analysis of MSE (17%, serious 1%).26 Superficial mucosal injury related to overtube was higher with MSE. Prior oesophageal bougie dilation, water irrigation and avoidance of manual pressure in case of non-progression can help minimise these injuries. No serious adverse events including perforation were reported.
Requirement of GA for antegrade MSE, need for hospitalisation, total overall time due to need for intubation and recovery, lack of tactile feedback (specially in postoperative settings), technical difficulty in low body mass index (BMI)/paediatric patients (large scope calibre) and need for additional training (although learning curve relatively small, nearly 5 for training and 20 for additional experience) are few drawbacks of MSE.23 28–30 The overall procedure time could actually be longer with MSE compared with SBE due to GA induction and recovery time. The presence of oesophageal varices, upper GI strictures, eosinophilic oesophagitis and antiplatelet use would also favour SBE over MSE. As MSE was seen to be feasible with relatively lower BMI in this study due to underlying disease and region of study, the results are likely to be generalisable. These have to be kept in mind before choosing one modality over other. We used GA for antegrade MSE with the rationale that in the event of sudden desaturation with deep sedation, it may be difficult to withdraw the MSE abruptly with backward rotation. However, recent studies have shown that antegrade MSE can be performed safely with deep sedation with similar diagnostic success and total enteroscopy rates.28 29 This highlights that the higher efficiency of MSE is unlikely to be merely due to stabilisation of the patient by GA. If further studies were to confirm that antegrade MSE could safely be performed under conscious sedation in the setting of anaesthetic emergencies, this would obviate associated drawbacks of performing the procedure under GA.
Histology was confirmatory in only 5% of patients with CD and suggestive in 80% as compared with 8% and 15%, respectively, in a study by Tun et al.10 We meticulously considered the histological factors and routinely took eight biopsies from the region of interest. In an earlier prospective study, histology was confirmatory in 20% and suggestive in 61.1%.13 Diagnosis in cases with non-specific active inflammation (n=10) was based on enteroscopic, radiologic and clinical picture (eg, prior failure of anti-TB therapy) and are being treated successfully (follow-up 5–10 months). Differentiating from ITB is important for distal ileal lesions whereas isolated jejunal lesions are usually CD. Ileocecal involvement is most common in ITB which is excluded from current study.31 Although latent TB screening may not be helpful in TB endemic areas, clinical history, radiologic features, endoscopy with histological correlation and response to therapy can give the right answer in most.18 27 32 Every attempt should be made to confirm diagnosis prior to therapy such as diagnostic laparoscopy with or without intraoperative enteroscopy specially if malignancy or alternate diagnosis is suggested based on imaging and clinical scenario (eg, sudden onset of symptoms).33
Our study has several strengths. This is the first randomised controlled study comparing two modalities of enteroscopy (MSE and SBE) in suspected small bowel CD. Earlier comparative studies between MSE and SBE analysed technical success of both these modalities considering the factors per procedure (antegrade and retrograde considered separate procedures).13 14 However, the true efficacy of these modalities should be compared in a bidirectional approach given that retrograde MSE was technically feasible in all attempted cases in the current study compared with earlier manual SE reports focussing only on the antegrade approach.23 We analysed the technical success and diagnostic yield in three individual small bowel segments. A detailed histological analysis was performed in the study emphasising its importance in separating other differential diagnoses such as ITB.
There are a few limitations in the study. It was a single-centre study done in a tertiary centre by experienced endoscopists. However, the significant differences like higher depth:time ratio and higher DMI are unlikely to be different in multicentre studies. The study was not adequately powered to show difference in technical success for mid small bowel lesions which can be addressed in future controlled studies with adequate sample size. The number of patients in each intestinal location was not exactly similar in both groups; however, the difference was not statistically different. We analysed depth:time ratio to adjust for this. We did not separately calculate time for ileal intubation (during retrograde enteroscopy) which can be challenging at times. However, these are part of the overall procedure and an earlier prospective study have already shown higher retrograde MSE depth:time ratio compared with retrograde SBE when analysed per procedure.13 Bidirectional enteroscopy was required in limited number of patients. Antegrade MSE was preferred in most due to higher likelihood of pan-enteric evaluation. Although we did not perform an intention to treat analysis, the exclusion of three subjects (two had terminal ileal involvement) is unlikely to change the results. We also did not compare the MSE with DBE although DBE and SBE have been shown to be comparable in all aspects as per systematic review and meta-analysis.34 We did not include paediatric or postoperative patients in which SBE could be advantageous.13 30
This randomised study shows that the overall technical success and diagnostic yield with bidirectional MSE and bidirectional SBE were similar. However, there was a trend towards higher technical success of MSE for deeper intestinal lesions (distal jejunum/proximal ileum) and can be a preferable option. MSE was a more efficient procedure with higher DMI, higher depth:time ratio and total enteroscopy rates. Both the modalities were safe although minor adverse events were more common with MSE. Hence, the choice among both the modalities in suspected small bowel CD should be based on the availability and experience considering the patient characteristics. MSE may have an edge over SBE in deeper intestinal lesions and complete small bowel examination in a shorter time.
Data availability statement
All data relevant to the study are included in the article or uploaded as online supplemental information.
Ethics statements
Patient consent for publication
Ethics approval
This study involves human participants and the study was approved (approval number: AIG/IEC-BH&R 26/04.2022-01) by the Institutional ethics committee (ECR/346/Inst/AP/2013/RR-19) (dated 9 April 2022). Participants gave informed consent to participate in the study before taking part.
References
Supplementary materials
Supplementary Data
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Footnotes
Twitter @ibd_pal, @drmohanjr, @DrRupaBanerjee1, @Piyush6888, @MDinternalmed, @drhrr, @gut_rp, @AnuradhaSekara1, @ZaheerNabi8
Contributors Guarantor: PP; Conceptualisation: PP, MoR, MT and DNR; Investigation: PP, MoR, RB, APS, HR, MaR, RaP, PV, ZN, RG, SL, ReP, GVR, MT and DNR; Acquisition of data: APS, PV, HR, PP, MaR, RaP, SK and AS; Analysis and interpretation of data: PP, PV, MT; Methodology: RB, PP, MT, MR, APS, MaR, HR, RaP, SK, SD, ZN, JS, RG, SL and ReP; Drafting of manuscript: PP, PV, MT and RB, Revision of the manuscript: MT, MR, RB, APS, HR, MaR, RaP, AS, SD, ZN, SK, SL, JS, RG, ReP, GVR and DNR; Statistical analysis: PP, PV and SK; Administrative support: DNR, MT, RB, RG, SL and GVR, Resources: DNR, MT and GVR; Study supervision: PP, RB and MR, Approval of final ver-sion of manuscript: all.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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