Abstract
Background and Aims
Perianal complications such as fistulas and abscesses are common in Crohn’s disease (CD) and contribute to significant morbidity. Transperineal ultrasonography (TPUS) has emerged as a non-invasive and accurate method for perianal fistulizing CD (pfCD). This review evaluates the diagnostic accuracy of TPUS compared with magnetic resonance imaging (MRI), transrectal ultrasonography (TRUS), and examination under anesthesia (EUA) for detecting and classifying perianal fistulas and abscesses.
Methods
A comprehensive literature search was conducted across multiple databases through January 2025 to identify studies evaluating TPUS accuracy in detecting perianal fistulas and abscesses compared with MRI, TRUS, or EUA as the reference standard. Meta-analysis was performed to assess TPUS accuracy for fistula detection (FD), fistula classification (FC), internal opening (IO) detection, and abscess detection (AD). The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to evaluate risk of bias.
Results
Of 1059 studies identified, 29 were included in this review. Pooled sensitivities for FD (18 studies, 1474 patients), FC (11 studies, 585 patients), IO detection (six studies, 481 patients), and AD (16 studies, 1276 patients) were 97.5%, 80.3%, 89.6%, and 93.5% respectively while pooled specificities for FD, IO detection, and AD were 69.0%, 66.3%, and 94.5% respectively. The overall TPUS accuracy for FD, FC, IO detection, and AD was 88.0%, 88.6%, 77.8%, and 91.8% respectively. Subgroup analysis on CD patients showed an accuracy of 86.4%, 87.6%, and 83.3% for FD, FC, and AD respectively.
Conclusions
TPUS demonstrates high accuracy in detecting perianal fistulas and abscesses, supporting its use as a non-invasive, first-line diagnostic tool.
Keywords: transperineal ultrasound, TPUS, perianal fistula, abscess, perianal fistulizing Crohn’s disease
1. Introduction
Crohn’s disease (CD) is a chronic, immune-mediated inflammatory disorder characterized by transmural inflammation affecting any location along the gastrointestinal tract.1 Perianal fistulizing CD (pfCD) contributes to considerable morbidity and poor disease prognosis. Perianal fistulizing CD can arise concurrently with, after, or even before the diagnosis of luminal CD.2 Accurate diagnosis and classification of pfCD are crucial for implementing timely and effective treatment.3
Multiple diagnostic methods exist for pfCD including examination under anesthesia (EUA), transrectal endoscopic ultrasonography (TRUS), magnetic resonance imaging (MRI), and transperineal ultrasonography (TPUS). Currently MRI is considered the gold standard for diagnosing pfCD, which provides detailed images of deep tissues and superior soft tissue differentiation, enabling comprehensive assessment of fistula tracts relative to perianal anatomy.4 However, MRI is associated with high cost, lengthy scan times, and waiting lists, which all make it less practical for patients requiring frequent evaluations to monitor pfCD progression or healing. TPUS, by contrast, offers a non-invasive, reliable, patient-friendly, and safe alternative for evaluating pfCD.5 It requires no special preparation and provides real-time images, making it well-suited for repeated assessments that also enable immediate adjustment of therapy.
Since the last comprehensive review in 2017,6 ultrasound imaging—particularly transperineal and transabdominal techniques—has seen notable advancements in inflammatory bowel disease (IBD), resulting in a significant increase in published studies. Additionally, improved image resolution in ultrasound technology has enhanced diagnostic precision.7 This systematic review and meta-analysis aim to provide an updated assessment of the diagnostic accuracy of TPUS in comparison to MRI, TRUS, and EUA for evaluating perianal manifestations of CD with a specific focus on detecting and classifying perianal fistulas and abscesses.
2. Methods
This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines.8 The review protocol was registered on PROSPERO under ID CRD 42024511822 and is accessible at PROSPERO (Supplementary Files 1).
2.1. Search strategy
The comprehensive literature search was conducted with the assistance of a scientific librarian from the Amsterdam University Medical Center (F.S.) utilizing MEDLINE [Ovid] and EMBASE [Ovid] databases, covering publications from inception to February 4, 2025. The search strategy included terms [“transperineal” OR “perineal” OR “perianal”] AND [“fistula” OR “abscess”] AND [“ultrasonography” OR “ultrasono-” OR “-sonography”]. Full search details and results are available in Supplementary Files 2.
2.2. Study eligibility criteria
Studies were included if they involved patients with a confirmed or suspected perianal fistula or abscess and TPUS was used in conjunction with at least one other modality of TRUS, MRI, and/or EUA. All studies meeting these criteria were included regardless of publication status or language. Case series or studies with small sample size (fewer than 10 patients) were excluded. For studies where the full article was unavailable, we contacted primary authors by email to request the complete text.
Two reviewers (C.T.L. and M.P.) independently screened study titles and abstracts, followed by full text assessment for eligibility. Any discrepancy was first resolved by consensus or, if required, by a third reviewer (K.G.). We also reviewed the references of previously published meta-analysis,6 reviews, and eligible articles to identify additional studies.
2.3. Data extraction
Data regarding study characteristics (title, authors, authors’ country, publication year, study design, and sample size), clinical characteristics (patients’ age, gender, and presence of CD), TPUS data and techniques (TPUS operator’s medical specialty, ultrasound system, transducer probe used, mode [B-mode, color Doppler and/or Power Doppler], use of contrast to enhance fistula tracts [hydrogen peroxide, SonoVue, and/or normal saline injection], and additional techniques described) and reference standard interpretation (types of confirmatory investigation performed, blinding for ultrasonographic findings, and time interval between TPUS to reference standard) were extracted by one reviewer (C.T.L.) and verified by a second reviewer (M.P.).
2.4. Outcomes
The primary outcome of this meta-analysis was to assess the diagnostic accuracy of TPUS in detecting perianal fistulas (FD) compared to TRUS, MRI, and/or EUA. Secondary outcomes included evaluating TPUS accuracy in classifying perianal fistulas (FC), identifying internal fistula openings (IO), and detecting perianal abscesses (AD).
2.5. Methodological quality
The methodological quality and risk of bias of each study were evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool.9 The QUADAS-2 tool consists of a series of questionnaires for each domain to assess quality with risk of bias classified as “low,” “high,” or “unclear” depending on the answer to the signaling questions. Quality assessment was performed by two reviewers (C.T.L. and M.P.) with any discrepancy resolved by consensus or by a third reviewer (K.G.) if required.
2.6. Data analysis
Data from eligible studies were analyzed using a bivariate random effects model. For all domains (FD, FC, IO, and AD), there were a few studies with no false positives or true negatives that did not permit specificity calculations. Studies with sparse data (defined as 100% sensitivity and/or 100% specificity resulting in zero-cell counts) were excluded from bivariate random effects meta-analysis because such data precluded estimation of sensitivity–specificity correlation. However, these studies were included in sensitivity analyses, where pooled sensitivity and specificity were estimated using a fixed-effects logistic regression model.10 Where more than one reference standard (MRI, EUA, and/or TRUS) was used within a study, these were treated as a composite reference standard in the primary analysis and weighted equally. Results were visualized using forest plots and summary receiver operating characteristics curves.
Analyses were conducted using Stata 17 (StataCorp, College Station, TX, USA). Specifically, the metadta, metandi, midas, and blogit functions were used.
3. Results
3.1. Study inclusion
From a total of 1059 articles identified through the search strategy, 989 were excluded after screening titles and abstracts (Figure 1). The full texts of the remaining 69 studies were retrieved, of which 29 studies met inclusion criteria for systematic review and meta-analysis. Reasons for exclusion included incorrect patient population (n = 13), non-applicable intervention (n = 10), lack of an appropriate reference standard (n = 9), duplicates (n = 7), and sample sizes under 10 patients (n = 1).
Figure 1.
PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart.
3.2. Risk of bias and concerns of applicability
Overall, the studies demonstrated a moderate risk of bias, with moderate applicability concerns (Table S1 and Figure 1). Of the 29 included studies,11–39 only five presented low risk of bias while nine had low applicability concerns. Patient selection and reference standard were the two key areas with high risk of bias. This was due to non-random sampling or non-consecutive enrolment in patient selection and insufficient reporting on IBD patients for applicability. Additionally, a moderate to high risk of bias was noted in the reference standard domain, due primarily to unblinded interpretations of the reference standard results.
3.3. Study characteristics
Table 1 summarizes the included studies. The aims of the studies include FD (n = 27), FC (n = 13), AD (n = 18), and IO detection (n = 14). Nineteen studies (65.5%)11–15,17,18,21–25,31,32,35–38 had a prospective design, with sample sizes ranging from 13 to 492 and a combined total of 2023 patients. Most participants (74.0%) were male. Thirteen studies11,13,14,16–19,21–23,26,30,34 reported IBD patient numbers, though only 10 studies11,14,17–19,21–23,26,30 (410 patients) provided sufficient data for analysis.
Table 1.
Characteristics of studies included.
| First author | Year | Design | Country | Language | Total number of participants | Gender (male) | Number of IBD patients | Age, years (mean unless stated otherwise) | Aims |
|---|---|---|---|---|---|---|---|---|---|
| Stewart 11 | 2001 | Prospective | Canada | English | 54 | 28 | 31 | Range (23-69) | FD, FC |
| Bonatti 12 | 2004 | Prospective | Germany | German (English abstract) | 44 | 34 | – | 49 | FD |
| Mallouhi 13 | 2004 | Prospective | Austria | English | 87 | 54 | 22 | 45 ± 15 | FD, AD |
| Wedemeyer 14 | 2004 | Prospective | Germany | English | 25 | 8 | 25 | 36.2 ± 2.5 | FD, AD |
| Zbar 15 | 2006 | Prospective | Barbados | English | 20 | 15 | – | 45.5 Range (28-82) | FD, FC, AD |
| Domkundwar 16 | 2007 | Retrospective | India | English | 30 | 26 | 1 | 37.9 Range (24-56) | FD, IO |
| Kleinubing 35 | 2007 | Prospective | Brazil | English | 43 | 32 | – | 39 Range (18-76) | FD, IO |
| Maconi 17 | 2007 | Prospective | Italy | English | 46 | 21 | 46 | Median: 37 Range (16-72) | FD, FC, AD |
| Maconi 18 | 2013 | Prospective | Italy | English | 59 | 27 | 59 | 39 Range (19-72) | FD, FC, AD |
| Nevler 19 | 2013 | Retrospective | Israel | English | 41 | 28 | 14 | Median a. CD: 28 b. non-CD: 40 | FD, FC, IO, AD |
| Plaikner 20 | 2014 | Retrospective | Austria | English | 67 | 40 | – | Median: 44 (IQR: 35-50) | FD, AD |
| Terracciano 21 | 2014 | Prospective (Abstract) | Italy | English | 13 | 7 | 13 | 11 | FD |
| Bor 23 | 2016 | Prospective | Hungary | English | 23 | 11 | 23 | 29.9 | FD, FC, AD |
| Terracciano 22 | 2016 | Prospective | Italy | English | 28 | 17 | 28 | 37.6 ± 16 | FD, FC, AD |
| Puranik 24 | 2017 | Prospective | India | English | 492 | 432 | – | Range (17-89) | FD, AD |
| Fateh 25 | 2017 | Prospective | Iraq | English | 51 | 42 | – | 37.2 Range (15-67) | FD, FC, IO, AD |
| Lee 26 | 2018 | Retrospective | South Korea | English | 38 | 26 | 38 | 14.7 Range (5.8-19.6) | FD, AD |
| Yan 27 | 2018 | Retrospective | China | Chinese (English abstract) | 36 | 36 | – | 39.9 ± 13.9 | FD, IO |
| Anand 28 | 2022 | Retrospective | India | English | 74 | 44 | – | NA | FD, AD |
| Ding 29 | 2022 | Retrospective | China | English | 203 | 203 | – | Range (0-3) | FC |
| Jung 30 | 2022 | Retrospective | South Korea | English | 125 | 19 | 125 | Median 14 Range (8-18) | FD |
| Boles 31 | 2022 | Prospective | Egypt | English | 30 | 25 | – | 43.5 Range (20-68) | FD, IO, AD |
| Singh 32 | 2022 | Prospective | India | English | 37 | 32 | – | Range (45-60) | FD, IO, AD |
| Altam 33 | 2023 | Retrospective | Yemen | English | 85 | 69 | – | 32.12 ± 13.83 | FD, FC, IO, AD |
| Hosokawa 34 | 2023 | Retrospective | Japan | English | 52 | 37 | 27 | 6.7 ± 6.4 | FD, AD |
| Garg 36 | 2023 | Prospective | India | English | 50 | 43 | – | 43.3 Range (30-60) | FD, FC, IO |
| Yang 37 | 2024 | Prospective | China | English | 60 | 42 | – | 37.1 ± 11.4 Range (20-72) | FC, IO |
| Islam 38 | 2024 | Prospective | Bangladesh | English | 50 | 43 | – | Range (21-60) | FD, IO |
| Chang 39 | 2025 | Retrospective | China | English | 60 | 57 | – | 38.5 Range (20-65) | FD, FC, IO, AD |
Abbreviations: FD, fistula detection; FC, fistula classification; IO, internal opening; AD, abscess detection; NA, not applicable.
Table 2a summarizes the characteristics of TPUS across studies. The TPUS operators were specified in 22 studies11–20,22,25,26,28–32,34–36,39 and were primarily radiologists (n = 15) followed by gastroenterologists (n = 4) and surgeons (n = 3). The reference standards varied and included EUA, TRUS, and cross-sectional imaging (MRI or computed tomography [CT]) with MRI usage increasing after 2012. There were 14 studies14,15,17–20,22,26,30,31,34,36,37,39 (48.3%) of which the TPUS operators were blinded to the reference standard. Time interval between reference standard and TPUS varied widely and were reported in 16 studies13–15,17–23,25,26,30,31,33,37 (55.2%).
Table 2a.
Characteristics of TPUS studies performed.
| Study | Year | TPUS operator | Blinding for RS | US system | Transducer Probe | RS | Time interval RS and TPUS |
|---|---|---|---|---|---|---|---|
| Stewart 11 | 2001 | Radiologist | NA | ATL US (USA) | Linear (7-12 MHz) Transvaginal (8-14 MHz) | EUA | NA |
| Bonatti 12 | 2004 | Radiologist | NA | NA | Linear (7 MHz) Sector (3.5 MHz) | MRI, CT, EUA | NA |
| Mallouhi 13 | 2004 | Radiologist | NA | HDI 5000 (Philips, USA) | Linear (4-7 MHz) | EUA | Mean 2.4 ± 3 days |
| Wedemeyer 14 | 2004 | Gastroenterologist | Yes | Aplio, Powervision (Toshiba, Japan) or Elegra (Siemens, Germany) | Linear (3.3-12 MHz) | MRI | Median 10 days (range: 0-75) |
| Zbar 15 | 2006 | Surgeon | Yes | B-K (Denmark) | Curvilinear (7.5 MHz) | TRUS, EUA | <28 days |
| Domkundwar 16 | 2007 | Surgeon | NA | Eccocee, Justvision, or Nemio (Toshiba, Japan) | Linear (7-11 MHz) Sector (3-6 MHz) Transvaginal (5-7 MHz) | EUA | NA |
| Kleinubing 35 | 2007 | Surgeon | NA | Diasonic Logic TM 400 (GE, USA) | Linear (7-10 MHz) Transvaginal (5-7.5 MHz) | EUA | NA |
| Maconi 17 | 2007 | Gastroenterologist | Yes | NA | Linear (7.5 MHz) Convex (3.5-5 MHz) | TRUS | Same day |
| Maconi 18 | 2013 | Gastroenterologist | Yes | NA | Microconvex (4-8 MHz) | MRI, EUA | Mean 10 days |
| Nevler 19 | 2013 | Gastroenterologist | Yes | B-K (Denmark) | Curvilinear (7.5 MHz) | EUA | Mean 35 days |
| Plaikner 20 | 2014 | Radiologist | Yes | HDI 5000 (Philips, USA) | Linear (5-7 MHz) Convex (5-8 MHz) | MRI, EUA | Mean 8 days (range 0-58) |
| Terracciano 21 | 2014 | NA | NA | NA | Mini Convex (4-7 MHz) | MRI, EUA | Mean 20 days |
| Bor 23 | 2016 | NA | NA | NA | Microconvex (16-36 MHz) | EUA | Mean 7 days (range 0-29) |
| Terracciano 22 | 2016 | Radiologist | Yes | NA | Microconvex (4-8 MHz) | MRI | Mean 11.4 ± 9.4 days |
| Puranik 24 | 2017 | NA | NA | Logiq 5 (GE, USA) | Linear (7-13 MHz) Sector (2-5 MHz) | Clinical, EUA, MRI | NA |
| Fateh 25 | 2017 | Radiologist | No | Medison 2.00 Sonoace X8 | Linear (7-12 MHz) | MRI | Mean 25.2 days (range 7–70) |
| Lee 26 | 2018 | Radiologist | Yes | iU22 (Philips, USA) | Linear (5-12 MHz) | MRI | Mean 4.6 ± 11.9 days |
| Yan 27 | 2018 | NA | NA | iU22, iU Elite or Epiq5(Philips, USA) | Linear (5-12 MHz) Convex (3-10 MHz) | EUA | NA |
| Anand 28 | 2022 | Radiologist | NA | NA | Linear (3-8 MHz) Sector (2-5 MHz) | MRI | NA |
| Ding 29 | 2022 | Radiologist | NA | Mylab Twice (Esaote, Italy) | Linear (18 MHz) | EUA | NA |
| Jung 30 | 2022 | Radiologist | Yes | iU22 or Epiq7 (Philips, USA) | Linear (5-12 MHz) | MRI | <14 days |
| Boles 31 | 2022 | Radiologist | Yes | Aplio 500 (Toshiba, Japan) | Linear (5-12 MHz) Curvilinear (5-8 MHz) | MRI | <14 days |
| Singh 32 | 2022 | Radiologist | NA | Voluson E8 (Wipro GE, India) | Linear (3-8 MHz) Sector (2-5 MHz) | MRI | NA |
| Altam 33 | 2023 | NA | NA | WS850 (Samsung, South Korea) | Curve (4-7 MHz) | EUA | <10 days |
| Hosokawa 34 | 2023 | Radiologist | Yes | Logiq7, E9, S8 or E10 (GE, USA) | Linear (9-15 MHz) | CT, MRI | NA |
| Garg 36 | 2023 | Radiologist | Yes | GE VOLUSON S6 | Linear (7-12 MHz) Curvilinear (2-5 MHz) | MRI | NA |
| Yang 37 | 2024 | NA | Yes | GE Voluson E10 diagnostic ultrasound system | 180 degrees rotating 3D volume probe (frequency 5-9 MHz) was used | EUA | <24 h |
| Islam 38 | 2024 | NA | NA | NA | NA | EUA | NA |
| Chang 39 | 2025 | Radiologist | Yes | GE LOGIQ 5 | Linear (12 MHz) | EUA | NA |
Abbreviations: TPUS, transperineal ultrasound; RS, reference standard; NA, information not available; TRUS, transrectal ultrasonography; CT, computed tomography; MRI, magnetic resonance imaging; EUA, examination under anesthesia. Bold type indicates primary RS.
3.4. TPUS techniques
Technical details of TPUS procedures varied across studies. Table 2b summarizes the patient positioning, transducer orientation, and additional techniques to enhance the detection of fistulas, internal openings, and abscesses. Twenty-three studies11–18,20,22,24,25,27–33,35–37,39 described patient positioning for TPUS, with the most commonly employed position being left lateral (20 studies), followed by the supine lithotomy position (11 studies). The positions were not mutually exclusive, as some studies utilized both.
Table 2b.
Characteristics of TPUS techniques performed.
| Study | Year | Mode | Position for TPUS | Transducer placed over external opening | Placement of transducer | Additional Techniques |
|---|---|---|---|---|---|---|
| Stewart 11 | 2001 | B-Mode | Supine lithotomy, left lateral | Yes | Longitudinal, oblique | – |
| Bonatti 12 | 2004 | B-Mode and color Doppler | Left lateral | NA | Longitudinal | – |
| Mallouhi 13 | 2004 | B-Mode and color Doppler | Left lateral | NA | Longitudinal, oblique | – |
| Wedemeyer 14 | 2004 | B-Mode and color Doppler | Left lateral | Yes | Longitudinal, oblique, transverse | Patients to bear down |
| Zbar 15 | 2006 | B-mode | Left lateral | Yes | Longitudinal, transverse | Use H2O2 to delineate fistula |
| Domkundwar 16 | 2007 | B-Mode and color Doppler | Supine lithotomy, left lateral | NA | Longitudinal, oblique | – |
| Kleinubing 35 | 2007 | B-mode | Supine lithotomy | NA | Longitudinal, oblique, transverse | Use H2O2 to delineate fistula |
| Maconi 17 | 2007 | B-mode | Left lateral | Yes | Longitudinal, oblique, transverse | – |
| Maconi 18 | 2013 | B-mode | Left lateral | Yes | Longitudinal, oblique, transverse | Translabial approach for anovulvular fistula |
| Nevler 19 | 2013 | B-mode | NA | Yes | Longitudinal, oblique, transverse | – |
| Plaikner 20 | 2014 | B-Mode and color Doppler | Left lateral | Yes | Longitudinal, oblique, transverse | – |
| Terracciano 21 | 2014 | B-mode | NA | NA | NA | – |
| Bor 23 | 2016 | B-mode | NA | NA | NA | – |
| Terracciano 22 | 2016 | B-mode, color Doppler and power Doppler | Left lateral | NA | Longitudinal, transverse | – |
| Puranik 24 | 2017 | B-mode | Supine lithotomy | Yes | Longitudinal, oblique, transverse | Bear down for air movement in fistula |
| Fateh 25 | 2017 | B-mode | Left anterior oblique, flexed knees | NA | Longitudinal, transverse | – |
| Lee 26 | 2018 | B-mode | NA | NA | NA | – |
| Yan 27 | 2018 | B-mode | Supine lithotomy, left lateral | Yes | Longitudinal, transverse | Empty bowels |
| Anand 28 | 2022 | B-mode | Supine lithotomy, left lateral | NA | Longitudinal, transverse | – |
| Ding 29 | 2022 | B-mode | Supine lithotomy | NA | NA | – |
| Jung 30 | 2022 | B-mode | Left lateral | NA | Longitudinal, transverse | – |
| Boles 31 | 2022 | B-mode | Supine lithotomy, left lateral | NA | NA | Injection of saline for high tract fistula |
| Singh 32 | 2022 | B-Mode and color Doppler | Supine lithotomy, left lateral | Yes | Longitudinal, oblique, transverse | Bear down for air movement in fistula |
| Altam 33 | 2023 | B-Mode and color Doppler | Supine lithotomy, left lateral | Yes | Longitudinal, transverse | – |
| Hosokawa 34 | 2023 | B-mode | NA | NA | Longitudinal, transverse | Use of oral analgesia if required |
| Garg 36 | 2023 | B-mode | Left lateral and lithotomy positioning | NA | NA | – |
| Yang 37 | 2024 | 3D B-mode and SonoVue enhanced | Left lateral | NA | Longitudinal, transverse, sagittal, and 3D | Use SonoVue to delineate fistula. Gentle knead over perineal area after injection |
| Islam 38 | 2024 | B-mode | NA | NA | NA | – |
| Chang 39 | 2025 | B-mode | Left lateral | Yes | NA | – |
Abbreviations: TPUS, transperineal ultrasound; NA, not available; H2O2, hydrogen peroxide.
Nine studies12–14,16,22,32,33,36,39 used Doppler ultrasound to aid in fistula characterization with two studies16,22 using it to distinguish between active and non-active fistulas, while one study14 used Doppler to differentiate between blood vessels and fistulas. Three studies14,24,32 recommended bearing down to enhance air movement within the fistula, thereby improving visualization of the fistulous tract. Several studies have explored injection of contrast agents for delineating the fistula tract, with two studies15,35 using hydrogen peroxide and one37 using SonoVue, while another31 used normal saline for high-tract fistulas. Additionally, one study27 recommended bowel emptying prior to TPUS, and another34 recommended the use of oral analgesia if necessary.
3.5. Diagnostic accuracy of TPUS for fistula detection
Of 27 studies11–28,30–36,38,39 that investigated FD, 18 studies12–14,16–18,22–25,27,29–36 defined a perianal fistula as the presence of a hypoechoic tract with or without air or fluid trapping while eight studies11,14–16,19,27,32,33 included sphincter defect assessment (Table S2).
Eighteen studies11,13,14,16–24,26,31–33 qualified for meta-analysis (Figure 2D, Table 3), yielding a pooled sensitivity and specificity for FD of 97.5% (95% confidence interval [CI] 92.6, 99.2) and 69.0% (95% CI 32.8, 91.0) respectively with a diagnostic odds ratio (DOR) of 86.11 (95% CI 8.27, 405.84). Significant heterogeneity was observed (I2=99.0%, χ2=134.6; P < .001) and the accuracy of TPUS for FD was 88.0% (Figure 2A, Table 3).
Figure 2.
(A–C) Summary receiver operating curves (SROC) for fistula detection (FD), internal opening (IO), and abscess detection (AD). (D–F) Forest plots for FD, IO, and AD.
Table 3.
Analysis for diagnostic accuracy of TPUS for fistula detection, fistula classification and abscess detection.
| Meta-analytic summary estimates |
|||||||||
|---|---|---|---|---|---|---|---|---|---|
| Category | Group | Number of patients | Sensitivity, % (95% CI) | Specificity, % (95% CI) | Positive LR (95% CI) | Negative LR (95% CI) | Diagnostic OR (95% CI) | AUC for SROC (95% CI) | Accuracy (%) |
| Fistula detection | Total | 1474a | 97.5 (92.6, 99.2) | 69.0 (32.8, 91.0) | 3.14 (1.11, 8.88) | 0.04 (0.01, 0.10) | 86.11 (18.27, 405.84) | 0.97 (0.95, 0.98) | 88.0 |
| CD | 337b | 96.2 (88.5, 98.8) | 62.5 (29.9, 86.7) | 2.57 (1.10, 6.00) | 0.06 (0.02, 0.20) | 42.68 (7.69, 236.89) | 0.93 (0.91, 0.95) | 86.4 | |
| Adult | 1369c | 97.7 (93.1, 99.3) | 75.8 (38.2, 94.1) | 4.04 (1.19, 13.66) | 0.03 (0.01, 0.09) | 132.60 (26.80, 656.30) | 0.98 (0.96, 0.99) | 89.3 | |
| Fistula classification | Total | 585d | 80.3 (76.9, 83.4) | 88.6 | |||||
| CD | 169e | 87.6 (81.7, 91.8) | 87.6 | ||||||
| IO detection | Total | 481f | 89.6 (77.2, 95.7) | 66.3 (24.1, 92.4) | 2.66 (0.82, 8.65) | 0.16 (0.07, 0.36) | 17.00 (3.04, 95.10) | 0.90 (0.87, 0.92) | 77.8 |
| Abscess detection | Total | 1276g | 93.5 (80.2, 98.1) | 94.5 (82.4, 98.4) | 17.00 (4.93, 58.70) | 0.07 (0.02, 0.23) | 247.90 (38.00, 1616.50) | 0.98 (0.97, 0.99) | 91.8 |
| CD | 209h | 85.5 (44.9, 97.7) | 78.1 (28.5, 96.9) | 3.90 (0.70, 21.70) | 0.19 (0.03, 1.05) | 21.00 (1.20, 366.40) | 0.89 (0.86, 0.92) | 83.3 | |
Abbreviations: TPUS, transperineal ultrasound; CD, Crohn’s disease; IO, internal opening; OR, odd’s ratio; LR, likelihood ratio.
3.6. Diagnostic accuracy of TPUS for fistula classification and detection of internal opening
FC is discussed in 23 studies11,13–20,22–30,32,33,36,37,39, with Park’s classification being the most commonly used, followed by the American Gastroenterology Association (AGA) classification (Table S2). Eleven studies11,15,17–19,22,25,33,36,37,39 reported FC data using Park’s classification, yielding a pooled sensitivity of 80.3% (95% CI 76.9, 83.4) and accuracy of 88.6%. The FC data demonstrate moderate heterogeneity (I2=45.2%, χ2=12.8; P = .08). Sensitivity for FC was further stratified by fistula type, with a pooled sensitivity of 80.4%, 89.7%, 36.6%, and 38.9% for intersphincteric fistula (ISF), transphincteric fistula (TSF), suprasphincteric fistula (SSF), and extrasphincteric fistula (ESF) respectively.
IO was defined in eight studies19,20,27,29,31,33,35,37 using the Cho criteria, which was developed for endosonographic detection of IO of fistula.40 Six studies16,31–33,38,39 were included for IO detection meta-analysis (Figure 2E, Table 3) and the pooled sensitivity and specificity were 89.6% (95% CI 77.2, 95.7) and 66.3% (CI 95% 24.1, 92.4) respectively while the DOR was 17.00 (95% CI 3.04, 95.1). There was significant heterogeneity among studies for IO detection (I2=92.0%, χ2=25.1; P < .001). The accuracy of TPUS for the detection of IO was 77.8% (Figure 2B, Table 3).
3.7. Diagnostic accuracy of TPUS for abscess detection
Of 18 studies13–15,17–20,22–26,28,31–34,39 on abscess detection, ten13,14,18,22–25,31,33,34 defined an abscess as a hypoechoic to anechoic mass with material, gas, or positive compression sign. Fourteen studies13–15,17–20,22–24,32–34,39 investigated fistula–abscess connections and four studies13,20,22,33 utilized Doppler to aid abscess detection (Table S3).
Sixteen studies13–15,17,18,20,22–26,28,31–33,39 were suitable for meta-analysis (Figure 2F, Table 3) showing pooled sensitivity and specificity of 93.5% (CI 95% 80.2, 98.1) and 94.5% (CI 95% 82.4, 98.4) respectively. The pooled DOR was 247.9 (95% 38.0, 1616.5). There was significant heterogeneity among studies (I2=92.0%, χ2=24.0; P < .001). The accuracy of AD with TPUS was 91.8% (Figure 2C, Table 3).
3.8. Subgroup analysis
Subgroup analysis on eight studies11,14,17,18,21–23,26 on CD patients described a pooled sensitivity and specificity of 96.2% (95% CI 88.5, 98.8) and 62.5% (95% CI 29.9, 86.7) respectively with a DOR and accuracy of 42.68 (95% CI 7.69, 236.89) and 86.4% for FD. The pooled sensitivity for FC and AD for CD patients was 87.6% (95% CI 81.7, 91.8) and 85.5% (95% CI 44.9, 97.7) respectively (Figure 3C, D, Table 3).
Figure 3.
(A–B) Summary receiver operating curves (SROC) for fistula detection (FD) and abscess detection (AD) in CD patients. (C–D) Forest plots for FD and AD in CD patients.
The diagnostic performance of TPUS was analyzed in comparison with MRI and EUA for FD and AD separately (Table S4). The pooled sensitivity of TPUS compared with MRI was 98.9% (95% CI 77.4, 99.9) for FD and 88.0% (95% CI 64.1, 96.8) for AD while comparing with EUA was 97.3% (95% CI 85.4, 99.6) for FD and 91.1% (95% CI 74.6, 97.2) for AD.
Sensitivity analyses showed an acceptable difference (±10% difference) for all primary domains tested except for specificity of FD (86.7% in sensitivity analyses vs 69.0% in primary analysis).
4. Discussion
This systematic review and meta-analysis provide an updated assessment of the diagnostic accuracy of TPUS for detecting perianal disease related to CD. Our results demonstrate that TPUS has a high diagnostic accuracy for FD, FC, IO detection, and AD, performing comparably to MRI, TRUS, and EUA.
Compared to the previously published meta-analysis by Maconi et al., our review demonstrates comparable pooled sensitivity for FD (97.5% vs 98.0%) and IO detection (89.6% vs 91.0%), higher pooled sensitivity for AD (93.5% vs 86.0%) but lower sensitivity for FC (80.3% vs 92.0%).6 The analysis of FC data was performed only on studies that reported classification based on Park’s classification because it is a widely used classification in studies and in surgical practice. Sensitivity of FC is reduced for high fistulas (such as suprasphincteric and extrasphincteric), probably reflecting the limitation of TPUS probes, which allow for detailed study of the superficial perineal layer at the expense of image resolution at deeper layers.22 In contrast, MRI does not share this limitation due to its consistency with superior soft-tissue contrast regardless of fistula depth.
In the management of perianal fistulas, the presence of proctitis, the fistula classification (in relation to the external sphincter), the number and location of internal openings, and the activity of the fistula tract play a crucial role in deciding for the best treatment option. Among the publications reviewed, fistula count, classification type, and presence of abscesses were generally included. The presence of proctitis was not included as a study or reporting criterion in any of the reviewed studies. This may be due to the previous lack of correlation between bowel wall thickness (BWT) and the definition of proctitis, though recent studies have identified a rectal BWT of 4 mm as indicative of inflammation.41 A recent collaborative review by leading European societies in IBD and gastrointestinal radiology proposed a standardized reporting template for the imaging of pfCD, applicable to both MRI and TPUS.42
While TPUS generally requires minimal preparation, various techniques have been explored to improve visualization of fistula tracts or abscesses. Among these, the injection of contrast agents directly into the fistula tract has been investigated in a limited number of studies. These contrast agents, in particular hydrogen peroxide and SonoVue, improve visualization by creating numerous hyperechogenic interfaces that delineate fistula tracts. However, outcomes have been variable. Two studies (n = 63) investigated the use of hydrogen peroxide with TPUS and found no overall improvement although it facilitated rectovaginal fistula tracking in two patients.15,35 More recently, injection of SonoVue contrast into fistula tracts has been shown to significantly improve accuracy of complex fistula classification (98.3% vs 85.0%), detection of fistula branches (92.6% vs 70.4%), and IO (97.1% vs 80.9%), although it did not significantly increases accuracy in FC (96.7% vs 95.0%).37 A comparative study using TRUS showed similar accuracy between hydrogen peroxide and SonoVue in detecting IO and outperformed non-contrast scans.43 Although these contrasts are generally safe, hydrogen peroxide can cause a transient local burning sensation around the perineal region or irritation to rectal mucosa whereas SonoVue has been associated with significantly less patient-reported pain.35,43,44 Moreover, image quality and accuracy of FD are enhanced with SonoVue due to the uniform distribution and sustained stability of microbubbles within the fistula tracts.37,43 Besides hydrogen peroxide and SonoVue, methods such as saline injection into the fistula tract and bearing down to induce air movement in the fistula have been described, though no comparative studies have evaluated their effectiveness in improving FD or FC.
TPUS showed lower accuracy for FD and AD in CD patients than in the overall population, probably due to the greater complexity of CD-related fistulas.4 However, the true incidence of pfCD in this meta-analysis is likely to be underestimated, as most studies do not specify the perianal fistula etiology. Furthermore, only one study on FD with a reference standard (n = 26) included CD and non-CD patients, limiting conclusions.11
This meta-analysis highlights the utility of TPUS as a valuable, highly accurate tool for diagnosing and assessing perianal conditions, particularly in patients with a suspected perianal abscess. TPUS has high diagnostic accuracy for AD, underscoring its importance in the initial evaluations of these patients. Given that 30%-70% of patients with perianal abscesses may present with a concomitant perianal fistula,45 practitioners are encouraged to thoroughly evaluate fistula presence during TPUS assessments. Moreover, TPUS has potential for monitoring perianal fistulas following treatment, though only one study has addressed this application.30 Delineating the different stages of healing in pfCD remains an unmet clinical need. While TPUS may serve as a practical first-line tool due to its accessibility and safety profile, initial MRI remains essential for comprehensive perianal fistula mapping prior to definitive management. Thereafter, TPUS could potentially be used for more frequent, non-invasive monitoring. Further research is warranted to establish standardized protocols for TPUS in the longitudinal management of perianal fistulas. This should establish its potential capacity to differentiate between fluid, granulation tissue, and fibrosis of the fistula tract. Additionally, future TPUS studies could explore its potential for differentiating between cryptoglandular and CD-related fistulas. This differentiation may be achieved by assessing specific features such as the presence of fistula debris, bifurcation, and associated rectal inflammation and could be further supported by deep learning models, as seen in recent MRI studies.46,47
Our systematic review has several limitations. First, the number of studies reporting the diagnostic accuracy of TPUS against a reference standard is small. Although we used broad search terms to increase the yield of available studies, the available evidence was of low quality, underscoring the need for further high-quality research in this area. Second, selection bias may occur due to the focus on patients with perianal complaints, potentially leading to higher sensitivities for FD and AD. Third, significant heterogeneity was observed due to variations in reference standards, procedural timing, imaging techniques, outcome definitions, data capture methods (per-patient vs per-lesion reporting), and patient demographics. To improve on consistency of reference standards, studies that included CT as part of a composite reference standards were removed from the meta-analysis.12,34 Additionally, a bivariate random-effects model was used to account for residual between-study heterogeneity and the correlation between sensitivity and specificity within and across studies. Finally, TPUS is operator-dependent, with its reliability influenced by the operator’s experience. The absence of operator experience data in many studies is a significant limitation of this review. Future research focused on assessing reliability and interobserver agreement is essential to address these limitations.
In conclusion, TPUS is a highly accurate, non-invasive tool for detecting perianal fistulas and abscesses in both CD and non-CD patients, supporting its role as a first-line diagnostic tool. Further research should investigate the utility of TPUS in the monitoring of perianal fistulas to better define its role in monitoring patients with pfCD.
Supplementary Material
Contributor Information
Chong-Teik Lim, Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Amsterdam, 1081 HV, The Netherlands; Department of Gastroenterology and Hepatology, Singapore General Hospital, 169856, Singapore.
Maarten Pruijt, Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Amsterdam, 1081 HV, The Netherlands.
Gek-Hsiang Lim, Health Services Research Unit, Singapore General Hospital, 169608, Singapore.
Faridi Jamaludin, Medical Library AMC, Amsterdam UMC location University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands.
Christoph Teichert, Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Amsterdam, 1081 HV, The Netherlands.
Floris de Voogd, Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Amsterdam, 1081 HV, The Netherlands.
Geert D’Haens, Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Amsterdam, 1081 HV, The Netherlands.
Britt Christensen, Department of Gastroenterology, The Royal Melbourne Hospital, Parkville,VIC 3050, Australia; Department of Medicine, University of Melbourne, Parkville, VIC 3050, Australia.
Giovanni Maconi, Gastroenterology Unit, Department of Biomedical and Clinical Sciences, ‘L. Sacco’ Hospital, University of Milano, Milan 20157, Italy.
Krisztina Gecse, Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Amsterdam, 1081 HV, The Netherlands.
Author contributions
C.L.: Study concept and design, data acquisition, statistical analyses, data analysis and interpretation, manuscript drafting; M.P.: Study concept and design, data acquisition, data analysis and interpretation, manuscript drafting; G.L.: Statistical analyses, data analysis and interpretation; F.J.: Data acquisition; C.T.: Revision of final manuscript; F.V.: Revision of final manuscript; G.D.: Revision of final manuscript; B.C.: Revision of final manuscript; G.M.: Revision of final manuscript; K.G.: Study concept and design, manuscript drafting, revision of final manuscript.
Supplementary material
Supplementary material is available at ECCO-JCC online.
Funding
No funding was received for this study.
Conflict of interest
Chong-Teik Lim: Nothing to disclose. Maarten Pruijt: Nothing to disclose. Gek-Hsiang Lim: Nothing to disclose. Faridi Jamaludin: Nothing to disclose. Christoph Teichert: Nothing to disclose. Floris de Voogd: speaker or honoraria fees from AbbVie, Janssen, Galapagos, Pfizer, and Takeda. Geert D’Haens: research grants from Abbvie, Alimentiv, BMS, J&J, Pfizer, Takeda; consulting fees from Abbvie, Agomab, Alimentiv, AstraZeneca, AMT, Bristol Meiers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Galapagos, Index Pharmaceuticals, Kaleido, Glaxo Smith Kline, Gossamerbio, Pfizer, Immunic, Johnson and Johnson, Polpharma, Procise Diagnostics, Prometheus laboratories, Prometheus Biosciences, Progenity, Protagonist, and Ventyx; speaker’s fees from Abbvie, Arena, Boehringer Ingelheim, Celltrion, Galapagos, Gilead, Pfizer, BMS, and Takeda; data monitoring board: Galapagos, AstraZeneca, and Seres Health. Britt Christensen: grants from Takeda, Celltrion, Pfizer, GSK, Janssen, AbbVie, Helmsley, Gesa, and Falk; personal fees from Takeda, GSK, Celltrion, AbbVie, Janssen Chiesi, and Falk. Giovanni Maconi: Fees from Samsung, Johnson&Johnson, and AbbVie. Krisztina Gecse: grants from Pfizer Inc, Celltrion, and Galapagos; consultancy fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, ImmunicTherapeutics, Janssen Pharmaceuticals, Novartis, Pfizer Inc., Samsung Bioepis, and Takeda; and speaker’s honoraria from Celltrion, Ferring, Janssen Pharmaceuticals, Novartis, Pfizer Inc, Samsung Bioepis, Takeda, and Tillotts.
Data Availability
Data, analytic methods, and study materials will be made available to other researchers on reasonable request.
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Associated Data
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Supplementary Materials
Data Availability Statement
Data, analytic methods, and study materials will be made available to other researchers on reasonable request.