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. 2019 Dec 30;14(12):e0226740. doi: 10.1371/journal.pone.0226740

Diagnostic utility of CT for small bowel obstruction: Systematic review and meta-analysis

Zhengyan Li 1, Ling Zhang 2, Xijiao Liu 1, Fang Yuan 1, Bin Song 1,*
Editor: Jiani Hu3
PMCID: PMC6936825  PMID: 31887146

Abstract

Background

To perform a systematic review and meta-analysis evaluating the diagnostic performance of computed tomography (CT) for small bowel obstruction (SBO), including diagnostic accuracy, ischemia, predicting surgical intervention, etiology and transition point.

Methods

PubMed/MEDLINE and related databases were searched for research articles published from their inception through August 2018. Findings were pooled using bivariate random-effects and summary receiver operating characteristic curve models. Meta-regression and subgroup analyses were performed to evaluate whether publication year, patient age, enhanced CT, slice thickness and pathogenesis affected classification accuracy.

Results

In total, 45 studies with a total of 4004 patients were included in the analysis. The pooled sensitivity and specificity of CT for SBO were 91% (95% confidence interval [CI]: 84%, 95%) and 89% (95% CI: 81%, 94%), respectively, and there were no differences in the subgroup analyses of age, publication year, enhanced CT and slice thickness. For ischemia, the pooled sensitivity and specificity was 82% (95% CI: 67%, 91%) and 92% (95% CI: 86%, 95%), respectively. No difference was found between enhanced and unenhanced CT based on subgroup analysis; however, high sensitivity was found in adhesive SBO compared with routine causes (96% vs. 78%, P = 0.03). The pooled sensitivity and specificity for predicting surgical intervention were 87% and 73%, respectively. The accuracy for etiology of adhesions, hernia and tumor was 95%, 70% and 82%, respectively. In addition, the pooled sensitivity and specificity for transition point was 92% and 77%, respectively.

Conclusions

CT has considerable accuracy in diagnosis of SBO, ischemia, predicting surgical intervention, etiology and transition point.

Introduction

Small bowel obstruction (SBO) is a common emergency diagnosis based on clinical signs and radiographic findings and is estimated to account for 2% of all patients with abdominal pain and 12–16% of hospital admissions in the United States [1, 2]. Although most SBO patients are treated successfully with nasogastric tube decompression, the mortality of SBO increases to 25% if bowel ischemia is present with delayed surgical management [3]. A challenge in the clinical management is that clinical presentation, physical examination findings, and laboratory tests are insufficient to make an accurate diagnosis of SBO, but the management has changed considerably since then due to advancements in imaging technology, such as computed tomography (CT) [3, 4].

There is a consensus regarding the use of CT in the evaluation of patients with SBO [5], and many studies reported that CT is a helpful tool to diagnose SBO, identify causes and the transition point, and most importantly, detect ischemia, which requires prompt surgical intervention [618]. However, CT findings about such points exhibit variable diagnostic performance. For example, the sensitivity of CT for diagnosis of SBO varied from 50% to 100%, and the specificity values varied from 57% to 100% [1, 8, 1922]. Furthermore, many studies reported that CT had high sensitivity and specificity for ischemia of SBO [7, 8, 12, 2325], but a prospective study [26] showed a poor sensitivity of 15% for ischemia. In addition, several studies showed CT could predict surgical intervention for patients with SBO [9, 11, 13, 27], but a recent study including 108 cases found no correlation between CT findings and surgical intervention [28].

Given the inconsistency in the existing literature, we performed a quantitative meta-analysis using bivariate random-effects and summary receiver operating characteristic models to evaluate the diagnostic performance of CT for SBO, including diagnostic accuracy, ischemia, predicting surgical intervention, etiology and transition point.

Materials and methods

No financial support was received for this research. We performed this systematic review using the guidelines proposed by the Cochrane Collaboration in the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy (http://srdta.cochrane.org/handbook-dta-reviews). The protocol was registered on PROSPERO (CRD42015024658) [29].

Study selection criteria

  1. Participants

            This review focused on patients with suspected diagnosis of SBO.

  2. Index tests

        CT was the test under evaluation.

  3. Target conditions

        The target condition of this review was to evaluate the diagnostic performance of CT for SBO, including diagnostic accuracy, ischemia, predicting surgical intervention, etiology and transition point.

  4. Reference standards

        The primary reference standard was surgical findings in patients who received surgical intervention. Alternatively, clinical findings and enteroclysis were the reference standards if the patients did not receive any surgical intervention.

Search methods for identification of studies

1). Study selection

We used the Cochrane risk of bias tool and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement methodology [30] to report systematic reviews and perform the meta-analysis (S1 Table). Two independent reviewers (Z.L. and L.Z.) conducted a search of Medline, Embase, the Cochrane Library, Google Scholar and relevant journals. Only studies published in English were included in the meta-analysis. We performed the last updated search on August 2018. The following text words and corresponding heading terms were used as search terms: “computed tomography”, “CT”, “bowel obstruction”, “small bowel obstruction”, “intestinal obstruction” and “small intestinal obstruction”. The MeSH terms and keywords used for the search are listed in S2 Table. Related articles and reference lists were manually searched to avoid omissions. After title screening, we evaluated abstracts for relevance and identified articles as included, excluded or requiring further assessment. At this stage, if a paper required further assessment, we contacted the study lead investigator by e-mail with a request for further information.

2). Data extraction

The inclusion criteria were as follows: (a) original research focusing on the diagnostic value of CT in SBO; (b) CT as diagnostic index test; and (c) sufficient data available to calculate construct 2×2 contingency tables and corresponding 95% confidence interval (95% CI). The following exclusion criteria were used: (a) index test and reference standard were both used in CT; (b) reviews of the literature; (c) nonhuman studies; (d) not published in English. For studies reporting the same or overlapping data by the same authors, the most suitable studies with the largest number of cases or latest publication dates were selected. Two investigators (Z.L. and L.Z.) assessed each study independently and recorded eligibility, quality and outcomes. Disagreements regarding eligibility were noted in 5% of the articles (κ = 0.89), which were resolved by a third party through consensus. A third investigator (F.Y.) provided arbitration in case of disagreement.

We extracted the following study features: (a) study design and patient characteristics (i.e., first author, year of publication, country of origin, department of the first author, consecutive recruitment, number of patients, age, sex ratio, and inclusion criteria); (b) imaging techniques (i.e., CT type, collimation, slice thickness, and use of contrast agent); (c) image evaluation (i.e., number of readers, retrospective or prospective CT reading, consensus reading, and interests of diagnosis); (d) reference standard (i.e., time between admission and surgery, histopathologic analysis, surgery findings, and duration of the medical follow-up).

3). Quantitative data synthesis

Independently and in duplicate, reviewers assessed the risk of bias using the tool of the second edition of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS 2) [31] using Review Manager 5.3 (RevMan, The Cochrane Collaboration, Oxford, United Kingdom). The QUADAS 2 consisted of four key domains that discuss patient selection, index test, reference standard and flow of patients through the study and timing of the index tests and reference standard (flow and timing). Each domain was assessed in terms of the risk of bias, and the first three domains were also assessed in terms of concerns about applicability. For each included study, a description, a comment, and a judgment as “high”, “unclear”, or “low” risk of bias were provided for each of the domains. Studies with high risk of bias for any one or more key domains were considered to exhibit high risk of bias. Studies with low risk of bias for all key domains were considered to exhibit low risk of bias. Otherwise, studies were considered to exhibit an unclear risk of bias. We classified high risk of bias studies as low-quality studies, and the other studies were classified as high-quality studies.

The data of the two-by-two tables were used to calculate sensitivity and specificity of each study. We present individual study results graphically by plotting the estimates of sensitivity and specificity (and their 95% confidence interval [CI]) based on forest plots using bivariate random-effects and summary receiver operating characteristic curve models (SROC) [32, 33]. Heterogeneity was evaluated using the Cochrane Q test and the I2 statistic to assess the degree of inter-study variation. I2 values of 0 to 24.9%, 25 to 49.9%, 50 to 74.9%, and 75 to 100% were considered to indicate no, mild, moderate, and significant thresholds for statistical heterogeneity, respectively [34, 35]. Subgroup analyses were performed based on age (adult or pediatric), publication year (2000 as cutoff point), different imaging techniques (enhanced CT or not; slice thickness ≤5 mm or >5 mm) and different causes of SBO using meta-regression analysis.

We used the Deek funnel plot asymmetry test, which is the recommended tool for assessing risk of publication bias in meta-analyses of diagnostic test accuracy [36]. A P-value less than 0.10 for the slope coefficient indicated significant asymmetry. P-values less than or equal to 0.05 were considered indicative of a significant difference. Analyses were performed with “midas” modules in the Stata software (version 12.0; StataCorp, College Station, Tex).

Results

Eligible studies

The study selection process is presented in Fig 1. The literature search yielded 1196 potentially relevant records. We removed 571 duplicate studies after screening the titles. After evaluating the abstract of each study, 533 studies were excluded because they did not meet the inclusion criteria. Subsequently, we carefully read the full text of each of the remaining 92 studies and excluded 47 studies for the following reasons: no relevant data (n = 37), not published in English (n = 7), overlapping data (n = 2) and review (n = 1). Finally, 45 studies were included in the meta-analysis.

Fig 1. Flow chart of selection of studies.

Fig 1

As shown in Table 1, the eligible studies were conducted from 1992 through 2018 with a total number of 4004 patients, and the sample size ranged from 20 to 256. All 45 studies focused on the diagnostic value of CT for SBO. Among them, 24 studies were from North America, 13 were from Asia and 8 were from Europe. A variety of outcomes were recorded in these studies, including diagnosis of SBO (n = 19), ischemia (n = 17), predicting surgical intervention (n = 7), etiology (n = 16) and transition point (n = 11).

Table 1. Key parameters extracted from the included studies.

Author, year Counrty Design Adult or pediatric No. of patients mean age (y) No. of male Reference standard Interests of diagnosis
Atri 2009[6] Canada Retrospective adult 99 65 43 SF or CF SBO, etiology, transition
Balthazar 1992[7] USA Retrospective adult 19 63 7 SF Ischemia
Balthazar 1997[8] USA Retrospective adult 100 NR NR SF or CF SBO, ischemia, etiology
Chang 2014[9] Taiwan Retrospective adult 151 62 89 SF PSI
Chang 2017[23] Taiwan Retrospective Pediatric 31 7 NR SF Ischemia
Chuong 2016[24] France Retrospective adult 158 71 61 SF or CF Ischemia
Daneshmand 1999[10] USA Retrospective adult 45 44 NR SF or CF SBO, etiology
Deshmukh 2011[11] USA Retrospective adult 129 62 68 SF or CF PSI
Donckier 1998[12] Belgium Retrospective adult 54 62 30 SF or CF Ischemia
Duda 2008[13] USA Retrospective adult 194 50 NR SF or CF PSI
Filippone 2007[14] Italy Retrospective adult 49 63 NR SF Etiology, transition
Frager 1994[16] USA Retrospective adult 90 NR NR SF or CF SBO, etiology, transition
Frager 1996[15] USA Retrospective adult 60 NR NR SF Ischemia
Fukuya 1992[17] USA Retrospective adult 60 NR NR SF SBO, etiology
Geffroy 2014[18] France Retrospective adult 44 73 10 SF Ischemia
Halepota 2018[47] Pakistan Retrospective Pediatric 98 8 65 SF SBO
He 2016[48] China Retrospective adult 57 58 31 SF or DSA Ischemia
Hwang 2009[27] Korea Prospective adult 128 NR NR SF PSI
Idris 2012[49] Pakistan Retrospective adult 59 48 22 SF Transition
Jabra 1997[50] USA Retrospective Pediatric 20 9 NR SF Etiology
Jabra 2001[51] USA Retrospective Pediatric 59 9 NR SF SBO
Jaffe 2006[52] USA Retrospective adult 100 55 40 SF or CF SBO
Jancelewicz 2009[53] USA Retrospective adult 192 59 81 SF Ischemia
Jang 2010[54] Korea Retrospective adult 60 29 54 SF Ischemia
Kato 2010[55] Japan Retrospective adult 115 73 60 SF Ischemia
Kim 2004[25] Korea Retrospective adult 136 51 71 SF Ischemia
Kulvatunyou 2015[56] USA Prospective adult 202 60 100 SF PSI
Maglinte 1993[57] USA Retrospective adult 55 NR NR EC or SF SBO
Maglinte 1996[38] USA Retrospective adult 78 NR NR EC or SF SBO
Makanjuola 1998[58] Saudi Arabia Retrospective adult 49 32 27
SF or CF

SBO, ischemia, etiology
Matsushima 2016[59] USA Retrospective adult 111 52 56 SF PSI
Memon 2014[60] Pakistan Retrospective adult 102 NR NR SF Transition
Millet 2017[43] France Retrospective adult 256 64 NR SF Ischemia
Obuz 2003[61] Turkey Retrospective adult 41 NR NR SF or CF SBO, ischemia, etiology
Peck 1999[19] USA Retrospective adult 55 56 NR SF or CF SBO
Pongpornsup 2009[62] Thailand Retrospective adult 35 56 25 SF or CF SBO, etiology
Scrima 2017[63] USA Retrospective adult 179 56 86 SF PSI, transition
Shah 2008[64] USA Retrospective adult 30 43 19 SF Etiology, transition
Sheedy 2006[26] USA Retrospective adult 61 67 25 SF SBO, ischemia
Taourel 1995[65] France Prospective adult 57 60 33 SF or CF Etiology
Walsh 1998[20] USA Retrospective adult 36 NR NR EC SBO
Wang 2012[21] Canada Retrospective Pediatric 47 10 32 SF Etiology, transition
Xu 2013[66] China Retrospective adult 94 NR 51 SF SBO, etiology
Yaghmai 2006[22] USA Retrospective adult 67 NR NR SF SBO, etiology, transition
Zalcman 2000[41] Belgium Retrospective adult 142 61 81 SF Ischemia

Abbreviation: SF, surgical findings; CF, clinical findings, EC, enteroclysis; PSI, prediction of surgical intervention; DSA, digital subtraction angiography; NR, not reported.

Assessment of methodological quality

The summary and details of risk of bias were summarized in Fig 2 and S1 File. In summary, twelve (27%) studies that fulfilled all of the methodological criteria were judged to be at low risk of bias, and 20 (44%) exhibited high risk of bias. The remaining 13 (28%) were judged to be at unclear risk of bias. Among included studies, 6 (13%) studies had a high risk in the domain of patient selection given that the selection was based on specific or nonexhaustive causes of SBO. There was a high risk of bias with the index test in 7 (16%) studies that did not report information on CT performance parameters or reader number and expertise. In addition, most (93%) of included studies had a retrospective design, and 17 (38%) of these studies did not provide any information about whether the results of the reference standard were blinded to readers. Thus, the diagnostic performance of CT could have been overestimated. Only 15 (33%) studies reported an acceptable delay between index test and reference standard, and the other studies were considered to have a high risk or potential risk of flowing and timing bias due to unclear intervals. Meta-regression was performed to compare the different qualities of included studies.

Fig 2. Quality assessment for risk of bias and applicability of included studies: QUADAS evaluation.

Fig 2

Value of CT in diagnosis of SBO

Overall, nineteen studies including 1269 patients reported data on diagnostic performance of CT on SBO. As shown in Fig 3, summary analysis results showed the sensitivity and specificity of CT for SBO were 91% (95% CI: 84%, 95%) and 89% (95% CI: 81%, 94%), respectively, and there significant heterogeneity (I2>75%) was noted. The SROC demonstrated an area under the curve of 0.96 (95% CI: 0.93, 0.97). Subgroup analysis results using meta-regression are presented in Table 2. There was no difference in diagnostic value of CT for SBO between adult and pediatric patients (sensitivity 89% vs. 96%, P = 0.12; specificity 86% vs. 90%, P = 0.08). Unenhanced CT was associated with a similar diagnostic value for SBO compared with enhanced CT. In addition, similar results were found between different slice thicknesses (≤5 mm or >5 mm), different study qualities (high or low quality) or publication year (<2000 or ≥2000).

Fig 3. Value of CT in diagnosis of SBO.

Fig 3

Table 2. Pooled estimates of the diagnostic performance of CT in SBO and SBO with ischemia.

Variable No. of studies Pooled Sensitivity (95% CI) P value Pooled Specificity (95% Cl) P value
Diagnosis for SBO
Over all 19 91% (84%, 95%) 89% (81%, 94%)
Age 0.12 0.08
Adult 16 89% (83%, 95%) 86% (79%, 93%)
Pediatric 3 96% (90%, 100%) 90% (84%, 97%)
Enhanced CT or not 0.39 0.74
Enhanced 16 90% (84%, 96%) 90% (84%, 97%)
Unenhanced 3 93% (83%, 100%) 82% (62%, 100%)
Publication year 0.56 0.61
<2000 9 88% (78%, 97%) 86% (75%, 97%)
≥2000 10 93% (87%, 99%) 82% (62%, 100%)
Slice thickness 0.66 0.26
≤5 mm 8 93% (87%, 100%) 89% (79%, 99%)
> 5mm 11 88% (78%, 97%) 86% (75%, 97%)
Quality of studies 0.81 0.87
High 13 93% (89%, 98%) 91% (84%, 98%)
Low 6 81% (66%, 95%) 83% (70%, 97%)
Diagnosis for ischemia
Over all 17 82% (67%, 91%) 92% (86%, 95%)
Enhanced CT or not
Enhanced 16 83% (71%, 94%) 92% (87%, 96%)
Unenhanced 1 64% 93%
Publication year 0.21 0.09
<2000 5 91% (78%, 100%) 93% (86%, 100%)
≥2000 12 77% (62%, 93%) 91% (86%, 96%)
Etiology 0.03 0.10
Adhesion 2 96% (89%, 100%) 85% (68%, 100%)
Routine causes 15 78% (65%, 91%) 92% (88%, 96%)
Quality of studies 0.79 0.27
High 12 83% (71%, 96%) 92% (88%, 97%)
Low 5 76% (50%, 100%) 89% (80%, 98%)

Value of CT in diagnosis of ischemia

Seventeen studies (including 1575 patients) reported the value of CT in diagnosis of SBO with ischemia. The pooled sensitivity and specificity were 82% (95% CI: 67%, 91%) and 92% (95% CI: 86%, 95%), respectively, and there was significant heterogeneity (I2>75%) (Fig 4). The SROC demonstrated an area under the curve of 0.94 (95% CI: 0.92, 0.96). Only one study (18) reported the value of unenhanced CT in diagnosis of ischemia and the sensitivity and specificity were 64% and 93%. In subgroup analysis (Table 2), no difference was found between the enhanced and the unenhanced CT (sensitivity 83% vs. 64%, P = 0.23; specificity 92% vs. 93%, P = 0.79). However, higher sensitivity was found in adhesive SBO compared with routine causes (96% vs. 78%, P = 0.03), but the specificity was not significant (85% vs. 92%, P = 0.1). In addition, no difference was found between different study qualities (high or low quality) or publication year (<2000 or ≥2000).

Fig 4. Value of CT in diagnosis of ischemia.

Fig 4

Value of CT in predicting surgical intervention

As shown in Fig 5, seven studies including 1094 patients presented the value of CT in predicting surgical intervention. Among them, 3 studies focused on adhesive SBO, and the other 4 studies focused on SBO with routine causes. The results of the summary analysis showed the sensitivity and specificity were 87% (95% CI: 68%, 95%) and 73% (95% CI: 55%, 85%), respectively, and there was significant heterogeneity (I2>75%). In subgroup analysis, higher sensitivity was found in adhesive SBO compared with routine causes (96% vs. 71%, P = 0.05), but the specificity was not significant (71% vs. 74%, P = 0.7).

Fig 5. Value of CT in predicting surgical intervention.

Fig 5

Value of CT in etiology

Sixteen studies (including 961 patients) reported the value of CT in SBO etiology. The pooled sensitivity was 83% (95% CI: 76%, 88%), and there was significant heterogeneity (I2>75%). Subgroup analysis results using meta-regression were presented in Table 3. The pooled sensitivity values of CT for adhesion, hernia and tumor were 95% (I2 = 52%), 70% (I2 = 57%) and 82% (I2 = 37%), respectively.

Table 3. Sensitivity of CT in diagnosis of etiology in SBO.

No. of studies Sensitivity (95% CI) I2
Over all 16 83% (76%, 88%) 77%
Adhesion 10 95% (89%, 98%) 52%
Hernia 9 70% (44%, 88%) 57%
Tumor 9 82% (72%, 89%) 33%

Value of CT in transition point diagnosis

Overall, eleven studies including 823 patients presented the value of CT in diagnosis of transition point of SBO. Summary analysis results showed that the sensitivity and specificity were 92% (95% CI: 87%, 95%) and 87% (95% CI: 74%, 95%), respectively, and significant heterogeneity was noted (I2>75%).

Publication bias

The impact of publication bias on meta-analysis results was assessed using Deeks’ funnel plots. The shapes of the funnel plots for the pooled sensitivity and specificity of CT performance for SBO revealed obvious symmetry (P = 0.64), indicating that the meta-analysis was not affected by publication bias (Fig 6).

Fig 6. Illustration of publication bias.

Fig 6

Discussion

We performed a systematic review of the literature and identified 45 studies (more than 4000 patients) reporting the diagnostic performance of CT for SBO. The results of this study showed that CT should be the choice for the overall diagnosis of SBO, which has considerable accuracy in diagnosis of SBO, ischemia, predicting surgical intervention, etiology and transition point. Similar diagnostic value of CT for SBO was found between adult and pediatric patients. We also found that unenhanced CT had similar power in diagnosis of SBO compared with enhanced CT. In addition, CT was associated with higher sensitivity for ischemia in adhesive SBO compared with routine causes of SBO, but no difference in specificity was noted. Furthermore, regarding etiology, CT had significant sensitivity for adhesion identification.

Currently, plain film radiography (X-ray), CT, ultrasound and magnetic resonance imaging (MRI) are utilized as diagnostic modalities for suspected SBO. Due to easier accessibility and lower cost, plain film radiography (X-ray) is typically the initial imaging choice for the evaluation of SBO. However, this imaging modality is often nondiagnostic with poor sensitivity (46–69%) and specificity (57–67%) [37, 38]. In contrast, our study reported significant sensitivity and specificity of CT for SBO at 91% and 89%, respectively. Ultrasound also represents a convenient and inexpensive diagnostic tool that could be performed at bedside, especially in the emergency department. A recent meta-analysis identified 11 studies and reported a high sensitivity (92%) and specificity (97%) of ultrasound for SBO [39]. However, limited evidence is available for the use of ultrasound for diagnosis of small bowel ischemia, which is an important complication of SBO and an indication for emergency surgical intervention [40]. Thus, CT, rather than X-ray or ultrasound, was recommended as the first choice in the overall diagnosis of SBO [67, 68].

As reported in our study, CT played a key role in the diagnosis of SBO and the diagnosis of small bowel ischemia. Many CT findings, such as decreased enhanced bowel wall, wall thickness, mesenteric congestion, mesenteric fluid, and peritoneal fluid, had been reported as findings related to bowel ischemia [8, 23, 24, 26, 41]. A previous meta-analysis [42] including nine studies reported that a hypoenhanced bowel wall (specificity 95%) was highly predictive of ischemia, and the absence of mesenteric fluid (sensitivity 89%) was a reliable finding to exclude strangulation. A recent study including 256 patients with adhesive SBO found that peritoneal fluid (sensitivity 89%) instead of mesenteric fluid (sensitivity 73%) had the highest sensitivity among CT findings, and hypoenhanced bowel wall, free peritoneal gas, pneumatosis or venous gas were all associated with high specificity (96–99%) [43].

Several studies [6, 18, 24] focused on the diagnostic value of unenhanced CT for SBO, which might be more safer for the patients with the high risk of contrast agent-induced nephropathy [69]. Atri et al [6] reported that unenhanced CT had similar accuracy to diagnose mechanical small bowel obstruction compared with enhanced CT. For ischemia, a retrospective study [18] showed that increased bowel-wall attenuation on unenhanced images had 100% specificity and 56% sensitivity. Furthermore, a recent study [24] found that the addition of unenhanced CT to contrast-enhanced CT could improve the sensitivity, diagnostic confidence, and observer agreement for the diagnosis of ischemia. However, due to the few evidence, the effect of unenhanced CT for ischemia should be reconfirmed in the future. Although similar diagnostic power between unenhanced and enhanced CT was found for SBO in this review, enhanced CT might be more powerful in the diagnosis of ischemia, etiology and predicting surgical intervention [67, 68].

In addition, a few studies [4446] reported the diagnostic value of MRI for patients with suspected SBO, especially for pregnant women. A small observational study [44] reported that cine MRI was a feasible and promising technique for diagnosing strangulation of SBO with high sensitivity (100%) and specificity (93%). However, compared with CT, MRI might not be convenient (especially at night), has a longer scan time, and might not be as reliable in identifying the etiology of SBO [67].

This study first comprehensively evaluated the diagnostic utility of CT for SBO, including multiple relevant outcomes, such as diagnostic accuracy, ischemia, predicting surgical intervention, etiology and transition point. This study included data from more than 4,000 patients, 45 studies, and 13 countries from different regions of North America, Asia and Europe. Two independent investigators also rigorously assessed its methodological quality.

However, this systematic review and meta-analysis has several limitations. First, most (93.3%) of included studies were retrospective studies, which may overestimate the diagnostic value of CT, thus, high-quality prospective studies are needed in the future. Second, 66% of included studies are considered to exhibit a high risk or potential risk of flowing and timing bias due to an unclear interval between index test and reference standard with significant heterogeneities of primary outcomes. However, similar outcomes was found in the subgroup analysis of high-quality included studies. Third, data are limited with respect to the pediatric population, limiting applicability to this subgroup. Fourth, the literature on the use of unenhanced CT for ischemia is also limited (only one study included), highlighting the need for future investigations on this topic. Finally, although no publication bias was found in this meta-analysis, only published studies with selective databases were included for analysis, and the unavailability of unreported outcomes could have resulted in reporting bias. Regardless of these limitations, we sought to minimize bias throughout our study by using strict method identification, data selection, and statistical analysis, as well as controlling for publication bias and performing sensitivity analyses.

Conclusion

This meta-analysis suggests that CT has considerable accuracy in diagnosis of SBO, ischemia, predicting surgical intervention, etiology and transition point. Further large-sample, high-quality prospective studies focusing on the performance of unenhanced CT for SBO with ischemia are needed.

Supporting information

S1 Table. PRISMA checklist.

(DOCX)

S2 Table. Characteristics of the computed-assisted literature search strategy.

(DOCX)

S1 File. Methodological criteria of the included studies: QUADAS evaluation.

(TIF)

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

The authors received no specific funding for this work.

References

  • 1.Nicolaou S, Kai B, Ho S, Su J, Ahamed K. Imaging of acute small-bowel obstruction. AJR Am J Roentgenol. 2005;185(4):1036–1044. 10.2214/AJR.04.0815 [DOI] [PubMed] [Google Scholar]
  • 2.Hastings RS, Powers RD. Abdominal pain in the ED: a 35 year retrospective. Am J Emerg Med. 2011;29(7):711–6. 10.1016/j.ajem.2010.01.045 [DOI] [PubMed] [Google Scholar]
  • 3.Paulson EK, Thompson WM. Review of small-bowel obstruction: the diagnosis and when to worry. Radiology. 2015;275(2):332–42. 10.1148/radiol.15131519 [DOI] [PubMed] [Google Scholar]
  • 4.Taylor MR, Lalani N. Adult small bowel obstruction. Acad Emerg Med. 2013;20(6):528–44. 10.1111/acem.12150 [DOI] [PubMed] [Google Scholar]
  • 5.Ros PR, Huprich JE. ACR Appropriateness Criteria on suspected small-bowel obstruction. J Am Coll Radiol. 2006;3(11):838–41. 10.1016/j.jacr.2006.09.018 [DOI] [PubMed] [Google Scholar]
  • 6.Atri M, McGregor C, McInnes M, Power N, Rahnavardi K, Law C, et al. Multidetector helical CT in the evaluation of acute small bowel obstruction: comparison of non-enhanced (no oral, rectal or IV contrast) and IV enhanced CT. Eur J Radiol. 2009;71(1):135–40. 10.1016/j.ejrad.2008.04.011 [DOI] [PubMed] [Google Scholar]
  • 7.Balthazar E, Birnbaum B, Megibow A, Gordon R, Whelan C, Hulnick D. Closed-loop and strangulating intestinal obstruction: CT signs. Radiology. 1992;185(3):769–75. 10.1148/radiology.185.3.1438761 [DOI] [PubMed] [Google Scholar]
  • 8.Balthazar EJ, Liebeskind ME, Macari M. Intestinal ischemia in patients in whom small bowel obstruction is suspected: evaluation of accuracy, limitations, and clinical implications of CT in diagnosis. Radiology. 1997;205(2):519–22. 10.1148/radiology.205.2.9356638 [DOI] [PubMed] [Google Scholar]
  • 9.Chang WC, Ko KH, Lin CS, Hsu HH, Tsai SH, Fan HL, et al. Features on MDCT that predict surgery in patients with adhesive-related small bowel obstruction. PloS One. 2014;9(2):e89804 10.1371/journal.pone.0089804 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Daneshmand S, Hedley CG, Stain SC. The utility and reliability of computed tomography scan in the diagnosis of small bowel obstruction. Am Surg. 1999;65(10):922–6. [PubMed] [Google Scholar]
  • 11.Deshmukh SD, Shin DS, Willmann JK, Rosenberg J, Shin L, Jeffrey RB. Non-emergency small bowel obstruction: assessment of CT findings that predict need for surgery. Eur Radiol. 2011;21(5):982–6. 10.1007/s00330-010-1983-4 [DOI] [PubMed] [Google Scholar]
  • 12.Donckier V, Closset J, Van Gansbeke D, Zalcman M, Sy M, Houben JJ, et al. Contribution of computed tomography to decision making in the management of adhesive small bowel obstruction. Br J Surg. 1998;85(8):1071–4. 10.1046/j.1365-2168.1998.00813.x [DOI] [PubMed] [Google Scholar]
  • 13.Duda JB, Bhatt S, Dogra VS. Utility of CT whirl sign in guiding management of small-bowel obstruction. AJR Am J Roentgenol. 2008;191(3):743–7. 10.2214/AJR.07.3386 [DOI] [PubMed] [Google Scholar]
  • 14.Filippone A, Cianci R, Grassedonio E, Di Fabio F, Storto ML. Four-section multidetector computed tomographic imaging of bowel obstruction: usefulness of axial and coronal plane combined reading. J Comput Assist Tomogr. 2007;31(4):499–507. 10.1097/01.rct.0000238013.87802.3c [DOI] [PubMed] [Google Scholar]
  • 15.Frager D, Baer JW, Medwid SW, Rothpearl A, Bossart P. Detection of intestinal ischemia in patients with acute small-bowel obstruction due to adhesions or hernia: efficacy of CT. AJR Am J Roentgenol. 1996;166(1):67–71. 10.2214/ajr.166.1.8571907 [DOI] [PubMed] [Google Scholar]
  • 16.Frager D, Medwid SW, Baer JW, Mollinelli B, Friedman M. CT of small-bowel obstruction: value in establishing the diagnosis and determining the degree and cause. AJR Am J Roentgenol. 1994;162(1):37–41. 10.2214/ajr.162.1.8273686 [DOI] [PubMed] [Google Scholar]
  • 17.Fukuya T, Hawes DR, Lu CC, Chang PJ, Barloon TJ. CT diagnosis of small-bowel obstruction: efficacy in 60 patients. AJR Am J Roentgenol. 1992;158(4):765–9; discussion 71–2. 10.2214/ajr.158.4.1546591 [DOI] [PubMed] [Google Scholar]
  • 18.Geffroy Y, Boulay-Coletta I, Julles MC, Nakache S, Taourel P, Zins M. Increased unenhanced bowel-wall attenuation at multidetector CT is highly specific of ischemia complicating small-bowel obstruction. Radiology. 2014;270(1):159–67. 10.1148/radiol.13122654 [DOI] [PubMed] [Google Scholar]
  • 19.Peck JJ, Milleson T, Phelan J. The role of computed tomography with contrast and small bowel follow-through in management of small bowel obstruction. Am J Surg. 1999;177(5):375–8. 10.1016/s0002-9610(99)00066-5 [DOI] [PubMed] [Google Scholar]
  • 20.Walsh DW, Bender GN, Timmons H. Comparison of computed tomography-enteroclysis and traditional computed tomography in the setting of suspected partial small bowel obstruction. Emerg Radiol. 1998;5(1):29–37. [Google Scholar]
  • 21.Wang Q, Chavhan GB, Babyn PS, Tomlinson G, Langer JC. Utility of CT in the diagnosis and management of small-bowel obstruction in children. Pediatr Radiol. 2012;42(12):1441–8. 10.1007/s00247-012-2497-9 [DOI] [PubMed] [Google Scholar]
  • 22.Yaghmai V, Nikolaidis P, Hammond NA, Petrovic B, Gore RM, Miller FH. Multidetector-row computed tomography diagnosis of small bowel obstruction: can coronal reformations replace axial images? Emerg Radiol. 2006;13(2):69–72. 10.1007/s10140-006-0513-9 [DOI] [PubMed] [Google Scholar]
  • 23.Chang YJ, Yan DC, Lai JY, Chao HC, Chen CL, Chen SY, et al. Strangulated small bowel obstruction in children. J Pediatr Surg. 2017;52(8):1313–7. 10.1016/j.jpedsurg.2017.03.002 [DOI] [PubMed] [Google Scholar]
  • 24.Chuong AM, Corno L, Beaussier H, Boulay-Coletta I, Millet I, Hodel J, et al. Assessment of Bowel Wall Enhancement for the Diagnosis of Intestinal Ischemia in Patients with Small Bowel Obstruction: Value of Adding Unenhanced CT to Contrast-enhanced CT. Radiology. 2016;280(1):98–107. 10.1148/radiol.2016151029 [DOI] [PubMed] [Google Scholar]
  • 25.Kim JH, Ha HK, Kim JK, Eun HW, Park KB, Kim BS, et al. Usefulness of known computed tomography and clinical criteria for diagnosing strangulation in small-bowel obstruction: analysis of true and false interpretation groups in computed tomography. World J Surg. 2004;28(1):63–8. 10.1007/s00268-003-6899-6 [DOI] [PubMed] [Google Scholar]
  • 26.Sheedy SP, Earnest Ft, Fletcher JG, Fidler JL, Hoskin TL. CT of small-bowel ischemia associated with obstruction in emergency department patients: diagnostic performance evaluation. Radiology. 2006;241(3):729–36. 10.1148/radiol.2413050965 [DOI] [PubMed] [Google Scholar]
  • 27.Hwang JY, Lee JK, Lee JE, Baek SY. Value of multidetector CT in decision making regarding surgery in patients with small-bowel obstruction due to adhesion. Eur Radiol. 2009;19(10):2425–31. 10.1007/s00330-009-1424-4 [DOI] [PubMed] [Google Scholar]
  • 28.Pricolo VE, Curley F. CT scan findings do not predict outcome of nonoperative management in small bowel obstruction: Retrospective analysis of 108 consecutive patients. Int J Surg. 2016;27:88–91. 10.1016/j.ijsu.2016.01.033 [DOI] [PubMed] [Google Scholar]
  • 29.Li Zhengyan, Song Bin. Diagnostic utility of CT for small bowel obstruction: systematic review and meta-analysis. PROSPERO. 2015; CRD42015024658 Available from http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015024658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535 10.1136/bmj.b2535 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155(8):529–36. 10.7326/0003-4819-155-8-201110180-00009 [DOI] [PubMed] [Google Scholar]
  • 32.Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol. 2005;58(10):982–90. 10.1016/j.jclinepi.2005.02.022 [DOI] [PubMed] [Google Scholar]
  • 33.Jones CM, Athanasiou T. Summary receiver operating characteristic curve analysis techniques in the evaluation of diagnostic tests. Ann Thorac Surg. 2005;79(1):16–20. 10.1016/j.athoracsur.2004.09.040 [DOI] [PubMed] [Google Scholar]
  • 34.Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58. 10.1002/sim.1186 [DOI] [PubMed] [Google Scholar]
  • 35.Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60. 10.1136/bmj.327.7414.557 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Deeks JJ, Macaskill P, Irwig L. The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol. 2005;58(9):882–93. 10.1016/j.jclinepi.2005.01.016 [DOI] [PubMed] [Google Scholar]
  • 37.Jang TB, Schindler D, Kaji AH. Bedside ultrasonography for the detection of small bowel obstruction in the emergency department. Emergency medicine journal: EMJ. 2011;28(8):676–8. 10.1136/emj.2010.095729 [DOI] [PubMed] [Google Scholar]
  • 38.Maglinte DD, Reyes BL, Harmon BH, Kelvin FM, Turner WW Jr, Hage JE, et al. Reliability and role of plain film radiography and CT in the diagnosis of small-bowel obstruction. AJR Am J Roentgenol. 1996;167(6):1451–5. 10.2214/ajr.167.6.8956576 [DOI] [PubMed] [Google Scholar]
  • 39.Gottlieb M, Peksa GD, Pandurangadu AV, Nakitende D, Takhar S, Seethala RR. Utilization of ultrasound for the evaluation of small bowel obstruction: A systematic review and meta-analysis. Am J Emerg Med. 2018;36(2):234–42. 10.1016/j.ajem.2017.07.085 [DOI] [PubMed] [Google Scholar]
  • 40.Wale A, Pilcher J. Current Role of Ultrasound in Small Bowel Imaging. Semin Ultrasound CT MR. 2016;37(4):301–12. 10.1053/j.sult.2016.03.001 [DOI] [PubMed] [Google Scholar]
  • 41.Zalcman M, Sy M, Donckier V, Closset J, Gansbeke DV. Helical CT signs in the diagnosis of intestinal ischemia in small-bowel obstruction. AJR Am J Roentgenol. 2000;175(6):1601–7. 10.2214/ajr.175.6.1751601 [DOI] [PubMed] [Google Scholar]
  • 42.Millet I, Taourel P, Ruyer A, Molinari N. Value of CT findings to predict surgical ischemia in small bowel obstruction: A systematic review and meta-analysis. Eur Radiol. 2015;25(6):1823–35. 10.1007/s00330-014-3440-2 [DOI] [PubMed] [Google Scholar]
  • 43.Millet I, Boutot D, Faget C, Pages-Bouic E, Molinari N, Zins M, et al. Assessment of Strangulation in Adhesive Small Bowel Obstruction on the Basis of Combined CT Findings: Implications for Clinical Care. Radiology. 2017;285(3):798–808. 10.1148/radiol.2017162352 [DOI] [PubMed] [Google Scholar]
  • 44.Takahara T, Kwee TC, Haradome H, Aoki K, Matsuoka H, Nakamura A, et al. Peristalsis gap sign at cine magnetic resonance imaging for diagnosing strangulated small bowel obstruction: feasibility study. Jpn J Radiol. 2011;29(1):11–8. 10.1007/s11604-010-0508-z [DOI] [PubMed] [Google Scholar]
  • 45.Rubio EI, Blask AR, Badillo AT, Bulas DI. Prenatal magnetic resonance and ultrasonographic findings in small-bowel obstruction: imaging clues and postnatal outcomes. Pediatr Radiol. 2017;47(4):411–21. 10.1007/s00247-016-3770-0 [DOI] [PubMed] [Google Scholar]
  • 46.Krishna S, McInnes MDF, Schieda N, Narayanasamy S, Sheikh A, Kielar A. Diagnostic Accuracy of MRI for Diagnosis of Internal Hernia in Pregnant Women With Prior Roux-en-Y Gastric Bypass. AJR Am J Roentgenol. 2018;211(4):755–9. 10.2214/AJR.17.19252 [DOI] [PubMed] [Google Scholar]
  • 47.Halepota HF, Mateen Khan MA, Shahzad N. Sensitivity and specificity of CT scan in small bowel obstruction among children. J Pak Med Assoc. 2018;68(5):744–6. [PubMed] [Google Scholar]
  • 48.He B, Gu J, Huang S, Gao X, Fan J, Sheng M, et al. Diagnostic performance of multi-slice CT angiography combined with enterography for small bowel obstruction and intestinal ischaemia. J Med Imaging Radiat Oncol. 2017;61(1):40–7. 10.1111/1754-9485.12514 [DOI] [PubMed] [Google Scholar]
  • 49.Idris M, Kashif N, Idris S, Memon WA, Tanveer UH, Haider Z. Accuracy of 64-slice multidetector computed tomography scan in detection of the point of transition of small bowel obstruction. Pediatr Radiol. 2012;30(3):235–41. [DOI] [PubMed] [Google Scholar]
  • 50.Jabra AA, Fishman EK. Small bowel obstruction in the pediatric patient: CT evaluation. Abdom Imaging. 1997;22(5):466–70. [DOI] [PubMed] [Google Scholar]
  • 51.Jabra AA, Eng J, Zaleski CG, Abdenour GE Jr, Vuong HV, Aideyan UO, et al. CT of small-bowel obstruction in children: sensitivity and specificity. AJR Am J Roentgenol. 2001;177(2):431–6. 10.2214/ajr.177.2.1770431 [DOI] [PubMed] [Google Scholar]
  • 52.Jaffe TA, Martin LC, Thomas J, Adamson AR, DeLong DM, Paulson EK. Small-bowel obstruction: coronal reformations from isotropic voxels at 16-section multi-detector row CT. Radiology. 2006;238(1):135–42. 10.1148/radiol.2381050489 [DOI] [PubMed] [Google Scholar]
  • 53.Jancelewicz T, Vu LT, Shawo AE, Yeh B, Gasper WJ, Harris HW. Predicting strangulated small bowel obstruction: an old problem revisited. J Gastrointest Surg. 2009;13(1):93–9. 10.1007/s11605-008-0610-z [DOI] [PubMed] [Google Scholar]
  • 54.Jang KM, Min K, Kim MJ, Koh SH, Jeon EY, Kim IG, et al. Diagnostic performance of CT in the detection of intestinal ischemia associated with small-bowel obstruction using maximal attenuation of region of interest. AJR Am J Roentgenol. 2010;194(4):957–63. 10.2214/AJR.09.2702 [DOI] [PubMed] [Google Scholar]
  • 55.Kato K, Mizunuma K, Sugiyama M, Sugawara S, Suzuki T, Tomabechi M, et al. Interobserver agreement on the diagnosis of bowel ischemia: assessment using dynamic computed tomography of small bowel obstruction. Jpn J Radiol. 2010;28(10):727–32. 10.1007/s11604-010-0500-7 [DOI] [PubMed] [Google Scholar]
  • 56.Kulvatunyou N, Pandit V, Moutamn S, Inaba K, Chouliaras K, DeMoya M, et al. A multi-institution prospective observational study of small bowel obstruction: Clinical and computerized tomography predictors of which patients may require early surgery. J Trauma Acute Care Surg. 2015;79(3):393–8. 10.1097/TA.0000000000000759 [DOI] [PubMed] [Google Scholar]
  • 57.Maglinte DD, Gage SN, Harmon BH, Kelvin FM, Hage JP, Chua GT, et al. Obstruction of the small intestine: accuracy and role of CT in diagnosis. Radiology. 1993;188(1):61–4. 10.1148/radiology.188.1.8511318 [DOI] [PubMed] [Google Scholar]
  • 58.Makanjuola D. Computed tomography compared with small bowel enema in clinically equivocal intestinal obstruction. Clin Radiol. 1998;53(3):203–8. 10.1016/s0009-9260(98)80101-3 [DOI] [PubMed] [Google Scholar]
  • 59.Matsushima K, Inaba K, Dollbaum R, Cheng V, Khan M, Herr K, et al. High-Density Free Fluid on Computed Tomography: a Predictor of Surgical Intervention in Patients with Adhesive Small Bowel Obstruction. J Gastrointest Surg. 2016;20(11):1861–6. 10.1007/s11605-016-3244-6 [DOI] [PubMed] [Google Scholar]
  • 60.Memon W, Khattak YJ, Alam T, Sconfienza LM, Awais M, Anwar SSM. MDCT of small bowel obstruction: How reliable are oblique reformatted images in localizing point of transition? Gastroenterol Res Pract. 2014:815802 10.1155/2014/815802 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.Obuz F, Terzi C, Sokmen S, Yilmaz E, Yildiz D, Fuzun M. The efficacy of helical CT in the diagnosis of small bowel obstruction. Eur J Radiol. 2003;48(3):299–304. 10.1016/s0720-048x(02)00382-0 [DOI] [PubMed] [Google Scholar]
  • 62.Pongpornsup S, Tarachat K, Srisajjakul S. Accuracy of 64 sliced multi-detector computed tomography in diagnosis of small bowel obstruction. J Med Assoc Thai. 2009;92(12):1651–61. [PubMed] [Google Scholar]
  • 63.Scrima A, Lubner MG, King S, Pankratz J, Kennedy G, Pickhardt PJ. Value of MDCT and Clinical and Laboratory Data for Predicting the Need for Surgical Intervention in Suspected Small-Bowel Obstruction. AJR Am J Roentgenol. 2017;208(4):785–93. 10.2214/AJR.16.16946 [DOI] [PubMed] [Google Scholar]
  • 64.Shah ZK, Uppot RN, Wargo JA, Hahn PF, Sahani DV. Small bowel obstruction: the value of coronal reformatted images from 16-multidetector computed tomography—a clinicoradiological perspective. J Comput Assist Tomogr. 2008;32(1):23–31. 10.1097/RCT.0b013e318063c66d [DOI] [PubMed] [Google Scholar]
  • 65.Taourel PG, Fabre JM, Pradel JA, Seneterre EJ, Megibow AJ, Bruel JM. Value of CT in the diagnosis and management of patients with suspected acute small-bowel obstruction. AJR Am J Roentgenol. 1995;165(5):1187–92. 10.2214/ajr.165.5.7572500 [DOI] [PubMed] [Google Scholar]
  • 66.Xu N, Li NE, Cao XL, Wang L, Li XT, Huang LY. The benefit of double-balloon enteroscopy combined with abdominal contrast-enhanced CT examination for diagnosing small-bowel obstruction. Acta Endoscopica. 2013;43(5–6):242–7. [Google Scholar]
  • 67.Ten Broek RPG, Krielen P, Di Saverio S, Coccolini F, Biffl WL, Ansaloni L, et al. Bologna guidelines for diagnosis and management of adhesive small bowel obstruction (ASBO): 2017 update of the evidence-based guidelines from the world society of emergency surgery ASBO working group. World J Emerg Surg. 2018;13:24 10.1186/s13017-018-0185-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 68.Maung AA, Johnson DC, Piper GL, Barbosa RR, Rowell SE, Bokhari F, et al. Evaluation and management of small-bowel obstruction: an Eastern Association for the Surgery of Trauma practice management guideline. J Trauma Acute Care Surg. 2012;73(5 Suppl 4):S362–9. [DOI] [PubMed] [Google Scholar]
  • 69.Garfinkle MA, Stewart S, Basi R. Incidence of CT Contrast Agent-Induced Nephropathy: Toward a More Accurate Estimation. AJR Am J Roentgenol. 2015;204(6):1146–51. 10.2214/AJR.14.13761 [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 Table. PRISMA checklist.

(DOCX)

S2 Table. Characteristics of the computed-assisted literature search strategy.

(DOCX)

S1 File. Methodological criteria of the included studies: QUADAS evaluation.

(TIF)

Data Availability Statement

All relevant data are within the manuscript and its Supporting Information files.


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