Comparison of standard vs auxiliary (contrast or elastography) endoscopic ultrasound-guided fine needle aspiration/biopsy in solid pancreatic lesions: A meta-analysis

Abstract

BACKGROUND

Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is the most common modality for tissue acquisition from pancreatic masses. Despite high specificity, sensitivity remains less than 90%. Auxiliary techniques like elastography and contrast-enhanced EUS may guide tissue acquisition from viable tumor tissue and improve the diagnostic outcomes theoretically. However, data regarding the same have shown conflicting results.

AIM

To compare the diagnostic outcomes of auxiliary-EUS-FNA/B to standard EUS-FNA/B for pancreatic lesions.

METHODS

The electronic databases of MEDLINE, EMBASE, and Scopus were searched from inception to February 2024 for all relevant studies comparing diagnostic outcomes of auxiliary-EUS-FNA/B to standard EUS-FNA/B for pancreatic lesions. A bivariate hierarchical model was used to perform the meta-analysis.

RESULTS

A total of 10 studies were identified. The pooled sensitivity, specificity, and area under the receiver-operated curve (AUROC) for standard EUS-FNA/B were 0.82 (95%CI: 0.79-0.85), 1.00 (95%CI: 0.96-1.00), and 0.97 (95%CI: 0.95-0.98), respectively. The pooled sensitivity, specificity, and AUROC for EUS-FNA/B with auxiliary techniques were 0.86 (95%CI: 0.83-0.89), 1.00 (95%CI: 0.94-1.00), and 0.96 (95%CI: 0.94-0.98), respectively. Comparing the two diagnostic modalities, sensitivity [Risk ratio (RR): 1.04, 95%CI: 0.99-1.09], specificity (RR: 1.00, 95%CI: 0.99-1.01), and diagnostic accuracy (RR: 1.03, 95%CI: 0.98-1.09) were comparable.

CONCLUSION

Analysis of the currently available literature did not show any additional advantage of EUS-FNA/B with auxiliary techniques for pancreatic solid lesions over standard EUS-FNA/B. Further randomized studies are required to demonstrate the benefit of auxiliary techniques before they can be recommended for routine practice.

Key Words: Endoscopic ultrasonography; Fine-needle aspiration Biopsies; Pancreatic ductal carcinomas; Contrast media; Elastography

Core Tip: Auxiliary techniques like elastography and contrast enhancement are being used during endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) to guide tissue acquisition from viable tumor tissue and improve diagnostic outcomes. However, the present meta-analysis reported comparable sensitivity, specificity, and diagnostic accuracy between EUS-FNA/B with and without auxiliary techniques. Subgroup analysis of studies exclusively using contrast-enhanced harmonic-EUS-FNA/B, randomized studies, and studies reporting diagnostic outcomes after the first pass reported no difference between both modalities. Thus, using EUS-FNA/B with auxiliary techniques for pancreatic solid lesions does not provide any additional advantage over standard EUS-FNA/B.

INTRODUCTION

The assessment of pancreatic head lesions has been greatly aided by the development of endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B). EUS-FNA/B has a sensitivity, specificity, and accuracy of 84%–92%, 96%–98%, and 86%–91%, respectively, in diagnosing malignant pancreatic masses[1]. The sensitivity depends upon several factors – the type of needle used, use of suction, stylet, use of rapid on-site evaluation (ROSE) or macroscopic on-site evaluation, and indwelling biliary stent[2-6]. The median survival in patients of pancreatic cancer who don’t receive a diagnosis on time and present with distant metastases is 8–12 months and 3–6 months, respectively[7]. On the flip side, the diagnosis of mass-forming chronic pancreatitis as pancreatic cancer, often to the tune of 5% to 35%[8], leads to unnecessary psychological trauma and needless surgeries. Auxiliary techniques that have been developed to increase the sensitivity and accuracy of EUS-FNA/B include real-time elastography (RTE)-EUS-FNA/B and contrast-enhanced harmonic (CEH)-EUS-FNA/B[9].

CEH-EUS-FNA/B uses a contrast agent with harmonic imaging to characterize tissue blood flow within the pancreatic masses and differentiate benign from malignant masses. The technique relies on generating a time-intensity curve (TIC) based on the temporal change in intensity of echo enhancement. CEH-EUS-FNA/B can differentiate benign from malignant pancreatic lesions[10]. For malignant lesions, the TIC is flat and low compared to benign lesions since the desmoplastic nature of the lesion limits blood supply[10]. The pooled sensitivity and specificity of CEH-EUS-FNA/B for diagnosis of pancreatic cancer are 91% and 86%, respectively[11]. However, there is a lack of uniformity concerning the standard cut-off values of TIC. CEH-EUS-FNA/B is also operator-dependent, and the endoscopist's experience may affect the results[12].

There have been conflicting results in studies comparing CEH-EUS-FNA/B to standard EUS-FNA/B. The aim of this meta-analysis was to compare the diagnostic outcome of auxiliary-EUS-FNA/B compared to standard EUS-FNA/B in the diagnosis of pancreatic solid lesions.

MATERIALS AND METHODS

The present meta-analysis was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines[13].

Information sources and search strategy

The electronic databases of MEDLINE, EMBASE, and Scopus were searched from their inception to February 2024 for all relevant studies. The following keywords were used for the search: (Endoscopic ultrasound OR EUS) AND (FNA OR Fine needle aspiration OR FNB OR Fine needle biopsy) AND (Elastography OR Contrast) AND (Pancreas OR Pancreatic). Furthermore, relevant studies were searched from the reference lists of all retrieved studies, guidelines, and reviews.

Study selection

Two reviewers independently reviewed the obtained search records for inclusion and exclusion criteria from the titles and abstracts. The same independent reviewers went through the full text of the shortlisted articles. Any dispute was settled by a third reviewer. Comparative prospective and retrospective studies (parallel as well as cross-over) fulfilling the following criteria were included in this meta-analysis: (1) Participants-patients with a solid pancreatic lesion; (2) Index test-RTE-EUS-FNA/B or CEH-EUS-FNA/B; (3) Comparator test-Standard EUS-FNA/B; and (4) Reference standards-surgical pathology for patients who underwent surgery or clinical and radiological follow-up of 12 months in unresectable cases. Conference abstracts, non-comparative single-arm studies, and case reports were excluded from the analysis.

Data extraction and risk of bias assessment

Two reviewers worked independently to retrieve the data. A third reviewer arbitrated any disputes. The following categories were utilized to gather data: Author and publication year, number of patients, age distribution, location and size of the lesion, type of needle and technique used, and the diagnostic outcomes.

The risk of bias and applicability in the included studies were evaluated using the QUADAS-2 tool[14]. Patient selection, index test, reference standard, and patient flow during the research and timing of the index tests are the four domains that make up this tool.

Statistical analysis

The sensitivity, specificity, likelihood ratio (LR), and diagnostic odds ratio (DOR) were determined using the true positive, false positive, false negative, and true negative data. The receiver operating characteristic curve (sROC) was summarized, and the area under the ROC (AUROC) was computed. The bivariate hierarchical model was used for meta-analysis of the summary estimate for sensitivity and specificity together, whereas the hierarchical summary ROC model was used to model the parameters for the sROC curve. The bivariate model models the sensitivity and specificity more directly, assuming that their logit (log-odds) transforms have a bivariate normal distribution between studies[15]. In random-effects meta-analysis, the extent of variation among the effects observed in different studies is referred to as tau-squared (τ²), which is a measure of heterogeneity. A sensitivity analysis was conducted to evaluate the reliability of the study's findings. Based on the LR of the diagnostic test, a Fagan nomogram was utilized to calculate the post-test probability. A P value of < 0.10 for the slope coefficient in Deek's plot indicated publication bias[16]. Data analysis was performed using Meta-DiSc version 1.4 (Madrid, Spain), RevMan version 5.4, and STATA version 17 (College Station, Tex).

RESULTS

Study characteristics and risk of bias assessment

Ten studies out of the 2698 retrieved records were included in the meta-analysis. The PRISMA flowchart for the inclusion and selection of studies is displayed in Figure 1. The baseline characteristics of the studies that were included in the meta-analysis are summarized in Table 1[17-26]. Only one study used RTE-EUS-FNA/B[24], while the other nine used CEH-EUS FNA/B. Five of these nine studies on CEH-EUS FNA/B used SonoVue[17,18,20,22,23], and four used Sonazoid[19,21,25,26]. Four studies were randomized trials[19,22,23,26], three were prospective[18,21,24], and three were retrospective[17,20,25]. The mean size of the lesion varied from 25 mm to 39.5 mm. Except for two studies[19,23], the rest all used a 22-G size needle. ROSE was available in only two studies. The study by Lai et al[25] reported data from only malignant lesions[25] and, hence, was not included in the calculation of sensitivity and specificity. Concerning study quality, three studies had low[22,24,26], four had intermediate[18,19,21,23], and three had high risk of bias[17,20,25] (Figure 2).

Figure 1 PRISMA flowchart for study identification, selection, and inclusion process.

Figure 2 Risk of bias assessment using QUADAS-2 tool. A: Methodological quality for individual studies; B: Methodological quality summary graph.

Table 1 Baseline characteristics of the studies included in the meta-analysis, mean ± SD/median (range/25^th-75^th percentiles).

Ref.	Country	Study design	Arm	Number of patients	Age	Lesion size, in mm	Lesion location (H/U-B/T)	Contrast	Needle	Suction	Number of passes	ROSE
Hou et al[17]	China	Retrospective	CEH-EUS FNA	58	55.1 ± 11.7	38 ± 12	35/23	SonoVue	22-G	-	3.7 ± 0.9	No
			EUS-FNA	105	56.2 ± 12.5	39 ± 8.0	65/40	-			3.6 ± 0.8
Seicean et al[18]	Romania	Prospective, cross-over	CEH-EUS FNA	51	64 (39-83)	35	31/10	SonoVue	22-G	-	2	No
			EUS-FNA					-			2
Sugimoto et al[19]	Japan	RCT	CEH-EUS FNA	20	69.5 ± 10.5	25.0 ± 8.0	13/7	Sonazoid	22-G	DS	1-5	Yes
			EUS-FNA	20	67.1 ± 9.9	26.5 ± 9.2	13/7	-	22-G or 25-G		1-5
Facciorusso et al[20]	Italy	Retrospective	CEH-EUS FNA	103	66 ± 6	32 ± 11	71/32	SonoVue	22-G	DS	2.4 ± 0.6	No
			EUS-FNA	103	66 ± 8	32 ± 10	71/32	-			2.7 ± 0.8
Itonaga et al[21]	Japan	Prospective, cross-over	CEH-EUS FNA	93	72.5 (34–89)	25.2 (12-56)	55/38	Sonazoid	22-G	DS	2.6 (2-5)	No
			EUS-FNA					-
Seicean et al[22]	Romania	RCT, cross-over	CEH-EUS FNA	148	64.5 (62.6 – 66.3)	30 (20.8- 35)	103/45	SonoVue	22-G	-	1	No
			EUS-FNA					-			1
Cho et al[23]	South Korea	RCT	CEH-EUS FNA/B	120	66.3 ± 11.8	30.9 ± 2.1	54/66	SonoVue	19- to 25-G	DS	1-5	No
			EUS-FNA/B	120	68.3 ± 11.9	33.1 ± 16.4	60/60	-			1-5
Gheorghiu et al[24]	Romania	Prospective, cross-over	RTE-EUS FNA	60	66.4 ± 10.0	30 (29.5 -35)	44/16	-	22-G	No	1	No
			EUS-FNA					-			1
Lai et al[25]	Taiwan	Retrospective	CEH-EUS FNB	48	63.6 ± 12.6	29.5 ± 11.5	29/11/8	Sonazoid	22-G	SSP	2.2 ± 0.7	No
			EUS-FNB	85		34.8 ± 18.2	39/36/10	-			3.6 ± 1.2
Kuo et al[26]	Taiwan	RCT	CEH-EUS FNB	59	64.7 ± 11.6	37.5 (28.8-45.9)	30/29	Sonazoid	22-G	No	1-6	Yes
			EUS-FNB	59	64.1 ± 12.6	37.5 (30.6-46.2)	34/25	-			1-6

EUS-FNA/B: Endoscopic ultrasound-guided fine-needle aspiration/biopsy; CEH-EUS-FNA/B: Contrast-enhanced harmonic-EUS-FNA/B; RTE-EUS-FNA/B: Real-time elastography EUS-FNA/B; Lesion location (H/U-B/T): Head or uncinate process-body or tail; RCT: Randomized controlled trial; ROSE: Rapid on-site evaluation; DS: Dry suction; SSP: Slow stylet pull.

Diagnostic utility of standard EUS-FNA/B

The pooled sensitivity estimates of standard EUS-FNA/B was 0.82 (95%CI: 0.79-0.85) (I² = 89.8%), and the pooled specificity estimate was 1.00 (95%CI: 0.96-1.00) (I² = 0.0%) (Figure 3A). Additionally, the pooled positive LR, negative LR, and DOR were 14.42 (95%CI: 5.64-36.90), 0.19 (95%CI: 0.13-0.30), and 105.51 (95%CI: 36.38-305.99), respectively (Table 2). Using the Fagan nomogram, a positive result raised the pre-test likelihood of diagnosis from 50% to 99%, whereas a negative result lowered the pre-test probability from 50% to 13% (Figure 4A). An sROC curve was plotted, and the AUROC with 95%CI was 0.97 (95%CI: 0.95-0.98) (Figure 3C).

Figure 3 Sensitivity and specificity for diagnosis of malignancy from pancreatic solid lesion with endoscopic ultrasound-guided fine needle aspiration/biopsy using. A and C: Standard; B: Auxiliary technique. The summary receiver operating characteristic curves for sensitivity and specificity of endoscopic ultrasound-guided fine needle aspiration/biopsy using; D: Auxiliary technique with their 95%CI and 95% prediction interval.

Figure 4 Fagan plot for endoscopic ultrasound-guided fine needle aspiration/biopsy using. A and B: Standard; C: Auxiliary technique. Deeks’ plot for endoscopic ultrasound-guided fine needle aspiration/biopsy using; D: Auxiliary technique.

Table 2 Summary of results of diagnostic test accuracy meta-analysis.

Parameters	Standard EUS-FNA/B		EUS-FNA/B with auxiliary techniques
	Values with 95%CI	Heterogeneity (I2)	Values with 95%CI	Heterogeneity (I2)
Sensitivity	0.82 (0.79-0.85)	89.8%	0.86 (0.83-0.89)	73.6%
Specificity	1.00 (0.96-1.00)	0.0%	1.00 (0.94-1.00)	2.7%
Positive LR	14.42 (5.64-36.90)	0.0%	11.11 (4.30-28.71)	21.6%
Negative LR	0.19 (0.13-0.30)	82.5%	0.17 (0.13-0.22)	40.4%
DOR	105.51 (36.38-305.99)	0.0%	126.87 (44.43-362.28)	0.0%
AUROC	0.97 (0.95-0.98)	-	0.96 (0.94-0.98)	-

LR: Likelihood ratio; DOR: Diagnostic odds ratio; AUROC: Area under the receiver operating characteristic curve; EUS-FNA/B: Endoscopic ultrasound-guided fine-needle aspiration/biopsy.

Diagnostic utility of EUS-FNA/B with auxiliary technique

The pooled sensitivity estimate was 0.86 (95%CI: 0.83-0.89) (I² = 73.6%), and the pooled specificity estimate was 1.00 (95%CI: 0.94-1.00) with evidence of statistical heterogeneity (I² = 2.7%) (Figure 3B). The pooled positive LR, negative LR, and DOR for EUS-FNA/B with auxiliary techniques were 11.11 (95%CI: 4.30-28.71), 0.17 (95%CI: 0.13-0.22), and 126.87 (95%CI: 44.43-362.28), respectively (Table 2). Using the Fagan nomogram, a positive result raised the pre-test likelihood of diagnosis from 50% to 100%, whereas a negative result reduced the pre-test probability from 50% to 11% (Figure 4C). An sROC curve was plotted, and the AUROC with 95%CI was 0.96 (95%CI: 0.94-0.98) (Figure 3D).

Comparison of standard vs auxiliary EUS-FNA/B

On comparison of standard vs auxiliary EUS-FNA/B, both sensitivity [Risk ratio (RR): 1.04, 95%CI: 0.99-1.09, P = 0.0828; τ² = 0.91] and specificity (RR: 1.00, 95%CI: 0.99-1.01, P = 0.8123; τ2 = 8.41) were comparable (Figure 5). The diagnostic accuracy between the two modalities (RR: 1.02, 95%CI: 0.98-1.07; I² = 50%, P = 0.04) was also comparable, with evidence of statistical heterogeneity (Figure 6).

Figure 5 Relative sensitivity and specificity of endoscopic ultrasound-guided fine needle aspiration/biopsy using auxiliary technique, compared to standard technique.

Figure 6 Forest plot for comparison of diagnostic accuracy between endoscopic ultrasound-guided fine needle aspiration/biopsy using auxiliary technique and standard technique. A: All studies; B: Studies reporting data after the first pass.

Publication bias, sensitivity analysis, and certainty of evidence

Assessment of Deeks’ plot did not show evidence of publication bias for standard EUS-FNA/B (Figure 4B) but for EUS-FNA/B with auxiliary technique (P = 0.054) (Figure 4D). A sensitivity analysis was conducted using studies on CEH-EUS-FNA/B, randomized studies, and first-pass data. Sensitivity analysis showed comparable sensitivity, specificity, and diagnostic accuracy between both groups (Table 3). Table 4 shows the certainty of evidence for the analyzed outcomes.

Table 3 Comparative analysis of endoscopic ultrasound-guided fine-needle aspiration/biopsy with auxiliary vs standard technique with sensitivity analysis.

Comparison of EUS-FNA/B with auxiliary vs standard techniques	No. of studies	Relative risk	P value	Tau2
Relative sensitivity
Overall	9	1.04 (0.99-1.09)	0.0828	0.91
Studies with CEH-EUS-FNA/B	8	1.05 (1.00-1.10)	0.0729	1.05
Randomized studies	4	1.00 (0.97-1.03)	0.9006	1.41
Relative specificity
Overall	9	1.00 (1.00-1.01)	0.8123	0.41
Studies with CEH-EUS-FNA/B	8	1.00 (1.00-1.01)	0.8096	8.42
Randomized studies	4	1.01 (0.96-1.06)	0.7840	6.31
				I2
Diagnostic accuracy
Overall	10	1.02 (0.98-1.07)	0.33	50%
Studies with CEH-EUS-FNA/B	9	1.03 (0.98-1.09)	0.23	55%
After single pass	5	1.01 (0.93-1.10)	0.19	35%
Randomized studies	4	0.99 (0.95-1.02)	0.45	0%

EUS-FNA/B: Endoscopic ultrasound-guided fine-needle aspiration/biopsy; CEH-EUS-FNA/B: Contrast-enhanced harmonic-EUS-FNA/B.

Table 4 Grade of evidence table¹.

Outcomes	Anticipated absolute effects (95%CI)		Relative effect (95%CI)	No. of patients (studies)	Certainty assessment				Overall certainty of evidence
	With standard EUS-FNA/B	With EUS-FNA/B and auxiliary techniques			Risk of bias	Inconsistency	Indirectness	Imprecision
Sensitivity	0.82 (0.79-0.85)	0.86 (0.83-0.89)	RR: 1.04 (0.99-1.09)	1471 (9 studies)	+	+	-	-	Low
Specificity	1.00 (0.96-1.00)	1.00 (0.94-1.00)	RR: 1.00 (0.99-1.01)	1471 (9 studies)	+	+	-	-	Low
Diagnostic accuracy	846 per 1000	17 higher per 1000 (17 lower to 59 more)	RR: 1.02 (0.98-1.07)	1604 (10 studies)	+	+	-	-	Low

¹Population: Patients with a solid pancreatic lesion. Index test: Real-time elastography-endoscopic ultrasound-guided fine-needle aspiration/biopsy/B or Contrast-enhanced harmonic-endoscopic ultrasound-guided fine-needle aspiration/biopsy. Comparator test: Standard Endoscopic ultrasound-guided fine-needle aspiration/biopsy.

EUS-FNA/B: Endoscopic ultrasound-guided fine-needle aspiration/biopsy.

DISCUSSION

EUS-guided advanced imaging techniques, such as elastography and contrast enhancement, offer the advantage of distinguishing between fibrotic/inflammatory tissues and malignant pancreatic lesions. These auxiliary techniques have been touted to improve the diagnostic performance of EUS in solid pancreatic lesions, and a recent guideline recommends using contrast guidance for EUS-guided tissue acquisition from solid lesions with avascular areas[27]. However, there is a paucity of data to support this argument fully. The present meta-analysis reported pooled sensitivity estimates of standard EUS-FNA/B and EUS-FNA/B with auxiliary technique as 82% (79%-85%) and 86% (83%-89%), without any significant difference (1.04, 95%CI: 0.99-1.09). Similarly, the pooled specificity estimates of standard EUS-FNA/B and EUS-FNA/B with the auxiliary technique were 100% (96%-100%) and 100% (94%-100%) with relative specificity of 1.00 (95%CI: 1.00-1.01). The odds of diagnostic accuracy were comparable also comparable between both groups (1.03, 95%CI: 0.98-1.09). These findings suggest that the auxiliary techniques may not improve the diagnostic outcome of EUS-FNA/B.

Other factors that may affect diagnostic outcomes of EUS-FNA/B include the size and location of the lesion. Itonaga et al[21] reported higher adequacy and sensitivity with CEH-EUS-FNA in lesion size > 15 mm and lesions located in the body/tail[21]. Kuo et al[26] reported reduced cytologic and histologic accuracy in lesions larger than 40 mm[26]. This may be due to the increased proportion of necrotic material in larger lesions. CEH-EUS may help target viable tissue in such lesions. However, Facciorusso et al[20] and Seicean et al[22] reported no difference with respect to size[20,22], and Cho et al[23] reported no difference with respect to the location of the lesion[23]. Hence, further studies are required to demonstrate the benefit of CEH-EUS-FNA/B in larger lesions.

Another benefit of the auxiliary technique, which has been reported in some studies, is the higher diagnostic yield in a single pass. Sugimoto et al[19] reported that a sufficient biopsy sample after a single needle pass was obtained in 60% of the CEH-EUS-FNA group compared with 25% of the standard EUS-FNA group[19]. Similarly, the rate of adequate sampling and sensitivity of one pass with EUS-FNA-CHI was higher in the study by Itonaga et al[21]. However, the studies by Cho et al[23] and Kuo et al[26] reported no difference in the diagnostic sensitivity after the first needle pass between the two techniques[23,25]. One reason for this difference between the studies may be that Sugimoto et al[19] and Itonaga et al[21] used FNA needles, while Cho et al[23] and Kuo et al[26] used FNB needles predominantly. However, a recent RCT using an FNA needle reported no significant difference between conventional and CEH-EUS-FNA in terms of diagnostic accuracy, sensitivity, specificity and positive and negative predictive values[28]. Also, a meta-analysis using the data on first-pass from four studies showed no difference in the diagnostic accuracy. Thus, with the increasing use of newer-generation FNB needles, auxiliary techniques may not be useful as a routine procedure.

Despite some studies highlighting the utility of CH-EUS-FNA, only one study has shown that CH-EUS-FNA enhances diagnostic sensitivity[21]. With the advent of precision medicine, particularly in the realm of oncogene panel testing on EUS-FNA specimens, it will be crucial to obtain cancer tissues from sites with a high cellular yield[29]. In this context, CH-EUS-FNA could be a valuable technique, especially for collecting tissue samples from solid pancreatic neoplasms. The ability of CH-EUS-FNA to provide high-quality, cell-rich samples can make it an indispensable tool in the advancement of personalized treatment strategies for pancreatic cancer patients, underscoring its significance in the diagnostic and therapeutic landscape of pancreatic cancer[30].

EUS elastography is being promoted because it offers important information complementary to B-mode imaging. However, elastography cannot be considered a required addition to EUS because most endosonographers achieve excellent EUS outcomes without it. No evidence indicates that elastography enhances clinical outcomes compared to traditional EUS, whether or not EUS-guided tissue acquisition is used. Specifically, no studies demonstrate that elastography is superior in targeting cancer within suspicious lesions. Despite its high sensitivity for diagnosing malignancy, the clinical utility of EUS elastography is limited by its low specificity. In one large prospective study, the specificity for characterizing solid pancreatic lesions was as low as 22%, undermining its overall effectiveness in clinical practice[31]. In addition, it has been observed that the accuracy of EUS-FNA largely depends on the expertise of the endosonographers and similarly, the evaluation of pancreatic lesions using CH-EUS or elastography is also reliant on their examination skills[32].

The other disadvantage of the contrast agent is that it is expensive, costing approximately $250 per bottle, and requires an additional 3 to 5 minutes to prepare the contrast injection and observe the enhancement pattern[26]. This information is valuable for healthcare providers and policy-makers aiming to optimize resource allocation. However, none of the studies compared the overall difference in cost between the two modalities.

There are a few limitations to the present analysis warranting discussion. First, not all studies were randomized, increasing the risk of selection and reporting bias. However, a subgroup analysis of randomized studies did not report any difference between both modalities. Second, an assessment of publication bias, using the Deeks plot, revealed the presence of publication bias for the auxiliary techniques. This suggests that the studies included in the analysis may not fully represent the entire spectrum of clinical scenarios, and the results should be interpreted cautiously. Third, we could not perform a meta-analysis to assess the impact of size on diagnostic outcomes due to limited data from the included studies. Fourth, there was heterogeneity concerning the type of needle, type of suction method, and use of ROSE. Fifth, we did not compare the occurrence of adverse effects between the two modalities. However, the existing literature does not suggest any increase in adverse events using auxiliary techniques. The reported adverse effects related to the use of ultrasound contrast medium do not pose any clinical problems[33].

CONCLUSION

In conclusion, EUS-FNA/B, both standard and with auxiliary techniques, demonstrates high diagnostic utility with excellent specificity. Comparable sensitivity, specificity, and diagnostic accuracy were reported in the current meta-analysis comparing EUS-FNA/B with and without auxiliary techniques. Subgroup analysis of studies exclusively using CEH-EUS-FNA/B, randomized studies, and studies reporting diagnostic outcomes after the first pass reported no difference between both modalities. Thus, the currently available literature for pancreatic solid lesions does not show any additional benefit from utilizing auxiliary techniques in conjunction with standard EUS-FNA/B. Further randomized studies are required before auxiliary techniques can be recommended for routine practice.