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Factors Influencing the Diagnostic Performance of Repeat Endoscopic Ultrasound-Guided Fine-Needle Aspiration/Biopsy after the First Inconclusive Diagnosis of Pancreatic Solid Lesions

Jae Hee Cho1 , Jaihwan Kim2 , Hee Seung Lee3 , Su Jeong Ryu3 , Sung Ill Jang1 , Eui Joo Kim4 , Huapyong Kang4 , Sang Soo Lee5 , Tae Jun Song5 , Seungmin Bang3

1Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; 2Division of Gastroenterology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea; 3Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; 4Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea; 5Division of Gastroenterology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to: Seungmin Bang
ORCID https://orcid.org/0000-0001-5209-8351
E-mail bang7028@yuhs.ac

Tae Jun Song
ORCID https://orcid.org/0000-0002-6156-8746
E-mail drsong@amc.seoul.kr

Jae Hee Cho and Jaihwan Kim contributed equally to this work as first authors.

Received: December 14, 2022; Revised: April 14, 2023; Accepted: April 23, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gut Liver 2024;18(1):184-191. https://doi.org/10.5009/gnl220529

Published online June 15, 2023, Published date January 15, 2024

Copyright © Gut and Liver.

Background/Aims: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is essential in diagnosing solid pancreatic lesions (SPLs), but without rapid on-site evaluation (ROSE), a repeat EUS-FNA/B is crucial for clarifying an inconclusive diagnosis. We aimed to evaluate factors associated with improved diagnostic performance of repeat EUS-FNA/B for initially inconclusive SPL diagnoses without ROSE.
Methods: Of 5,894 patients subjected to EUS-FNA/B, 237 (4.0%) with an initially inconclusive diagnosis of SPLs were retrospectively enrolled from five tertiary medical centers between January 2016 and June 2021. Diagnostic performance and procedural factors of EUS-FNA/B were analyzed.
Results: The diagnostic accuracies of first and repeat EUS-FNA/B were 96.2% and 67.6%, respectively. Of 237 patients with an inconclusive diagnosis from initial EUS-FNA/B, 150 were pathologically diagnosed after repeat EUS-FNA/B. In multivariate analysis of repeat EUS-FNA/B, tumor location (body/tail vs head: odds ratio [OR], 3.74; 95% confidence interval [CI], 1.48 to 9.46), number of needle passes (≥4 vs ≤3: OR, 4.80; 95% CI, 1.44 to 15.99), needle type (FNB vs FNA: OR, 3.26; 95% CI, 1.44 to 7.36), needle size (22 gauge vs 19/20 gauge: OR, 2.35; 95% CI, 1.19 to 4.62), and suction method (suction vs others: OR, 5.19; 95% CI, 1.30 to 20.75) were associated with a significantly improved diagnostic performance.
Conclusions: Repeat EUS-FNA/B is essential for patients with an inconclusive EUS-FNA/B without ROSE. To improve the diagnostic performance of repeated EUS-FNA/B, it is recommended that 22-gauge FNB needles, ≥4 needle passes, and suction methods are used.

Keywords: Endoscopic ultrasound-guided fine needle aspiration, Biopsy, Pancreatic neoplasms

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. Unfortunately, only 15% to 20% of patients can be treated surgically because pancreatic cancer is often diagnosed in an advanced stage, even though surgical resection is the exclusive curative method.1,2 The incidence of pancreatic cancer has increased steadily over the past 30 years, and the 5-year survival rate is only approximately 10%. Furthermore, diagnosis of pancreatic cancer is extremely difficult as the organ is deeply situated in the retroperitoneum, and aggressive behavior elicits poor prognosis even after complete resection.

Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is not only an essential diagnostic imaging modality3 but can also be used to obtain targeted tissues of solid pancreatic lesions (SPLs) for neoadjuvant and palliative anticancer treatment.4,5 The diagnosis accuracy of EUS-FNA/B has significantly increased, compared to the past, due to newly developed FNA/B needles. According to a recently published meta-analysis and guidelines, the diagnosis rate of initial EUS-FNA/B is 90% to 95% for pancreatic solid lesions, and repeat EUS-FNA/B is essential in 5% to 10% of patients with inconclusive diagnosis of SPLs.6-9

Although repeat EUS-FNA/B exhibits a relatively lower diagnostic accuracy than initial EUS-FNA/B, the usefulness of repeat EUS-FNA/B has been demonstrated in several studies.6,7,10-13 However, the utility of repeat EUS-FNA/B without rapid on-site evaluation (ROSE) remains unclear, and studies on means with which to maximize its diagnostic performance are lacking. Therefore, we aimed to analyze the outcomes of repeat EUS-FNA/B in inconclusive EUS-FNA/B diagnoses without ROSE and to identify procedural and patient factors that increase the diagnostic performance of repeat EUS-FNA/B.

1. Patients and study design

Of 5,894 patients subjected to EUS-FNA/B between January 2016 and June 2021, 237 (4.0%) with an inconclusive SPL diagnosis after their initial EUS-FNA/B were retrospectively enrolled from five tertiary medical centers in the Republic of Korea (Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul National University Bundang Hospital, Asan Medical Center, and Gil Medical Center). This study was approved by each center’s institutional review board (Yonsei University College of Medicine, IRB number: 2020-0378-002). The informed consent was waived.

The inclusion criteria were age >20 years and having undergone more than two EUS-FNA/B procedures because of initial inconclusive diagnoses of EUS-FNA/B. An inconclusive diagnosis was defined as cytopathological diagnostic uncertainty, which included cases in which material obtained from EUS-FNA/B was inappropriate and led to false negative results for pancreatic malignancies. The exclusion criteria included pancreatic cystic lesions, gastric and hepatobiliary surgical history, severe blood coagulation disorders, and pregnancy.

Clinicopathological data were collected by reviewing medical records, and the final diagnosis of SPL was made based on the cytopathology results of EUS-FNA/B samples or surgical specimens. Among patients for whom a pathological diagnosis was not possible, malignancy was confirmed when lesion progression or metastasis was observed on 6-month follow-up imaging, whereas benign disease was confirmed in cases with a stable lesion without increasing size or metastasis. Additionally, factors influencing the diagnostic performance of EUS-FNA/B were evaluated.

2. EUS-guided FNA/B

EUS-FNA/B procedures were performed with a linear array echoendoscope (GF-UCT2000; Olympus Medical Systems, Tokyo, Japan) using commercially available FNA needles (EchoTip Ultra needle; Cook Medical, Bloomington, IN, USA) or FNB needles (ProCore needle, Cook Medical; Acquire needle, Boston Scientific, Marlborough, MA, USA; EZ Shot3 needle, Olympus, Tokyo, Japan).

In this study, the diagnostic yield and procedure-related factors of EUS-FNA/B were analyzed: needle type (FNA or FNB), puncture route (transgastric or transduodenal), number of needle passes, and needle size (19/20-, 22-, and 25-gauge) were analyzed. Moreover, the application of suction, slow pull back (capillary), or combined methods for EUS-FNA/B was also reviewed (Tables 1 and 2).

Table 1. Baseline Characteristics (n=237)

VariableNo. (%)
Patients related variable
Male sex128 (54.0)
Age at diagnosis, mean±SD, yr63.87±9.79
Tumor-related variable
Site
Head162 (68.4)
Body or tail75 (31.6)
Size, mm
Mean±SD27.27±10.92
≤20 mm (T1 stage)51 (21.5)
>20 mm186 (78.5)
Final diagnosis
Pancreatic ductal adenocarcinoma212 (89.5)
Pancreatic neuroendocrine neoplasms6 (2.5)
Benign disease10 (4.2)
Tuberculous lymphadenopathy1 (0.4)
Autoimmune pancreatitis9 (3.8)
Other malignancy9 (3.8)


Table 2. Baseline Characteristics of First and Second (Repeat) EUS-Guided FNA/B

Variable1st FNA/B-related
variable, No. (%)
Repeat FNA/B-related variable, No. (%)
Route of FNA/B
Transgastric approach94 (39.7)92 (38.8)
Transduodenal approach143 (60.3)145 (61.2)
No. of FNA/B passes
≤3 Passes216 (91.1)208 (87.8)
≥4 Passes21 (8.9)29 (12.2)
Needle type
FNA needle49 (20.7)42 (17.7)
FNB needle188 (79.3)195 (82.3)
Needle size
19G03 (1.3)
20G80 (33.8)86 (36.3)
22G147 (62.0)141 (59.5)
25G10 (4.2)7 (2.9)
EUS
Conventional EUS216 (91.1)230 (97.0)
CEH-EUS21 (8.9)7 (3.0)
Method
Suction223 (94.1)223 (94.1)
Others14 (5.9)14 (5.9)

EUS, endoscopic ultrasound; FNA/B, fine-needle aspiration/biopsy; G, gauge; CEH, contrast-enhanced harmonic.



3. Statistical analysis

The baseline characteristics of EUS-FNA/B are expressed as means (with standard deviations) or medians (with interquartile range and full range) for continuous data and as frequency and proportion for categorical data. The analysis of factors influencing EUS-FNA/B results was undertaken using univariate and multivariate logistic regression analysis. A p-value of <0.05 was considered statistically significant. All statistical analyses were performed using IBM SPSS Statistics for Windows, version 25.0 (IBM Corp., Armonk, NY, USA).

1. Diagnostic performance of EUS-FNA/B

Of 5,894 patients who underwent EUS-FNA/B, 237 (4.0%) patients underwent repeat EUS-FNA/B. One hundred and fifty (63.3%) had a definite pathological diagnosis: 140 (93.3%) with pancreatic ductal adenocarcinoma and five (3.3%) with pancreatic neuroendocrine neoplasms and other malignancies. Compared with the 96.2% accuracy of the first EUS-FNA/B (sensitivity 96%, specificity 100%, positive predictive value 100%, and negative predictive value 46.84%), that of the second EUS-FNA/B was 67.5% (sensitivity 66%, specificity 100%, positive predictive value 100%, and negative predictive value 11.5%). Among 87 patients whose diagnoses remained inconclusive in repeat EUS-FNA/B, pancreatic ductal adenocarcinoma, pancreatic neuroendocrine neoplasm, other malignancies, tuberculosis, and autoimmune pancreatitis were finally confirmed in 72, one, four, one, and nine patients, respectively, via various diagnostic modalities, including a third EUS-FNA/B, endoscopic retrograde cholangiopancreatography biopsy, liver biopsy, and surgery. In particular, in the third EUS-FNA/B for 18 patients, 13 (72.2%) were finally diagnosed with pancreatic cancer. The accuracy of the third EUS-FNA/B was 83.3% (Fig. 1).

Figure 1.Flowchart of the study population and design. EUS, endoscopic ultrasound; FNA/B, fine-needle aspiration/biopsy; SPLs, solid pancreatic lesions; ERCP, endoscopic retrograde cholangiopancreatography.

2. Baseline characteristics of repeat EUS-FNA/B

Of 237 patients, 128 (54.0%) were men, with an average age of 63.9±9.6 years. The lesions were located in the pancreatic head and body/tail in 162 (68.4%) and 75 (31.6%) patients, respectively. The size of SPLs was 27.3±10.9 mm. Fifty-one patients (21.5%) had lesions ≤20 mm and 186 (78.5%) had lesions >20 mm. In the first and second EUS-FNA/B, 94 (39.7%) and 92 (38.8%) patients underwent a transgastric approach, respectively. Of these patients, 21 (8.9%) and 29 (12.2%) patients underwent more than four needle passes in the first and second EUS-FNA/B, respectively. Based on the fine needle type of initial EUS-FNA/B, 20-, 22-, and 25-gauge needles were selected for 80 (33.8%), 147 (62.0%), and 10 (4.2%) patients, respectively; however, in repeat EUS-FNA/B, 19-, 20-, 22-, and 25-gauge needles were used in three (1.3%), 86 (36.3%), 141 (59.5%), and seven (2.9%) patients, respectively. In both the first and second EUS-FNA/B, samples were obtained from 223 (94.1%) patients by the suction method (Tables 1 and 2).

3. Factors related to the diagnostic performance of repeat EUS-FNA/B

The baseline characteristics of the enrolled patients who underwent repeat EUS-FNA/B were compared according to confirmative tissue diagnosis. In the univariate analysis of factors affecting repeat-EUS-FNA/B, tumor location in the body/tail, more than four FNA/B passes, FNB needles, and application of suction during the procedure were related to successful pathological diagnosis. However, needle type crossover between the initial and repeat EUS-FNA/B was not significantly associated with diagnosis rate (odds ratio [OR], 1.587; p=0.187) (Table 3).

Table 3. Characteristics of Repeat EUS-Guided FNA/B Depending on Whether or Not a Final Diagnosis Was Made

VariableDefinitive diagnosis at 2nd FNA/B (n=150)Inconclusive diagnosis at 2nd FNA/B (n=87)p-value
Patient-related variable
Male sex77 (51.3)51 (58.6)0.278
Age at diagnosis, mean±SD, yr63.93±9.5763.76±10.190.895
Tumor-related variable
Site0.01
Head93 (62.0)69 (79.3)
Body or tail57 (38.0)18 (20.7)
Size, mm0.162
Mean±SD28.08±11.3425.86±10.060.131
≤20 mm (T1 stage)28 (18.7)23 (26.4)
>20 mm122 (81.3)64 (73.6)
Final diagnosis
Pancreatic ductal adenocarcinoma140 (93.3)72 (82.8)
Pancreatic neuroendocrine neoplasms5 (3.3)1 (1.1)
Benign disease010 (11.5)
Pancreatic tuberculosis01 (1.1)
Autoimmune pancreatitis09 (10.3)
Other malignancy5 (3.3)4 (4.6)
Metastatic renal cell carcinoma4 (2.7)1 (1.1)
Gastrointestinal stromal tumor1 (0.7)0
Lymphoma01 (1.1)
Schwannoma01 (1.1)
Multiple myeloma01 (1.1)
2nd FNA/B-related variable
Route of FNA/B0.11
Transgastric approach64 (42.7)28 (32.2)
Transduodenal approach86 (57.3)59 (67.8)
No. of FNA/B passes0.006
≤3 Passes125 (83.3)83 (95.4)
≥4 Passes25 (16.7)4 (4.6)
Needle type0.02
FNA needle20 (13.3)22 (25.3)
FNB needle130 (86.7)65 (74.7)
Needle cross over0.185
Same needle as the first one115 (76.7)73 (83.9)
Different needle from the first one35 (23.3)14 (16.1)
Needle size0.138
19G/20G51 (34.0)38 (43.7)
22G96 (64.0)45 (51.7)
25G3 (2.0)4 (4.6)
EUS
Conventional EUS144 (96.0)86 (98.9)0.212
CEH-EUS6 (4.0)1 (1.1)
Method0.027
Suction145 (96.7)78 (89.7)
Others5 (3.3)9 (10.3)

Data are presented as number (%) unless otherwise indicated.

EUS, endoscopic ultrasound; FNA/B, fine-needle aspiration/biopsy; G, gauge; CEH, contrast-enhanced harmonic.



Factors with a significance of p<0.2 (tumor site, tumor size, route of FNA/B, number of FNA/B passes, needle type, needle cross over, needle size, and suction method) in the univariate analysis were included in the multivariate logistic regression model to identify independent factors. In the multivariate analysis of factors associated with confirmative diagnosis upon repeat EUS-FNA/B, tumor location in the pancreatic body/tail had a relatively higher diagnosis rate (OR, 3.742; p=0.005). However, the route of FNA/B was not found to be significant. In terms of procedure-related factors, the number of fine needle passes (≥4 vs ≤3: OR, 4.795; 95% confidence interval [CI], 1.439 to 15.985), needle type (FNB vs FNA: OR, 3.260; 95% CI, 1.443 to 7.363), needle size (22 gauge vs 19/20 gauge: OR, 2.345; 95% CI, 1.189 to 4.623), and suction method (suction vs others: OR, 5.188; 95% CI, 1.297 to 20.746) significantly improved the diagnostic performance of repeat EUS-FNA/B (Table 4).

Table 4. Logistic Regression Analysis of Factors Related to Confirmative Diagnosis with Repeat EUS-Guided FNA/B

VariableUnivariate analysisMultivariate analysis
OR (95% CI)p-valueOR (95% CI)p-value
Patient-related variable
Male sex1.000
Female sex1.343 (0.788–2.290)0.278
Tumor-related variable
Site
Head1.0001.000
Body or tail2.349 (1.271–4.344)0.0063.742 (1.480–9.462)0.005
Size
≤20 mm (T1 stage)1.0001.000
>20 mm1.566 (0.835–2.937)0.1621.807 (0.890–3.669)0.101
Procedure-related variable
Route of FNA/B
Transgastric approach1.0001.000
Transduodenal approach0.638 (0.366–1.110)0.1121.437 (0.616–3.350)0.401
No. of FNA/B passes
≤3 Passes1.0001.000
≥4 Passes4.150 (1.393–12.360)0.0114.795 (1.439–15.985)0.011
Needle type
FNA needle1.0001.000
FNB needle2.200 (1.120–4.320)0.0223.260 (1.443–7.363)0.004
Needle cross over
Same needle as the first one1.0001.000
Different needle from the first one1.587 (0.799–3.150)0.1871.808 (0.816–4.009)0.145
Needle size
19G or 20G1.0001.000
22G1.590 (0.918–2.753)0.0982.345 (1.189–4.623)0.014
25G0.559 (0.118–2.645)0.4631.475 (0.168–12.919)0.726
EUS
Conventional EUS1.000
CEH-EUS3.583 (0.424–30.268)0.241
Method
Others1.0001.000
Suction3.346 (1.084–10.331)0.0365.188 (1.297–20.746)0.020

EUS, endoscopic ultrasound; FNA/B, fine-needle aspiration/biopsy; OR, odds ratio; CI, confidence interval; G, gauge; CEH, contrast-enhanced harmonic.


Currently, several studies have shown repeat EUS-FNA/B to be beneficial and necessary because it increases diagnostic yield after obtaining inconclusive and nondiagnostic results. However, there is a lack of recommendations on the technical aspects of repeat EUS-FNA/B. Accordingly, we aimed to identify factors that improve the diagnostic performance of repeat EUS-FNA/B in this study. In repeat EUS-FNA/B without ROSE, the diagnostic yield increased when SPLs were located in the pancreatic body/tail and when using 22-gauge FNB needles, as well as application of more than four needle passes and the suction method.

In this study, clinical and technical factors of EUS-FNA/B were analyzed, the accuracy of which was affected by the location of the target lesion. In EUS-FNA/B, SPLs of the pancreas head, which is more difficult to access, had low diagnostic yield. In contrast, SPLs of the pancreatic body/tail had relatively high diagnostic accuracy as they are readily accessible via a transgastric route.

In terms of technical factors influencing repeat EUS-FNA/B sampling, several important factors were identified. In initial EUS-FNA/B, at least three needle passes are recommended.14 However, in this study, the diagnostic yield was improved when the number of needle passes was four times or more.12,13 Increasing the number of FNA/B passes to obtain more tissue for analysis is considered a reasonable option.

Regarding needle size, it is assumed that larger diameter needles are advantageous for tissue diagnosis. However, in this study, 19/20-gauge and 25-gauge needles showed lower diagnostic accuracy than 22-gauge needles. This is probably because a 22-gauge needle targets the pancreatic tissue in EUS-FNA/B more accurately and easily, and facilitates procurement of a histologic core. Similarly, a recent study on the use of FNB needles also reported a higher diagnostic rate with 22-gauge needles.15-17

Among needle types, the FNB needle obtains a larger histology core and is also useful in difficult diagnosis cases, such as neuroendocrine tumors and autoimmune pancreatitis.18,19 Similarly, although the suction method is subject to blood contamination, it can retain more tissue than the slow pullback method, contributing to a higher diagnostic yield in repeat EUS-FNA/B.20,21

In this study, only 87 of 5,894 patients (1.4%) were not diagnosed after repeat EUS-FNA/B. However, additional histological diagnosis was attempted for these patients using a third EUS-FNA/B, surgery, percutaneous biopsy, and endoscopic retrograde cholangiopancreatic biopsy. Interestingly, a third EUS-FNA/B was performed in 18 undiagnosed patients after repeated EUS-FNA/B, and the accuracy was 83%, which was higher than 67.5% for a second EUS-FNA/B. However, with a small number of samples, statistical comparison is difficult and additional research is needed. Furthermore, in five patients with nondiagnostic and inconclusive results, a final diagnosis could only be made by surgery (two patients) and percutaneous liver biopsy (one patient). As such, in actual clinical practice, if possible, histological diagnosis through a route other than EUS-FNA/B should be considered.

This study has several strengths and limitations. The major strength of this study was that numerous, meaningful variables of EUS-FNA/B were analyzed to authenticate the influence of needles and technical aspects on EUS-FNA/B outcomes based on a multicenter, large-scale study. The first limitation was selection bias from retrospective study design. Second, the heterogeneity of the EUS-FNA/B procedure is another limitation. Although the participating institutions are tertiary medical centers that perform many EUS-FNBs, there may be differences in the proficiency of the EUS endoscopists and the types of FNB needles could not be unified due to various products from different manufacturers. Third, the absence of ROSE was the shortcoming of this study. The usefulness of ROSE in repeat EUS-FNA/B is controversial. While previous studies have reported that ROSE is helpful in repeat EUS-FNA for the diagnosis of nondiagnostic results,11 a recent large-scale multicenter study demonstrated that comparable diagnostic accuracies were obtained between FNB with ROSE and FNB without ROSE (96.4% vs 97.4%, p=0.396).22 As such, although there are debates about the value of ROSE, our findings are clinically meaningful. Lastly, there is an imbalance in that needle sizes of 19- and 25-gauge were scarcely used in this study. This is because of operator concerns regarding the technical difficulty related to manipulation of 19-gauge needles and the insufficient tissue yield from 25-gauge needles.

In conclusion, repeat EUS-FNA/B for SPLs is helpful to obtaining confirmative histologic diagnosis in patients with initially inconclusive and nondiagnostic results of EUS-FNA/B, especially without ROSE. In order to improve the diagnostic yield of repeat EUS-FNA/B, using FNB needles, 22-gauge size, four or more needle passes, and the suction method could be recommended. Nevertheless, further prospective multicenter studies will be required to expand our technical understanding of EUS-FNA/B.

This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. NRF-2022R1A2C1009842) and was implemented as a research project of the EUS Research Group of the Korean Society of Gastrointestinal Endoscopy.

No potential conflict of interest relevant to this article was reported.

Study concept and design: J.H.C., S.B. Data acquisition: S.J.R., S.I.J., J.K., E.J.K., H.K., S.S.L., T.J.S. Data analysis and interpretation: J.H.C., H.S.L., S.J.R. Drafting of the manuscript: J.H.C., S.J.R. Critical revision of the manuscript for important intellectual content: S.B., J.K., T.J.S. Statistical analysis: J.H.C. Obtained funding: J.H.C. Administrative, technical, or material support; study supervision: S.B., T.J.S. Approval of final manuscript: all authors.

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  14. Jeong SH, Yoon HH, Kim EJ, Kim YJ, Kim YS, Cho JH. High-resolution endoscopic ultrasound imaging and the number of needle passages are significant factors predicting high yield of endoscopic ultrasound-guided fine needle aspiration for pancreatic solid masses without an on-site cytopathologist. Medicine (Baltimore) 2017;96:e5782.
    Pubmed KoreaMed CrossRef
  15. Stathopoulos P, Pehl A, Breitling LP, et al. Endoscopic ultrasound-fine needle biopsies of pancreatic lesions: prospective study of histology quality using Franseen needle. World J Gastroenterol 2020;26:5693-5704.
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  16. Karsenti D, Palazzo L, Perrot B, et al. 22G Acquire vs. 20G Procore needle for endoscopic ultrasound-guided biopsy of pancreatic masses: a randomized study comparing histologic sample quantity and diagnostic accuracy. Endoscopy 2020;52:747-753.
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  17. Oh D, Kong J, Ko SW, et al. A comparison between 25-gauge and 22-gauge Franseen needles for endoscopic ultrasound-guided sampling of pancreatic and peripancreatic masses: a randomized non-inferiority study. Endoscopy 2021;53:1122-1129.
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  18. Ku L, Shahshahan MA, Hou LA, Eysselein VE, Reicher S. Improved diagnostic yield of endoscopic ultrasound-fine needle biopsy with histology specimen processing. World J Gastrointest Endosc 2020;12:212-219.
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  19. Paik WH, Lee HS, Lee KJ, et al. Malignant potential of small pancreatic neuroendocrine neoplasm and its risk factors: a multicenter nationwide study. Pancreatology 2021;21:208-214.
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  20. Li SY, Zhou W, Shi L, et al. Diagnostic efficacy of three suction techniques for endoscopic ultrasound-guided fine-needle biopsy of solid pancreatic lesions: protocol for a multicenter randomized cross-over clinical trial. Dig Liver Dis 2020;52:734-739.
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  21. Young Bang J, Krall K, Jhala N, et al. Comparing needles and methods of endoscopic ultrasound-guided fine-needle biopsy to optimize specimen quality and diagnostic accuracy for patients with pancreatic masses in a randomized trial. Clin Gastroenterol Hepatol 2021;19:825-835.
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  22. Crinò SF, Di Mitri R, Nguyen NQ, et al. Endoscopic ultrasound-guided fine-needle biopsy with or without rapid on-site evaluation for diagnosis of solid pancreatic lesions: a randomized controlled non-inferiority trial. Gastroenterology 2021;161:899-909.
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Article

Original Article

Gut and Liver 2024; 18(1): 184-191

Published online January 15, 2024 https://doi.org/10.5009/gnl220529

Copyright © Gut and Liver.

Factors Influencing the Diagnostic Performance of Repeat Endoscopic Ultrasound-Guided Fine-Needle Aspiration/Biopsy after the First Inconclusive Diagnosis of Pancreatic Solid Lesions

Jae Hee Cho1 , Jaihwan Kim2 , Hee Seung Lee3 , Su Jeong Ryu3 , Sung Ill Jang1 , Eui Joo Kim4 , Huapyong Kang4 , Sang Soo Lee5 , Tae Jun Song5 , Seungmin Bang3

1Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; 2Division of Gastroenterology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea; 3Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; 4Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea; 5Division of Gastroenterology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to:Seungmin Bang
ORCID https://orcid.org/0000-0001-5209-8351
E-mail bang7028@yuhs.ac

Tae Jun Song
ORCID https://orcid.org/0000-0002-6156-8746
E-mail drsong@amc.seoul.kr

Jae Hee Cho and Jaihwan Kim contributed equally to this work as first authors.

Received: December 14, 2022; Revised: April 14, 2023; Accepted: April 23, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is essential in diagnosing solid pancreatic lesions (SPLs), but without rapid on-site evaluation (ROSE), a repeat EUS-FNA/B is crucial for clarifying an inconclusive diagnosis. We aimed to evaluate factors associated with improved diagnostic performance of repeat EUS-FNA/B for initially inconclusive SPL diagnoses without ROSE.
Methods: Of 5,894 patients subjected to EUS-FNA/B, 237 (4.0%) with an initially inconclusive diagnosis of SPLs were retrospectively enrolled from five tertiary medical centers between January 2016 and June 2021. Diagnostic performance and procedural factors of EUS-FNA/B were analyzed.
Results: The diagnostic accuracies of first and repeat EUS-FNA/B were 96.2% and 67.6%, respectively. Of 237 patients with an inconclusive diagnosis from initial EUS-FNA/B, 150 were pathologically diagnosed after repeat EUS-FNA/B. In multivariate analysis of repeat EUS-FNA/B, tumor location (body/tail vs head: odds ratio [OR], 3.74; 95% confidence interval [CI], 1.48 to 9.46), number of needle passes (≥4 vs ≤3: OR, 4.80; 95% CI, 1.44 to 15.99), needle type (FNB vs FNA: OR, 3.26; 95% CI, 1.44 to 7.36), needle size (22 gauge vs 19/20 gauge: OR, 2.35; 95% CI, 1.19 to 4.62), and suction method (suction vs others: OR, 5.19; 95% CI, 1.30 to 20.75) were associated with a significantly improved diagnostic performance.
Conclusions: Repeat EUS-FNA/B is essential for patients with an inconclusive EUS-FNA/B without ROSE. To improve the diagnostic performance of repeated EUS-FNA/B, it is recommended that 22-gauge FNB needles, ≥4 needle passes, and suction methods are used.

Keywords: Endoscopic ultrasound-guided fine needle aspiration, Biopsy, Pancreatic neoplasms

INTRODUCTION

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. Unfortunately, only 15% to 20% of patients can be treated surgically because pancreatic cancer is often diagnosed in an advanced stage, even though surgical resection is the exclusive curative method.1,2 The incidence of pancreatic cancer has increased steadily over the past 30 years, and the 5-year survival rate is only approximately 10%. Furthermore, diagnosis of pancreatic cancer is extremely difficult as the organ is deeply situated in the retroperitoneum, and aggressive behavior elicits poor prognosis even after complete resection.

Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is not only an essential diagnostic imaging modality3 but can also be used to obtain targeted tissues of solid pancreatic lesions (SPLs) for neoadjuvant and palliative anticancer treatment.4,5 The diagnosis accuracy of EUS-FNA/B has significantly increased, compared to the past, due to newly developed FNA/B needles. According to a recently published meta-analysis and guidelines, the diagnosis rate of initial EUS-FNA/B is 90% to 95% for pancreatic solid lesions, and repeat EUS-FNA/B is essential in 5% to 10% of patients with inconclusive diagnosis of SPLs.6-9

Although repeat EUS-FNA/B exhibits a relatively lower diagnostic accuracy than initial EUS-FNA/B, the usefulness of repeat EUS-FNA/B has been demonstrated in several studies.6,7,10-13 However, the utility of repeat EUS-FNA/B without rapid on-site evaluation (ROSE) remains unclear, and studies on means with which to maximize its diagnostic performance are lacking. Therefore, we aimed to analyze the outcomes of repeat EUS-FNA/B in inconclusive EUS-FNA/B diagnoses without ROSE and to identify procedural and patient factors that increase the diagnostic performance of repeat EUS-FNA/B.

MATERIALS AND METHODS

1. Patients and study design

Of 5,894 patients subjected to EUS-FNA/B between January 2016 and June 2021, 237 (4.0%) with an inconclusive SPL diagnosis after their initial EUS-FNA/B were retrospectively enrolled from five tertiary medical centers in the Republic of Korea (Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul National University Bundang Hospital, Asan Medical Center, and Gil Medical Center). This study was approved by each center’s institutional review board (Yonsei University College of Medicine, IRB number: 2020-0378-002). The informed consent was waived.

The inclusion criteria were age >20 years and having undergone more than two EUS-FNA/B procedures because of initial inconclusive diagnoses of EUS-FNA/B. An inconclusive diagnosis was defined as cytopathological diagnostic uncertainty, which included cases in which material obtained from EUS-FNA/B was inappropriate and led to false negative results for pancreatic malignancies. The exclusion criteria included pancreatic cystic lesions, gastric and hepatobiliary surgical history, severe blood coagulation disorders, and pregnancy.

Clinicopathological data were collected by reviewing medical records, and the final diagnosis of SPL was made based on the cytopathology results of EUS-FNA/B samples or surgical specimens. Among patients for whom a pathological diagnosis was not possible, malignancy was confirmed when lesion progression or metastasis was observed on 6-month follow-up imaging, whereas benign disease was confirmed in cases with a stable lesion without increasing size or metastasis. Additionally, factors influencing the diagnostic performance of EUS-FNA/B were evaluated.

2. EUS-guided FNA/B

EUS-FNA/B procedures were performed with a linear array echoendoscope (GF-UCT2000; Olympus Medical Systems, Tokyo, Japan) using commercially available FNA needles (EchoTip Ultra needle; Cook Medical, Bloomington, IN, USA) or FNB needles (ProCore needle, Cook Medical; Acquire needle, Boston Scientific, Marlborough, MA, USA; EZ Shot3 needle, Olympus, Tokyo, Japan).

In this study, the diagnostic yield and procedure-related factors of EUS-FNA/B were analyzed: needle type (FNA or FNB), puncture route (transgastric or transduodenal), number of needle passes, and needle size (19/20-, 22-, and 25-gauge) were analyzed. Moreover, the application of suction, slow pull back (capillary), or combined methods for EUS-FNA/B was also reviewed (Tables 1 and 2).

Table 1 . Baseline Characteristics (n=237).

VariableNo. (%)
Patients related variable
Male sex128 (54.0)
Age at diagnosis, mean±SD, yr63.87±9.79
Tumor-related variable
Site
Head162 (68.4)
Body or tail75 (31.6)
Size, mm
Mean±SD27.27±10.92
≤20 mm (T1 stage)51 (21.5)
>20 mm186 (78.5)
Final diagnosis
Pancreatic ductal adenocarcinoma212 (89.5)
Pancreatic neuroendocrine neoplasms6 (2.5)
Benign disease10 (4.2)
Tuberculous lymphadenopathy1 (0.4)
Autoimmune pancreatitis9 (3.8)
Other malignancy9 (3.8)


Table 2 . Baseline Characteristics of First and Second (Repeat) EUS-Guided FNA/B.

Variable1st FNA/B-related
variable, No. (%)
Repeat FNA/B-related variable, No. (%)
Route of FNA/B
Transgastric approach94 (39.7)92 (38.8)
Transduodenal approach143 (60.3)145 (61.2)
No. of FNA/B passes
≤3 Passes216 (91.1)208 (87.8)
≥4 Passes21 (8.9)29 (12.2)
Needle type
FNA needle49 (20.7)42 (17.7)
FNB needle188 (79.3)195 (82.3)
Needle size
19G03 (1.3)
20G80 (33.8)86 (36.3)
22G147 (62.0)141 (59.5)
25G10 (4.2)7 (2.9)
EUS
Conventional EUS216 (91.1)230 (97.0)
CEH-EUS21 (8.9)7 (3.0)
Method
Suction223 (94.1)223 (94.1)
Others14 (5.9)14 (5.9)

EUS, endoscopic ultrasound; FNA/B, fine-needle aspiration/biopsy; G, gauge; CEH, contrast-enhanced harmonic..



3. Statistical analysis

The baseline characteristics of EUS-FNA/B are expressed as means (with standard deviations) or medians (with interquartile range and full range) for continuous data and as frequency and proportion for categorical data. The analysis of factors influencing EUS-FNA/B results was undertaken using univariate and multivariate logistic regression analysis. A p-value of <0.05 was considered statistically significant. All statistical analyses were performed using IBM SPSS Statistics for Windows, version 25.0 (IBM Corp., Armonk, NY, USA).

RESULTS

1. Diagnostic performance of EUS-FNA/B

Of 5,894 patients who underwent EUS-FNA/B, 237 (4.0%) patients underwent repeat EUS-FNA/B. One hundred and fifty (63.3%) had a definite pathological diagnosis: 140 (93.3%) with pancreatic ductal adenocarcinoma and five (3.3%) with pancreatic neuroendocrine neoplasms and other malignancies. Compared with the 96.2% accuracy of the first EUS-FNA/B (sensitivity 96%, specificity 100%, positive predictive value 100%, and negative predictive value 46.84%), that of the second EUS-FNA/B was 67.5% (sensitivity 66%, specificity 100%, positive predictive value 100%, and negative predictive value 11.5%). Among 87 patients whose diagnoses remained inconclusive in repeat EUS-FNA/B, pancreatic ductal adenocarcinoma, pancreatic neuroendocrine neoplasm, other malignancies, tuberculosis, and autoimmune pancreatitis were finally confirmed in 72, one, four, one, and nine patients, respectively, via various diagnostic modalities, including a third EUS-FNA/B, endoscopic retrograde cholangiopancreatography biopsy, liver biopsy, and surgery. In particular, in the third EUS-FNA/B for 18 patients, 13 (72.2%) were finally diagnosed with pancreatic cancer. The accuracy of the third EUS-FNA/B was 83.3% (Fig. 1).

Figure 1. Flowchart of the study population and design. EUS, endoscopic ultrasound; FNA/B, fine-needle aspiration/biopsy; SPLs, solid pancreatic lesions; ERCP, endoscopic retrograde cholangiopancreatography.

2. Baseline characteristics of repeat EUS-FNA/B

Of 237 patients, 128 (54.0%) were men, with an average age of 63.9±9.6 years. The lesions were located in the pancreatic head and body/tail in 162 (68.4%) and 75 (31.6%) patients, respectively. The size of SPLs was 27.3±10.9 mm. Fifty-one patients (21.5%) had lesions ≤20 mm and 186 (78.5%) had lesions >20 mm. In the first and second EUS-FNA/B, 94 (39.7%) and 92 (38.8%) patients underwent a transgastric approach, respectively. Of these patients, 21 (8.9%) and 29 (12.2%) patients underwent more than four needle passes in the first and second EUS-FNA/B, respectively. Based on the fine needle type of initial EUS-FNA/B, 20-, 22-, and 25-gauge needles were selected for 80 (33.8%), 147 (62.0%), and 10 (4.2%) patients, respectively; however, in repeat EUS-FNA/B, 19-, 20-, 22-, and 25-gauge needles were used in three (1.3%), 86 (36.3%), 141 (59.5%), and seven (2.9%) patients, respectively. In both the first and second EUS-FNA/B, samples were obtained from 223 (94.1%) patients by the suction method (Tables 1 and 2).

3. Factors related to the diagnostic performance of repeat EUS-FNA/B

The baseline characteristics of the enrolled patients who underwent repeat EUS-FNA/B were compared according to confirmative tissue diagnosis. In the univariate analysis of factors affecting repeat-EUS-FNA/B, tumor location in the body/tail, more than four FNA/B passes, FNB needles, and application of suction during the procedure were related to successful pathological diagnosis. However, needle type crossover between the initial and repeat EUS-FNA/B was not significantly associated with diagnosis rate (odds ratio [OR], 1.587; p=0.187) (Table 3).

Table 3 . Characteristics of Repeat EUS-Guided FNA/B Depending on Whether or Not a Final Diagnosis Was Made.

VariableDefinitive diagnosis at 2nd FNA/B (n=150)Inconclusive diagnosis at 2nd FNA/B (n=87)p-value
Patient-related variable
Male sex77 (51.3)51 (58.6)0.278
Age at diagnosis, mean±SD, yr63.93±9.5763.76±10.190.895
Tumor-related variable
Site0.01
Head93 (62.0)69 (79.3)
Body or tail57 (38.0)18 (20.7)
Size, mm0.162
Mean±SD28.08±11.3425.86±10.060.131
≤20 mm (T1 stage)28 (18.7)23 (26.4)
>20 mm122 (81.3)64 (73.6)
Final diagnosis
Pancreatic ductal adenocarcinoma140 (93.3)72 (82.8)
Pancreatic neuroendocrine neoplasms5 (3.3)1 (1.1)
Benign disease010 (11.5)
Pancreatic tuberculosis01 (1.1)
Autoimmune pancreatitis09 (10.3)
Other malignancy5 (3.3)4 (4.6)
Metastatic renal cell carcinoma4 (2.7)1 (1.1)
Gastrointestinal stromal tumor1 (0.7)0
Lymphoma01 (1.1)
Schwannoma01 (1.1)
Multiple myeloma01 (1.1)
2nd FNA/B-related variable
Route of FNA/B0.11
Transgastric approach64 (42.7)28 (32.2)
Transduodenal approach86 (57.3)59 (67.8)
No. of FNA/B passes0.006
≤3 Passes125 (83.3)83 (95.4)
≥4 Passes25 (16.7)4 (4.6)
Needle type0.02
FNA needle20 (13.3)22 (25.3)
FNB needle130 (86.7)65 (74.7)
Needle cross over0.185
Same needle as the first one115 (76.7)73 (83.9)
Different needle from the first one35 (23.3)14 (16.1)
Needle size0.138
19G/20G51 (34.0)38 (43.7)
22G96 (64.0)45 (51.7)
25G3 (2.0)4 (4.6)
EUS
Conventional EUS144 (96.0)86 (98.9)0.212
CEH-EUS6 (4.0)1 (1.1)
Method0.027
Suction145 (96.7)78 (89.7)
Others5 (3.3)9 (10.3)

Data are presented as number (%) unless otherwise indicated..

EUS, endoscopic ultrasound; FNA/B, fine-needle aspiration/biopsy; G, gauge; CEH, contrast-enhanced harmonic..



Factors with a significance of p<0.2 (tumor site, tumor size, route of FNA/B, number of FNA/B passes, needle type, needle cross over, needle size, and suction method) in the univariate analysis were included in the multivariate logistic regression model to identify independent factors. In the multivariate analysis of factors associated with confirmative diagnosis upon repeat EUS-FNA/B, tumor location in the pancreatic body/tail had a relatively higher diagnosis rate (OR, 3.742; p=0.005). However, the route of FNA/B was not found to be significant. In terms of procedure-related factors, the number of fine needle passes (≥4 vs ≤3: OR, 4.795; 95% confidence interval [CI], 1.439 to 15.985), needle type (FNB vs FNA: OR, 3.260; 95% CI, 1.443 to 7.363), needle size (22 gauge vs 19/20 gauge: OR, 2.345; 95% CI, 1.189 to 4.623), and suction method (suction vs others: OR, 5.188; 95% CI, 1.297 to 20.746) significantly improved the diagnostic performance of repeat EUS-FNA/B (Table 4).

Table 4 . Logistic Regression Analysis of Factors Related to Confirmative Diagnosis with Repeat EUS-Guided FNA/B.

VariableUnivariate analysisMultivariate analysis
OR (95% CI)p-valueOR (95% CI)p-value
Patient-related variable
Male sex1.000
Female sex1.343 (0.788–2.290)0.278
Tumor-related variable
Site
Head1.0001.000
Body or tail2.349 (1.271–4.344)0.0063.742 (1.480–9.462)0.005
Size
≤20 mm (T1 stage)1.0001.000
>20 mm1.566 (0.835–2.937)0.1621.807 (0.890–3.669)0.101
Procedure-related variable
Route of FNA/B
Transgastric approach1.0001.000
Transduodenal approach0.638 (0.366–1.110)0.1121.437 (0.616–3.350)0.401
No. of FNA/B passes
≤3 Passes1.0001.000
≥4 Passes4.150 (1.393–12.360)0.0114.795 (1.439–15.985)0.011
Needle type
FNA needle1.0001.000
FNB needle2.200 (1.120–4.320)0.0223.260 (1.443–7.363)0.004
Needle cross over
Same needle as the first one1.0001.000
Different needle from the first one1.587 (0.799–3.150)0.1871.808 (0.816–4.009)0.145
Needle size
19G or 20G1.0001.000
22G1.590 (0.918–2.753)0.0982.345 (1.189–4.623)0.014
25G0.559 (0.118–2.645)0.4631.475 (0.168–12.919)0.726
EUS
Conventional EUS1.000
CEH-EUS3.583 (0.424–30.268)0.241
Method
Others1.0001.000
Suction3.346 (1.084–10.331)0.0365.188 (1.297–20.746)0.020

EUS, endoscopic ultrasound; FNA/B, fine-needle aspiration/biopsy; OR, odds ratio; CI, confidence interval; G, gauge; CEH, contrast-enhanced harmonic..


DISCUSSION

Currently, several studies have shown repeat EUS-FNA/B to be beneficial and necessary because it increases diagnostic yield after obtaining inconclusive and nondiagnostic results. However, there is a lack of recommendations on the technical aspects of repeat EUS-FNA/B. Accordingly, we aimed to identify factors that improve the diagnostic performance of repeat EUS-FNA/B in this study. In repeat EUS-FNA/B without ROSE, the diagnostic yield increased when SPLs were located in the pancreatic body/tail and when using 22-gauge FNB needles, as well as application of more than four needle passes and the suction method.

In this study, clinical and technical factors of EUS-FNA/B were analyzed, the accuracy of which was affected by the location of the target lesion. In EUS-FNA/B, SPLs of the pancreas head, which is more difficult to access, had low diagnostic yield. In contrast, SPLs of the pancreatic body/tail had relatively high diagnostic accuracy as they are readily accessible via a transgastric route.

In terms of technical factors influencing repeat EUS-FNA/B sampling, several important factors were identified. In initial EUS-FNA/B, at least three needle passes are recommended.14 However, in this study, the diagnostic yield was improved when the number of needle passes was four times or more.12,13 Increasing the number of FNA/B passes to obtain more tissue for analysis is considered a reasonable option.

Regarding needle size, it is assumed that larger diameter needles are advantageous for tissue diagnosis. However, in this study, 19/20-gauge and 25-gauge needles showed lower diagnostic accuracy than 22-gauge needles. This is probably because a 22-gauge needle targets the pancreatic tissue in EUS-FNA/B more accurately and easily, and facilitates procurement of a histologic core. Similarly, a recent study on the use of FNB needles also reported a higher diagnostic rate with 22-gauge needles.15-17

Among needle types, the FNB needle obtains a larger histology core and is also useful in difficult diagnosis cases, such as neuroendocrine tumors and autoimmune pancreatitis.18,19 Similarly, although the suction method is subject to blood contamination, it can retain more tissue than the slow pullback method, contributing to a higher diagnostic yield in repeat EUS-FNA/B.20,21

In this study, only 87 of 5,894 patients (1.4%) were not diagnosed after repeat EUS-FNA/B. However, additional histological diagnosis was attempted for these patients using a third EUS-FNA/B, surgery, percutaneous biopsy, and endoscopic retrograde cholangiopancreatic biopsy. Interestingly, a third EUS-FNA/B was performed in 18 undiagnosed patients after repeated EUS-FNA/B, and the accuracy was 83%, which was higher than 67.5% for a second EUS-FNA/B. However, with a small number of samples, statistical comparison is difficult and additional research is needed. Furthermore, in five patients with nondiagnostic and inconclusive results, a final diagnosis could only be made by surgery (two patients) and percutaneous liver biopsy (one patient). As such, in actual clinical practice, if possible, histological diagnosis through a route other than EUS-FNA/B should be considered.

This study has several strengths and limitations. The major strength of this study was that numerous, meaningful variables of EUS-FNA/B were analyzed to authenticate the influence of needles and technical aspects on EUS-FNA/B outcomes based on a multicenter, large-scale study. The first limitation was selection bias from retrospective study design. Second, the heterogeneity of the EUS-FNA/B procedure is another limitation. Although the participating institutions are tertiary medical centers that perform many EUS-FNBs, there may be differences in the proficiency of the EUS endoscopists and the types of FNB needles could not be unified due to various products from different manufacturers. Third, the absence of ROSE was the shortcoming of this study. The usefulness of ROSE in repeat EUS-FNA/B is controversial. While previous studies have reported that ROSE is helpful in repeat EUS-FNA for the diagnosis of nondiagnostic results,11 a recent large-scale multicenter study demonstrated that comparable diagnostic accuracies were obtained between FNB with ROSE and FNB without ROSE (96.4% vs 97.4%, p=0.396).22 As such, although there are debates about the value of ROSE, our findings are clinically meaningful. Lastly, there is an imbalance in that needle sizes of 19- and 25-gauge were scarcely used in this study. This is because of operator concerns regarding the technical difficulty related to manipulation of 19-gauge needles and the insufficient tissue yield from 25-gauge needles.

In conclusion, repeat EUS-FNA/B for SPLs is helpful to obtaining confirmative histologic diagnosis in patients with initially inconclusive and nondiagnostic results of EUS-FNA/B, especially without ROSE. In order to improve the diagnostic yield of repeat EUS-FNA/B, using FNB needles, 22-gauge size, four or more needle passes, and the suction method could be recommended. Nevertheless, further prospective multicenter studies will be required to expand our technical understanding of EUS-FNA/B.

ACKNOWLEDGEMENTS

This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. NRF-2022R1A2C1009842) and was implemented as a research project of the EUS Research Group of the Korean Society of Gastrointestinal Endoscopy.

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

AUTHOR CONTRIBUTIONS

Study concept and design: J.H.C., S.B. Data acquisition: S.J.R., S.I.J., J.K., E.J.K., H.K., S.S.L., T.J.S. Data analysis and interpretation: J.H.C., H.S.L., S.J.R. Drafting of the manuscript: J.H.C., S.J.R. Critical revision of the manuscript for important intellectual content: S.B., J.K., T.J.S. Statistical analysis: J.H.C. Obtained funding: J.H.C. Administrative, technical, or material support; study supervision: S.B., T.J.S. Approval of final manuscript: all authors.

Fig 1.

Figure 1.Flowchart of the study population and design. EUS, endoscopic ultrasound; FNA/B, fine-needle aspiration/biopsy; SPLs, solid pancreatic lesions; ERCP, endoscopic retrograde cholangiopancreatography.
Gut and Liver 2024; 18: 184-191https://doi.org/10.5009/gnl220529

Table 1 Baseline Characteristics (n=237)

VariableNo. (%)
Patients related variable
Male sex128 (54.0)
Age at diagnosis, mean±SD, yr63.87±9.79
Tumor-related variable
Site
Head162 (68.4)
Body or tail75 (31.6)
Size, mm
Mean±SD27.27±10.92
≤20 mm (T1 stage)51 (21.5)
>20 mm186 (78.5)
Final diagnosis
Pancreatic ductal adenocarcinoma212 (89.5)
Pancreatic neuroendocrine neoplasms6 (2.5)
Benign disease10 (4.2)
Tuberculous lymphadenopathy1 (0.4)
Autoimmune pancreatitis9 (3.8)
Other malignancy9 (3.8)

Table 2 Baseline Characteristics of First and Second (Repeat) EUS-Guided FNA/B

Variable1st FNA/B-related
variable, No. (%)
Repeat FNA/B-related variable, No. (%)
Route of FNA/B
Transgastric approach94 (39.7)92 (38.8)
Transduodenal approach143 (60.3)145 (61.2)
No. of FNA/B passes
≤3 Passes216 (91.1)208 (87.8)
≥4 Passes21 (8.9)29 (12.2)
Needle type
FNA needle49 (20.7)42 (17.7)
FNB needle188 (79.3)195 (82.3)
Needle size
19G03 (1.3)
20G80 (33.8)86 (36.3)
22G147 (62.0)141 (59.5)
25G10 (4.2)7 (2.9)
EUS
Conventional EUS216 (91.1)230 (97.0)
CEH-EUS21 (8.9)7 (3.0)
Method
Suction223 (94.1)223 (94.1)
Others14 (5.9)14 (5.9)

EUS, endoscopic ultrasound; FNA/B, fine-needle aspiration/biopsy; G, gauge; CEH, contrast-enhanced harmonic.


Table 3 Characteristics of Repeat EUS-Guided FNA/B Depending on Whether or Not a Final Diagnosis Was Made

VariableDefinitive diagnosis at 2nd FNA/B (n=150)Inconclusive diagnosis at 2nd FNA/B (n=87)p-value
Patient-related variable
Male sex77 (51.3)51 (58.6)0.278
Age at diagnosis, mean±SD, yr63.93±9.5763.76±10.190.895
Tumor-related variable
Site0.01
Head93 (62.0)69 (79.3)
Body or tail57 (38.0)18 (20.7)
Size, mm0.162
Mean±SD28.08±11.3425.86±10.060.131
≤20 mm (T1 stage)28 (18.7)23 (26.4)
>20 mm122 (81.3)64 (73.6)
Final diagnosis
Pancreatic ductal adenocarcinoma140 (93.3)72 (82.8)
Pancreatic neuroendocrine neoplasms5 (3.3)1 (1.1)
Benign disease010 (11.5)
Pancreatic tuberculosis01 (1.1)
Autoimmune pancreatitis09 (10.3)
Other malignancy5 (3.3)4 (4.6)
Metastatic renal cell carcinoma4 (2.7)1 (1.1)
Gastrointestinal stromal tumor1 (0.7)0
Lymphoma01 (1.1)
Schwannoma01 (1.1)
Multiple myeloma01 (1.1)
2nd FNA/B-related variable
Route of FNA/B0.11
Transgastric approach64 (42.7)28 (32.2)
Transduodenal approach86 (57.3)59 (67.8)
No. of FNA/B passes0.006
≤3 Passes125 (83.3)83 (95.4)
≥4 Passes25 (16.7)4 (4.6)
Needle type0.02
FNA needle20 (13.3)22 (25.3)
FNB needle130 (86.7)65 (74.7)
Needle cross over0.185
Same needle as the first one115 (76.7)73 (83.9)
Different needle from the first one35 (23.3)14 (16.1)
Needle size0.138
19G/20G51 (34.0)38 (43.7)
22G96 (64.0)45 (51.7)
25G3 (2.0)4 (4.6)
EUS
Conventional EUS144 (96.0)86 (98.9)0.212
CEH-EUS6 (4.0)1 (1.1)
Method0.027
Suction145 (96.7)78 (89.7)
Others5 (3.3)9 (10.3)

Data are presented as number (%) unless otherwise indicated.

EUS, endoscopic ultrasound; FNA/B, fine-needle aspiration/biopsy; G, gauge; CEH, contrast-enhanced harmonic.


Table 4 Logistic Regression Analysis of Factors Related to Confirmative Diagnosis with Repeat EUS-Guided FNA/B

VariableUnivariate analysisMultivariate analysis
OR (95% CI)p-valueOR (95% CI)p-value
Patient-related variable
Male sex1.000
Female sex1.343 (0.788–2.290)0.278
Tumor-related variable
Site
Head1.0001.000
Body or tail2.349 (1.271–4.344)0.0063.742 (1.480–9.462)0.005
Size
≤20 mm (T1 stage)1.0001.000
>20 mm1.566 (0.835–2.937)0.1621.807 (0.890–3.669)0.101
Procedure-related variable
Route of FNA/B
Transgastric approach1.0001.000
Transduodenal approach0.638 (0.366–1.110)0.1121.437 (0.616–3.350)0.401
No. of FNA/B passes
≤3 Passes1.0001.000
≥4 Passes4.150 (1.393–12.360)0.0114.795 (1.439–15.985)0.011
Needle type
FNA needle1.0001.000
FNB needle2.200 (1.120–4.320)0.0223.260 (1.443–7.363)0.004
Needle cross over
Same needle as the first one1.0001.000
Different needle from the first one1.587 (0.799–3.150)0.1871.808 (0.816–4.009)0.145
Needle size
19G or 20G1.0001.000
22G1.590 (0.918–2.753)0.0982.345 (1.189–4.623)0.014
25G0.559 (0.118–2.645)0.4631.475 (0.168–12.919)0.726
EUS
Conventional EUS1.000
CEH-EUS3.583 (0.424–30.268)0.241
Method
Others1.0001.000
Suction3.346 (1.084–10.331)0.0365.188 (1.297–20.746)0.020

EUS, endoscopic ultrasound; FNA/B, fine-needle aspiration/biopsy; OR, odds ratio; CI, confidence interval; G, gauge; CEH, contrast-enhanced harmonic.


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Gut and Liver

Vol.18 No.3
May, 2024

pISSN 1976-2283
eISSN 2005-1212

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