Biopsia Endoscopica Guiada Por Us
Biopsia Endoscopica Guiada Por Us
Biopsia Endoscopica Guiada Por Us
https://doi.org/10.1007/s00464-020-08053-x
Abstract
Background Endoscopic ultrasonography (EUS)-guided liver biopsy is a novel technique to obtain adequate liver samples
for diagnosis of liver parenchymal diseases. There are studies that have evaluated the feasibility and safety of EUS-guided
parenchymal liver biopsy (EUS-LB), however, factors that can influence specimen quality are yet to be determined. Our aim
was to determine the diagnostic accuracy of EUS-LB and evaluate factors associated with specimen quality.
Methods We performed a detailed search of PubMed/MEDLINE and Web of Science™ databases to identify studies in
which results of EUS-guided liver parenchymal biopsies were reported published up to July 2020. A random effects model
was used to estimate pooled values (mean ± SE) for total specimen length (TSL) and complete portal tracts (CPT). Subgroup
analyses were applied to find out the procedural factors associated with better specimen quality using Cochran’s Q test. A
total of 10 meta-analyses were done focusing on international studies. Total of 1326 patients who underwent EUS-LB. EUS-
LBs performed for suspicion of parenchymal liver disease. Pooled mean values for TSL and CPT with subgroup analyses.
Results Twenty-three studies with a total of 1326 patients were included in our meta-analysis. Overall pooled mean TSL and
CPT were 45.3 ± 4.6 mm and 15.8 ± 1.5, respectively. In subgroup analysis, core biopsy needles proved to better in terms
of CPT than fine-needle aspiration needles (18.4 vs 10.99, p = 0.003). FNB with slow-pull or suction technique provided a
similar TSL (44.3 vs 53.9 mm, p = 0.40), however, slow-pull technique was better in terms of CPT (30 vs 14.6, p < 0.001).
Heterogeneity was present among the studies. Another limitation is the low number randomized control trials.
Conclusion EUS-guided parenchymal liver biopsy is a good alternative to other methods of liver sampling. Using FNB
needles with a slow-pull technique can provide better results.
Keywords Endoscopic ultrasonography · Fine-needle biopsy · Liver biopsy · Liver parenchymal disease · Liver histology
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Endoscopic ultrasonography (EUS) has become an patients included, (2) the outcome measure for liver sample
important tool for gastroenterologists both for diagnostic quality was reported as total specimen length (TSL) in mm
and therapeutic purposes. It allows for the identification and/or number of complete portal tracts (CPT) (3) human
of liver lesions as well as making it possible to perform studies involving adult patients who has not been included
fine-needle aspiration (FNA) or biopsy (FNB) [5, 6]. It also in another publication. The studies that do not report either
appears to be superior in the detection of very small hepatic of those outcome measures were excluded from the study.
lesions (< 1 cm) that are not identified by cross-sectional The studies that included patients or cohorts overlapping
imaging. This has important implications for staging of can- with other published study cohorts were determined using
cer that can affect the treatment strategy. Although the use the name of participating study center(s), investigator(s) and
of EUS for liver sampling is as safe and effective as PLB patient enrollment time frames.
[7], it cannot visualize the entire organ and is limited to
the most proximal regions of both liver lobes. Recently, a Data extraction
new role for EUS-guided parenchymal liver biopsy (EUS-
LB) has emerged and feasibility of this technique have been We extracted the data onto a preset data extraction form
evaluated in multiple studies that showed diagnostic yield of (Microsoft Excel, Microsoft Corporation, Redmond,
90–100% and low rate of adverse events [8]. In those stud- Wash). This form was pilot tested using randomly selected
ies, EUS-LB was performed using different needles (tru-cut, articles to check if all variables of interests were success-
FNA or FNB) and tissue acquisition methods (slow-pull or fully extracted. From each article following information
suction) that makes describing an optimal technique more were recorded: first author’s last name, journal and year
complicated. In this study, we aimed to determine the overall of publication, country of origin, study setting and design,
diagnostic accuracy and safety of EUS-LB, and to evaluate sample size, types, sizes and brands of EUS needles used,
technical factors associated with the specimen quality. tissue acquisition method, number of passes/actuations, and
median and/or mean ± standard deviation (SD) values for
outcome measures. In studies that only reported median
Methods outcome measures, data for range and/or interquartile range
were also recorded. After completing the data extraction, we
Data sources and search strategy reviewed the data extraction form for accuracy.
This systemic review was performed using the current guide- Quality criteria
lines for conducting a systematic review [9]. We performed
a literature search of PubMed/MEDLINE and Web of Sci- The latest PRISMA guideline for systemic review and meta-
ence™ databases using terms as follows: [(endoscopic ultra- analysis of diagnostic test accuracy studies states that those
sound) OR (EUS)] AND (guided) AND (liver biopsy). The studies may be at risk of bias and there also can be concerns
papers and abstracts published until July 2020 in English regarding applicability [10]. Therefore, it recommends indi-
language were included in the study. There was no restric- cating the methods of assessing risk of bias and applicability.
tion of study design but studies with < 6 patients were Current quality assessment methods focus on randomization,
excluded from the analysis. We checked the reference list selection bias of the arms in the study, concealment of allo-
of published clinical reviews and original articles to find cation, and blinding of outcome to evaluate the quality of the
relevant published articles. Two independent reviewers (B.B. clinical trials with the control arm [11]. There is no consen-
and S.K.) screened the title and abstract of retrieved articles. sus or criteria to evaluate the quality of the studies without a
Studies that meet the inclusion criteria were selected for a control arm. Most of the studies focusing on EUS-LB were
full-text review. Disagreements between the two reviewers either retrospective or non-randomized prospective studies
were resolved by a discussion in consecutive meetings with that reported outcome measures in terms of specimen qual-
the participation of investigators. ity. Therefore, for this systematic review and meta-analysis,
we selected studies based on our predefined inclusion and
Inclusion and exclusion criteria exclusion criteria and completeness of data reporting in the
studies.
The study population consisted of patients with clinical evi-
dence or suspicion of parenchymal liver disease who under- Statistical analysis
went EUS-LB procedure. Studies that satisfies the following
criteria were included in the meta-analysis: (1) randomized The Comprehensive Meta-Analysis (CMA) software ver-
controlled trials, prospective or retrospective cohort stud- sion V2 (Biostat Inc, Englewood, NJ) was used in this
ies, case–control studies and case series with more than 5 meta-analysis. We calculated the pooled mean ± SE values
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for predefined outcome measures of TSL (mm) and CPT (n) review articles, 1 study included pediatric patients [20], 9
using the information reported in the studies. The studies were non-human, cadaveric or ex vivo studies, and 14 pub-
differed in methods of reporting their outcome measures. lications were case reports, correspondences or editorials.
In studies where mean ± SD of outcome measures were Fifty-one articles were eligible for further full-text screen-
reported or can be calculated from individual case values; ing. Eleven publications were excluded for being conference
those data were inputted on the datasheet. In studies that abstract of a full-text paper, and 10 studies were excluded
only report median and range and/or interquartile range for being previous publication including the same patient
(IQR), mean and SD needed to be estimated by methods cohort either partially or completely. Five studies did not
previously described by Luo et al. [12] for “mean” and Wan provide sufficient information to calculate or estimate mean
et al. [13] or Shi et al. [14] for SD when appropriate. In these and/or SD of outcome measures [21–25], and 2 studies were
studies that is from the same group, the authors suggested excluded due to the low number of patients included [26,
three specific methods for estimation of mean and SD to 27]. In total, 23 articles were selected for meta-analysis
perform meta-analysis from clinical studies using sample [28–43] of which 7 of them was presented in an abstract
size, median, range and/or IQR. In the present study, we form [44–50].
used each one of those three methods for individual stud- Two publications by Sey et al. [40] and Patel et al. [39]
ies according to the availability of median, range and/or were conducted in the same institution including the same
IQR as follows: method 1 for median and range, method cohort from 2007 to 2014 and 2007–2017, respectively.
2 for median and IQR, and method 3 for median, range The former study only reported TSL, and Patel et al. had
and IQR. Heterogeneity was assessed using I2 measure of results for CPT, therefore both studies were included in the
inconsistency and Cochran’s Q test [15–17]. Heterogeneity respective analyses. In the prospective uncontrolled study
was determined to be present when the value I2 was > 50% by Diehl et al. [31], 110 patients with elevated transami-
or if the Q-statistic was significant at a p < 0.05. Because nases or parenchymal liver diseases underwent EUS-LB by
significant heterogeneity was detected among the studies a a 19-gauge FNA needle. In the study by the same group
random effects model was used to estimate pooled values (Pineda et al.) [51], same patient cohort of 110 were used
(mean ± SE) for TSL and CPT. Subgroup analyses were in a retrospective setting in comparison to a prospectively
applied to find out the procedural factors associated with recruited group of patients that underwent PLB and TLB by
better specimen quality using Cochran’s Q test with a fully interventional radiology in the same institution [51]. Those
random effects analysis. A random effects model is used two studies were considered as a single study and informa-
to combine studies within each subgroup and to combine tion in both studies were extracted to use for analysis. A
subgroups for yielding the overall effect. The study-to-study flow-diagram summarizing the study selection process is
variance (tau2) is assumed to be the same for all subgroups shown in Fig. 1.
which is computed within subgroups and then pooled across
subgroups. Comparisons for diagnostic yield is performed
using Pearson Chi-square test. A two-tailed p value of < 0.05 EUS technique
was considered significant.
Since this is a Meta-Analysis/Systematic Review, no IRB Diagnostic EUS was performed in most of the studies
approval is needed from the institution beforehand hereby. with curvilinear echoendoscopes including Olympus GF-
UC140P, GF-UC160-AL5, GF-UE160-AL5, GF-UC160P-
AT8, GF-UC140-AL5, GF-UCT140-AL5, GF-UCT180, GF-
Results UC30P, GFUC140P or GF-UCT140P (Olympus America,
Center Valley, PA) and Pentax EG-3870UTK [29] (Pentax
Literature search Medical Co, Montvale, NJ, USA).
In 12 studies EUS-LB was solely performed to the left
A total of 978 titles and/or abstracts were initially retrieved liver lobe, and both left and right lobes were biopsied in 6
using the search strategy. Two more articles were retrieved studies. In the study by Diehl et al. [31], there were 3 groups
using manual search and review of reference lists [18, 19]. in terms of biopsied liver lobe: both lobes (68 patients), left
Of them, 258 articles were found to be duplicates either lobe (34 patients) and right lobe (8 patients). In the study
published as an abstract or were present in both databases. by Hasan et al. 40 patients included were intended to be
Of remaining 722 articles, 622 excluded by 2 independent biopsied from both left and right lobes, but 2 patients were
reviewers (B.B. and S.K.) after preliminary review of titles biopsied from the left lobe only because of surgically altered
and abstracts, which left 100 articles for detailed evaluation anatomy [34]. Right, left or both lobes were biopsied vari-
of full-texts. Among those papers, 49 articles failed to meet ably in the remaining 5 studies.
the predefined selection criteria: 25 were meta-analysis or
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Table 1 Summary of characteristics, techniques, equipment and diagnostic yield of studies evaluating feasibility of EUS-LB
Index Author/year Study type No of Approach Type of Needle brand Technique No of Diagnostic
patients needle passes yield (%)
(median)
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Table 1 (continued)
Index Author/year Study type No of Approach Type of Needle brand Technique No of Diagnostic
patients needle passes yield (%)
(median)
22 Hashimoto/2020 Randomized 22 Left or EUS-FNB Acquire 19G Wet suction 2 100
crossover right lobe vs Shark-
study Core 19G
23 Nieto/2020 Retrospective 420 Both lobes EUS-FNB Acquire 19G Wet suction 2 100
vs Shark-
Core 19G
No number, EUS-TB endoscopic ultrasonography-guided tru-cut biopsy, FNA fine-needle aspiration, FNB fine-needle biopsy, RCT randomized
controlled trial, Q-C Quick-Core, 19G FNB needle (SharkCore or Acquire 19G)
a
Studies by Diehl and Pineda et al. reported same cohort of 110 patients
b
Studies by Sey et al. and Patel et al. are from the same institution and have cohort overlap. Data from Sey et al. was used in analyses for TSL
only
c
Right, left or both liver lobes were biopsied
The study characteristics of individual studies are shown in p = 0.21), yet Fork and Franseen-tip needles performed
Table 1. superior than reverse-bevel core needle (ProCore; Cook
Two recent studies by Mok et al. [36, 37] used a crossover Medical, Bloomington, IN, US) (96%, 768/797 vs 89.6%,
design in their respective cohorts. In the first study, inves- 52/58, respectively, p < 0.013). Foor-Pessin et al. used
tigators compared wet-heparin, dry-heparin and dry-needle either 19G FNA or FNB needles in their cohort with-
EUS-LB techniques in prospectively included 40 patients. out providing details, therefore the study was excluded
Each patient underwent 3 passes with each technique in a from the analyses regarding needle-type. After exclud-
crossover design (120 biopsies in total), and best specimen ing patients who underwent left lobe EUS-TB because of
quality was obtained by wet-heparin technique versus dry significantly lower performance compared with standard
techniques. The latter study compared nitinol 19G FNA nee- and core-type needles, pooled diagnostic yield for bilobar
dle (Expect Flexible 19G, Boston Scientific, Marlborough, approach resulted better than single lobar EUS-LB (99.7%
MA, US) with 22G fork-tip core needle (SharkCore, Covi- 704/706 vs 91.4%, 544/595, respectively, p < 0.001). The
dien-Medtronic Inc, Minneapolis, MN, US) in 20 patients studies by Patel et al. and El Chafic et al. were excluded
using a randomized crossover design. Left and right lobes of from this analysis regarding lobar approach due to missing
the liver were biopsied using both needle types for all study information.
patients, resulting in a total of 80 biopsies. The results were Outcome measures of TSL were available in 20 studies
reported per needle basis. Another randomized crossover and CPT were available in 22 studies. Overall pooled mean
study by Hashimoto et al., included 22 patients who were TSL and CPT were 45.3 ± 4.6 mm and 15.8 ± 1.5, respec-
randomized to either left or right liver lobe for biopsy, as tively (Fig. 2). In subgroup analysis, pooled values of TSL
well as the sequence of needle used (19G franseen-tip— and CPT for FNA and core needles were as follows: TSL;
Acquire; Boston Scientific, Marlborough, MA, US—vs 19G 48.9 ± 7.3 vs 51.9 ± 5.2 mm, p = 0.74; CPT; 10.99 ± 1.97 vs
fork-tip). We included all techniques in the meta-analysis to 18.4 ± 1.6, respectively, p = 0.003 (Fig. 3).
ensure a per biopsy/needle analysis with a pooled compari- FNB with or without suction (no stylet or slow-pull tech-
son of different techniques. nique) provided following pooled TSL and CPT values,
The diagnostic yield of EUS-LB was reported in all respectively: TSL; 53.9 ± 4.7 vs 44.3 ± 10.6 mm, p = 0.40
studies except the study by El Chafic et al. which was and CPT; 14.6 ± 1.7 vs 30 ± 4.1, p < 0.001 (Supplementary
published as a conference abstract [46]. The number of Fig. 1).
patients with inadequate/non-diagnostic liver biopsy The comparison of 19G vs 22G EUS needles in terms
were 100. Overall diagnostic yield of EUS-LB was 93% of pooled TSL and CPT values were as follows, respec-
(1336/1436). Diagnostic yield achieved by EUS-FNB nee- tively: TSL; 52.6 ± 4.5 vs 41.6 ± 9.7 mm, p = 0.30 and CPT;
dles (standard or core needles) was found to be better than 14.7 ± 1.44 vs 17.3 ± 3.18, p = 0.47 (Supplementary Fig. 2).
EUS-TB (95%, 1271/1332 vs 63%, 65/104, respectively, The analysis of studies using a Fork-tip or Franseen-tip
p < 0.001). EUS-FNB technique carried out using a stand- FNB needle for EUS-LB, were as follows, respectively: TSL;
ard or core-type needle resulted with comparable diag- 39.3 ± 6.8 vs 75.9 ± 9.9 mm, p = 0.002 and CPT; 17.7 ± 3.47
nostic yield (94%, 436/462 vs 96%, 820/855, respectively, vs 22.3 ± 3.97, p = 0.38 (Supplementary Fig. 3).
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Fig. 2 Forrest plots of studies for A total specimen length (TSL) and B complete portal tracts (CPT)
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Fig. 3 Forrest plots for A total specimen length (TSL) and B complete portal tracts (CPT) for comparison of EUS-guided fine-needle aspiration
(FNA) needle versus core needle biopsy
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included, and previous meta-analyses did not consider Compliance with ethical standards
cohort overlaps while selecting studies to include. Moreo-
ver, Mohan et al. did not consider TSL and CPT which are Disclosures Dr. Nirav Thosani reports other from Boston Scientific,
the most important quality indicators for liver biopsy. Lastly, other from Medtronic, primarily as a consultant outside the submitted
work. Drs. Bulent Baran, Santosh Kale, Prithvi Patil, Bijun Kannadath,
they did not include the studies by Mok et al. published in Srinivas Ramireddy, Ricardo Badillo and Tomas Davee have no con-
2018 and 2019. flicts of interest or financial ties to disclose.
EUS-LB may not be a first-line approach given its cost
and requisite for sedation. However, its evident safety, high
specimen quality and diagnostic yield in patients already
undergoing endoscopic procedures may expand the role of
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