Endoscopic ultrasound-guided
fine needle aspiration of liver lesions
Biopsias de lesiones
hepáticas guiadas por ultrasonido endoscópico
Félix I. Téllez-Ávila,* Gilberto Duarte-Medrano,* Víctor Gallardo-Cabrera,*
David Herrera-Mora,* Javier Elizondo-Rivera,* Francisco Valdovinos-Andraca,* Miguel Ramírez-Luna*
* Gastrointestinal Endoscopy Department,
Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Mexico City, Mexico.
Recibido el 20 de enero de 2017. Aceptado el 01 de marzo de 2017.
ARTÍCULO ORIGINAL
ENDOSCOPIA
ENDOSCOPIA
ENDOSCOPIA
ENDOSCOPIA
ENDOSCOPIA
www.amegendoscopia.org.mx
RESUMEN
Objetivo. Describir el rendimiento diagnóstico, las complicaciones y el impacto clíni-co de las biopsias por aspiración guiadas por ultrasonido endoscópiclíni-co (USE-BAAF) de las lesiones hepáticas sólidas.
Material y métodos. Se analizaron de manera retrospectiva datos obtenidos prospec-tivamente de pacientes sometidos a USE-BAAF de lesiones hepáticas. Se incluyeron todos los pacientes para el USE-BAAF debido a la detección de una lesión sólida por TC, RMI o ultrasonido. Todos los procedimientos se realizaron con agujas estándar de calibre 19 o 22. El acceso al lóbulo hepático izquierdo fue por vía transgástrica, y las lesiones en el lóbulo hepático derecho por vía transgástrica o transduodenal.
Resultados. Se realizaron un total de 74 procedimientos en 71 pacientes, de los cua-les 39 (54.9%) fueron mujeres con una media (DE) de edad de 62.4 (14.2) años. El ren-dimiento diagnóstico de la USE-BAAF fue de 95.7% (68/71 pacientes). Se usó una aguja de calibre 19 en 36 (50.7%) y una aguja 22 en 35 (49.3%). No se detectó ninguna dife-rencia en la sensibilidad, diagnóstico citológico, complicaciones o impacto clínico del USE-BAAF para las lesiones sólidas del hígado muestreadas con las agujas del 19 vs. 22. El resultado histológico final fue maligno en 57/71 pacientes (80.2%), benignos en 12/ 71 (16.9%) y no diagnósticos en 2/71 (2.8%). Los resultados de la USE-BAAF cambiaron el tratamiento de 21% de casos (se detectó malignidad en seis pacientes y la cirugía fue evitada en nueve pacientes). No se informaron complicaciones.
Conclusiones. Según nuestros resultados, la USE-BAAF es un procedimiento útil y se-guro con un buen rendimiento diagnóstico. No se observaron diferencias entre el uso de las agujas del 19 y del 22 para las biopsias del hígado guiadas por USE.
PALABRAS CLAVE.
Ultrasonidoendoscópico. Biopia. Higado. Diagnóstico.
Autor para correspondencia: Dr. Félix I. Téllez-Ávila, M.D., MSc, Ph.D.
Department of Gastrointestinal Endoscopy, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”. Vasco de Quiroga, Núm. 15. Col. Sección XVI. Del. Tlalpan. C.P. 14000, Ciudad de México, México.
INTRODUCTION
Over the past few years, the use of endoscopic ultra-sound (EUS) has provided a new method for obtaining material through liver biopsy. This technique provides a new approach for the diagnosis of liver disease, the be-nefits of which include the characterization of the lesio-ns, reduce complications and facilitating better biopsy procedures for analysis of histopathological features. Traditionally, there have been two procedural options for liver sampling: percutaneous biopsy (PCB), and intra-vascular approach. The PCB method is the main proce-dure, reported to have a diagnostic yield of between 67-94%,1 with potential adverse effects described in
0.09-3.1% of patients.2 The vascular transjugular approach has
contraindications, and is usually used as a procedural al-ternative to percutaneous intervention. However, this procedure is not without complications, with a compli-cation rate of 0.56-6.5% of biopsies.2
Recent evidence suggests that EUS is a useful appro-ach for liver pathologies.2-6 However, there is no
agree-ment on whether there are any differences in diagnostic yield based on the caliber of the needles used for the procedure. In the case of pancreatic le-sions, it remains controversial whether the caliber of needles confer an advantage with respect to accuracy or complications.
The aim of this study was to evaluate the diagnostic yield, complications and clinical impact of EUS FNA for sampling of solid liver lesions. As a secondary aim, we compared the outcomes from the use of 19G vs. 22G needles for aspiration.
MATERIAL AND METHODS
A retrospective analysis of prospectively collected data from patients that underwent EUS FNA for hepatic
focal lesions was performed. All patients that un-derwent this procedure over a 7-year period were in-cluded. All patients had been referred for EUS FNA due to the detection of a solid lesion by CT, MRI or ultra-sound, or with indication of EUS due to pancreatic le-sion and need for EUS FNA.
Before the procedure, laboratory tests were perfor-med on all patients, including prothrombin time and a full blood count. For the procedure, the patients were placed in the left decubitus position, and sedated using a combination of midazolam, propofol and fentanyl by the anesthetist. Patients were continually monitored throughout the procedure with an automated non-invasive blood pressure device, electrocardiogram and pulse oximetry. The EUS FNA procedure was performed by two echoendoscopists using the FUJI EG-530UT li-near array echoendoscope with console SU-8000 (Fuji-film Corporation, Minato-Ku, Tokyo, Japan), or with a linear array echoendoscope GFUCT-140 (Olympus Ameri-ca Inc.; Center Valley, PA, USA). All patients were hos-pitalized, and were observed for at least 4 hours after the procedure using an automatic monitor for survei-llance of possible complications.
All procedures were performed with standard 19- or 22-gauge EchoTip Ultra needles (Cook medical, Inc., Wins-ton Salem, NC, USA) according to the endosonographer’s criteria. The left hepatic lobe was sampled via the trans-gastric route, while lesions in the right hepatic lobe were sampled via the transgastric or transduodenal route. Patients underwent EUS FNA using the standard technique, as evi-dence of the fanning technique was not available at the time of patient inclusion.3
Endoscopic ultrasound-guided
fine needle aspiration technique
The transducer was initially placed in a stable posi-tion in front of the targeted lesion. The metal spiral ABSTRACT
Aim. To describe the diagnostic yield, complications and clinical impact of endoscop-ic ultrasound-guided fine needle aspiration (EUS FNA) of solid liver lesions.
Material and methods. Prospectively collected data from patients that underwent EUS FNA for hepatic focal lesions was retrospectively analyzed. All patients were re-ferred for EUS FNA due to detection of a solid lesion by CT, MRI or ultrasound. All procedures were performed with standard 19- or 22-gauge needles (EchoTip Ultra). The left hepatic lobe was accessed via the transgastric route, and lesions in the right hepatic lobe via the transgastric or transduodenal route.
Results. A total of 74 hepatic EUS FNA procedures were performed in 71 patients, 39 (54.9%) of which were women, with a mean age ± SD of 62.4 ± 14.2 years. The diagnos-tic yield for EUS FNA was 95.7% (68/71 patients). A 19-gauge needle was used in 36 (50.7%) patients and a 22G needle in 35 (49.3%). No differences in sensitivity, cytologi-cal diagnosis, complications or clinicytologi-cal impact of EUS FNA were detected for solid liv-er lesions sampled with 19G vs. 22G needles. The final histological result was malignant in 57/71 (80.2%) patients, benign in 12/71 (16.9%), and nondiagnostic in 2/71 (2.8%) patients. Results of EUS FNA changed the management of 21% of cases (malig-nancy was detected in six patients and surgery was avoided in nine patients). No complications were reported.
Conclusions. According to our results, EUS FNA is a useful and safe procedure with good diagnostic yield. There were no differences between the use of 19G and 22G needles for liver biopsies guided by EUS.
was then introduced into the biopsy channel, ensuring that the needle piston was securely locked and the needle was completely retracted. The spiral was com-pletely inserted, and the handle with the Luer-lock was firmly screwed into the biopsy channel. To ensure that the sheath was protecting the entire length of the working channel, we employed the optics of the endos-cope. With the stylet retracted, but still inside the needle, the biopsy needle was moved forward into the lesion under complete real-time ultrasound control. After it had penetrated into the middle of the lesion, the stylet was completely removed. Upon reaching the optimal needle position in the middle of the lesion, a 10 mL syringe with a locking device was firmly screwed onto the needle while pulling on the syringe piston to create low pressure. The syringe piston was locked into this position for permanent suction. The needle was moved back and forth 10-15 times inside the lesion under complete ultrasonic monitoring. With the needle tip still inside the lesion, the suction was released and the needle was safely retracted inside the needle sheath, where it was locked in a secure position.
All specimens were recovered, fixed in formalin and processed for histological and cytological analyses. A single expert pathologist evaluated the tissue samples. The cytological diagnoses of material obtained by EUS FNA were then categorized into the following groups: positive for malignancy (unequivocal cytological evi-dence of malignancy), benign/reactive process (be-nign or nondiagnostic samples that were confirmed to be benign by alternative sampling, intraoperative exa-mination or appropriate clinical follow-up), or nondiag-nostic. For the purpose of this study, material reported as suspicious for malignancy or atypical cells indeterminate for malignancy were considered to be negative for malignancy. A false negative aspirate is a nondiagnostic or benign specimen, which is subse-quently found to be malignant by percutaneous FNA or intraoperative findings. The final diagnosis (the gold standard) was based on the results of the surgical spe-cimen, or follow-up of at least 6 months in nonopera-ted cases with global clinical and radiological assessment.
Complications were defined as any of the following: excessive bleeding at the FNA site, perforation, and hypotension. Immediate (intraprocedural and in the reco-very area) complications were evaluated in all patients.
Statistical analysis
The results were evaluated using descriptive statis-tics for parametric distribution, including the mean and SD, and absolute and relative frequencies. Using the χ2
test or Mann-Whitney U test, according to variables, dif-ferences between groups were tested. A two-tailed P-value < 0.05 was considered significant. For evaluation of diagnostic yield and the sensitivity and specificity of the technique, positive and negative predictive values were calculated based on the final result of the gold standard. All analyses were conducted using SPSS 20 for Mac.
RESULTS
Initially, the clinical records of 79 patients that un-derwent EUS FNA of the liver were evaluated, and eight patients were excluded due to incomplete medical re-cords. A total of 74 EUS FNA procedures of the liver were performed in 71 patients, 39 (54.9%) patients were women, and the mean age ± SD was 62.4 ± 14.2 years. The global diagnostic yield from the first EUS FNA pro-cedure was 95.7% (68/71). Three patients underwent a second EUS FNA, and in the second biopsy, diagnosis was achieved in one patient (69/71). The location of the lesions in the liver was as follows: right hepatic
Table 2. Diagnoses of malignant aspirates of the liver.
Diagnosis n (%)
Pancreatic adenocarcinoma 44 (77.1) Pancreatic neuroendocrine tumor 5 (8.6) Hepatocarcinoma 4 (7.1) Small cell carcinoma 2 (3.5) Non-Hodgkin lymphoma 1 (1.8) Squamous cell carcinoma 1 (1.8)
Table 1. Sensitivity, cytological diagnoses, complications and clinical impact of endoscopic ultrasound-guided fine needle
aspira-tion (EUS FNA) for liver lesions.
EUS FNA with 19G EUS FNA with 22G P-value needle (n = 36) needle (n = 35)
Sensitivity (%) 100 100 1
Specificity (%) 100 75 0.4
PPV (%) 100 93 0.7
NPV (%) 100 100 1
Accuracy (%) 100 94 0.8
Cytological diagnoses 32 (88.8) 25 (71.4) 0.14 Malignant, n (%)
Complications, n (%) 0 0 1
lobe n = 30 (42.3%), left hepatic lobe n = 40 (56.3%), and lesion occupying both lobes n = 1 (1.4%). The mean ± SD for the lesion size was 30.4 ± 17.9 mm. A 19G EchoTip needle was used in 36 (50.7%) patients, and a 22G Echo-Tip needle was used in 35 (49.3%). The sensitivity, cyto-logical diagnoses, complications and clinical impact of EUS FNA of solid liver lesions obtained with 19G vs 22G aspiration needles is presented in table 1.
The final histologic result was malignant in 57/71 (80.2%) patients, benign in 12/71 (16.9%) patients, and nondiagnostic in 2/71 (2.8%) patients (Table 2). A total of 12 lesions were confirmed to be negative for malig-nancy by follow-up (median 729 days, range 299-2016 days) or intraoperative examination; however, two le-sions could not be classified as benign or malignant. Of the 57 patients with malignancy, as identified by EUS FNA, EUS detected malignancy in six (8.4%) patients with previously negative examinations. For the 57 sub-jects with cytological positivity for malignancy, the re-sults of the EUS FNA changed the management in nine (12.6%) subjects. Patients with hypoechoic lesions or more than one lesion were more likely to have a malig-nant result in the histopathological analysis (Table 3). The patient gender, age, needle gauge, size of the le-sion and location of the lele-sion (left or right lobe) were not associated with the likelihood of a positive result (malignant or benign) in the EUS FNA. No complications were reported.
DISCUSSION
According to our results, EUS FNA is a useful and safe procedure with good diagnostic yield in patients
with solid liver lesions. There were no differences in patient outcomes between the 19G and 22G needles for liver biopsies guided by EUS.
Our results are consistent with current evidence that suggests that EUS is a useful methodological appro-ach for diagnosis of liver pathologies.2-4,6,7 The reported
diagnostic yield of EUS FNA ranges from 91-100%.2-4,6,7 In
our series, the yield of EUS FNA was greater than 95%, which is consistent with that previously reported by tenBerge8 of 96% (160/167), Diehl3 of 98% (108/110) and
Gor4 of 100% (10/10). However, there are some other
reports with conflicting results.9 Previous studies only
make reference to biopsies collected with one caliber of needle (mainly 19G needles; Table 4). We used both calibers 19G and 22G to determine whether this repre-sents a factor that alters the diagnostic performance (Table 1). Our results are important, as it is well known among endosonographers that it is technically very dif-ficult to use a 19G needle in some cases, mainly when access via the transduodenal route is required. In the case of pancreatic lesions, studies have reported simi-lar results, with no differences in outcomes between needle calibers.10
The patients included in our study came from a sin-gle center, all with focal liver lesions. Other reports have included patients with nonspecific alterations in liver function tests, in which the biopsy was taken randomly from the parenchyma, which may explain discrepancies in the results.2-4,6 A point to consider, besides its
diag-nostic impact, is the change in management strategy due to the results of EUS FNA. In our study, the results of EUS FNA altered the management of patients in 21% of cases (malignancy was detected in six patients and
sur-Table 4. Summary of available data for endoscopic ultrasound-guided liver biopsy of focal lesions.
Study Wiersema (1997) Nguyen (1997) DeWitt (2003) Gleeson (2008) Type of needle used 21-25 G 22-25 G 22 G 19 G
Patients (n) 12 9 77 9
Number of passes (mean) 2 2.4 1.8 2
Diagnostic yield (%) 96 100 91 100
Complications Yes* No No No
Follow-up (days)** 720 (300-1,800) 762 (512-1,556) 288 (7-947) * Five complications observed: two patients with GI tract perforation (one patient needed surgery), two patients with fever post-procedure, and one patient with GI bleeding. **Expressed as median (range). EUS-LB: Liver biopsy guided by endoscopic ul-trasound.
Table 3. Characteristics of endoscopic ultrasound examination.
Characteristic Malignant (n = 57), n (%) Benign (n = 12), n (%) P-value Echogenicity
Hypoechoic 50 (92.6) 9 (75) 0.025
Size (mm)* 30 (2–92) 32.5 (10-50) 0.30 Number of lesions* 3 (1–7) 1 (1-3) 0.039 Patients with > 1 lesions 35 (65) 4 (33) 0.05 Site of FNA
Left lobe 31 (57.4) 7 (58.3) 0.8
gery was avoided in nine patients). Previous studies have reported that the results of EUS FNA can avoid surgery in up to 27% of cases.9
Although few complications have been reported from procedures, generally less than 4%,3,8 no
complica-tions were documented in our study. An important fin-ding of our study is the identification of pre-EUS FNA characteristics that identified patients with a higher risk of having a malignant lesion. According to our data, patients with hypoechoic lesions or more than one le-sion were more likely to have a malignant result in the histopathological analysis. This is highly important in cli-nical practice, and could be useful information for ul-trasonographers.
The limitations of our study include the sample size and the retrospective design. The design of this study meant that patients were not randomized, which may have affected the outcomes. However, in general, all physicians preferred to perform FNA procedures via the duodenum using 22-gauge needles, and all FNA proce-dures via the gastric route with 19-gauge needles. Pre-vious studies have reported bigger samples sizes but with patients and physicians from different centers. To our knowledge, this study represents one of the lar-gest cohorts from a single center. This is important be-cause EUS is an operator-dependent procedure, and therefore, there may be greater homogeneity in the EUS FNA technique and sample handling in our study.
In conclusion, according to our results, EUS FNA of the liver is a useful and safe procedure that can have a significant impact on patient management. There were no differences between 19G and 22G needles for liver biopsies guided by EUS, in terms of the sensitivity, cyto-logical diagnoses, complications and clinical impact.
AUTHOR CONTRIBUTIONS
Téllez-Ávila FI designed the report; Téllez-Ávila FI, Duarte-Medrano G, Gallardo-Cabrera V, Herrera D and Ramírez-Luna M were attending doctors for the pa-tients; Téllez-Ávila FI and Ramírez-Luna M performed en-doscopies; Téllez-Ávila FI, Duarte-Medrano G, Gallardo-Cabrera V, Herrera-Mora D, Elizondo-Rivera J and Valdovinos-Andraca F organized the report; and Té-llez-Ávila FI and Duarte-Medrano G wrote the paper.
DISCLOSURE
All authors disclose no financial relationships rele-vant to this publication.
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