EUS guided tissue acquisition - Nottingham Digestive ... guided tissue acquisition Jayapal Ramesh Advanced Endoscopist Royal Liverpool and Broadgreen University Hospitals NHS Trust

EUS guided tissue acquisition

Jayapal Ramesh

Advanced Endoscopist

Royal Liverpool and Broadgreen University Hospitals NHS Trust

Honorary Senior Lecturer, University of Liverpool

Learning Objectives and Outline

•To review the different tissue acquisition techniques

•Practical tips based on current evidence for effective tissue acquisition

•To apply evidence to everyday practice EUS FN tissue procurement

Background

•EUS 1980

•EUS FNA 1990-Vilmann and Hancke – pancreatic biopsy

•Now considered Disruptive Innovation

•Excellent sensitivity, specificity and accuracy

• Impacts patient management

Pancreatic Cytology from 1990-2010

EUS Instituted 07/2000

Disruptive Innovation 2761 samples

Eltoum IA: Arch Pathol Lab Med 2012

Non-EUS-guided FNAC: 36% to 1%

Needle Biopsy: 29% to 9%

55%

78%

16% 16%

7%

88%

96%

3% 4% 1%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Sen

sitiv

ity

Sp

ecific

ity

Su

sp

icio

us

Aty

pic

al

Un

sa

tisfa

cto

ry

1990-2000

2001-2010

EUS tissue acquisition

Lesion Size

Location

Needle Size

Type FNA

FNB

Tech. Factors

Suction

Dry

Slow Pull

Wet Stylet

Sampling

Standard

Fanning

Movements Operator

Pathology ROSE

Off- site

All FNAs the same?

• Location

• Pancreas

• Bile Duct

• Mediastinal

• Perigastric

• Adrenal

• Kidney

• Liver- SOL, Parenchyma

• Rectal

• GI Wall

• Size of the lesion

• Nature of the target • Mobile

• Solid organ

• GI Wall

• Morphology • Solid

• Cystic

• Mixed Echogenic

Location

Trans-

duodenal FNA

Trans-gastric FNA

Trans-esophageal/rectal FNA

Sensitivity >95%

Sensitivity 80-85%

TD Lymph node>

Pancreas head>

Pancreas Uncinate>

Bile Duct

Beware Blind Spots –

uncinate, neck, tail,

porto-caval, aorto-

caval, right adrenal

Performance characteristic of endoscopic ultrasound-guided fine needle aspiration is

unaffected by pancreatic mass size

Group A Group B Group C Group D Total

Sensitivity 0.7333 0.8738 0.8776 0.7846 0.8595

Diagnostic

accuracy 0.7333 0.8661 0.8811 0.8158 0.8644

Ramesh J et al Endosc Int Open. 2016 Apr; 4(4): E434

Size does not matter

Size without ROSE

Needle Selection

Needle Selection

Author No. Lesion Needle Diagnostic Accuracy

Camellini L

Fabbri C

Siddiqui UD

Song TH

Ramesh J

127

50

131

117

72

All Lesions

Pancreatic Masses

All Lesions

Pancreatic Masses

Pancreatic Masses

22 vs. 25G

22 vs. 25G

22 vs. 25G

22 vs. 19G

19 vs. 25G

77.8 vs. 78.1%

86 vs. 94%

87.5 vs. 95.5%

78.1 vs. 94.5%

94.4 vs. 88.9%

25G for Head/Uncinate Masses

22G = 25G for FNA’s

Meta-analysis Lesions 22 vs. 25G Pooled Sensitivity p

Madhoun MF 1364 799 vs. 565 0.85 (95% CI=82-88)

vs. 93 (95% CI-91-96)

0.0003

25G for Pancreatic Masses

Bang JY: Endoscopy 2016

ProCore FNA

Outcome Measure ProCore

(n)

FNA

(n) Mean % (95% CI) Mean % (95% CI) Pooled RR (95%CI) p-value

Diagnostic Adequacy: 742 745 82.7 (74.2-89.8) 79.3 (70.4-87.0) 1.06 (0.97-1.16) 0.221

All Masses

Diagnostic Adequacy: 317 324 84.8 (70.4-95.0) 88.5 (80.1-94.9) 0.98 (0.85-1.12) 0.721

Pancreatic Masses

Diagnostic Accuracy: 421 474 84.9 (76.1-92.0) 79.3 (71.8-85.9) 1.06 (0.99-1.14) 0.083

All Masses

Diagnostic Accuracy: 225 277 88.4 (82.4-93.3) 79.9 (73.6-85.5) 1.12 (0.99-1.26) 0.067

Pancreatic Masses

Histology: 104 108 66.8 (49.7-81.9) 68.7 (54.5-81.3) 1.02 (0.85-1.22) 0.864

All Masses

Histology: 66 70 75.4 (60.2-87.8) 75.2 (63.2-85.5) 1.03 (0.84-1.26) 0.756

Pancreatic Masses

Mean passes for

diagnosis: All Masses 209 209 - -

SMD -0.90 (-1.80 -

0.005) 0.051

Meta-analysis: ProCore and FNA needles

Mean passes for

diagnosis: All Masses 209 209 - -

SMD -0.90 (-1.80 -

0.005) 0.051

Needle Selection

Summary of studies evaluating the role of suction

Author Study design No. of

patients

With

suction

Without

suction

P value

Wallace et al.

2001

RCT 43 Higher NA 0.01

Puri et al. 2009 RCT 52 100% 100% NS

Lee et al. 2013 RCT 81 72.8% 58.6% 0.001

Adequate specimens

Puri et al. Scand J Gastroenterol, 2009; 44: 499-504.

Wallace et al. Gastrointest Endosc, 2001; 54: 441-7.

Lee et al. Gastrointest Endosc 2013;77:745-51.



patients

With

suction

Without

suction

P value

Wallace et al.

2001

RCT 43 Higher NA 0.0004

Puri et al. 2009 RCT 52 76.9% 88.5% 0.14

Lee et al. 2013 RCT 81 6.2% 0.6% <0.001

Bloodiness






patients

With

suction

Without

suction

P value

Wallace et al.

2001

RCT 43 No difference 0.19

Puri et al. 2009 RCT 52 85.7% 66.7% 0.05

Lee et al. 2013 RCT 81 82.4% 72.1% 0.005

Diagnostic Yield of Malignancy




Wet vs Dry Suction Technique

•22G needle

•117 lesions

•Either wet suction or standard ‘dry’ suction

•Subsequent passes using alternating techniques.

Wet Technique Dry technique P value

Mean Cellularity 1.83 (+/- 0.79) 1.44 (+/-0769) < 0.001

Diagnostic Yield 85.5% 74.4% <0.001

Gastrointest Endosc. 2015;81(6):1401-7.

Suction vs Capillary

• 367 passes in 93 solid pancreatic lesions were retrospectively analyzed

• 181 by suction and 186 by slow pull (capillary)

Nakai et al. Dig Dis Sci. 2014; 59:1578–1585.

Overall Suction Slow pull P value

Diagnostic accuracy 75.1 % 83.9 % 0.039

Cellularity 71.8 % 52.2 % <0.001

Bloodiness 60.8 % 51.1 % 0.074

Suction vs Capillary

Nakai et al. Dig Dis Sci. 2014; 59:1578–1585.

22 gauge needle Suction Slow pull P value


Cellularity 66.7 % 58.9 % 0.261

Bloodiness 54.4 % 62.0 % 0.268

25 gauge needle Suction Slow pull P value


Cellularity 76.7 % 37.5 % <0.001

Bloodiness 66.7 % 25.0 % <0.001

Standard vs Fanning Technique of FNA

Bang, Endoscopy

RT of Standard vs. Fanning FNA

Standard Fanning

n= 26 n = 28

First pass diagnosis

57.7% 85.7%

No Needle Dysfunction

Bang, Endoscopy

Standard Fanning P

value

No. of passes for

diagnosis

1.7±0.88 1.2 ±0.57

0.02

76.90%

57.70%

96.40% 85.70%

Diagnostic accuracy Diagnostic yield of passone

Standard Fanning

P=0.05 P=0.02

No of jabs

43.20% 44.60%

48.60%

39.10%

55.40%

48.60%

67.60%

60.90%

86.50%

82.40%

87.80%

82.60%

26.20%

38.10%

34.50% 32.30%

51.20% 50.00% 52.40%

53.80%

59.50%

71.40% 72.60%

69.20%

10 15 20 25

Pe

rce

nta

ge

No of jabs

Cellular (S) Blood (S) Yield (S) Cellular (NS) Blood (NS) Yield (NS)

Na S: DDW 2013 AB 404

Suction (n=94) No suction (n=99)

All cases (N = 82) DKM CM P value

Tissue acquisition (cellularity score ≥1) 91.5% (75/82) 89.0% (73/82) .37

High-cellularity tissue acquisition (cellularity score = 3) 54.9% (45/82) 41.5% (34/82) .03

Adequate quality (quality score ≥2) 78.0% (64/82) 80.5% (66/82) .42

Accuracy 76.8% (63/82) 78.0% (64/82) .50

Transgastric (n = 63)




Accuracy 84.1% (53/63) 76.2% (48/63) .11

Transduodenal (n = 19)

Tissue acquisition (cellularity score ≥1) 84.2% (16/19) 100% (19/19) .13



Accuracy 52.6% (10/19) 84.2% (16/19) .02

Mass size ≥20 mm (n = 53)




Accuracy 83.0% (44/53) 81.1% (43/53) .50

Mass size <20 mm (n = 29)




Accuracy 65.5% (19/29) 72.4% (21/29) .36

Door Knocking Method Gastrointest Endosc. 2015 Oct 30.




Accuracy 52.6% (10/19) 84.2% (16/19) .02

Author Number of patients Comparators Diagnostic Accuracy

Fisher JM 268 Stent vs. No stent 92.4% vs. 88.5%

Siddiqui AA 677 Plastic vs. metal stent 97.1 vs. 97 %

Varadarajulu S 241 Stent vs. no stent

Plastic vs. metal

95% vs. 93%

95% vs. 95%

Relationship between stents and EUS-FNA

No of passes

After 7 passes point of “Diminishing Return”

Jhala N: Cancer 2004

Onsite Cytopathology vs. No Onsite

Author No. Diagnostic Yield Indeterminate Unsatisfactory

Klapman

Iglesias

Garcia

Alsohaibani

198

182

104

78% vs. 32%,

p=0.001

97% vs. 86%,

p=0.01

77% vs. 53%,

p=0.01

10% vs. 12%,

p=0.9

2.1% vs. 10.3%,

p=0.02

23% vs. 47%,

p=0.001

9% vs. 20%, p=.003

1 vs. 13%, p=0.002

0 vs. 17%, p=NS

Diagnostic Sensitivity = Onsite cytopathology

Meta analysis

• A total of 33 studies including 3208 patients with 1767 pancreatic adenocarcinomas were included.

• The pooled sensitivity and specificity of EUS-FNA for diagnosis of PANCAN was 90.9% (95% CI: 89.5- 92.1) and 99.4% (95% CI: 98.8-99.7)

• Subgroup analysis showed higher sensitivity in the presence of an onsite cytopathologist 95.1% (95%CI: 93.7-96.2) vs. 78.7% (95%CI: 74.1-82.8); p=0.003.

• Studies that included >100 patients had better sensitivity than those with <100 patients: 94.3% (95% CI: 92.8-95.5) vs. 84.5% (95%CI: 81.5-87.2); p =0.003.

• When clinical follow up was used in combination with histology as reference standard, the pooled sensitivity was significantly higher than when using only histology, 92.2% (95%CI: 90.8-93.4)] vs. 61.0 (95%CI: 49.2-72.0); p=0.004.

• The overall pooled diagnostic odds ratio was excellent at 392.42 (95% CI: 211.70-727.43) and SROC recorded an impressive AUC of 0.98.

Ramesh DDW 2013

Indeterminate FNAs

Author Proportion of

Total cases

Indication Diagnostic

Accuracy

Eloubeidi

Dewitt

Nicaud

24/517 (4.6%) Pan.

Masses

73/8396 (0.8%)

EUS exams

30/3895 (0.77%)

EUS exams

Panc. Mass

55% Panc. Mass

Panc. Mass

84%

63%

61%

Most common indication is Pancreatic Mass

Diagnostic accuracy of repeat FNA > 60%

Why histology?

•Better assessment of tumors

•Definitive for benign diseases

•No need for on-site assessment

•Parenchymal biopsy- Liver, Pancreas for AIP

•Lymphoma

•SMT

•Molecular studies

• Immunohistochemistry for characterization

•Chronic Pancreatitis

• IPMN Cancer

•Characterization of tumors

Shark core 22G

19G

19-TCB

19-Procore

22 Procore

19G

Flex-19G

HISTOLOGY

Yasuda 2006: Lymphoma

Sakomoto 2009: Pan Head: 8%

Iglesias Garcia 2011: Accuracy >90% Difficult Pan Head

JY Bang 2012: FNB = FNA Accuracy: 89.3 vs. 100%

Larghi A 2011: Accuracy 90% No Pancreatic Head

Varadarajulu 2012 Cytology 92% Histology 95% Combined 100% Kandel 2016: Pancreas lesions

Newer Needles

• 33 underwent 312 passes in 42 different lesions.

• A diagnosis of malignancy was more likely with FNB than FNA (72.7% vs 66.7%, p=0.727)

• FNA and FNB had similar sensitivities, specificities, and accuracies for cancer (81.5% vs 88.9%, 100% vs 100%, and 84.8% vs 90.9%, respectively)

• FNB provided qualitative information not reported on FNA, such as degree of differentiation in malignancy, metastatic origin, and rate of proliferation in neuroendocrine tumors.

Impact of EUS-guided fine-needle biopsy with a new core needle on the need

for on-site cytopathological assessment: a preliminary study.

Gastrointest Endosc. 2016 Jun 23.

EUS-guided fine needle biopsy sampling using a novel fork-tip needle: a case-control study.

Median no. of passes

Size for histologic screening

Median histology score

Two groups

Total number 156

25% (n = 39)

FNB

4 (sufficient for adequate histology)

95%

2

75% (n = 117)

FNA

2 (sufficient for cytology but not histology)

59%

4

P = .01

P = .001

There was significant difference in the median number of passes to all lesion sites

and needle gauges.

Gastrointest Endosc. 2016 Mar 24

Retrospective case control study with 1:3 matching by lesion site and needle gauge

EUS Guided Liver Biopsy

Patients Median tissue length,

mm (range)

Median CPTs

(range)

Both lobes 68 40 (9 – 148) 17 (65)

Left only 34 32 (0 – 203) 13 (0 – 68)

Right only 8 49 (8 – 113) 14 (6 – 34)

• 110 patients (62 women; median age, 53 years)

• 8 participating centers

• Persistent unexplained elevation in serum transaminases (n = 96)

• Evaluation of hepatic parenchyma for suspected underlying liver disease (n = 14)

Quantified yields from endoscopic ultrasound liver biopsies

CPTs, complete portal triads Diehl et al Endosc Int Open. 2015 Jun; 3(3): E210–E215.

Summary

• Question asked – mass, cyst, LN, SMT, GI Wall, parenchyma

• Pathologist discussion key • Plan early

• Set your parameters

• Have a system in place

• Consistency

Aim is to acquire adequate good quality specimen

with minimal number of passes, efficiently and

safely

Thank You

Documents

EUS guided tissue acquisition - Nottingham Digestive ... guided tissue acquisition Jayapal Ramesh Advanced Endoscopist Royal Liverpool and Broadgreen University Hospitals NHS Trust