EUS-CPN

Celiac plexus neurolysis, Brachytherapy
or others?
Siyu Sun
Endoscopic Ultrasound Editorial office
Shengjing Hospital of China Medical University

Pancreas cancer
 Pancreatic cancer (PC) is a lethal malignancy resulting in more than
250,000 deaths per year worldwide.
 In contrast to the stable or declining trends for most cancer types,
incidence rate is increasing for pancreas cancer.
Feig C, Gopinathan A, Neesse A, et al. Clinical Cancer Research, 2012, 18(16): 4266-4276.
Cancer statistics, 2014. CA: a cancer journal for clinicians, 2014, 64(1): 9-29.

Trends in 5-Year Survival Rates
in the last 30 years
2% 4% 6%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1975-1977 1987-1989 2003-2009
5-Year Survival Rates (%)

What can we do?
The quality of life
(QOL)
The survival time

PAIN
80–85% of patients with PC
Yan B M, Myers R P. The American journal of gastroenterology, 2007, 102(2): 430-438.
Moore J C, Adler D G. The journal of supportive oncology, 2008, 7(3): 83-7, 90.

EUS-guided
Celiac Plexus Neurolysis (CPN)

The celiac plexus
Percutaneous CPN EUS-CPN
Techniques for CPN
Posterior and
percutaneous
Without
guidance by
Kappis in 1914
Under
fluoroscopic
guidance
Under CT
guidance
Anterior
approach
transabdominal
ultrasound
CT
intra-
operatively

The celiac plexus is located below and anterior to the diaphragm and
surrounds the origin of the celiac trunk.
the level of L1 vertebra, but may vary from T12~L2.
The celiac plexus is comprised of a dense network of ganglia and
interconnecting fibers.
2-5 ganglia are present.
The right ganglia are 0.6 cm, the left are 0.9 cm
The celiac ganglion The celiac trunk

2007 2008 2009 2010 2011 2012 2013 20141996 …
First discribed
By Wiersema and Wiersema.
A Brief History of EUS-CPN
RCT: CPNvsCGN
RCT:Central vs Bilateral
RCT: EUS-CPN
EUS-BPN
First EUS-CGN

2007 2008 2009 2010 2011 2012 2013 20141996 …
First discribed
Wiersema M J, Wiersema L M. Gastrointestinal endoscopy, 1996, 44(6): 656-662.

 Using a linear array echo-endoscope,
the region of the celiac ganglia is
located from the lesser curve of the
stomach, following the emergence of
the celiac trunk from the aorta.Location of the celiac ganglia

Needle direction to the right celiac area.

Randomized Controlled studies
Wallace et al., 36 pts EUS-CPN vs sham.
no difference
• pain scores
• quality of life (QOL)
small sample size
very short life expectancy
• 15/36 pts reached the 1 month end-point.
Wallace MB, et al. Gastrointest Endosc 2010;71:AB224.

2007 2008 2009 2010 2011 2012 2013 20141996 …
 A: EUS-CPN provided greater pain relief .
 B: significantly greater at 3 months.
 Morphine consumption was similar in both groups
 tended toward lower consumption at 3 months
Doubled-blind, controlled
Wyse J M, Carone M, Paquin S C, et al. Journal of Clinical Oncology, 2011, 29(26): 3541-3546.

2007 2008 2009 2010 2011 2012 2013 20141996 …
The pooled proportion
of pain relief:
80.12%
Puli S R, Reddy J B K, Bechtold M L, et al. Dig Dis Sci, 2009, 54(11): 2330-2337.
Pain relief

Narcotic requirements and opioid
consumption
Non EUS-CPN
• Yan and Myers * narcotic use ,VA scores and constipation
• Arcidiacono PG （n= 358 ) * in VAS and opioid consumption
Puli et al ：（N=283） no information on narcotic
requirements
Kaufman et al ：(N=119 pts） not evaluate opioid use.
Nagels et al. ： no conclusion on opioid consumption.

2007 2008 2009 2010 2011 2012 2013 20141996 …
 Pain scores before and after EUS-CPN
Persistent Pain relief
Nagels W, Pease N, Bekkering G, et al. Pain Medicine, 2013, 14(8): 1140-1163.

62-88% of patients
with pancreatic cancer
81-88% of unselected
patients
EUS-CGN?

• retrospectively 33 pts
– 18 pts with PC
– 94% of pts pain relief at wks 2-4.
– 34% of pts initial pain exacerbation
correlated with better pain relief.
First Study on CGN
Levy MJ, et al. Am J Gastroenterol 2008;103:98-103

2007 2008 2009 2010 2011 2012 2013 20141996 …
Doi S, Yasuda I, Kawakami H, et al. Endoscopy, 2013, 45(05): 362-369.
CPN < CGN

Nonrandomized study, in 160 consecutive pts (72 ts with PC）,
bilateral injection was the only predictor of >50% pain
reduction by day 7.
A single-blinded trial, randomized 50 pts with PC , no
difference
The meta-analysis: 283 pts, bilateral injection, 84% and
central 46%
Central or Bilateral?
Sahai AV, et al. Am J Gastroenterol 2009;104:326-9
LeBlanc JK, et al. Gastrointest Endosc 2011;74:1300-7
Puli SR, et al. Dig Dis Sci 2009;54:2330-7.

2007 2008 2009 2010 2011 2012 2013 20141996 …
Téllez-Ávila F I, Romano-Munive A F, Jd H E, et al. Endoscopic Ultrasound, 2013, 2(3): 153.
Central or Bilateral?

Endoscopic Ultrasound-Guided Broad Plexus Neurolysis
（BPN） Over The Superior Mesenteric Artery
• EUS-CPN vs EUS-BPN
• EUS-BPN uses 25-g needle to inject both sides of the SMA.
• BPN group had more patients with 6 contrast-bearing areas (42%)
than the CPN group (0%).
• These patients had significantly better short-term and long-lasting pain
relief than pts with <5 contrast-bearing areas.
• EUS-BPN pts exhibited significantly greater reductions in days 7 and 30
Sakamoto H, et al. Am J Gastroenterol 2010;105:2599-606

Dose of alcohol and anesthetic
Not standardized
•LeBlanc et al. found that CPN (ganglia or central injection) with 10 or 20 ml of 98% alcohol
resulted in similar complications and pain relief
•bupivacaine was used in a concentration ranging between 0.25% and 0.75% and in a dose
ranging between 3 and 20 ml.
•Other studies have used lidocaine 1%, dose ranging from 3 to 10 ml.
There are no studies accessing effectiveness of different anesthetics or
dosage.
In addition, it is unclear if when neurolysis is being performed with
anesthesiologist support the use of anesthetic is needed.

Types of needle
Most standard 22-gauge needles
A 20-gauge needle specifically designed for CPN (EchoTip celiac plexus needle;
Cook Medical)
• no removable stylet.
• a solid, sharp, conical tip, and an array of side holes for radial delivery of the desired agent into the celiac
plexus
• This "spray" needle provides easy and quick injection, with multidirectional delivery of the agent in the
celiac area, however echogenic "blush" is not seen at the time of injection.
A 19-G needle offers little resistance.
There are no studies specifically comparing various needle types or sizes in CPN.

Repeat celiac plexus neurolysis
In a retrospective study including 24 pts
• the success rate decreased from 67% after initial CPN to 29% following repeat
CPN (P = 0.13), mean duration of pain relief from 3.4 months for initial CPN to
1.6 months of repeat CPN (P = 0.03).
In a recent retrospective study, including 50 pts with PC
• the mean number of EUS-CPN was 2.2. The mean duration of pain relief after
the first CPN was 13 weeks and after the second CPN 8 weeks (P < 0.0001).
Prospective studies are needed to further confirm the safety and
determine efficacy of repeat EUS-CPN.
McGreevy K, et al. Pain Pract 2013;13:89-95.
Sey MA, Am J Gastroenterol 2013;108:s572-620.

No
89%
Yes
11%
Hypotension
No
83%
Yes
17%
Diarrhea
No
92%
Yes
8%
Alcohol intoxication
No
91%
Yes
9%
Transient pain exacerbation
A B
C D
37/218 15/135
5/58 1/12
Adverse events

Serious Complications 0.2%
Retroperitoneal bleeding by laceration of left adrenal artery
•Sahai AV et al. EUS-CPN
Ischemia-related complications
•Loeve and Mortensen et al. bleeding necrotic area of the aorta just above the celiac
trunk and a large perforation of the posterior wall of the stomach.
•Gimeno-Garcνa et al. complete thrombosis of the celiac artery take-off
•Jang et al hepatic and splenic infarction, EUS-CPN (central injection).
Paralysis due to anterior spinal cord infarction
•Fujii L, et al EUS-CGN
•Mittal MK, et al EUS-CGN
Infectious complications
•5 reports EUS-CPB

Contraindication
Coagulopathy
(international
normalized ratio
>1.5)
Thrombocytopenia
(platelets
<50,000/L)
Hemodynamic or
respiratory
instability
Inability to visualize
anatomical
landmarks
large tumor mass Lymphadenopathy
Eccentric origin of
the celiac artery
Ectatic aorta

EUS-guided
Interstitial Brachytherapy (IBT)
Interstitial chemotheraphy (ICT)

Interstitial brachytherapy(IBT)
Interstitial chemotherapy(ICT)
 Intraoperative IBT and ICT has been effective when utilized during
laparotomy to improve local control in locally advanced pancreatic cancer.

Implants：Weapons of Mass destruction
 Iodine 125
 4.5 mm long, 0.84 mm thick
 Half-life: 60 days
 5−fluorouracil
 4mm long, 0.8mm thick
 Sinofuan, 100 mg
Seeds and polymers

EUS-guided Injection therapy
 Implantation equipment

Sun S, Xu H, Xin J, et al. Endoscopy, 2006, 38(04): 399-403.

needle
tumor
seeds
 During a median follow−up period of 10.6 months, the objective tumor response
was classified as “partial” in 27% of patients (with a median duration of partial
response of 4.5months), “minimal” in 20% patients, and indicative of “stable
disease” in 33% of patients.
Methods: EUS-IBT for Pancreatic Cancer

Results: Data on 5 patients who achieved
Clinical Benefit Response (CBR)
Patien
t
KP Score Pain Score
CBR Duration
(mon)
Baselin
e
Achiev
ed
Baselin
e
Achiev
ed
2 70 90 2 0 6.5
6 60 60 7 3 1.2
8 70 70 5 3 1.3
13 70 70 4 1 1
14 70 80 1 1 1.1
5/15 Pts experienced clinical
benefit
4/15 Pts experienced partial
tumor reponse.

IBT & systemic chemotherapy
22 pts received EUS-brachytherapy and routine gemcitabine-
based 5-fluorouracil chemotherapy 1 week after brachytherapy.
The estimated median survival time was 9.0 months
Partial remission was achieved in three cases
VAS dropped from 5.07 +/- 2.63 to 1.73 +/- 1.91 ( P< 0.01) 1
week
The data showed improvement in pain, but no long-term
survival benefit.
Jin Z, et al. Endoscopy. 2008 Apr;40(4):314-20.

EUS-guided celiac ganglion irradiation with iodine-125
seeds for pain control in pancreatic carcinoma
23 Pts
The use of iodine-125 as a neurolytic agent
The mean number of seeds was 4 (range 2-6)
The VAS score and mean analgesic consumption were significantly less than
preoperative values
The authors postulate that iodine-125 may be a superior neurolytic agent
compared with ethanol due to its longer half-life and deeper tissue penetration
Wang KX, et al. Gastrointest Endosc 2012;76:945-52

EUS guided interstitial chemoradiation
Sun S, Ge N, Wang S, et al. Endoscopic Ultrasound, 2012, 1(1): 41-47.

EUS-IBT and ICT

 CEA
 CA19-9
EUS-IBT and ICT

Kaplan–Meier Curves
 EUS-guided placement of brachytherapy seeds and chemotherapeutic
implants into unresectable pancreatic tumors (a mean of 19 seeds per
patient) had a moderate effect on the tumors (12.5 % showed a partial
response and 25 % a minor response) and on the patients’ symptoms (1/2
showed a clinical response), when tested in 8 patients

Tumor
EUS-guided fiducial placement

EUS-guided fiducial placement
 To demarcate the extent of
tumors to facilitate image-
guided radiation therapy
 Fiducial markers:
radiopaque spheres, coils,
or seeds implanted in or
near the tumor.
Fabbri C, Luigiano C, Lisotti A, et al. World journal of gastroenterology: WJG, 2014, 20(26): 8424.
Dávila Fajardo R, Lekkerkerker S J, van der Horst A, et al. Gastrointestinal endoscopy, 2014, 79(5): 851-855.

Endoscopic ultrasound-guided fiducial placement

Lack of evidence with high level
 Rigorously designed RCTs are needed

Conclusions
Since first description of EUS-CPN, investigators have employed
several technical variations in terms of target of injection and
composition.
Direct injection at the visualized celiac ganglia offers clear advantages
over other approaches
Brachytherapy and Fiducial placement are lack of evidence with high
level.
Future large studies are also necessary for the continued evaluation of
these techniques.

4/25/2020 56
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Editor's Notes