Transcript Enterra Therapy: A New Era in the Treatment of Gastroparesis

Gastroparesis and
Gastric Electrical Stimulation
Dr. Mario Costantini
Clinica Chirurgica 1
Università ed Azienda
Ospedaliera di Padova
U.O.S. Fisiopatologia
Esofago-Gastrica
Gastroparesis
A chronic disorder of gastric motility
characterized by delayed gastric emptying
in the absence of mechanical obstruction.
Main symptoms:
• Nausea, vomiting
• Early satiety, bloating
• Post-prandial fullness
• Abdominal pain
• Weight loss, dehydration
• Difficult glycaemic control
Gastroparesis: Ætiology
Miscellaneous
Intestinal
causes (post-infective)
pseudoobstruction
6.0%
4.1%
Collagen
Vascular disease
4.8%
Idiopathic
35.5%
Parkinson's
disease
7.6%
Postsurgical
13.0%
Diabetic
29.0%
Kendall and McCallum. Gastroenterology 1993.
Soykan et al. Dig Dis Sci 1998.
Gastroparesis: Incidence*
M = 2.5/100.000/yrs
F = 9.8/100.000/yrs
5-yr survival 80%
“Gastroparesis is an uncommon condition in the community,
but is associated with a poor outcome”
*Olmsted County
Jung H-K et al. Gastroenterology 2009;136:1225-33
Gastroparesis: Pathophysiology
Excessive
relaxation
Poor
antro-pyloro-duodeno
synchronization
Abnormal
duodenum
motility
Antral
hypomotility
Gastroparesis: a proposed classification
Ad da Abell TL et al, Neurogastroenterol Motil 2006
Gastroparesis: Treatment
Botulinum toxin
GES
The History of Gastric Stimulation
1963 – Bilgutay et al.: The concept of electrical stimulation was
born, when gastric stimulation was practiced for the treatment of
postoperative ileus.
The History of Gastric Stimulation
1972: Kelly and Laforce at Mayo Clinic induced antegrade and
retrograde conduction of slow waves in canines with gastric
stimulation.
1988: McCallum et al. at University of Virginia showed increased
gastric emptying in canines with vagotomy
1997: Familoni et al. reported improved peristalsis in canines with
GES
1998: The WAVESS Study Group demonstrated the feasibility of
GES, leading to Enterra Therapy
XIth International Symposium
on Gastrointestinal Motility
Oxford, September 7-11, 1987
Gastric Electric Stimulation
?
Neural sequential GES (experim. only)
Gastric Neurostimulation (Enterra)
12 bpm
 High Frequency (~ 4 x Slow Wave Freq)
Frequency
Low Energy with short pulse
Gastric Pacing:

3 bpm
Energy
Low Frequency (~ Slow Wave Freq)
High Energy with long pulse
Gastric Pacing vs. Neurostimulation
 Pacing is an application of an electrical stimulus that
activates contraction of gastric smooth muscle, entraining
at that rate of the intrinsic slow wave by a low-frequency,
high-energy, long pulse stimulation
 too large and heavy batteries to be implanted
 Neurostimulation activates a nausea- and vomitingcontrol mechanism, utilizing a high-frequency, low-energy,
short pulse stimulation to achieve symptomatic relief
 miniaturization and possible implantation
Enterra Therapy:
Humanitarian Device Exemption
Enterra Therapy was granted approval as a
HUD (humanitarian use device) to be
used in patients with refractory diabetic or
idiopathic gastroparesis, restricted to
Institutions where Institutional Review
Board approval has been obtained.
FDA, 2000
Enterra Therapy CE mark Indication
“Enterra Therapy is indicated for the
treatment of patients with chronic,
intractable (drug refractory) nausea and
vomiting secondary to gastroparesis.”
August 2002
Surgery
 Laparoscopy (Laparotomy)
 3-4 Ports
 Upper right port becomes
stimulator pocket
 Length of stay: 2-3 days
 Evaluate neurostimulator
parameters before discharge
Lead Location
 Greater curvature
 Leads placed
10cm from pylorus
 Utilize measuring tape
or 10cm suture length
 Leads 1cm apart
Lead Placement
Proximal anchoring
point utilizing
winged/trumpet anchor
One centimeter
electrode length in
stomach wall
Lead Fixation
 Disc sutured to
stomach wall
 1-2 sutures
 Lead suture wire
clipped to disc
 1-2 clips
Lead Connection
 Leads connected and
tightened
 Stimulator placed
engraving up
 Extra lead length
wound behind
stimulator
Gastric Electrical Stimulation
for the Treatment of Gastroparesis: A Meta-Analysis
26 papers  13 excluded (duplicate series, case reports)
13 papers
Author
Year
Pats.
Study type
Population
Study quality
Foster
2001
25
Prosp. case series
Diab (19) Idiop (3) Post-Surg (3)
Low
Jones
2003
13
Prosp. case series
Diab (12) Idiop (1)
Low
Abell
2003
33
RCT (2 mos) 
Prosp. case series (10 mos.)
Diab (17) Idiop (16)
Moderate,
then low
Lin
2004
48
Prosp. case series
Diabetic (48)
Low
McCallum
2005
16
Prosp. case series
Post-Surgical (16)
Low
Mason
2005
29
Retrosp. case series
Diab (24) Idiop (5)
Low
Van der Voort
2005
17
Prosp. case series
Diabetic (17)
Low
De Csepel
2006
16
Prosp. case series
Diab (7) Idiop (7) other (2)
Low
Gray
2006
7
Retrosp. case series
Diab (5) Idiop (2)
Low
Gourcerol
2007
15
Prosp. case series
Diab (5) Idiop (6) Post-Surg (4)
Low
Filichia
2008
13
Retrosp. case series
Post-transplant (13)
Low
Maranki
2008
28
Prosp. case series
Diab (12) Idiop (16)
Low
Velanovich
2008
42
Prosp. case series
Diab (24) Idiop (17) Post-Surg (1)
Low
302
O’Grady G, et al. World J Surg 2009; 33:1693-1701
Gastric Electrical Stimulation
for the Treatment of Gastroparesis: A Meta-Analysis
13 papers
Total Symptom Severity Score
Requirement for Enteral or
Parenteral Nutritional Support
SF-36 Physical Composite Score
Vomiting Symptom Severity Score
SF-36 Mental Composite Score
Change in Weight (kg)
Nausea Symptom Severity Score
O’Grady G, et al. World J Surg 2009; 33:1693-1701
Gastric Electrical Stimulation
for the Treatment of Gastroparesis: A Meta-Analysis
Complications
8.3 %
(22/265 patients, 10/13 studies)
 Infection
8
 Skin erosion
6
 Pain at site
4
 Gastric perforation
2
 Device migration
1
 Volvulus
1
O’Grady G, et al. World J Surg 2009; 33:1693-1701
WAVESS*: Study Design
Multicenter double blind crossover
ON
R
Baseline
a
n
d
Implant o
m
1/2
1/2
OFF
Phase I
0
N=
33
Phase II
1
2
33
33
6
12
Months
27
24
Patients
17 diabetic
16 idiopathic
* Worldwide Anti-Vomiting Electrical Stimulation Study
WAVESS Outcomes
Vomiting frequency reduction
33, 17, 16
33, 17, 16
33, 17, 16
27, 13, 14
24, 11, 13
n
Episodes / Week
30
25
All
20
15
* *
10
Diabetic
*
Idiopathic
†
* *
*
* p < 0.05 vs.
baseline
† p < 0.05 on
vs. off
5
0
Baseline
OFF (1mth)
ON (1mth)
6 mths
12 mths
Mean
HQOL SF-36 Score Improvements (All patients)
90
80
70
60
50
40
30
20
10
0
*
*
*
*
*
*
US norms
12 mths
*
Baseline
* p < 0.005
n = 24
PF
RP
BP
GH
VT
SF
RE
MH
 77% efficacy in
idiopathic patients
 70% efficacy in
diabetic patients
Glucose Control in Diabetic
Gastroparesis Patients
HbA1c Reduction
at 6 and 12 months vs. Baseline
10.0%
Baseline 9.8%
Difference vs
Baseline
HbA1c
Baseline 9.4%
9.0%
At 6 mths
At 6 mths
At 12 mths
8.5%
Baseline 8.6%
At 12 mths
8.4%
Baseline
6 mths
12 mths
6m
12m
Forster 2003
9.8%
9.0%
8.5%
-0.8
-1.3*
Lin 2004
9.4%
8.7%
8.4%
-0.7
-1.0*
Van der Voort
2005
8.6%
6.2%
6.5%
-2.4
-2.1
* P < 0.05
 P < 0.01
8.0%
•Forster et al: Further experience with gastric stimulation to treat drug
refractory gastroparesis. Am J Surgery 2003; 186(6): 690-695
•Lin et al: Treatment of Diabetic Gastroparesis by High-Frequency
Gastric Electrical Stimulation. Diabetes Care 2004; 27(5), 1071-1076.
7.0%
At 12 mths
6.5%
At 6 mths
6.0%
Forster 2003
Lin 2004
Van der Voort
2005
•Van Der Voort et al: Gastric Electrical Stimulation Results in Improved
Metabolic Control in Diabetic Patients Suffering From Gastroparesis.
Exp Clin Endocrinol Diabetes 2005; 113:38-42
Nutritional Support
Nutritional Support Reduction
Patient Number
25
20
9
15
TPN
10
J-tubes
5
13
5*
* p < 0.05
0
Baseline
12 mths
48
28
n
Lin et al: Treatment of Diabetic Gastroparesis by High-Frequency Gastric
Electrical Stimulation. Diabetes Care 2004; 27(5), 1071-1076
Post-Surgical Gastroparesis
16 post-Surgical patients
 Nissen fundoplication (5)
 Vagotomy and pyloroplasty (3)
 Billroth I and vagotomy (2)
 Billroth II and vagotomy (2)
 Cholecystectomy (1)
 Spinal surgery (2)
 Esophagectomy with colonic
interposition (2)
Frequency Score
4.5
4
3.5
3
Baseline
2.5
6 months
2
12 months
1.5
1
0.5
0
Vomiting
Nausea
Early
Satiety
Bloating
Postprandial
Fullness
Epigastric
Pain
1-Year Average Hospitalization Days
45
40
35
Days
 63% efficacy at 12 months
 50% of patients required no
hospitalizations after implant
30
25
20
15
31
10
5
6*
0
n=
Baseline
16
12 months
16
McCallum et al, Clin J Gastro Hep 2005; Clinical Response to Gastric Electrical Stimulation in Patients With Postsurgical Gastroparesis
Gastric Electrical Stimulation
for the Treatment of Gastroparesis:
Predictive factors
 Diabetic vs Idiopathic * #
 Main symptom:
Nausea/vomiting vs Abdominal pain * #
 No narcotic use vs Narcotic use *
 No effect of gender, BMI, gastric emptying test or
HbA1c at baseline *
(n = 28)
# Musunuru S, et al. World J Surg 2010;34:1853-58 (n = 15)
* Maranki JL, et al. Dig Dis Sci 2008;53:2072-78
Gastric Electrical Stimulation
for the Treatment of Gastroparesis:
Mechanisms of action
Unknown
 Gastric emptying not consistently improved
 Gastric dysrhythmias not normalized
 Increased gastric accommodation
 Increased vagal afferent activity
 Increased thalamic activity
McCallum RW et al. Neurogastroenterol & Motil 2010;22:161-e51
Temporary Percutaneous
Gastric Electrical Stimulation
Abdominal wall
27 Pats.  22 “responders”  20 permanent GES
Andersson S et al. Digestion 2011;83:3-12
The Padua Experience
Patient Age Ætiology
Implant Outcome
Notes
1, m
40
Idiopathic
9/05 &
10/05
No changes
5/07 removal
2, f
40
CIIP
11/06
No changes
Roux-Y 
Total gastrectomy
(open)
3, f
24
Post-surgical
(Nissen)
9/06 +
Toupet
Good
4, m
33
Diabetic
1/08
Good /fair
5, f
28
Diabetic
7/08
Good
No changes x 3 mos.
6, f
35
Diabetic
9/09
Fair/good
“off”  poor
7, f
36
Diabetic
Pancreas Tx
9/09
No changes
No surgical complications observed
Gastric Electrical Stimulation
for the Treatment of Gastroparesis:
Italian preliminary experience
5
3
27 implants:
7
5
3
4
10 diabetic
 7 post-surgical
 7 idiopathic
 3 other
neuromuscular dis. 2
post-viral
1
7 male – 20 female
Medin age 42 years (24-68)
Follow-up 25 mos. (1-84)
Gastric Electrical Stimulation
for the Treatment of Gastroparesis:
Results
n=27
n=10
n=7
n=7
100%
6
80%
5
1
1
3
3
(Other n = 3)
60%
6
1
40%
16
6
TOTAL
Diabetic
3
20%
0%
Good
>30%
Fair
10 - 30%
Postsurgical
Idiopathic
No changes
<10%
score reduction
Conclusions
Gastric Electrical Stimulation
• improves:
•
•
•
•
Nausea and vomiting symptoms
Quality-of-life
Glycemic control (HbA1c)
Nutritional status
• is safe:
• Low adverse events
• No cardiac side effect
• is reversible:
• Device can be removed (laparoscopically)
Conclusions
Gastric Electrical Stimulation
• Lack of EBM studies (Grade “C” recommendation)
• Only (but 1) observational and uncontrolled studies
• Costs ( ~ USD 20,000) - Complications
• Temporary stimulation ?
• In Italy: sporadic implants and disomogeneous
patients (etiology, work up, follow up)
• Need for a National Registry (GISMAD ?)
 It may represent the only way to treat these patients