Gastroparesis and Gastric Electrical Stimulation

Dr. Mario CostantiniClinica Chirurgica 1

Università ed Azienda Ospedaliera di Padova

U.O.S. Fisiopatologia Esofago-Gastrica

A chronic disorder of gastric motility characterized by delayed gastric emptying in the absence of mechanical obstruction.

Gastroparesis

Main symptoms:• Nausea, vomiting• Early satiety, bloating • Post-prandial fullness• Abdominal pain • Weight loss, dehydration• Difficult glycaemic control

Gastroparesis: Ætiology

Idiopathic35.5%

Diabetic29.0%

Postsurgical13.0%

Miscellaneouscauses6.0%

Parkinson'sdisease

7.6%

Intestinalpseudoobstruction

4.1%

CollagenVascular disease

4.8%

(post-infective)

Kendall and McCallum. Gastroenterology 1993.Soykan et al. Dig Dis Sci 1998.

Gastroparesis: Incidence*

“Gastroparesis is an uncommon condition in the community, but is associated with a poor outcome”

Jung H-K et al. Gastroenterology 2009;136:1225-33

M = 2.5/100.000/yrs F = 9.8/100.000/yrs 5-yr survival 80%

*Olmsted County

Excessive relaxation

Abnormal duodenum

motility

Poorantro-pyloro-duodeno

synchronization

Antral hypomotility

Gastroparesis: Pathophysiology

Ad da Abell TL et al, Neurogastroenterol Motil 2006

Gastroparesis: a proposed classification

Gastroparesis: Treatment

Botulinum toxin GES

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

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 Symposiumon Gastrointestinal MotilityOxford, September 7-11, 1987

Energy

Fre

quen

cyGastric Electric Stimulation

3 bpm

12 bpm

Gastric Pacing:

Gastric Neurostimulation (Enterra) High Frequency (~ 4 x Slow Wave Freq)

Low Energy with short pulse

Low Frequency (~ Slow Wave Freq) High Energy with long pulse

? Neural sequential GES (experim. only)

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 vomiting-control 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

One centimeter electrode length in

stomach wall

Proximal anchoring point utilizing

winged/trumpet anchor

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

O’Grady G, et al. World J Surg 2009; 33:1693-1701

26 papers 13 excluded (duplicate series, case reports)

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

13 papers

302

Gastric Electrical Stimulation for the Treatment of Gastroparesis: A Meta-Analysis

O’Grady G, et al. World J Surg 2009; 33:1693-1701

Total Symptom Severity Score

SF-36 Physical Composite Score

SF-36 Mental Composite Score

Requirement for Enteral or Parenteral Nutritional Support

Change in Weight (kg)

Vomiting Symptom Severity Score

Nausea Symptom Severity Score

13 papers

Gastric Electrical Stimulation

for the Treatment of Gastroparesis: A Meta-Analysis

O’Grady G, et al. World J Surg 2009; 33:1693-1701

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

Baseline

ON

Implant

1/2

1/2

OFF

Random

1 20 Months6 12

WAVESS*: Study DesignMulticenter double blind crossover

* Worldwide Anti-Vomiting Electrical Stimulation Study

Phase I Phase II

N= 33 33 33 27 24 Patients17 diabetic16 idiopathic

HQOL SF-36 Score Improvements (All patients)

0

1020

30

4050

60

7080

90

PF RP BP GH VT SF RE MH

Me

an

US norms

12 mths

Baseline

*

** * *

*

*

* p < 0.005

n = 24

WAVESS OutcomesVomiting frequency reduction

0

5

10

15

20

25

30

Baseline OFF (1mth) ON (1mth) 6 mths 12 mths

Ep

iso

de

s /

We

ek

All

Diabetic

Idiopathic†

* **

* * *

* p < 0.05 vs. baseline† p < 0.05 on vs. off

33, 17, 16 33, 17, 16 33, 17, 16 27, 13, 14 24, 11, 13 n

77% efficacy in idiopathic patients

70% efficacy in diabetic patients

Glucose Control in Diabetic Gastroparesis Patients

Difference vs Baseline

HbA1c 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

•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.

•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

* P < 0.05 P < 0.01

Baseline 8.6%

Baseline 9.4%

Baseline 9.8%

At 6 mths

At 12 mths8.5%

At 12 mths8.4%

At 12 mths6.5%

At 6 mths

At 6 mths

HbA1c Reduction at 6 and 12 months vs. Baseline

Lin et al: Treatment of Diabetic Gastroparesis by High-Frequency Gastric Electrical Stimulation. Diabetes Care 2004; 27(5), 1071-1076

Nutritional Support

Nutritional Support Reduction

13

9

5*0

5

10

15

20

25

Baseline 12 mths

Pat

ien

t N

um

ber

TPN

J-tubes

48 28 n

* p < 0.05

McCallum et al, Clin J Gastro Hep 2005; Clinical Response to Gastric Electrical Stimulation in Patients With Postsurgical Gastroparesis

Post-Surgical Gastroparesis16 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)

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

Vomiting Nausea EarlySatiety

Bloating PostprandialFullness

EpigastricPain

Baseline

6 months

12 months

Frequency Score

31

6*0

5

10

15

20

25

30

35

40

45

Baseline 12 months

Day

s

n= 16 16

1-Year Average Hospitalization Days

63% efficacy at 12 months 50% of patients required no

hospitalizations after implant

Gastric Electrical Stimulation for the Treatment of Gastroparesis:

Predictive factors

* Maranki JL, et al. Dig Dis Sci 2008;53:2072-78 (n = 28)

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 *

# Musunuru S, et al. World J Surg 2010;34:1853-58 (n = 15)

Gastric Electrical Stimulation for the Treatment of Gastroparesis:

Mechanisms of action

McCallum RW et al. Neurogastroenterol & Motil 2010;22:161-e51

Gastric emptying not consistently improved

Gastric dysrhythmias not normalized

Increased gastric accommodation

Increased vagal afferent activity

Increased thalamic activity

Unknown

Temporary Percutaneous Gastric Electrical Stimulation

Andersson S et al. Digestion 2011;83:3-12

27 Pats. 22 “responders” 20 permanent GES

Abdominal wall

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 (open)

No changes Roux-Y Total gastrectomy

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 7

4

3

3

5

27 implants:

10 diabetic 7 post-surgical 7 idiopathic 3 other

neuromuscular dis. 2post-viral 1

7 male – 20 femaleMedin age 42 years (24-68)Follow-up 25 mos. (1-84)

Gastric Electrical Stimulation for the Treatment of Gastroparesis:

Results

0%

20%

40%

60%

80%

100%

TOTAL Diabetic Post-surgical

Idiopathic

Good Fair No changes

n=10 n=7 n=7

6

6

3

13

1

1

3

n=27

>30% score reduction10 - 30% <10%

16

6

5(Other n = 3)

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