1. GASTROPARESIS
September 12, 2015
SGNA

2. GASTROPARESIS
Definition: a disorder in which patients exhibit signs and symptoms of delayed gastric emptying without an anatomic cause (obstructing ulcer, inflammatory stenosis, malignancy)

3. Causes of Gastroparesis
Systemic disorder: diabetes mellitus, muscular dystrophy, amyloidosis, scleroderma
Idiopathic: post-viral
Post-surgical: vagotomy, fundoplication

4. Symptoms of Gastroparesis
Nausea
Vomiting
Abdominal pain
Early satiety
Heartburn
Dysphagia

11. CASE NM-1 30 YO female transferred to UH with nausea/vomiting
“Flu” symptoms 4 mo prior
Hospitalized 2x in Ft Wayne:GB US, Abd CT, HIDA, EGD all negative
Serology: mono, hep B, ANA: negative
Enteroclysis: “mucosal thickening in jejunum”

12. CASE NM- 2 Exploratory lap: neg; feeding J tube, appy
Small intestinal Bx: neg
Transfer to UH
PMH: facial herpes zoster 2 yr PTA
Physical Exam: normal; normal liver and spleen

13. CASE NM-3 Lab: ALT 139, AST 36, GGTP 99 CMV (IgM) Pos 1:80 titer
GE scan: borderline slow gastric emptying
ID consult: transient viral illness

14. CASE NM-4 Small intestinal manometry: abnormal MMC
EGG: abnormal: no increase in post-prandial 3 cpm activity
EGD: normal
Histology: acute/chronic inflammation
Antral Bx viral culture: CMV

15. Case NM-5 Patient eating, discharged home; N/V return
Treatment with E-mycin, Reglan ineffective
EGD (6 mo after onset of Sx): NL; antral Bx culture: CMV
9 mo after onset of Sx: Rx with leuprolide

16. CASE NM- 6 Good response to leuprolide: eating well, no N/V
MONTH 13: leuprolide stopped
Month 17: hosp at IU with N/V, abd pain; surgical J tube, decompression g tube
MONTH 30: Mayo Clinic: delayed gastric emptying, delayed colon transit
Transient response to cisapride

17. CASE NM- 7
Hosp IUMC with abdominal pain; colonoscopy shows ulcers: Bx pos CMV culture
Rx with gancyclovir: colon ulcers heal, pain improves, vomiting and tube feeding continue
Rx with domperidone: no response
Rx with leuprolide: no improvement

18. CASE NM-8
Gastric pacemaker implanted 8 yr after onset of Sx. Patient does well over next two years; J tube and G tube removed two years later. Patient require high current output from pacemaker and requires replacement every two years.

19. FACTORS REGULATING GI MOTILITY
Intrinsic properties of visceral smooth muscle
Intrinsic and extrinsic nervous system
Gastrointestinal hormones

20. MOTOR FUNCTIONS OF THE STOMACH
Accomodation
Mixing
Emptying
Sensation

21. ASSESSMENT OF GASTRIC EMPTYING
Nuclear scan
Endoscopy
Ultrasound
“SMART” pill

23. PROBLEMS WITH NUCLEAR SCINTIGRAPHY
Need standardized meal
Liquids empty faster than solids
Proteins and carbohydrates empty faster than fats
Digestible solids empty faster than digestible solids

44. ASSESSMENT OF GASTRIC ACCOMODATION
SPECT scan
Barostat

45. ASSESSMENT OF GASTRIC SENSATION
Satiety test

46. TREATMENT OF GASTROPARESIS
Diet: low fat, low residue; supplements
Medications: avoid anticholinergics, narcotics
Promotility agents
Antiemetics
GJ tube feeding
TPN
Gastric electrical stimulation

47. PROMOTILITY AGENTS Reglan: FDA advisory: 3 months
E-mycin: suspension expensive
Domperidone: not FDA approved, insurance coverage
Cisapride: drug interaction

48. ANTIEMETICS Phenergan: tablets, suspension, suppository, cream
Zofran/Kytril: ODT, pill, patch
Marinol
Benadryl
Scopolamine
Ginger
Acupuncture

49. TUBE FEEDING Radiologic GJ tube Endoscopic GJ tube Surgical J tube
Venting gastrostomy optional
Temporary: gastric function may return after several months of enteral nutrition

50. TPN Temporary measure Enteral feeding effective in most patients
Infection
Thrombosis

52. GASTRIC ELECTRICAL STIMULATION
How does it work?
Effective for nausea and vomiting
Does not “pace” stomach
May, or may not, accelerate gastric emptying
Lag phase: may take 6 months to work

53. GES SURGERY Laparoscopy Risk of infection Electrode migration
Warning: No MRI
FDA approved: not experimental
Insurance issues

54. RATIONALE FOR GASTRIC ELECTRICAL STIMULATION
Cardiac pacing effective for some dysrhythmic disorders
Stomach also has a “pacemaker” rhythm
Gastric “dysrhythmias” identified
Smooth muscle “pacemakers” identified in small intestine, colon, ureter, bladder, uterus

55. Background
ECA: electrical control activity; 3 cpm in humans, 5 cpm in dogs
ERA: electrical response activity, ie gastric contractions
GES entrains electrical activity in man and dogs
Unclear whether GES can generate muscular contractions

59. Gastric Electrical Stimulation for Medically Refractory Gastroparesis
GASTROENTEROLOGY 2003; 125:
Gastric Electrical Stimulation for Medically Refractory Gastroparesis
THOMAS ABELL, RICHARD McCALLUM, MICHAEL HOCKING, KENNETH KOCH, HASSE ABRAHAMSSON, ISABELLE LEBLANC, GREGER LINDBERG, JAN KONTUREK, THOMAS NOWAK, EAMMON M. M. QUIGLEY, GERVAIS TOUGAS, AND WARREN STARKEBAUM. University of Mississippi, Jackson, Mississippi; University of Kansas, Kansas City, Kansas; University of Florida, Gainesville, Florida; Penn State University, Hershey, Pennsylvania; University of Goteborg, Sweden; Hospital Charles Nicolle, Rouen, France; Karolinska Institute, Stockholm, Sweden; Elbe Kliniken Stade, Stade, Germany; St.Vincent Hospital, Indianapolis, Indiana; National University of Ireland, Cork, Ireland; McMaster University, Hamilton, Ontario, Canada; and Medtronic, Inc., Minneapois, Minnesota.

62. EFFICACY OF GES Diabetic gastroparesis: 80-90% Idiopathic: 70%
Postoperative: 60%

66. Thomas V. Nowak1, Gary Hutchins2, Lyn Ring1 and Kativa Leal1
EFFECT OF GASTRIC STIMULATION ON CEREBRAL BLOOD FLOW IN PATIENTS WITH GASTROPARESIS
Thomas V. Nowak1, Gary Hutchins2,
Joel Hammond1, Yang Wang2,
Lyn Ring1 and Kativa Leal1
1Department of Medicine, St.Vincent Hospital, Indianapolis, Indiana, USA
and
2 Department of Radiology, Indiana University Medical Center,
Indianapolis, Indiana, USA.

67. PURPOSE
To determine whether GES produces changes in
regional cerebral blood flow using positron emission tomography (PET).

72. CONCLUSIONS
Gastric electrical stimulation of the stomach in gastroparetic patients produces significant alterations
in cerebral blood flow.
Gastric electrical stimulation both increases and decreases blood flow to respective regions of the brain.
Central nervous system mechanisms during gastric electrical stimulation may be responsible for the relief
of nausea and vomiting in these patients.

73. GES: Issues Remain Mechanism: How does it work?
Which patients are best candidates for GES?
Optimal stimulus parameters
How to monitor treatment
Electrode placement: serosa, mucosa, fundus, vagus nerve?
What about symptomatic patients with normal or fast gastric emptying?

74. GES Collaboration IU Gastroenterology/Hepatology Purdue Biomedical/Electrical Engineering
VNS approved since 1997 for drug-resistant epilepsy (2005 for drug-resistant MDD).
19 Aug 2013

76. Experimental Setup Record VN Response Record SM Response [1] [1]
[2]
[1]
Diaphragm
Record VN Response
Stimulate Antrum
Record SM Response
[1]
[1] M.P. Ward et al. (In preparation ). “A flexible closed-loop platform for rapid biofeedback control and personalization of electroceutical therapies.”
[2] Richard M. Peek, Jr & Martin J. Blaser. (2002). “Helicobacter pylori and gastrointestinal tract adenocarcinomas.” Nature Reviews Cancer 2, pp

78. Cutaneous Recordings of Vagal Afferents

79. Current and Future Directions
Finalize research objectives and submit proposals for funding
Biomarker discovery
Directly measure and characterize smooth muscle response
Multi-electrode recordings (ECoG electrodes)
fMRI studies
Purdue: Rodents
IUSM: GES patients
Investigate VNS as an alternative to GES