Richard I. Rothstein, MDRichard I. Rothstein, MDInterim Chair, Department of MedicineInterim Chair, Department of Medicine

Chief, Section of Gastroenterology and HepatologyChief, Section of Gastroenterology and HepatologyProfessor of Medicine and of SurgeryProfessor of Medicine and of Surgery

Dartmouth Medical SchoolDartmouth Medical SchoolHanover, NHHanover, NH

Medical Device Therapy for ObesityMedical Device Therapy for Obesity and Metabolic Disease and Metabolic Disease –– The Current LandscapeThe Current Landscape

Focus on Endoscopic Therapies Focus on Endoscopic Therapies for Primary Treatmentfor Primary Treatment

Devices will be mentioned to illustrate mechanismsNo endorsement intended for any devices or mechanismsNot all devices will be reviewed

1999

Obesity Trends (BMI 30) Among U.S. Adults 1990, 1999, 2008

2008

1990

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

CDC.GOV

The Environment: Portion SizeThe Environment: Portion Size

Non-surgical Treatment for Obesity

Diet and exercise

(5 - 7% weight loss)

Behavioral therapy plus diet & exercise (10%)

Pharmacotherapy• modest efficacy• weight regain after stopping meds• adverse effects• uncertain long-term safety

After Stylopoulos, Aguirre GIE 2009; 70:1167-75

Vertical Banded Vertical Banded Gastroplasty Gastroplasty

(VBG)(VBG)

Surgery for Surgery for ObesityObesity

Restrictive and Restrictive and MalabsorptiveMalabsorptive

ProceduresProcedures

Adjustable Adjustable Gastric Band Gastric Band

(AGB)(AGB)

Sleeve Sleeve Gastrectomy Gastrectomy

(SG)(SG)

Biliopancreatic Biliopancreatic diversion (BPD)diversion (BPD)

Duodenal Switch Duodenal Switch (DS)(DS)

RouxRoux--enen--Y Y Gastric Bypass Gastric Bypass

(RYGB)(RYGB)

Surgery for Surgery for ObesityObesity

Restrictive Restrictive ProceduresProcedures Gastric Gastric

Imbrication Imbrication (GI)(GI)

Weight Change after Surgery

Sjostrom L et al. N Engl J Med 2007;357:741-752

Rates of Remission of Diabetes

AdjustableGastric Banding

Roux-en-YGastric Bypass

BiliopancreaticDiversion

98%38% 84%Buchwald H., JAMA 2004

RYGB: A Complex of 5 Operations

CONFIDENTIAL

Gastric Bypass: Five Operations

1. Isolation of gastric cardia

CONFIDENTIAL

Gastric Bypass: Five Operations

2. Exclusion of distal stomach

CONFIDENTIAL

Gastric Bypass: Five Operations

3. Exclusion of duodenum and proximal jejunum

CONFIDENTIAL

Gastric Bypass: Five Operations

4. Exposure of distal jejunum to undigested nutrients

CONFIDENTIAL

Gastric Bypass: Five Operations

5. Partial vagotomy

CONFIDENTIAL

Effects of Surgery on Diabetes

Potential Mechanisms

Weight loss

Decreased nutrient intake

Changes in GI physiology or signaling

Weight and diabetes control after RYGBWeight and diabetes control after RYGB

Mason E. Obes Surg 2005; 15: 459Mason E. Obes Surg 2005; 15: 459--6161Rubino F et al. Ann Surg 2006; 244: 741Rubino F et al. Ann Surg 2006; 244: 741--99

«« DistalDistal

mechanism mechanism ––

Hindgut theoryHindgut theory

»»

Nutrients – fat, carbs, protein

L Cells

GLP-1, PYY, Oxyntomodulin

Effects on glucose homeostasis (incretins)

- Insulin secretion- insulin sensing

and sensitivity- Beta cell mass - Glucagon secretion

Effects on appetite and weight

- Gastric emptying- Appetite- Acid secretion

Hindgut theory – increased nutrients

to distal gut

«« ProximalProximal

mechanism mechanism ––

Foregut theoryForegut theory

»»

Weight and diabetes control after RYGBWeight and diabetes control after RYGB

Ghrelin

Eating

Nutrients to the foregut

“Anti-incretins”

Effects on appetite and weight

- Gastric emptying- Appetite- Acid secretion

Effects on glucose homeostasis

- Insulin secretion- insulin sensing

and sensitivity- Beta cell mass

Foregut theory – bypass duodenal nutrient passage

Rubino , F. Diabetes Care Feb 2008 Vol. 31 No. 2; S290-S296Spector, D, Shikora S. Int J Clin Pract. Feb 2010, 62 (Suppl. 66) 53-58

Endoscopic PossibilitiesEndoscopic Possibilities

•• Bypass proximal duodenum and/or stomachBypass proximal duodenum and/or stomach

•• Compartmentalize stomach/restrict volumeCompartmentalize stomach/restrict volume

•• Delay stomach emptyingDelay stomach emptying

•• Mimic effects of surgery on weight and DMMimic effects of surgery on weight and DM

EndoBarrier EndoBarrier

Alteration of gastric outlet

Food goes down liner – duodenal exclusion

Digestive juices go around liner

EndoBarrier SystemEndoBarrier System

Implant

Co-axial Delivery CatheterRetrieval System

•• AnchorAnchor•• NitinolNitinol•• Large proximal openingLarge proximal opening•• Barbs in each directionBarbs in each direction•• Retrieval drawstringsRetrieval drawstrings

•• SleeveSleeve•• Impermeable fluoropolymerImpermeable fluoropolymer•• 61 cm (2 ft) length61 cm (2 ft) length•• Radiopaque markersRadiopaque markers

ValenTxA b s t r a c t :

The present invention provides devices and methods for attachment of an implanted device, such as an artificial stoma device (202), a gastrointestinal sleeve device (200, 258, 278, 428, 458, 560) or an attachment cuff (214, 550, 570), within a patient's digestive tract for treatment of obesity. Special surgical fasteners (100, 130, 222, 240, 250, 276, 530, 542) provide a lasting and durable attachment to the gastrointestinal tissue without causing excessive pressure that could result in tissue erosion and detachment of the implanted device. Fastener delivery devices (150) that facilitate peroral placement and deployment of fasteners (100, 130, 222, 240, 250, 276, 530, 542) and secondary devices are also provided. Also described are implantable devices and attachment means (230, 234) that avoid causing excessive pressure within the tissue by having compliance that is compatible with the gastrointestinal tissues where it is attached.

VALENTX, INC. [US/US]; 200 Homedale Rd., Hopkins, MN 55343 (US) (All Except US). KAGAN, Jonathan [US/US]; 200 Homedale Rd., Hopkins, MN 55343 (US) (US Only). DANN, Mitchell [US/US]; 4020 West Lake Creek Dr., Wilson, WY 83014 (US) (US Only). FLUET, Greg [US/US]; 620 1/2 East Hall St., Jackson, WY 83002 (US) (US Only). IKRAMUDDIN, Sayeed [US/US]; Rm. 304, 410 E. River Rd., Minneapolis, MN 55455 (US) (US Only). SWAIN, Paul [--/GB]; 41 Willow Rd., London NW3 1TN (GB) (US Only). THOMAS, Richard [US/US]; 556 Trapelo Rd., Belmont, MA 02478 (US) (US Only). VON HOFFMANN, Gerard [US/US]; 3 Via Presea, Trabuco Canyon, CA 92679 (US) (US Only). WILMORE, Mary, Lynn [US/US]; P.O. Box 516, Victor, ID 83445 (US) (US Only).

Valentx Endo Bypass SleeveValentx Endo Bypass Sleeve

Endo Bypass SleeveRYGB

Techniques for Reduction of Techniques for Reduction of Gastric VolumeGastric Volume

•• Balloons and bezoarsBalloons and bezoars

•• SewingSewing

•• StaplingStapling

•• ImplantsImplants

Balloons and Devices Balloons and Devices to Fill Gastric Spaceto Fill Gastric Space

•

ReShape DuoReShape Duo Delivery SystemDelivery System

ReShape

ReShapeReShape

Spatz BalloonSpatz BalloonAdjustable

Prevents migration of

balloon

Visible on imaging

Retrievable

Full Sense Device

Full Sense Device

Some Sewing ToolsSome Sewing Tools

NDONDO

EndoCinchEndoCinch

GG--ProxProx

TASTAS

Eagle ClawEagle Claw

SpidermanSpiderman

SafeStitchSafeStitch

StomaPhyxStomaPhyx

OverStitchOverStitch

Gastric restriction and Gastric restriction and CompartmentalizationCompartmentalization

EndoCinch concept

(Swain 2002)

EndoCinch attempt

SafeStitchSafeStitch

Charles Filipi, 2007

The TOGa System (Satiety)The TOGa System (Satiety)TOGa Sleeve StaplerTOGa Sleeve Stapler

•• 54F (18mm) diameter54F (18mm) diameter•• Designed to use an 8.6 mm OD endoscopeDesigned to use an 8.6 mm OD endoscope•• Direct visualizationDirect visualization•• Creates stapled sleeve along lesser Creates stapled sleeve along lesser curvecurve

TOGa Restrictor • 45F (15mm) diameter• Delivered alongside endoscope• Creates stapled “pleats”

at distal end of sleeve, restricting outflow

Sleeve Stapler inserted over guidewire, positioned on lesser

curveSail / septum deployed to

spread tissueendoscopic view –

Sail / septum

vacuum applied to capture anterior and

posterior tissuestapler jaws closed and

fired

Result is stapled sleeve. Repeat to create longer sleeve

, then use restrictor

BaroSense Transoral Platform

Creates a Small proximal Pouch distal to the GE

junction

Full thickness plication anchor points

Food Outlet

•TERIS (Transoral Endoscopic Restrictive Implant System)

Hour Glass Procedure

Alteration of Gastric MotilityAlteration of Gastric Motility

•• BOTOXBOTOX

•• NeuromodulationNeuromodulation

•• Pyloroduodenal obstructing devicesPyloroduodenal obstructing devices

BOTOX InjectionBOTOX Injection

•• In animal studies In animal studies -- delayed gastric emptying delayed gastric emptying

from antral injectionsfrom antral injections

•• Human studies showed variable results for Human studies showed variable results for antral injectionsantral injections

•• Adding fundic injection in RCT:Adding fundic injection in RCT:wt loss 11 vs 5 kg; p<0.001wt loss 11 vs 5 kg; p<0.001BMI reduction 4 vs 2; p<0.001BMI reduction 4 vs 2; p<0.001Delayed stomach emptyingDelayed stomach emptying

Foschi D, et al. Int J Obes 2007; 31: 707-12

Electrical Neuro-modulation• EnteroMedics• Leptos Biomedical• IntraPace• MetaCure• Medtronic (Transneuronix)

Current surgical placement could evolve to endoscopic

Mechanisms:increase satietyreduce appetite and food intakealter neuro-endocrine responsesaffect gastric and intestinal motility

Transpyloric Shuttle TPS™Intermittent sealing of pylorus in concert

with peristalsis may:

• Delay gastric emptying• Induce early satiety

TPS™ within delivery sleeve TPS™ prior to locking

Locked TPS™

Entirely endoscopic … Self-placing… Non-anchored…Multi-year dwell

TPS™ after unlocking

SatiSphereSatiSphere

Endocore Pyloric ValveEndocore Pyloric Valve

Aspire BariatricsAspire Bariatrics

•• Divert ingested nutrient flow out of the Divert ingested nutrient flow out of the bodybody

•• BariAssist GBariAssist G--ShuntShunt

Future DevelopmentsFuture Developments

•• NOTESNOTES

•• CapsulesCapsules

Role of NOTES

• Compartmentalization

• Gastrojejunostomy

• Sleeve Gastrectomy

“Human transvaginal sleeve gastrectomy: initial experience”

Ramos AC, Zundel N, Neto MG, Maalouf MSurg Obes Relat Dis. 2008 Sep-Oct;4(5):660-3

• The endoscope advanced into the peritoneal cavity

• A loop of jejunum identified and pulled into the stomach

Gastrojejunostomy

The loop of jejunum is secured with sutures to the stomach

Incision made into the jejunal loop using a needle-knife

The open ends of the incision are secured to the gastric incision with a second line of sutures completing the gastrojejunostomy

Bariatrion Gastric Bypass Device Currently Lap-Endo Hybrid Approach

Schurr MO, HO C, Rieber F et al. Min Invas Surg 2009; 18:273-9

Capsular Intragastric BalloonCapsular Intragastric Balloon

(a) Deflated balloon ) Inflated balloon

Endolumenal Treatment for ObesityEndolumenal Treatment for Obesity

Less Expensive Less Effective

More Expensive More Effective

Surgery

EndoscopicEndoscopicProceduresProcedures

Medication

Diet and Exercise

We anticipate the development of We anticipate the development of endoscopic treatments that will help endoscopic treatments that will help

manage our most recent human manage our most recent human evolutionevolution……..