Improving Outcomes in Hereditary Gastrointestinal - PowerPoint Presentation

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Improving Outcomes in Hereditary Gastrointestinal Polyposis Syndromes in the Mediterranean Region

Thomas M Attard MD FAAP FACG

Associate Professor, Pediatrics, Gastroenterology, University of Malta, Malta.

Consultant Gastroenterologist Children’s Mercy Hospital, Kansas MO, USA.

Content:

Overview

: Hereditary Gastrointestinal

Polyposis

Syndromes in Childhood and Adolescence

Polyposis

Burden

in Children in the Mediterranean Basin

Obstacles

for Management of Childhood

Polyposis

Syndromes

Pilot Project to

Improve Outcomes

in Children with Hereditary Gastrointestinal

Polyposis

Syndromes in the

Medicel

Forum

Genotypic and Phenotypic Heterogeneity in Hereditary Colorectal Cancer Syndromes.

AC-I, Amsterdam Criteria I

MMR, mismatch repairFAP, familial adenomatous polyposis AFAP, attenuated familial adenomatous polyposis; HBCC, hereditary breast and colorectal cancerPJS, Peutz–Jeghers syndromeFJP, familial juvenile polyposisCD, Cowden’s disease BRRS, Bannayan-Ruvalcaba–Riley syndrome.

Lynch et al. 

Cancer

 2004;100:53–64

Hereditary Gastrointestinal Cancer Syndromes in Childhood

~ 5% of individuals with colorectal cancer will have a recognizable hereditary gastrointestinal cancer predisposing syndrome

Polyposis syndromes frequently present in the first two decades of life with intestinal / extraintestinal manifestations

Management of hereditary polyposis syndromes includes genetic testing, screening and in many cases surgery during childhood / adolescence

Hereditary Cancer Syndromes that present in childhood / adolescence

Familial Adenomatous Polyposis (FAP 1:8,000)Peutz-Jeghers Syndrome (PJS, 1:15,000)Juvenile Polyposis Syndrome (JPS, 1:35 – 50,000)

HNPCC

PTEN Hamartoma Syndrome (Cowden’s Syndrome, BRRS)

Hereditary Mixed Polyposis Syndrome HMPS

MEN IIB

MYH-Associated Polyposis (MAP)

Polyposis: Defining the syndrome

(age)

Polyp

Histology

Number

Distribution

Associated Clinical features / findings

Family History

Familial Adenomatous PolyposisPeutz-Jeghers SyndromeJuvenile Polyposis SyndromePTEN-Hamartoma SyndromePolyp distributionColorectal, most will develop gastric, small intestinalPanintestinal (primarily small intestinal ) Colorectal, gastric Colorectal Polyp histologyPanintestinal Adenomatous and(Gastric) fundic gland polypsHamartomatous polyps¥ψ

Ψ a significant proportion of syndromic juvenile polyps will harbor areas of adenomatous transformation ¥ Peutz-Jeghers polyps have characteristic - prominent smooth muscle component in the submucosa

Hereditary Cancer Syndromes – polyps by anatomic localization & histology

modified from Lynch HT, Attard TM, Gastroent. & Hepatology 2005

Hereditary Gastrointestinal Cancer Syndromes: Management

FAP

JP

PJS

PTEN – HS

Before age 10

α Fetoprotein and abdominal ultrasound annually from birth to age 10years

10 – 20 years

Annual colonoscopy from age 10-12years

Colectomy when dx established

Annual upper endoscopy*, as soon as colonic polyps appear or 15 years in AFAP

†

(no current consensus on thyroid screening but clinical examination and ultrasound of suspicious lesions needs to be part routine HCM visits)

Colonoscopy with polypectomy, annually if not all polyps removed, otherwise every 3 years from age 15 years

Upper endoscopy every 3 – 5 years from age 15 years; repeated annually if the patient is not polyp free

Annual clinical exam and baseline ultrasound of the thyroid from adolescence

Every 2-3 years, Upper endoscopy (EGD / EGD and enteroscopy), SBFT (? role of capsule endoscopy)

Annual testicular exam, ultrasound if clinically suspected

Every 2 year colonoscopy, upper endoscopy

SBFT (? enteroscopy) from age 15 years

Monthly breast self exam from age 18 years

Baseline thyroid US at age 18 years, annual neck exam

Hereditary colorectal Cancer Syndromes in the Mediterranean Basin

Population specific data is lacking for most countriesInSIGHT membership incl. Italy, Spain*, Israel, Serbia* Multiple observations on unique disease manifestations and natural historyNo significant participation in pediatric chemopreventive trials

*Adult Gastroenterology Programs

Population

Children

0-14

FAP

(

1:8,000)

FJP

(

1:50,000)

PJS

(

1:60,000)

ALBANIA

3.639.453

714.250

89

14

12

ALGERIA

34.178.188

8.696.320

1,087

173

144

BOSNIA

3.842.566

668.063

83

13

11

CROATIA

4.489.409

698.458

87

13

11

EGYPT

78.866.635

26.020.307

3,252

520

433

FRANCE

64.057.792

11.968.654

1,496

239

199

GREECE

10.737.428

1.530.992

191

30

25

ISRAEL

7.233.701

2.015.859

251

40

33

ITALY

58.126.212

7.870.226

984

157

131

LEBANON

4.017.095

1.034.885

129

21

17

MALTA

403.532

65.306

8

1

1

MOROCCO

31.285.174

8.967.576

1,120

179

149

SLOVENIA

2.046.976

287.275

35

4

5

SPAIN

40.525.002

5.864.419

733

117

98

TUNISIA

10.486.339

2.377.034

297

47

40

TURKEY

72.561.312

18.859.334

2,357

377

314

455.668.897

97.930.679

12,241

1,958

1,632

Obstacles for Management of Childhood Polyposis Syndromes

individually

these are rare conditions → very different, complex management algorithms:

Genetic testing / Endoscopy / Surgery/ Chemoprevention / Surveillance

need for

team

approach:

Gastroenterology / Surgery / Adult GI services / Genetic Counseling / Psychology

changing / unclear

management algorithms

access to research protocols / chemoprevention

Obstacles for Management

Recognizing

symptoms and family history at risk.

Access

and timely

referral

for comprehensive services

Long term

surveillance planning

and follow-up including family screening

Lack of medical guidelines / discrepancy in provider competence

Hereditary Gastrointestinal Polyposis Syndromes: Healthcare Provider Training

Pediatric residents overall knowledge of gastrointestinal syndromes; proportion of correct answers by syndrome: pathogenesis and clinical features

Variation in percent

correct response rate by level of training

FAP

PJS

JP

PTEN - HS

Attard TM et. al

submitted

J Cancer Edu. 2008

Hereditary Colorectal Cancer Registries

National, institutional, regional entity that serves as repository of expertise and academic interest on the group of diseasesDemonstrable patient benefit from belonging to a registry → earlier recognition and treatmentRegistries as the only resource able to liase and effect drug (egs. chemoprevention) trials

Järvinen

Hj

et al. Gastroenterology. 2000 May;118(5):829-34.

Informational / Educational Cooperation

Coordination of Epidemiologic / Observational Studies

Registry Based Family based recommendations

Registry Based prospective

Chemopreventive

Studies

STEPWISE MODEL OF THE DEVELOPMENT OF A REGIONAL HEREDITARY GASTROINTESTINAL CANCER REGISTRY

Step 1: Informational / Educational Cooperation

Initial development of a network for individual case consultation

Commitment toward timely, comprehensive – structured consultation

Academic network to pool, study, publish interesting cases

Identification – development of regional / national resources toward Step 2.

Step 1: Informational / Educational Cooperation

Multidisciplinary team:

pediatric gastroenterologists + trainee (fellow) based in

UoM

(Malta, EU),

Children’s Mercy

Kansas City (MO, USA)

Genetic counselor

Psychologist

e-mail based structured consultation with management plan

De-identified clinical outline retained in dedicated database / Children’s Mercy Hospital, Kansas City (pending IRB approval)

Step 1: Informational / Educational Cooperation

structured consultation:

Summary of salient clinical, endoscopic, +/- genetic testing findings

Outline of differential

Dx

, current diagnostic testing recommendations

Outline long term management incl. surveillance planning

Preparing for Step 2 and beyond

How did step 1 go?

Is there a perceived need for more structured resources?

Are communication channels adequate?

Does the model work?

Coordinating epidemiologic and observational studies in regional heterogeneity of disease

Questions

Acknowledgements