slide1 n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Presented at: Neuroendocrine Cancer Regional Conference 2011 Sponsor: The Ohio State Medical Center, CCC-The James Col PowerPoint Presentation
Download Presentation
Presented at: Neuroendocrine Cancer Regional Conference 2011 Sponsor: The Ohio State Medical Center, CCC-The James Col

Loading in 2 Seconds...

play fullscreen
1 / 32

Presented at: Neuroendocrine Cancer Regional Conference 2011 Sponsor: The Ohio State Medical Center, CCC-The James Col - PowerPoint PPT Presentation


  • 85 Views
  • Uploaded on

Overview of Carcinoid Tumors. Presented at: Neuroendocrine Cancer Regional Conference 2011 Sponsor: The Ohio State Medical Center, CCC-The James Columbus, Ohio December 3, 2011. Presenter Thomas M. O’Dorisio, M.D. Professor of Medicine Director Carcinoid & Neuroendocrine Tumor Program.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Presented at: Neuroendocrine Cancer Regional Conference 2011 Sponsor: The Ohio State Medical Center, CCC-The James Col' - elmer


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
slide1

Overview of Carcinoid Tumors

Presented at:

Neuroendocrine Cancer Regional Conference 2011

Sponsor: The Ohio State Medical Center, CCC-The James

Columbus, Ohio

December 3, 2011

Presenter

Thomas M. O’Dorisio, M.D.

Professor of Medicine

Director

Carcinoid & Neuroendocrine Tumor Program

slide2

Evolution of Neuroendocrine

Medical Therapy

Dawn Wray

Teresa Ruggle

© University of Iowa

slide5

Siegfried Oberndorfer

Coined the term

‘karzinoide’

Frank Z. Pathol

1907;1:425

Modified from IM Modlin & K Oberg, 2007.

slide6

Clinical Era

Zollinger-Ellison Syndrome

1955

R.M. Zollinger

E.H. Ellison

Gastrinoma

slide7

Era of Gut Peptide

Chemistry

R.A. Gregory

H.J. Tracy

V. Mutt

J.E. Jorpes

slide9

SMS 201-995: A Very Potent and Selective Octapeptide Analogue of Somatostatin with Prolonged Action

W. Bauer, U. Briner, W. Doepfner, R. Haller, R. Huguenin, P. Marbach, T.J. Petcher & J. Pless

Life Sciences. 31(11);113-1140: 1982.

slide10

Enrico Solcia

University of Pavia, Pavia, Italy

Histological Typing of Endocrine Tumors (WHO) Springer 2000; pp1-160

neuroendocrine tumors of the gastrointestinal tract annual incidence 38 4 cases per million
Neuroendocrine Tumors of the Gastrointestinal Tract : Annual Incidence 38.4 cases per million*

%

Vinik, A.I., Perry, R.R. Neoplasms of the Gastroenteropancreatic Endocrine System, Chapt 103.

In: Cancer Medicine, Fourth ed. Vol. 1.

Edited by Holland JF, et alBaltimore: Williams & Wilkins, pg. 1605-1641, 1997.

Modified by T.M.O. to include Lung Carcinoid

* Annals of Surgery 2004. Vol 240 (1): 117-122

carcinoid natural history
Carcinoid: Natural History

Diagnosis

Irritable Bowel

Correct

Diagnosis

Death

Vague abdominal symptoms

Diarrhea

Flushing

Metastases

Primary Tumor Growth

0 2 4 6 8 10 12 14 16 18 20

Years

Vinik, Moattari Amer J Dig Dis, Sci , 1989;34:14-27.

slide15

TTP = 3-5 yrs

TTP = 3-4 yrs

TTP = 7 mo

TTP =

4-5 yrs

iowa neuroendocrine database ined
IOWA NEUROENDOCRINE DATABASE ( INED )
  • Database begun in 1996 with Denise Soble, RN, E.W. Martin, Jr., M.D., and TMO at Ohio State.
  • Captures Phenotypic Patient Information
        • 80 Fields of Data
          • Visits, diagnoses, pathology, radiology, outcomes, survival
      • Captures Genotype Patient data
        • FISH, Exome sequencing, GPCR expression

https//net.eng.uiowa/mode/add/diagnosis2

Username is “user”

Password is “quest”

problems with neuroendocrine tumor therapeutic intervention s
Problems with Neuroendocrine Tumor Therapeutic Intervention(s)
  • Decisions made primarily based on the “Gold Standard” CT, MR, Ultrasound demonstration of disease progression
  • Both “symptomatic” and “asymptomatic” changes are subjective and clinical signs, like art, are often in the eye of the beholder
  • Tumor-secreting amines and neuropeptides may be episodic initially & sustained later with tumor progression
  • In U.S., calibrations between neuropeptide plasma markers are sorely lacking between commercial labs
functioning neuroendocrine tumors
Functioning Neuroendocrine Tumors

Basic Principles:

  • Syndromes and symptoms (e.g., hypoglycemia) are due to sudden or sustained elevations of circulating amines (e.g. serotonin, catecholamine, or neuropeptides (e.g., insulin, VIP).
  • Documentation of elevated amines and neuropeptides should be done whenever possible.
carcinoid tumors
Carcinoid Tumors
  • Serotonin EOTA (Plasma + ascorbic acid)
    • most sensitive, episodic
    • Collection critical for preservation
  • 5-HIAA (5-hydroxy-indoleacetic acid, urine) formed by metabolism of serotonin by monoamine oxidase
      • Best measured by HPL (measure Creat as well)
      • Almost NEVER elevated without liver METS (usually 15-20% burden)
serotonin and carcinoids
Serotonin and Carcinoids
  • Mid-gut carcinoids are rich in serotonin containing granules and are frequently associated with carcinoid syndrome
  • Foregut carcinoids (Stomach, Lungs) have few serotonin granule
  • Hind-gut carcinoids have very few serotonin granules

Modified: AC Deacon. Ann Clin Biochem 1994:31;215-232

chromogranin a cga
Chromogranin A (CgA)
  • Acidic, water soluble, secretory glycoprotein (ng/ml)
  • Stored in matrix of secretory granules of nervous & neuroendocrine cells / tumors
  • Cleared by prohormone convertase I (PC-1) to pancreastatin (pg/ml)
  • An accurate “marker” of neurocrine tumor burden and metastasis
pearls on chromogranin a cga
“Pearls” on Chromogranin A (CgA)
  • Try and stay with the same lab (five in US)
  • Is very helpful when you know you have a N/E tumor.
  • May be elevated when there is no actual N/E tumor
      • Severe hypertension
      • Gastric acid suppression (PPI’s)
      • Renal insufficiency
slide23

Development of a Highly Sensitive and Specific Carboxy-terminal Human Pancreastatin Assay to Monitor Neuroendocrine Tumor Behavior

TM O’Dorisio1, SR Krutzik2, EA Woltering3, E Lindholm3, S Joseph3, Y-Z Wang3, JP Boudreaux3, AI Vinik4, VLW Go5, JR Howe1,

T Halfdanarson1, MS O’Dorisio1, G Mamikunian2

PANCREAS 39(5):611-616, 2010

University of Iowa Neuroendocrine Tumor Program

results

700

600

500

400

Marker in Appropriate Units

5-HIAA

CGA

Pancreastatin

300

200

100

0

4/13/2005

2/13/2007

2/13/2008

6/13/2005

4/13/2007

6/13/2007

8/13/2007

8/13/2005

4/13/2008

6/13/2008

8/13/2008

8/13/2006

2/13/2006

4/13/2006

6/13/2006

12/13/2007

10/13/2007

10/13/2008

10/13/2005

12/13/2005

10/13/2006

12/13/2006

12/13/2008

Date

Results

Sequential Marker Measurement

PANCREAS 39(5):611-616, 2010

results1
Results

Comparison of ISI vs URL Pancreastatin Values

1000000

ISI

URL

100000

10000

Pancreastatin Value (pg/ml)

1000

100

10

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

Subject Number

PANCREAS 39(5):611-616, 2010

slide26

Validation of Neurokinin A (NKA) Assays in the U.S. and Europe

P. Mamikunian, J.E. Ardill, T.M. O’Dorisio…E.A. Woltering et al.

Pancreas 2011;40(7):1000-1005

kaplan meier survival curve
Kaplan-Meier Survival Curve

1.0

0.5

0.0

NKA < 50 ng/L

NKA > 50 ng/L

Cumulative survival probability

0

24

48

72

96

Survival (Months)

P. Mamikunian..E.A. Woltering

Pancreas 2011, In press

biomarkers
Biomarkers
  • CgA levels can reflect total tumor burden (when metastatic) for both pancreatic and mid-gut (ileal) N/E tumors
  • Neurokinin A may be a predictor for aggressive mid-gut (ileal) tumors
  • Pancreastatin may be a very early marker for liver tumor activity
slide30

Evolution of Neuroendocrine

Medical Therapy

Dawn Wray

Teresa Ruggle

© University of Iowa

slide32

Theranostics

“Molecular targeting of VECTORS which can be used for both therapies and diagnosis, when modified accordingly…

(it) embodies both molecular and personalized medicine.”

Rosch, F, Baum R.P. Generator-based PET radiopharmaceuticals for molecular imaging of tumours: On the way to THERANOSTICS. Dalton Trans 2011; 40:6104-11.