MACGN - Familial Adenomatous Polyposis (FAP)

TABLE OF CONTENTS

Introduction
What are Polyps?
What is Familial Adenomatous Polyposis (FAP)?
What is the Gastrointestinal Tract?
How is FAP Inherited?
DNA test for FAP
Why is Early Diagnosis Important?
Exam Guidelines for People at Risk
What are the Symptoms of FAP?
How is FAP Diagnosed?
What is the Treatment?
What is an Ileostomy?
Sexual Function After Surgery
Follow-up Care After Surgery
Support Groups for Individuals and Families
Resources
Glossary
Appendix

INTRODUCTION

This booklet is written for individuals with familial adenomatous polyposis (FAP) and their families. The information provided is intended to add to, and is not a substitute for, discussions with doctors, nurses and other members of the health care team. We encourage you to read the entire booklet in the order in which it is written, since each section is built on information in preceding sections. We want to emphasize the need for regularly scheduled, thorough medical examinations for persons who already have FAP. More important, relatives at risk for this condition need to have regular examinations beginning at an early age. Names of support groups and additional publications concerning this condition are found at the end of the booklet.

WHAT ARE POLYPS?

Polyps are abnormal, mushroom-like growths. When found in the gastrointestinal tract, they occur most commonly inside the colon (large intestine, large bowel). Less often they develop in the stomach and small intestine (small bowel). Polyps vary in size from less than one-tenth of an inch to 1-2 inches. They may be so large as to block part of the intestine. In some people polyps may be inherited, while in others they are not inherited.

WHAT IS FAMILIAL ADENOMATOUS POLYPOSIS (FAP)?

FAP is a condition in which polyps are inherited. This hereditary (genetic) disease affects the gastrointestinal tract. Other names for this condition are hereditary polyposis of the colon, familial polyposis, and the Gardner syndrome. Individuals with this condition develop hundreds to thousands of polyps throughout the colon at a young age, usually as a teenager or young adult. The major danger of this condition is that the polyps will become cancerous.

WHAT IS THE GASTROINTESTINAL TRACT?

The gastrointestinal digestive tract is a hollow tube which begins at the mouth and ends at the anus. It has several parts including the esophagus, stomach, small intestine and colon (large intestine). Its total length is about 28 feet. The last 5-6 feet of the intestine is called the colon (large intestine, large bowel). The last 5 or 6 inches of the colon is the rectum. After food is digested, solid wastes move through the colon and rectum to the anus, where they are passed out of the body.

HOW IS FAP INHERITED?

People with FAP have a 50% chance of passing the condition to each of their children. The condition can be passed on even if the parent has had his or her own colon removed. Children who do not inherit the condition can not pass it to their own children.

About one-third of people with PAP do not have an affected parent. These individuals, who are the first to have the condition, are referred to as new mutations. They can pass FAP to their children.

Genetic counseling is available, and recommended, for individuals with FAP who plan to have children. Such counseling should be obtained before pregnancy occurs. Counseling services are available through genetics departments in many hospitals. Also it is recommended that PAP families contact local registries (see RESOURCES) for access to resources and for help with identification of family members at risk.

DNA TEST FOR FAMILIAL ADENOMATOUS POLYPOSIS (FAP)

The abnormal gene that causes PAP in most patients is now known. The gene is called APC (for Adenomatous Polyposis Coli. This means that a blood test can be per-formed to find out whether or not a person who is the child of an individual with PAP has the abnormal APC gene and will eventually develop PAP. However, an abnormal APC gene can not be detected in some PAP families.
The test requires a small blood sample. The gene tests results will influence the future management of individuals who are at risk for PAP. For example, if the test shows that a person does not have the abnormal APC gene, colon examinations can be spaced at longer intervals. If the test shows that a person does have the abnormal APC gene, then the physician will need to be alerted to schedule at least yearly colon examinations.

George Jones has PAP. His wife, Susan, is unaffected. They have three children, George, Jr., Stephen and Carol. All were at 50% risk of developing PAP. George, Jr., and Carol are affected.
George, Jr., and his wife Connie have two children. Although both children had a 50% chance of inheriting PAP, neither did.
Stephen and his wife, Gloria have two children. Since Stephen is unaffected there was no risk of FAP to his children.
Carol and Bill Mears have two children. Both had a 50% chance of inheriting PAP and both are affected.

WHY IS EARLY DIAGNOSIS IMPORTANT?

Early diagnosis is important for early detection and prevention of cancer. Regular screening should start as a young teenager, because when FAP is detected early, treatment will nearly always be effective. Furthermore, early and frequent examination might reassure a person without polyps that he or she does not have the disorder even though relatives do.

EXAM GUIDELINES FOR PEOPLE AT RISK

AGE (yrs)

11-24
25-34
35-44
over 44

EXAMINATION

Flexible sigmoidoscopy every year
Flexible sigmoidoscopy every other year
Flexible sigmoidoscopy every 3 years
Flexible sigmoidoscopy every 3-5 years

IF POLYPS ARE FOUND, SURGERY WILL BE RECOMMENDED

If DNA testing for the APC gene (see page 4) has been performed, and the test indicates that a person probably does have the abnormal APC gene or the abnormal APC gene can not be detected in the family, then there should be no change from the exam guidelines given above.
If the DNA test results indicate that a person has probably not inherited the abnormal APC gene, then a baseline colon examination should be performed at age 18. To be certain that the genetic test was correct, follow-up examinations should be performed at ages 25 and 35 or the genetic test can be repeated.

WHAT ARE THE SYMPTOMS OF FAP?

Most patients develop polyps without symptoms. However, the following symptoms may occur:

I. Bright red blood in the stool
2. Diarrhea that is not the result of diet or flu
3. A long period of constipation
4. Crampy pain in the stomach region
5. Persistent decrease in size of stool
6. Frequent feeling of distention (or bloating) in the abdominal or bowel region
7. Weight loss
8. Unusual and continuing lack of energy

In addition to polyps, abnormalities in other areas of the body may give early clues to the presence of FAP. These signs include: bumps or lumps on the bones of the legs, arms, skull, and jaw; cysts of the skin; teeth which do not erupt when they should; and freckle-like spots on the retina of the eye.

It should be emphasized that there is no safety in simply waiting for symptoms to develop. It is vital that parents and guardians make every effort to have examinations of their children starting at age 11 years even if they do not have symptoms.

HOW IS FAP DIAGNOSED?

Persons at risk for FAP initially need yearly examinations of the colon. Several tests are available to tell whether polyps are present.

1. Flexible sigmoidoscopy is the primary test used to examine the inside of the lower part of the colon. It is done with a lighted, flexible, hollow tube called a sigmoidoscope which is inserted into the anus. With the sigmoidoscope, the doctor can determine whether polyps or cancer are present. At the time of sigmoidoscopy, a biopsy forceps may be inserted through the inside of the sigmoidoscope to remove a bit of tissue for examination under the microscope. Most patients feel little or no discomfort during this examination.

2. Colonoscopy is an examination by means of a flexible, lighted tube, slightly larger in diameter than an enema tube. It permits the doctor to see much farther into the bowel than with the sigmoidoscope. Tissue may be removed from any part of the colon for microscopic study during this procedure. Before a person undergoes a colonoscopy a sedative is given; many persons sleep through the whole procedure and feel little or no discomfort. During this procedure it is sometimes necessary for the doctor to insert some air into the colon. Occasionally, air will cause the same kind of discomfort as a gas pain.

3. Barium enema is a test in which a white liquid called barium is inserted as an enema into the colon. This test allows the colon to be outlined when an x-ray picture is taken. If polyps are present they can be seen on the x-ray. The barium enema feels much like an ordinary enema, causing a feeling of fullness. This test should not be performed on pregnant women because of the risk of x-rays to the fetus.

For all these tests of the colon the patient must undergo a preparation before examination. The preparation, which includes a liquid diet and laxatives, clears stool from the colon so that all areas of the colon can be inspected. Exact instructions will be provided by the doctor before the examination.

WHAT IS THE TREATMENT?

If polyps are found at examination the doctor will recommend colon surgery. Removing the colon which is full of polyps is the only way to prevent the develop-ment of colon cancer.

Several different operations are currently available for treatment of FAP. The three most commonly performed operations are: 1) total colectomy with ileostomy, 2) ileorectal anastomosis and 3) ileoanal pull-through (pouch procedure). All three oper-ations involve removal of all or most of the colon. After a complete discussion of these operations, the patient and surgeon together can decide which one is best.

WHAT IS AN ILEOSTOMY?

In some cases, after colon removal, a person may have an ileostomy. An ileostomy is an opening on the abdomen through which stool leaves the body. An ileostomy can be temporary or permanent. In most cases it is necessary to wear an appliance called an ileostomy bag to collect body wastes.

An ileostomy should not be considered a handicap, although it is an inconve-nience. With proper care, there should be no odor or uncleanliness. Thousands of peo-ple of every age and of both sexes have had ileostomy surgery. After surgery, people can be just as busy, successful, and involved in daily routines as before surgery; in fact, they may be more active because of improved health.

SEXUAL FUNCTION AFTER SURGERY

Sexual function is not impaired after surgery or ileostomy. It is important that both marital partners understand the surgery, by talking with the surgeon or the family physician. There need be no change in established sex practices or in ones capacity to enjoy sexual intercourse, remembering, of course, that the rectal area will be tender for some time after surgery. It is also possible to have successful pregnancies. However, a woman who plans to become pregnant should consult her physician before becoming pregnant. Physicians usually recommend that a woman wait about a year after a colon operation before becoming pregnant. This delay gives plenty of time for abdominal scars to heal soundly and for the woman's health to return to normal. An ileostomy should not harm the baby or endanger the mother during childbirth.

FOLLOW-UP CARE AFTER SURGERY

Early diagnosis of FAP in many patients has led to early surgery, resulting in prevention or cure of colon cancer and increased life span. However, other complications of this hereditary condition may still occur. For example, precancerous polyps may develop in other parts of the gastrointestinal system, such as the stomach and small intestine. Although most polyps that develop in the stomach and small intestine are benign, cancer can occur in them. Tumors may also occur in the thyroid gland, adrenal gland, ovaries, breast, bile ducts, pancreas, and uterus. Thus, physicians recommend that patients continue with lifelong follow-up examinations for cancer prevention.

GUIDELINES FOR
FOLLOW UP CARE FOR PEOPLE WITH FAP

1. Sigmoidoscopy every 6 months to 3 years (depending on type of surgery)

2. Stool blood testing every year.

3. Upper endoscopy at least every 4 years

4. Complete physical exam every 1-2 years

5. Follow American Cancer Society guidelines for cancer surveillance
See Appendix, page 18

SUPPORT GROUPS FOR INDIVIDUALS AND FAMILIES

1. IMPACC
(Intestinal Multiple Polyposis And Colorectal Cancer)
Mrs. Ann Fagan, Administrator
P.O. Box 11
Conyngham, Pennsylvania 18219
(717) 459-1200

Assistant Administrators:

Mr. Ronald Droll
1608 Second Street, N.E.
Minneapolis, Minnesota 55413
(612) 789-6704

Mrs. Delores Boone
13860 Southwest Burlwood Street
Beaverton, Oregon 97005
(503) 626-4263

A support group for families with FAP and/or hereditary colon cancer.

2. UNITED OSTOMY ASSOCIATION, INC.
National Headquarters
36 Executive Park
Suite 120
Irvine, California 92714
(714) 660-8624

The United Ostomy Association is a national organization of individuals with ostomies who work together for the benefit of all. More than 500 chapters are made up of ostomates whose goal is to provide mutual aid, moral support, and education to those who have had colostomy or ileostomy surgery. Individuals who have undergone this surgery may want to take the training course offered by the Ostomy Association so that they might help others who have had a similar operation. Check the telephone directory for your local chapter.

RESOURCES

1. THE AMERICAN CANCER SOCIETY
National Headquarters
1599 Clifton Road, N.E.
Atlanta, Georgia 30329
(404) 320-3333

The ACS can offer assistance if cancer should occur. Check the telephone directory for your local chapter.

2. STATE VOCATIONAL REHABILITATION SERVICE
This service offers training for another vocation if one should be physically unable to return to the same kind of work performed prior to surgery. Check your telephone directory for your state services.

3. NEWSLETTER: HEREDITARY COLON CANCER
The NEWSLETTER is a quarterly publication, established in 1984. It deals with polyposis and hereditary colon cancer and is free to all individuals with these conditions and their families. The NEWSLETTER welcomes articles and letters from patients, their families, and professionals. Articles concerning new research and treatments are welcome. This publication may be obtained by contacting the Coordinator, Hereditary Cancer Registry, University of Texas M.D. Anderson Cancer Center, Box 78, 1515 Holcombe Boulevard, Houston, Texas 77030. Phone (713) 792-2828.

4. POLYPOSIS AND HEREDITARY COLON CANCER REGISTRIES
Registries, located throughout the United States, Canada and in some other countries, are listed once a year in the NEWSLETTER. You may contact them for the names of experts in the management of FAP Registries can also help to identify relatives at risk for the disorder. Further information concerning Polyposis Registries may be obtained by contacting Coordinator, The Johns Hopkins Polyposis Registry, Blalock 1008, The Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, Maryland 21287-4922. Phone (410) 955-3875.

5. CANCER INFORMATION SERVICE (ClS)
Toll Free: 1-800-4-CANCER

The Cancer Information Service is a national toll-free telephone inquiry system that provides information about cancer and cancer-related resources to the general public, patients and their families, as well as health professionals. Most CIS offices are associated with Comprehensive Cancer Centers or community hospitals. CIS offices do not diagnose or recommend treatment for individuals. They provide support, understanding and rapid access to the latest information, as well as referral to local services and resources. Telephone information may be supplemented by printed materials. All calls are kept confidential, and individuals do not need to give their name.

PUBLICATIONS

Contact the suppliers of the publications listed below for prices and/or mailing charges before ordering.

The Pelvic Pouch Procedure at the Toronto General Hospital, K. Forrest-Witkowski. Polyposis Registry, Toronto General Hospital, 200 Elizabeth Street, EC 10-315, Toronto, Ontario, M5G 2C4 Canada.

Ileal Pouch Pull-Through, Lee Elton Smith, M.D. The George Washington University Medical Center, Division of Colon and Rectal Surgery, 2150 Pennsylvania Avenue, NW., Washington, D.C. 20037.

Ileoanal Reservoir: A Patient Resource, Bonnie Sue Rolstad, R.N.,B.A.,E.T. Upjohn, Co., Surgical Specialty Unit, Kalamazoo, Michigan 49001. This booklet is available in English, French and Spanish.

Managing Your Ostomy. Hollister, Inc., 2000 Hollister Drive, Libertyville, Illinois 60048.

The Ostomy Book, B.D. Mullen and K.A. McGuinn. Bruce Medical Supply, 411 Waverly Oaks Road, Waltham, Massachusetts 02254.

Understanding DNA Testing: A Basic Guide for Families, National Center for Education in Maternal and Child Health, 38th and R St., NW., Washington, D.C. 20057.

The following publications, and many others, may be obtained from the United Ostomy Association, Inc., 36 Executive Park, Suite 120, Irvine, California 92714. Send for their publication brochure for a complete list.

Ostomy Quarterly.

Ileostomy, A Guide, L. Gross.

The Continent Ileostomy, SA. Griffith.

GLOSSARY

Adenoma - A precancerous polyp.

Anus - Outlet of the rectum.

APC - The abbreviated name of the gene (Adenomatous Polyposis Coli) that, when abnormal, causes PAP It is located on chromosome S (at position 5q21).

At risk - A person at risk has the possibility of developing the condition which is present in his/her family.

Barium enema - A test in which a chalky liquid which is resistant to x-rays is inserted into the large intestine, making it visible on x-ray film and permitting the doctor to see any defects, obstructions or masses.

Biopsy - Removal of a small bit of tissue for examination under the microscope.

CAT scan - (Computerized Axial Tomography) - a form of x-ray that shows the size and shape of body organs layer by layer.

Chromosome - The carrier of the genetic material of a cell (genes). The normal number of chromosomes in a human cell is 46 (23 pairs).

CHRPE (Congenital Hypertrophy of the Retinal Pigment Epithelium) See POFL. Colectomy - The surgical removal of the colon (large intestine).

Colon - (Large intestine, large bowel), The last portion of the intestine. It comprises the cecum, ascending colon, transverse colon, descending colon and sigmoid colon, and is 5-6 feet in length.

Colonoscopy - A test in which a flexible tube, about 5 feet in length, is used to exam-me the inside of the entire colon. The tube has a light source, a magnifying eye-piece, and an open channel through which air can be passed and a biopsy taken.

Desmoid - a benign connective tissue (fibrous) growth that may occur in the abdomen or abdominal wall. It may enlarge and may cause pressure on or encircle the bowel, stomach and other organs.

DNA - (DeoxyriboNucleic Acid). The molecule that contains the code for the genetic blueprint. It is found in the nucleus of cells.

Duodenum - The first part of the small intestine. It is 12-15 inches in length.

Epidermoid (epidermal) cyst - a benign cyst generally found on the face, scalp, arms, legs, and back. It is common in adults but is unusual before puberty. It is a signal for investigation of possible intestinal polyps.

Esophagogastroduodenoscopy (EGD, Upper Endoscopy) - A test in which a flexible tube is used to examine the interior of the upper GI tract (esophagus, stomach, and duodenum). The tube has a light source, a magnifying eyepiece, and an open channel through which a biopsy can be taken.

ET - Enterostomal Therapist; a specialist, often a nurse, who assists individuals who wear an external abdominal appliance to collect body waste.

Extracolonic manifestations - Lesions or abnormal growths occurring outside the large intestine in people with FAP.

FAP (Familial adenomatous polyposis) - An inherited disorder of the gastrointestinal tract in which there are 100 or more precancerous polyps.

Flexible sigmoidoscopy - A test in which a flexible tube about 2 1/2 feet in length is used to examine the rectum and lower part of the large bowel. The tube has a light source, a magnifying eyepiece, and an open channel through which air can be passed and a biopsy taken.

Gardner syndrome - A hereditary condition characterized by intestinal polyposis, soft-tissue tumors of the skin, jaw lesions, and other abnormalities.

GI (gastrointestinal) tract - The digestive system, consists of the esophagus, stomach, small intestine (22-25 feet in length), and large intestine (5-6 feet in length).

Gene - The basic unit of heredity, each one occupying a certain place on a chromosome.

Hemoccult test - A test using specially treated cardboard slides to check for hidden blood in the stool.

Hereditary - genetically transmitted from parent to children.

Ileoanal pull-through (pelvic pouch procedure, ileoanal anastomosis procedure) -An operation removing the colon and the lining of the rectum, leaving the underlying anal muscles, or sphincters. The last part of the small intestine is joined to the anus and an internal pelvic pouch is created.

Ileorectal anastomosis - An operation that removes the colon and joins the last part of the small intestine (ileum) to the rectum.

Ileostomy (proctocolectomy) - An operation that removes the colon, rectum, and anus. An opening is then made from the ileum through the abdominal wall.

Ileum - The last part of the small intestine, 12-15 feet long.

Jejunum - The middle part of the small intestine, 8-10 feet long.

Karyotype - A picture of the chromosomes.

Marker - A physical abnormality that may indicate the presence of, or may predict the future occurrence of a specific disorder in an individual.

Metastasis - Spread of cancer by the lymphatics or bloodstream to other sites in the body.

Mutation - A change in a gene which may result in a specific disorder.

Odontoma - A group of small, unerupted teeth.

Osteoma - A bony enlargement most commonly found in the skull, jaws and limbs.

Ostomate - A person with an ileostomy (or colostomy).

Pedigree - family tree; genealogy.

POFL - (Pigmented Ocular Eundus Lesion). Freckle-like spots on the retina of the eye that can be seen by a special eye examination. They are harmless. If present in sufficient numbers they indicate that a person has FAP. Their absence in an
individual does not indicate freedom from the disease. Also called CHRPE.

Propositus/Proposita - (Proband; Index case). The first individual to be identified in a family that has a specific hereditary disorder.

Stoma - Artificially created opening in the abdomen.

Syndrome - A collection of abnormal physical characteristics occurring in an individual (Example: Gardner syndrome with epidermoid cysts, osteomas, and sclerotic jaw lesions, in addition to polyposis).

APPENDIX

The American Cancer Society recommends the following guidelines
for early detection of cancer in people without symptoms:

Age 20-40	Cancer-related checkup every 3 years Should include the procedures listed below plus health counseling (such as tips on quitting cigarettes) and examinations for cancers of the thyroid, testes, prostate, oral region, ovaries, skin and lymph nodes. Some people are at higher risk for certain cancers and may need to have tests more frequently.
Breast	Exam by doctor every 3 years Self-exam every month One baseline breast x-ray by age 40 Higher risk for breast cancer: Personal or family history of breast cancer, never had children, first child after 30.
Female Reproductive System	Pelvic exam every 1-3 years with PAP test. Includes women age 18 and over. Pap test - after 3 initial negative tests 1 year apart, test should be done at the discretion of the physician, includes women who are, or who have been, sexually active, or have reached age 18. Higher risk for cervical cancer: Early age at first intercourse, multiple sex partners.

Age 40 & over	Cancer-related checkup every year Should include the procedures listed below plus health counseling (such as tips on quitting cigarettes) and examinations for cancers of the thyroid, testes, prostate, oral region, ovaries, skin and lymph nodes. Some people are at higher risk for certain cancers and may need to have tests more frequently.
Breast	Exam by doctor every year Self-exam every month Breast x-ray every year after 50; between ages 40-49, 1 every 1-2 years Higher risk for breast cancer: Personal or family history of breast cancer, never had children, first child after 30.
Female Reproductive System	Pelvic exam every year Pap test - after 3 initial negative tests 1 year apart test should be done at the discretion of the physician Endometrial tissue sample at menopause if at risk Higher risk for cervical cancer: Early age at first intercourse,multiple sex partners. Higher risk for endometrial cancer: Infertility, obesity, failure of ovulation, abnormal uterine bleeding, estrogen therapy.
Colon/ Rectum	For family members not at risk for FAP Flexible sigmoidoscopy every 3-5 years based on advice of physician-age 50 and over Fecal occult blood test every year-age 50 and over Digital rectal exam every year-age 40 and over Higher risk for colorectal cancer: Personal or family history of colon or rectal cancer, personal or family history of polyps in the colon or rectum, ulcerative colitis. The cancer-related checkup guidelines are not rules and only apply to people without symptoms

If you have any of the Seven Warning Signals listed below, see your doctor or go to your clinic without delay

CANCER"S SEVEN WARNING SIGNALS

Change in bowel or bladder habits
A sore that does not heal
Unusual bleeding or discharge
Thickening or lump in breast or elsewhere
Indigestion or difficulty in swallowing
Obvious change in wart or mole
Nagging cough or hoarseness

ACKNOWLEDGMENTS

This booklet was prepared by the following members of The Johns Hopkins Polyposis Clinic and Registry in 1988, revised 1994: Susan Viles Booker, BA., Paul Celano, M.D., Donna Cox, M.Ed., Susan Cross-Skinner, RN., M.S.N., Francis M. Giardiello, M.D., Pearl Campbell, B.S., Stanley R. Hamilton, M.D., Anne J. Krush, MS., L. Stefan Levin, D.D.S., M.S.D., Gloria M. Petersen, Ph.D., Kathy Potter, RN., Elias I. Traboulsi, M.D., and John Yardley, M.D.

The gastrointestinal tract illustration on page 3 was reprinted with permission of Bonnie Sue Rolstad, R.N.,B.A.,E.T., from the booklet "Ileoanal Reservoir: A Patient Resource."

We would like to thank Linda M. Welch for secretarial assistance, Theresa Berk, MS., for assistance in compiling the glossary, and Joanna Strayer Amberger, BA. for technical assistance on the pedigree illustration, page 5.

We would also like to thank the Clayton Fund, The Johns Hopkins Oncology Centers Community Programs and the Cancer Research Foundation of America for their support in the development of this booklet.

Supported by Roche Biomedical Laboratories, Inc.

To order copies of this booklet, please contact the Coordinator, The Johns Hopkins Polyposis Registry, Blalock 1008, The Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287-4922, phone (410) 955-3875.