Download adenomas

Upper GI lesions in Patients with
Familial Adenomatous Polyposis
Jun Haeng Lee, M.D.
Department of Medicine, Samsung Medical Center
Sungkyunkwan University School of Medicine, Seoul, Korea
Just above anus
rectum
AV 18 cm
Natural course of FAP
0
16
33
39
Adenoma
Symptom
Cancer
42
50
Death
Feldman: Sleisenger's GI and Liver Disease, 7th:2002;p2199
Extracolonic features in FAP
Cancers
Other lesions
Meduloblastoma
CHRPE
Thyroid
Nasopharangeal angiofibroma
Duodenal
Osteomas
Periampullary
Radiopaque jaw lesions
Pancreas
Supernumerary teeth
Hepatoblastoma
Lipomas, fibromas, epidermoid cysts
Biliary tree
Desmoid tumors, Gastric adenomas
Fundic gland polyps
Duodenal, jejunal, ileal adenomas
Feldman: Sleisenger's GI and Liver Disease, 7th:2002
FAP with gastric & ampullary adenoma
detected at follow up endoscopy
Gastric adenoma
Ampullary adenoma
Surgery at age 47
Colon cancer, adenocarcinoma (M/D)
6x4cm, Duke C2
Adenomatous polyposis
0.3cm to 3cm, x about 200
No fundic gland polyp
Adenoma at remnant
rectal mucosa
Duodenal Lesions in FAP
Jun Haeng Lee, M.D.
Department of Medicine, Samsung Medical Center
Sungkyunkwan University School of Medicine, Seoul, Korea
Relative risk of upper GI cancers in FAP
• The Johns Hopkins Registry
• Relative risk
– Duodenal adenocarcinoma: 331
– Ampullary adenocarcinoma: 124
• No significant increased risk was found for
gastric or nonduodenal small intestinal cancer.
Offerhaus. Gastroenterology 1992;102:1980-1982
Duodenal adenomas in FAP
• Lifetime incidence of duodenal
polyps in FAP: 97%
• Multiple
• Second portion of the
duodenum, especially the
peripapillary region
• Second common site of
malignancy in FAP
• After colectomy
- incidence: 4.5% – 8.5%
- leading cause of death
Kim. Gastrointest Endosc 2001;54:609-620
Lee (Yonsei). J Korean Soc Coloproctol 2006;22:24-28
Ampullary + duodenal adenomas
- s/p colectomy due to FAP
FAP + duodenal adenoma
FAP + duodenal adenomas
Genotype-phenotype correlation is
inconsistent but mostly in exon 15
• Most reports indicate that mutations in exon 15
of the APC gene, particularly distal to codon
1400, give rise to a severe duodenal phenotype.
Brosens. Gut 2005;54:1034-1043
Spigelman. Lancet 1989;783-785
Spigelman. Lancet 1989;783-785
Spigelman stage of duodenal lesions
Spigelman . Lancet 1989;334:783-785. Groves. Gut 2002;50:636-641
Cumulative risk of developing duodenal
adenomas, Spigelman stage IV, and Cancer
- a retrospective study of 180 patients
Bjork. Gastroenterology 2001;121:1127-1135
Duodenal adenomatosis in FAP
- an experience in Finland
• By the age of 60 years, the cumulative
incidence was 80% for any adenomatosis and
23% for severe dysplasia or cancer.
• Duodenal cancer was observed in 4.7% (6/129).
• 9.3% underwent pancreaticoduodenectomy.
• High-risk patients with Spigelman IV
adenomatosis or adenomas with persisting
severe dysplasia should undergo surgery with
PPPD
Lepisto (Finland). Endoscopy 2009;41:504-50
Management of Spigelman I & II
- European guideline on FAP (2008)
Vasen. Gut 2008;57:704-713
Management of Spigelman III (& II)
- European guideline on FAP (2008)
Vasen. Gut 2008;57:704-713
Surveillance interval recommendation
- European guideline on FAP (2008)
Vasen. Gut 2008;57:704-713
When to start surveillance?
- European guideline on FAP (2008)
Vasen. Gut 2008;57:704-713
Regression of duodenal adenoma by
celecoxib in patients with FAP
Phillips. Gut 2002;50:857-860
Results of chemoprevention/regression
studies are equivocal or disappointing
Brosens. Gut 2005;54:1034-1043
FGPs, AoV adenoma and duodenal
adenomas in a patient with FAP
Gastric Lesions in FAP
Jun Haeng Lee, M.D.
Department of Medicine, Samsung Medical Center
Sungkyunkwan University School of Medicine, Seoul, Korea
Gastric lesions in FAP
• Non-neoplastic hyperplastic polyps (fundic gland polyps)
– Occur in 30% to 100%
– First decade of life
– Little malignant potential, but can progress
• Adenomas
– 5% can progress to malignancy
– Antrum
– Particular concern to families with FAP in Korea and
Japan
Feldman: Sleisenger's GI and Liver Disease, 7th:2002
Fundic gland polyposis in FAP
FGPs in FAP are neoplasms with
frequent somatic APC gene alterations
Abraham. Am J Pathol 2000;157:747-754
FGP with atypia in FAP
Sekine, Shimoda. Stomach Intest 2004;39:740-745
EGC from FGP in FAP
Sekine, Shimoda. Stomach Intest 2004;39:740-745
Gastric lesions in FAP
• Non-neoplastic hyperplastic polyps (fundic gland polyps)
– Occur in 30% to 100%
– First decade of life
– Little malignant potential, but can progress
• Adenomas
– 5% can progress to malignancy
– Antrum
– Particular concern to families with FAP in Korea and
Japan
Feldman: Sleisenger's GI and Liver Disease, 7th:2002
Colon cancer plus three gastric adenomas
in patients with FAP
FAP + gastric adenomas
– total colectomy and APC ablation
FAP with ampullary & gastric adenoma
– ampullectomy and APC ablation
Gastric cancer in Korean FAP
• Only the Japanese and Korean literature have
found an increased prevalence of gastric cancer
in FAP (2.1% in Japan and 4.2% in Korea).
• The rates of gastric cancer in Japanese and
Korean FAP patients are 10- and 7-fold higher
than in the general population.
• Gastric cancer occurs more frequently than
duodenal cancer in East Asian FAP patients.
• The reason for this is unknown.
Garrean. Am Surg 2008;74(1):79-83
• In a recent survey, we collected data from 72 Korean
patients with FAP. Among them, three (4.2 percent)
were found to have associated gastric cancer.
• The expected cumulative incidence of gastric cancer
among these 72 patients was 0.44, which gives the
standardized incidence ratio of 6.9 (95 percent CI, 1.4–
20.1).
Park. Dis Colon Rectum 1992;35;996-998
EGC in FAP treated endoscopically
- no endoscopic picture was available in the article
Shimoyama. Dig Dis Sci 2004;49:260-265
Multiple hepatic mets from multifocal
microscopic gastric cancers in FAP
Hofgartner. Am J Gastroenterol 1999;94:2275-2281
Shimoyama. Dig Dis Sci 2004;49:260-265
Mangement of gastric lesions in FAP
• Fundic gland polyp  observation
• Ademoma  endoscopic treatment (resection or
ablation?)
• EGC
– Total gastrectomy
– Subtotal gastrectomy with B-I anastomosis
– ESD for selected cases
EMR-P for EGC in a patient with FAP
Take home message
• More clinical studies are necessary for Korean
patients with FAP.
• First screening for upper gastrointestinal
adenomas is recommended at age 25–30.
• Because of the frequent complications of the
endoscopic procedures and high rate of
recurrence, careful observation may be a good
option, especially for duodenal adenomas.