GI EMERGENCIES Acute Abdominal Pain Marcia Cruz-Correa, MD, PhD, AGAF. FASGE Associate Professor of Medicine, Biochemistry, Surgery Director Translational Research University of Puerto Rico Comprehensive Cancer Center
CASE 18 y/o male patient presents with acute onset abdominal pain localized around the umbilical area Pain is 10/10 in intensity, associated with nausea, and had a 1 hour duration Family history is significant for history of pancreatic cancer (maternal grandfather) PE HR 115, BP 130/90, RR 22 Otherwise unremarkable exam
CT SCAN
SURGERY
P A T H O L O G Y
Most Common Hamartomatous Syndromes Juvenile Polyposis Peutz-Jeghers Cowden
Causes of Hereditary Susceptibility to CRC Sporadic (65% 85%) Familial (15% 20%) Hamartomatous polyposis (<0.1%) Familial adenomatous polyposis (FAP, AFAP and MAP) (1%) Hereditary nonpolyposis colorectal cancer (HNPCC, including Lynch) ( 3%)
Hamartomatous Polyposis Syndromes Juvenile Polyposis Peutz- Jeghers Cowden Syndrome Incidence 1/100,000 1/200,000 1/200,000 Gene MADH(SMAD4) BMPR1A STK11 (LKB1) PTEN Inheritance Autosomal Dominant Autosomal Dominant Autosomal Dominant Polyps Location (1) Colon (2) Small Bowel (1) Small Intestine (2) Stomach (1) Small Intestine (2) Stomach (3) Colon (3) Colon
Skin Manifestations of Hamartomatous Polyposis Syndromes PJS Cowden Cowden Cowden Mucosal pigmentation Trichilemmomas Skin papillomas Acral Keratosis
Peutz Jeghers Syndrome Hyperpigmentation
Cancer Lifetime Risk Hamartomatous Polyposis Syndromes JPS PJS COWDEN Colorectal 68 40? Breast -- 54 25-50 Small Int. 21 13 - Gastric 21 30 - Pancreatic 11 15 - Ovarian -- 18 5 Thyroid -- -- 5-10 Endometrial -- 10 5 Testes -- 5 Giardiello et al, Gastroenterology 2000; Hearle et al, Clin Can Res 2006
Peutz-Jeghers Syndrome Screening Recommendations Cancer Age to Begin Interval Diagnostic Test Colon 8-18 2 yrs Colon/EGD Gastric/ Small Intestine 8-18 2-3 yrs SBFT/Enteroscopy Capsule Endo Pancreas 30 1-2 EUS, Abd US?? Breast 25-30 2 MRI/US Mamography Uterus 20 1 Transvaginal US Endometrial Biopsy Cervix 20 1 Pap Smear Testicular 10 1 PE/Ultrasound Beggs et al, Gut 2010; McGarrity et al. GeneTest 2003
Juvenile Polyposis Syndrome Screening Recommendations Cancer Age to Begin Interval Diagnostic Test Colon 15 2 yrs Colon Gastric/S mall Intestine 15 2 yrs EGD & SBFT/Enteroscop y Capsule Endo Boardman 2002, Burt 2002, Dunlop 2002
Cowden Screening Recommendations Cancer Age to Begin Interval Diagnostic Test Colon 15 2 yrs Colon Gastric/Small Intestine Breast 21 30 15 2 yrs EGD & SBFT Capsule Endo Monthly Annual Self Exam Mamography Thyroid Adolescence 1 yr Clinical exam & Ultrasound Boardman 2002, Burt 2002, Dunlop 2002
Capsule Endoscopy for PJS & JPS Increase diagnostic yield of CE vs. SBS 1 MR Enteroscopy similar to CE for detection of SB polyps 2 Double balloon enteroscopy is not recommended for routine surveillance 2 Gupta et al. AJR 2010 1 Brown et al. Endoscopy 2006 Costamagna et al, Gastroenterology 2002 Mata et al., GIE 2005
Genetic Counseling & Testing for Hereditary GI Cancer Syndromes
Objectives of Genetic Testing To identify the disease-causing germline mutation in an index person who has developed cancer To distinguish asymptomatic mutation carriers from non-mutation carriers within a given family
Guidelines for Genetic Testing: Who May Benefit? People with multiple primary cancers People with multiple family members affected by cancer of any type People with cancer at young age of onset First-degree relatives of known mutation positive individuals
American Society of Clinical Oncology Guidelines for Genetic Testing Personal or family history features suggestive of a genetic cancer susceptibility condition Test can be adequately interpreted Test results will aid in diagnosis or influence medical management of the patient and/or family JCO 2003;21:2397-406
Interpreting Genetic Testing Results Positive Identify deleterious mutation for the patient May test at-risk family members No-Mutation Detected Mutation(s) previously identified in the family No known mutation in the family Genetic Variant Uncertain Clinical Significance Need additional information from affected and unaffected family members Ethnic and racial differences
Caveats of Genetic Testing If a pedigree mutation is not identified No further genetic testing of at-risk individuals Relatives should undergo endoscopic screening If cancer-affected member is unavailable Testing of unaffected members provides positive or inconclusive results
Summary Hamartomatous polyposis syndromes have a significantly increased risk of gastric, small bowel and colorectal cancer Surveillance strategies need to be individualized Early EGD/Colonoscopies Capsule endoscopy/mr enterography Breast, Pancreatic, Thyroid, GYN screening Genetic counseling & testing should be considered as part of medical management