Endoscopic techniques for surveillance and treatment of FAP Evelien Dekker MD PhD Department of Gastroenterology & Hepatology Academic Medical Center Amsterdam The Netherlands
FAP: endoscopic surveillance & treatment Colon Duodenum Stomach Small bowel
Questions for GE in FAP: Who do we surveil? What age to start Frequency of surveillance Method of surveillance When to intervene Which treatment-options
Colon: who do we surveil? Presymptomatic: Persons with familiar risk APC-mutation carriers If no mutation is detected in proband: all 1 st degree family members Symptomatic..
Symptomatic 52 yr old man
Colon: Age, frequency & method Classic FAP: from 12 yrs 2-yearly sigmoidoscopy Attenuated FAP (AFAP): from 18 yrs 2-yearly colonoscopy
Colon: Method Careful non-magnified endoscopy All general quality measures must be taken into account: adequate bowel prep, withdrawal time etc Role for advanced imaging?
Chromoendoscopy Contrast stains Indigo-carmine (0,1 0,5%) Absorptive stains Methylene blue (0,1%)
Chromoendoscopy Targetted Directly through the workingchannel Segment or full colon With use of a spraycatheter
Chromoendoscopy in patient with AFAP
Colon: Method Use chromo (targeted or through a spraycatheter) At any discolouration If there is suspicion on genetic or familial basis
Colon: when to intervene? No guidelines.. If burden of polyps is severe and cancer cannot be ruled out
Colon: when to intervene? Classic FAP: Try to wait until adulthood Attenuated FAP: Possible to manage endoscopically??
Which treatment-options? Surgical Subtotal colectomy with ileorectal anastomosis Proctocolectomy with ileoanal pouch-reconstruction with ileostomy
Which operation?? Subtotal colectomy Best functional outcome However, chance of need for secondary proctectomy Related to genotype, phenotype & age at surgery Sinha et al, Br J Surg 2010
AMC: Proctocolectomy with ileoanal pouchreconstruction, stapeled Final operation Can be performed laparoscopically Functional outcome is good
Risks of pouch: 212 pats in Netherlands, 7.9 yrs follow-up Risk of adenomas 45% Risk of advanced pathology 11.8% Risk of cancer 1.9%, 10-year cumulative risk 75.5% However, due to retrospective nature no exact location of lesions possible.. Friederich et al, Clin Gastro Hep 2008
Patient 52 yr
And: Risk of adenoma formation Pouch In (small) anorectal segment Risk is larger if anastomosis is stapeled and not handsewn (St Marks Polyposis registry, 206 pats with pouch, 10.3 yrs follow-up) Von Roon et al, Ann Surg 2011
Patient 64 yr
Patient 36 yr
Patient 31 yr
Patient 20 years
Patient 40 years
Now in AMC: All patients undergo colonoscopy before colonic surgery If polyps close to anorectal verge: first polypectomies If in doubt: surgical mucosectomy and inlay with ileal mucosa
Surveillance after surgical resection: Ileorectal anastomosis: 6 monthly sigmoidoscopy (yearly??) Ileoanal pouch-reconstruction: Yearly pouch-scopy with gastroscope (NB minute inspection of anorectal segment, also in retroflex!) Ileostomy: No data on endoscopy of stoma
Duodenum
Questions for duodenum in FAP: Who do we surveil? Method of surveillance Frequency of surveillance When to intervene Which treatment-options
Duodenal polyposis in FAP In past: patients died from CRC Genetic testing & awareness of risk surveillance and colectomy better survival Most important causes of death in FAP: desmoïds and duodenal carcinoma
Duodenal polyposis Prevalence 60% Life-time cumulative risk 100% Björk et al Gastro 01 Groves et al Gut 02 Bülow et al Gut 04
Duodenal polyposis Prevalence 60% Life-time cumulative risk 100% Estimated cumulative risk duodenal carcinoma 4-10% Björk et al Gastro 01 Groves et al Gut 02 Bülow et al Gut 04
Duodenal polyposis in FAP How to assess who is at risk for duodenal carcinoma??
Spigelman classification # points 1 2 3 # Polyps 1-4 5-20 >20 Size (mm) 1-4 5-10 >10 Type adenoma Degree of dysplasia tubulair tubulovillous villous low-grade high-grade Spigelman et al, Lancet 1989
Spigelman classification Stage 0: 0 points Stage I: 1-4 points Stage II: 5-6 points Stage III: 7-8 points Stadium IV: 9-12 points
Who is most at risk? Correlation between Spigelman stage and chance of getting duodenal cancer highest risk in patients with stage IV Groves Gut 02: 36% vs 2.4% Sp III Bülow Gut 04: 7% vs 0.7% Sp 0-III
Duodenum: method, age & frequency Gastroduodenoscopy with assessment of Spigelman stage Start at 25-30 yrs Interval depending on Spigelman-stage (5 yearly 6 monthly)
Duodenum: method Use of advanced imaging techniques? To detect polyps To assess margins To differentiate to target biopsies
Duodenum: chromo
Duodenum: chromo
Study on chromo in duodenum in 45 pats: Mean Before indigo After indigo p # polyps 17 21 0.02 Size mm 8 10 0.02 Dekker at al, Endoscopy 2009
Chromoendoscopy per patient: More duodenal polyps detected in 13 pats Maximum size of the polyps increased in 7 pats Total number of points for the Spigelmanclassification was increased in 8 pats However, this resulted in an increased Spigelman-classification in only 5 pats (11%) Dekker at al, Endoscopy 2009
Spigelman classifications: chromoendoscopy Spigelman Before indigo After indigo O 3 (7%) 2 (4%) I 2 (4%) 2 (4%) II 11 (24%) 10 (22%) III 16 (36%) 17 (35%) IV 13 (29%) 14 (31%)
Chromoendoscopy duodenal FAP: Extra work No proven additonal benefit Not routinely Dekker at al, Endoscopy 2009
NBI in duodenal FAP? No studies published, 1 case-report Prospective study ongoing in AMC (with Spanish help) Yamao et al, Med Sci Monit 2009
TVA with LGD
TVA with LGD
TVA with HGD
Duodenum: When to intervene?? Correlation between Spigelman stage and chance of getting duodenal cancer highest risk in patients with stage IV However many patients are nowadays in stage IV
Netherlands 45 FAP patients (22, median age 47 yrs) Forward and sideward viewing gastroscopy
Spigelman stages Spigelman This study Historical Bülow Groves 0 3 (7%) 34% - 2% I 2 (4%) 15% - 13% II 11 (24%) 27% - 39% III 16 (36%) 17% - 36% IV 13 (29%) 7% - 10% Dekker at al, Endoscopy 2009
Reasons for many stage IV? Age of patients? Better quality of endoscopy?
Also: 44% had papillary adenoma
In whom to intervene? Assess during gastroscopy Spigelman-stage (so count, measure and take biopsies) PLUS papilla separately
In whom to intervene? Growing papillary adenoma: papillectomy Multiple adenomas with HGD or lage polyp-burden and one with HGD: surgical resection
Surgical options: Sparing: Transduodenal polypexcision Partial duodenectomy Definitive, high morbidity & mortality Pancreaticoduodenectomy ( Whipple ) Pancreassparing duodenectomy
In whom to intervene? Growing papillary adenoma: papillectomy Multiple adenomas with HGD or lage polyp-burden and one with HGD: surgical resection Relatively low polyp-burden and one adenoma with HGD: EMR??
Endoscopic ampullectomie Retrospective analysis 59 FAP-pats: Multipele sessions only 34% resulted in normal histology (NB is that required??) Norton et al 2002
St Marks All FAP-pats with duodenal polyps >1 cm NO papillary adenoma Endoscopic polypectomy +/- APC Latchford et al, InSight 2007
Interim analysis 46 pats 85 therapeutic procedures Median follow-up 24 mo (3-111) 14 downstaged, 3 upstaged, 13 stable, 16 await staging 10 bleedings (4 transfusions), no perforations or deaths Latchford et al, InSight 2007
AMC Patients with FAP en duodenal polyps with HGD òr papillary adenoma increasing in size Endoscopic treatment of only those polyps: EMR, APC, ampullectomy etc (propofol, 1 night cinical observation) Re-endoscopy after 3 months If necessary re-treatment
Endoscopic ampullectomy Growing TVA with LGD
Duodenal TVA met HGD
Duodenal TVA with HGD
After surgical resection: Also surveillance of jejunum, especially area of neopapilla..
Stomach: fundic gland polyps
Stomach: fundic gland polyps Benign Literature: one doubtful cancer.. Practice: inspect and biopsy if abnormality
Stomach: antral adenomas
Stomach: antral adenomas Incidence increased?? Chance of malignant transformation? Practice: inspect antrum and biopsy any abnormalities If proven by histopathology: polypectomy??
Patient 40 years
Jejenum & ileum
Surveillance jejunum & ileum in FAP? Almost all patients have polyps Several case reports.. However, what is true incidence of cancer?? Ruys et al, Clin Gastro Hep 2010
Surveillance jejunum & ileum in FAP? Capsule endoscopy SBE DBE
Surveillance jejunum & ileum in FAP? No proven benefit Exceptions: Before duodenal resection After duodenal resection Spigelman IV??
Conclusions FAP-patients deserve close endoscopic surveillance and timely surgical (medical??) intervention No evidence-based guidelines for both diagnosis and treatment Uniformly collected, prospective data are difficult to gather but needed!