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Dysplas’c Barre-’s Esophagus: Cut, Burn, Freeze or Watch Very Very Closely Felice SchnollSussman, MD, FACG Director, Jay Monahan Center Associate Professor Clinical Medicine Weill Cornell Medical Center

Dysplas’c)Barre-’s)Esophagus:) - NYSGE Course Presentations/SchnollSussman Opt1...Before)you)treatit,)you)mustfind)it Surveillance)mustbe)done) me’culously)and) systemacally)

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Page 1: Dysplas’c)Barre-’s)Esophagus:) - NYSGE Course Presentations/SchnollSussman Opt1...Before)you)treatit,)you)mustfind)it Surveillance)mustbe)done) me’culously)and) systemacally)

Dysplas'c  Barre-’s  Esophagus:  Cut,  Burn,  Freeze  or  Watch  Very  Very  Closely  

Felice  Schnoll-­‐Sussman,  MD,  FACG  Director,  Jay  Monahan  Center  

Associate  Professor  Clinical  Medicine  Weill  Cornell  Medical  Center  

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We  just  want  to  do  the  right  thing  but…  

•  Only  7%  of  the  10,000  EC  dx  in  USA  are  iden'fied  by  screening  or  surveillance  

•  40%  of  people  with  EC  do  not  have  reflux  •  90%  of  people  with  EC  did  not  know  they  had  Barre-’s    

•  Screening  and  surveillance  of  BE  have  not  been  proven  to  prevent  deaths  

•  Fatal  cases  nearly  as  likely  to  have  received  surveillance  (55.3%)  as  were  controls  (60.4%)  

 

 

Nature  Reviews  Gastro  &  Hep  2015;  12;243  Gastro  2013;142:312  

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Before  you  treat  it,  you  must  find  it  

Surveillance  must  be  done  me'culously  and  systema'cally  •  BE  early  dysplasia  oeen  presents  as  subtle  flat  Paris  type  II-­‐b  

•  Direct  correla'on  between  'me  inspec'ng  each  cm  of  BE  and  neoplasia  detec'on  

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Hazewinkel,  Y.  &  Dekker,  E.  (2011)  Hepatol.  2011  *Likely  to  contain  invasive  Ca  

Pedunclated

Sub Pedunclated

Sessile

Slightly Elevated

Flat

Depressed

Excavated

I  p      I  sp      I  s*    II  a    II  b    II  c    III*  

Paris  Classifica'o

n  

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How  long  should  you  take  to  look?    

112  pa'ents  surveillance  endoscopy  -­‐  11  individual  endoscopists  -­‐  Barre-’s  inspec'on  'me  (BIT)  

measured    

BIT  >1  minute  per  cm  Barre-’s  mucosa  •  Detec'on  rate  of  HGD/EAC    

–  40.2%  vs  6.7%  p  =  0.06  

•   Longer  BIT  correlated  w/  detec'on  HGD/EAC        p  =  0.63,  p  =  0.03  

                           1  

Gupta  et  al.  GIE  2012  

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What  should  we  be  repor'ng?    

Repor'ng  should  include:  1.  Barre-'  segment  length  –  Prague  Criteria  2.  Document  presence  and  size  of  hiatal  hernia  3.  Document  presence  of  esophagi's  above  BE  

segment  

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Prague  Classifica'on  

Most  reliable  and  validated  classifica'on  of  Barre-’s  

C  =  length  of  esophagus  lined  circumferen'ally  M  =  maximal  length  of  esophagus  involved  at  any  point  

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History  of  an  endoscopist’s  ‘view’  of  Barre-’s  Esophagus  

•  2001-­‐2010  –  regular  light,  bx,  bx,  bx,  bx  •  2009  –  High  defini'on  white  light…bx,  bx,  bx,  bx  •  2011  –  HDWL  +  NBI+  EMR…bx,bx,bx  •  2012  –  HDWL  +NBI  +EMR  +  pCLE  +  WATS...bx,bx  •  2013  –  HDWL  +  EMR  +  pCLE  +  OCT  +  WATS…bx    

“Look  longer...look  be-er…(maybe)  biopsy  less”  

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BE Patients

HD-WLE

NBI

suspicious  loca'ons  marked  w/  APC  

Do we need multimodality advanced imaging?

pCLE

OCT  

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Do  we  need  mul'modality  imaging?  

•  HR-­‐WLE  is  2-­‐5  fold  superior  quality  than  SD-­‐WLE  –  Expert  opinion:  HR-­‐  WLE  minimum  standard      

•  HR  +  dye-­‐based  (ace'c,indigo  carmine,  methylene  blue)  –  Time  consuming,  tedious,  need  high-­‐magnifica'on  –  Limited  added  benefit  to  HR-­‐WLE  alone  

•  Op'cal  chromoendoscopy  (NBI,  FICE,  I-­‐Scan)  –  NBI  w/target  bx  =  detec'on  rate  IM  vs.  HR  w/standard  bx  –  NBI  detects  higher  propor'on  dysplasia  (30%  vs  21%,  P=.01)  –  Requires  fewer  biopsies  (3.6  vd  7.6  p<.0001)  –  Useful  as  adjunc've  tool  to  HR-­‐WLE  

Benne-  C.  Gastro  2012;143:336-­‐46  (Delphi  Process)  Sharma  P  Gut  2013:62:15-­‐21  

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Do  we  need  mul'modality  imaging?  

Confocal  Laser  Endomicroscopy    (CLE)  •  Increases  sensi'vity  detec'ng  dysplasia  to  HR-­‐WLE  alone  

from  40-­‐60%  (p<.001)  •  Triples  diagnos'c  yield    (22%  vs  6%,  P=.002)  •  Requires    1/5  of  biopsies  •  BUT    sampling  error    (small  field)  ,  all  studies  from  expert  

centers  with  high  risk  pa'ents  •  May  be  imprac'cal  for  prac'cing  GI  

Op'cal  Coherence  Tomography  

Canto  MI.  Gastro  Endosc  2014;79:211-­‐21  Dunbar  KB.  Gastro  Endosc  2009;70:645-­‐54  

•  Preabla'on  -­‐Assess  esophagus  for    predictors  of  prolonged  or  failed  abla'on  

Ø  BE  thickness,  buried  glands  •  Postabla'on  –  assess  for  buried  glands  

Desai.  ACG  2015  

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What  is  the  Best  Biopsy  Protocol?  1.  Erosive  esophagi's  should  be  healed  before  

biopsy    –  Inflamma'on  causes  cytologic  atypia  in  crypts;  mimics  dysplasia  

2.  Four  quadrant  biopsy  every  1-­‐  2  cm  (Sea-le)  –  Each  segment  submi-ed  in  separate  containers  

3.  Samples  from  any  visible  abnormali'es  (nodules  or  suspicious  areas  )  

4.  Wide  angle  transepithelial  sampling  (WATS3D)  The  Sad  Truth:    Biopsy  guidelines  followed  in  only  51.2%  of  pa'ents  in  community  sexng  

•  Na'onal  pathology  database  of  2200  surveillance  cases                                                                                                                              Abrams.  Clin  Gastro  Hep  2009;7(7);736    

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If  you  iden'fy  a  nodule  it  must    undergo  EMR  

   EMR  is  an  essen'al  staging  procedure  •  Prospec've  study  of  75  pa'ents  with  biopsy-­‐proven  HGD  or  

early  cancer  •  EMR  altered  the  original  grading  or  staging  in  48%  of  pa'ents  

(down  28%,  up  20%)                                                                                                          Moss  A,  et  al.  Am  J  Gastroenterol  2010;105:1276–83    

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What is the risk of lymph node metastasis in HGD and Early Esophageal Cancer?

•  HGD ~ 0 •  Tis ~ 0 •  T1m ≤ 1-2% •  T1sm1 ~ 9-20% •  T1sm3 ~ 24-50%

•  Dunbar  KB,  Am  J  Gastro  2012;107:850-­‐62    

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What is the risk of lymph node metastasis in HGD and Early Esophageal Cancer?

•  HGD ~ 0 •  Tis ~ 0 •  T1m ≤ 1-2% ---------------------------------- •  T1sm1 ~ 9-20% •  T1sm3 ~ 24-50% Ablative techniques not appropriate Surgical resection indicated

•  Dunbar  KB,  Am  J  Gastro  2012;107:850-­‐62    

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The  Barre-’s  Dysplasia  Paradox  

 Accurate  diagnosis  and  staging  is  essen'al  

   

Interobserver agreement among expert pathologists can be less than 50%

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What  Really  is  Low-­‐Grade  Dysplasia?  

•  147  subjects  with  a  diagnosis  of  LGD  made  in  a  community  prac'ce  in  the  Netherlands  

•  Path  reviewed  by  2  expert  pathologists  – Disagreements  resolved  by  consensus  

•  85%  of  cases  were  down-­‐graded  •  In  remaining  15%:    incidence  rate  of  HGD  or  EAC  was  13.4%/pt-­‐yr  (mean  f/u:  51  mo)  

Curvers WL et al. Am J Gastroenterol 2010

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Is  EUS  Necessary  in  Staging?  

Virtually  no  risk  of  LN  metastasis  in  HGD  1-­‐2%  risk  in  ImCa    Factors  that  predict  risk  of  LN  metastasis  

1)  Depth  of  tumor  invasion  (sm1  and  deeper)  2)  Tumor  diameter  >  3  cm  3)  Lymph  vascular  invasion  on  ER  specimen  4)  Degree  of  differen'a'on  (poorly  or  G3  tumor  biology)    Consider  EUS  in  conjunc'on  with  EMR  if  concern  for  LNs  or  tumor  has  high  risk  features    

Dunbar  KB,  Am  J  Gastro  2012;107:850-­‐62    

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Pardigm  Shie  in  BE  Treatment  

Those  who  treat  pa'ents  with  Barre-’s  must  think  of  themselves  not  only  as  gastroenterologists  but  as:    

                                 “Gastro-­‐oncologicalsurgeons”  

 Accurate  staging  =  Appropriate  treatment  

 

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Now  that  you  have…  detected  dysplasia  and  staged  it  correctly  

what  should  you  do?  

1.  EMR  resec'on  of  all  nodular  disease      -­‐  Diagnos'c  and  therapeu'c  

2.  Ablate  all  remaining  Barre-’s  mucosa  3.  Control  acid  4.  Lifelong  surveillance    

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Endoscopic  Eradica'on  Therapies  

A.  Endoscopic  resec'on  1.  EMR  –  focal  or  complete  2.  ESD  

B.  Endoscopic  abla'on  1.  Radiofrequency  abla'on  2.  Cryotherapy  3.  Photodynamic  therapy  4.  Argon  plasma  coagula'on  

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Endoscopic  Eradica'on  Therapies  

A.  Endoscopic  resec'on  1.  EMR  –  focal  or  complete  2.  ESD  

B.  Endoscopic  abla'on  1.  Radiofrequency  abla'on  2.  Cryotherapy  3.  Photodynamic  therapy  4.  Argon  plasma  coagula'on  

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Radiofrequency  Abla'on  RCT  of  127  pa'ents  with  LGD  &  HGD  •  RFA+PPI  vs  Sham+PPI  (2:1)  •  12  months  follow  up  •  Bx’s  q3  mos  (HGD)/  6  mos  (LGD)  •  Complete  eradica'on  of  all  dysplasia:  

•  81%  of  HGD  •  91%  of  LGD  •  19%  of  controls  

•  Complete  eradica'on  of  IM  •  77%  of  Rx,  2%  Sham  

•   Strictures  occurred  in  6%  of  pts  –  Resolu'on  with  mean  2.6  dila'ons  

05

1015202530

CancerIncidence (%)

Sham+PPIRFA +PPI

Shaheen  NJ  et  al.  N  Engl  J  Med,  2009  

The  AIM-­‐D  Trial  

19%

2%

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3  year  Durability  Following  RFA  

Shaheen NJ et al, Gastroenterology 2011

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Is  LGD  an  indica'on  for  abla'on?  

                       SURF  study    RCT,  n=140  Surveillance  EGD  vs.  RFA  Primary  outcome:  Occurrence  of  HGD/EAC  

Phoa KN et al. JAMA 2014

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Is  Cryotherapy  an  Op'on?  

•  98  subjects  w/  HGD    –  10  ins'tu'ons  –  61  completed  Rx,  27  ongoing  

•  281  total  procedures  –  4.0/pt  

•  No  significant  adverse  events  •  One  progression  to  CA  

97 86

58

Shaheen NJ et al. Gastrointest Endosc, 2010

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Is  Cryotherapy  an  op'on?  •  Cryospray  abla'on  using  pressurized  CO2  

•  Aimed  to  enroll  30  pts  with  HGD  or  IMC  –  All  nodules  EMR’ed  –  Cryospray  performed  q  month  un'l  CEBE  or  7  sessions  

–  Aeer  enrolling  10  pa'ents  insufficient  effect  of  cryo  was  observed  –  study  terminated  

•  1  gastric  perfora'on  

 Verbeek  RE.  Endosc  Internatl  Open  2015;03:E107-­‐E112  

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0  

25  

50  

75  

100  

CR-­‐IM   Stricture  Rate  

EMR+RFA  

SRER  

Van Vilsteren FGI et al. Gut 2010.

•  Mul'ple  studies  show  high  CEIM  with  stepwise  EMR  

•  Risk  of  stricture  forma'on  higher  if  >3/4  circumferen'al  tx  

               What  about  complete  resec'on  of  IM  with  EMR?  

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Maintenance  of  acid  suppression  is  essen'al  to  achieve  abla'on  

•  45  subjects  underwent  pre-­‐RFA  pH  studies  

•  Degree  of  acid  control  correlated  with  abla'on  outcomes  

Akiyama J et al. Dig Dis Sci 2012; 57: 2625-32.

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Recurrences  Unfortunately  Do  Occur  0.

000.

250.

500.

751.

00

0 1 2 3Time after CEIM (years)

Nondysplastic BE Indefinite dysplasiaLGD HGDIMC

Recurrence  rates  stra'ified  by  baseline  histology  

RFA  Registry  Data  

Gupta  M.  Gastro  2013  

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�  

Management  of  HGD/IMC  

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Management  of  LGD  

Page 34: Dysplas’c)Barre-’s)Esophagus:) - NYSGE Course Presentations/SchnollSussman Opt1...Before)you)treatit,)you)mustfind)it Surveillance)mustbe)done) me’culously)and) systemacally)

What  have  we  learned?  

•  High  quality  EGD  essen'al  to  correctly  stage  •  Mul'modality  advanced  imaging  helpful  but  may  not  be  essen'al  

•  Endoscopic  management  of  low  and  high  grade  dysplas'c  BE  is  effec've  

•  Endotherapy    with  mul'modality  approach,  combining  'ssue-­‐acquiring  and  abla've  techniques  

•  Following  eradica'on,  surveillance  and  acid  suppression  must  con'nue  

•  Recurrence  can  be  managed  endoscopically  


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