HGD to LGD and LGD to HR Flashcards

0
Q

What does DDS say about the behavior of NDBE?

A

Review of treatment strategies relating to LGD and NDBE

  • NDBE displays neoplastic behavior and these changes occur prior to morphologic expression of neoplasia (dysplasia).
  • Morphologic evaluation of dysplasia is fraught with error, and, as a result, often leads to false-negative and false-positive diagnoses.
  • Surveillance is cost-ineffective and dangerously permissive of the development of EAC
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1
Q

DDS (LGD to HR)

A

Title: Case for Endoscopic Treatment of Title: Non-Dysplasia and Low Grade Dysplastic BE

Journal: Digestive Disease Science, 2010

Authors: Fleischer (+ 16 KOL - GI, Surgery and Path)

Use: LGD to HR
discuss Surveillance; Pathology; Prog; Anxiety

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2
Q

DDS - 5 reasons to consider RFA

A
  1. ) Inability to predict what patients will progress to HGD
  2. ) Inability to predict the time course of such progression.
  3. ) Risk for mis-diagnosis due to poor sampling; lack of consistent sampling and pathology discordanance
  4. ) Patient anxiety for harboring a pre-malignant lesion and impact in their QOL.
  5. ) Availability of safe effective methods compared to surveillance only.
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3
Q

ASGE - Peer Review {HGD to LGD and LGD to HR}

A

Title: The role of endoscopy in B.E. and other pre-malignant conditions of the esophagus.

Journal: Gastrointestinal Endoscopy; Dec 2012

Authors: ASGE Standards of Practice Committee (23 members)

Use: HGD to LGD and LGD to HR

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4
Q

What is the ASGE recommendation for treatment of LGD/ NDBE

A

LGD - abaltion as an alternative should be considered and discussed in select patients with LGD.

NDBE- No recommendation is included in the section that pertains to ablation.

However, the authors comment “Endoscopic eradication therapy as an alternative to surveillance in NDBE has been suggested to be cost effective in a cost utility model and may be a preferred management option in select patients with NDBE such as those with a family history of EAC

**No recommendation against using RFA”

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5
Q

Name the risk factors the ASGE list for BE and EAC

A

Male, White, Age (older than 50); Family History of BE; Smoking; Obesity; Increased Duration of Reflux Symptoms

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6
Q

AGA - Peer Review {HGD to LGD and LGD to HR}

A

Title: American Gastroenterology Association (AGA) Medical Position Statement on the management of B.E.

Journal: Gastroenterology; 2011

Authors: 14 panel members (P. Sharma; Shaheen; Inodami; Spechler; Souza), one community based physician (Pruitt), one Gen. surgeon, PCP, Pathologist, Ins. provider rep (BC of CA)

Use: HGD to LGD and LGD to HR

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7
Q

What does AGA recommend for HGD?

A

We recommend endoscopic eradication therapy with RFA, PDT or EMR rather than surveillance for treatment of patients with confirmed HGD within B.E.

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8
Q

What does AGA recommend for LGD?

A

Endoscopic Eradication Therapy with RFA should be a therapeutic option for treatment of patients with confirmed LGD in B.E.

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9
Q

What does AGA recommend for NDBE?

A

Although endoscopic eradication therapy is not suggested for the general population of BE patients in the absence of dysplasia. We suggest RFA with or without EMR as a therapeutic option for select individuals who are at an increased risk for progression to HGD or Cancer

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10
Q

What does the AGA state about progression?

A

Because Dysplasia progresses to cancer in a manner that lacks definitive markers of progression there are no well defined cutoff points that separate LGD from HGD at this time.

Risk Factors - age, BMI

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11
Q

BEst Study {HGD to LGD and LGD to HR}

A

Title: Dysplasia and Cancer in a Multicenter Cohort of patients with BE

Journal: Clinical Gastro and Hepatology 2006

Author: P. Sharma et. al.

Use: HGD to LGD and LDG to HR
Discussion on Pathology

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12
Q

What are the Summary Points of the BEST 2006 study

A

Multicenter (5) study to determine the time and progression rate of NDBE to LGD/HGD/EAC

  • 3 VA/1 Naval/1,376 patients with 1st diagnosis of B.E.
    -83% NDBE (1,142); 17% LGD/HGD/EAC
    -618 met inclusion criteria of 1yr repeat endo and NDBE.
    -Surveillance with biopsy and mean follow up of 4.12 years
    -Findings: .
    -.5% pp/yr IM to EAC (12 pts)
    -.9% pp/rm IM to HGD (22 pts)
    -.6% pp/yr LGD to EAC
    -1.4% pp/yr to HGD or EAC
    -Of the 34 patients whom progressed to HGD or EAC; 53% with two consecutive endoscopies had only prior finding of NDBE.
    -Sharma agrees that the major (suggesting sampling error). ~ 4-6 %
    problems with LGD include variable pathologic classifications and the interobserver disagreement in the reading of
    LGD.
    -
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13
Q

Wani “Continuation of best” {LGD to HR}

A

Title: Patients with NDBE have Low Risks for Developing Dysplasia or EAC

Journal - Clinical Gastro and Hepatology; 2011

Author: Wani et al.

Use: HGD to LGD and LDG to HR
discuss progression

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14
Q

What are the summary points 2011 Wani (BEst) continuation study.

A

Continuation study of BEst (2006 - Sharma).
-5 Centers (3 VA/1 Naval) and Clev. Clinic
-3300 Patients with1204 meeting criteria (greater than 1 year of follow up with no LGD/HGD or EAC).
-Followed for a mean of 5.52 years
FINDINGS:
-.27%/yr IM to EAC (18 pts)
-.48%/yr IM to HGD (32 pts)
-.63%/yr IM to HGD/EAC (44 pts)
Using Kaplan Meyer Survival Graphs:
2.9% risk for NDBE to EAC progression 10 years and
7.3% risk for NDBE to HGD/EAC progression 10 years

  • Of 32 pts who developed HGD - 25% prog to EAC
  • NNT was 769 / 1 yr. (calculate that out to 5 yrs - 139)
  • No central pathology - but authors state even discordance with expert GI
  • NDBE greater than 6cm .65% prog to EAC
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15
Q

AIM II (LGD to HR)

A

Title: Endoscopic RFA of BE - 5 year outcomes from a prospective multi-center trial

Journal: Endoscopy - Sept 2010

Authors: Fleischer (+ 13 KOL) Overhold, V.K. Sharma; Chutanni; Chang; Muth; Lightdale; Pleskow

Use: LGD to HR
discuss durability

16
Q

Key Point Summary AIM II

A

Prospective Multi-Center US Trial. Follow up to AIM (I) which was 2.5 years
-5 year data of NDBE patients after RFA
-60 eligible patients and 50 consented
-CR-IM was 92% (98.2 @ 21/2 yrs).
8% (4pts) had focal NDBE and converted to CR-IM after one session.
-No BG (5000 biopsies) / No Strictures (170 procedures).

18
Q

Orman (HGD to LGD)

A

Title: Intestinal Metaplasia recurs infrequently in patients successfully treated for BE with RFA

Journal: American Gastro; Dec 2012

Author: Orman, Cotton, Shaheen

Use: HGD to LGD
discuss progression

19
Q

Key Point Summary of Orman study?

A

Retrospective study for the recurrence of BE. Largest study reporting RFA outcomes and durability HGD/IMC.
262 patients - Univ. of NC between 2006 and 2011 who received RFA.
-Expert GI path and 2nd for discordance.
-231 met criteria: with 119 CE-D 112 CE-IM
-Surveillance median 397 days
-8 recurred who had pre ablation grade HGD (1 IMC, 2 EAC and 5 NDBE)
-Annual recurrence 2.4% for LGD; 5.5% HGD; 9.4% IMC
-Overall recurrence was 5.2%/yr
-97% CE-D / 89% CE-IM
75% (6/8) were successfully retreated or kept in surveillance.
85% of CE-D patients remained D free after 1 year.
**No pre ablated LGDpt had ever recurred
**Only 63% had Halo 360.

20
Q

Skacel (HGD to LGD)

A

Title: The diagnosis of LGD in BE and it’s implications for disease progression.

Journal: American Journal of Gastroenterology 2000

Author: Skacel et. al.

Use: HGD to LGD
discuss pathology

21
Q

What are the Key Points of Skacel paper?

A

Retrospective review from Cleveland Clinic between 1986 and 1997
-43 randomized and blindly reviewed LGD diagnosis by 3 GI pathologists
-Follow up in 25 pts.
-Discovered that if 2 of the pathologists agreed on the original diagnosis that 41% (7/17) of the patients progressed to HGD/EAC
If 3 of the pathologist agreed 80% (4/5) of subjects had progressed to HGD/EAC
-Over 11 months
-If no agreement, no progression
Thus - consensus diagnosis between pathologists suggest higher progression rates.
*Among the GI path, only 65% had agreed with their own original diagnosis (35% discordance).

22
Q

NEJM AIM Dysplasia Trial (HGD to LGD)

A

Title: RFA in BE with Dysplasia

Author: Shaheen et. al. (P. Sharma, Overholt, Jobe, Fleischer, Chang, 2009

Use: HGD to LGD
discuss effectiveness/BG/progresssion

23
Q

Key Point Summary AIM Dysplasia Trial - NEJM

A

RCT comparing RFA to sham to assess whether RFA could erradicate Dysp and decrease progression. 19 centers
-127 subjects and 2:1 (RFA to sham) with primary outcomes @ 12 mo.
LGD-CE
91% RFA vs. 23% sham (ITT) - 95% ppp
HGD-CE
81% RFA vs. 19% sham (ITT) - 90% ppp

77% overall IM-CE (ITT) - 83%ppp
-87% lower incidence of cancer (1.2 vs 9.3) and 78% lower incidence of disease progression (3.6 vs 16.3)
-25% with BG - 5% after RFA and 40% sham
30% discordance between pathology

24
Q

RCT Extension Trial - Shaheen (HGD to LGD)

A

Title: Durability in BE with Dysplasia

Journal: Gastroenterology 2011

Authors: Shaheen et. al

Use: HGD to LGD
discuss durability, progression

25
Q

Key Point Summary Disp. Durability study

A

Extension of NEJM RCT (2009).

  • Durability out to 3 years
  • 119 patients crossed over - 106 were followed
  • 95% CE-D / 93% CE-IM - 2yrs (106)
  • 98% CE-d / 91% CE-IM - 3 yrs (56)

Disease progression rates in dysplastic patients after RFA

•LGD: annual rate of overall disease progression = 2.04% pp/yr.
• vs. Curvers 13.4% *
LGD: annual rate of progression to EAC = 0.51% pp/yr
• vs. Curvers 3.4%
HGD: annual rate of progression to EAC = 0.60% pp/yr
• vs. AIM Dysplasia Sham 19% pp/yr
• vs. Wani et al. meta-analysis: 6.6% per pp/yr.

26
Q

Curvers (HGD to LGD)

A

Title: Low Grade Dysplasia in BE is overdiagnosed and under estimated.

Journal: American Journal of Gastro - 2010

Author: Curvers et. al. (Bergman)

Use: HGD to LGD
discuss progression and pathology

27
Q

Dutch LGD Progression Study

A

Low Grade Dysplasia in BE has a high risk of progression when confirmed by a panel of expert pathologists
2013 DDW abstract
Phoa, Curvers, Bergman

Largest cohort of patients undergoing path revision and longest patient years follow up. 
2000-2011
466 patients 
71% downgrade NDBE
28% diagnosis confirmed 
2% (9 patients) upstage to HGD/EAC
397 patients analyzed
Mean follow 59 months
LGD to EAC/HGD 
2.4% PP/year initial
9.0% confirmed 

0.9% NDBE to HGD/EAC

27
Q

What is key point summary of Curvers

A

Population based study out of Amsterdam using BE Registry from 6 comm hospitals from 2000 - 2006
-1198 patients diagnosed with BE
-147 had LGD with 122 having follow up bx 51 months.
85% of the 147 patients were downgraded to NDBE
-13.4% rate of HGD or EAC.(twice conf)
-3.4% rate of LGD to EAC
-NDBE not endpoint but .49% pp/yr
-In their opinion progression rates in these patients and safety profile of RFA may justify RFA in confirmed LGD.

28
Q

BMI Meta Anaylsis

A

A meta-analysis of BMI and esophageal and gastric cardia adenocarcinima.
2012 Annals of Oncology
Turati (et al)

22 studies + 8000 EgCA
RR 1.71 % BMI 25-30
RR 2.34 BMI > 30

29
Q

Length of BE and risk HGD/EAC of NDBE

A

Association between length of BE and risk of HGD or EAC in patients without Dysplasia.
2013 Clinical Gastro and Hepatology
Anaparthy (et al)

Continuation of BEST 2

1175 patients 5 tertiary referral centers
Mean follow 5.5 years / mean length 3.6cm
EAC risk 3cm increments (<3cm; 4-6; 7-9; 10-12; >13)

.31 
.97
1.26
1.64
2.41

44 developed HGD/EAC .67% pp/yr
28% increase risk for every 1cm increase BE length
Longer segment shorter dev HGD/EAC

30
Q

S.U.R.F

A

RFA in BE with confirmed LGD reduces neoplastic progression. Results of SURF RCT
2013 abstract
Phoa, Bergman (et al)

Multicenter RCT
136 patients RFA 2-3 months 
12-24-36 month follow up
94% CE-D
90% CE-IM
Control 

26.5% progression HGD/EAC RFA grp 24 months
1.5% control
94% reduction in risk by treating.
(25%-1.5%= 23.5% 23.5%/25%= 94%)

Stated: The difference between the Surveillance cohort (25%) and the control RFA cohort (1.5%) equals 23.5%. This difference divided by the total progression % of the Surveillance cohort gives you the percentage of difference that the RFA cohort presents in progression reduction.

31
Q

Systematic Review and Meta-Anaylis
Orman et. Al
2013
Clinical Gasto and Hepatology

A

18 studies - (efficacy and durability) 3082 patients
6 Abstracts - 540 patients
CE IM - 78%
CE D - 91% (NEJM 2009)

Progression to cancer

  1. 2% during treatment
  2. 7% after

IM recurrence was 13%

NDBE to EAC 0.09%
LGD to EAC 0.2
HGD to EAC 0.4%

5% stricture