La terapia chirurgica
dell’adenocarcinoma della
giunzione esofago-gastrica
Ermanno Ancona & Alberto Ruol
Bolzano 3
marzo 2007
I.O.V. – Cl.
Chir. III unipd
Esophageal and Gastric Cardia AdenoCa
Incidence rates in USA between 1977 and 1996
El-Serag HB Gut 2002
Esophageal adenocarcinoma
Age-specific incidence in the USA (1977-1996)
The incidence of esophageal adenocarcinoma
rose approximately fourfold
El-Serag HB Gut 2002
Esophagel cancer:
SCC/Adeno ratio 1975-2004*
% 100
80
60
SCC
Adeno
Altro
40
20
5
00
-0
9
95
-9
4
90
-9
9
85
-8
4
80
-8
75
-7
9
0
* CC3 University of Padova
Classification for adenocarcinoma at the esophago-gastric junction
based on topographic/anatomic characteristics
Type I. Adenocarcinoma of the
distal esophagus which may
infiltrate the E-G junction from
above & mostly develops in
Barrett’s esophagus
Type II. True carcinoma of the
cardia, arising at the E-G junction
Type III. Subcardial gastric
carcinoma which infiltrates the E-G
junction from below
Siewert classification 1998
Figure 2 Incidence of Barrett's oesophagus per 1000 upper gastrointestinal endoscopies over
calendar time, with upper and lower confidence intervals (CI).
van Soest, E M et al. Gut 2005;54:1062-1066
Copyright ©2005 BMJ Publishing Group Ltd.
Natural History of Barrett’s Esophagus
BE with LGD
0
BE with HGD
Invasive carcinoma
Many years
Guido Berlucchi Foundation Research Grant 2003
G. Zaninotto: Esofago di Barrett
The Veneto Region’s Barrett’s
Oesophagus Registry:
Aims, Methods, Preliminary Results
The Veneto Region's Barrett's Oesophagus Registry:
Aims, methods, preliminary results.
Dig Liver Dis. 2007 Jan;39
METHODS I
2004, A INTERDISCIPLINARY COMMITTEE
Endoscopists, Pathologists, Information technology Experts
organized a computer based
Barrett's Esophagus (BE) Registry
Standardised
Endoscopic
Nomenclature
Standardised
Report for
Pathologists
Strict Biopsy
Protocol
www.esofagodibarrett.com
RESULTS
I
IL REGISTRO NEL TEMPO
1000
900
800
700
600
500
400
300
200
100
0
giu-04 set-04 apr-05 ott-05 dic-05 ott-06 feb-07
Arruolati
32
117
323
486
618
682
922
Completi
0
24
190
361
494
559
616
RESULTS II : Indication for Endoscopy
Reflux symptoms
Dyspeptic symptoms
BE
Epigastric pain
Upper GI bleeding
Dysphagia
FU gastric surgery
Atypical symptoms
3% 2%2%
6%
9%
52%
24%
RISULTATI : ISTOLOGIA AL 1° RISCONTRO
400
93%
350
300
250
200
150
7%
100
2%
50
0
HG-NIN
LG-NIN
Indef NIN NIN assente
NiN: STORIA NATURALE
(almeno 2 controlli)
Diagnosi iniziale
Follow-up
Barrett’s esophagus
15 pazienti
NiN indef
1 pazienti
NiN LG
29 pazienti
NiN LG
10 pazienti
NiN HG
1 paziente
Adenocarcinoma
2 pazienti
NiN: STORIA NATURALE II
(almeno 2 controlli)
Diagnosi iniziale
Follow-up
NiN HG
3 pazienti
NiN HG
1 paziente
Adenocarcinoma
2 pazienti
STAGES OF TUMOR DEPTH
IN EARLY CANCER
HGD
MC
T1 M
T1SM
STAGES OF TUMOR IN
ADVANCED CANCER
METASTASI
Clinical tumoral stadiation in patients observed at
our Center for Diseases of the Esophagus
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
stadio 4
stadio3
stadio 2
stadio 1
1991-95
19962000
2001-05
Which Therapy in presence of
Adenocarcinoma of E-G Junction
• No doubt on surgery in invasive
cancer
• No doubt on neoadjuvant treatment in
locally advanced cancer
• Only palliation in metastatic disease ?
• No agreement on the best treatment
of HGD or Early Cancer
Treatment options in operable cases
• Immediate Surgery
• Neoadjuvant Chemotherapy
• Neoadjuvant Chemoradiotherapy
• Adjuvant postoperative C-R therapy
Adenocarcinoma del cardias tipo 1 e 2
Problemi relativi all’intervento chirurgico
via di accesso:
• laparotomia + toracotomia destra o accesso
transiatale ?
• laparoscopia +/toracoscopia ?
estensione della resezione esofagea
• almeno 8-10 cm di esofago indenne a monte del k
• tutta la mucosa di Barrett in presenza di k su
Barrett
A. De Boer, J Van Lanschot et al. Quality of Life after Transthiatal
compared with Transthoracic Resection for Adenocarcinoma of the
Esophagus. J Clin Onc 2004, 20
J. Hulscher, J van Lanschot Dig. Surg 2005 22:130-34
Benefit of transthoracic approach vs transhiatal in Siewert I
J. Hulscher, J van Lanschot Dig. Surg 2005 22:130-34
No benefit of transthoracic approach vs transhiatal in Siewert II
La Chirurgia Mininvasiva nella
cura dell’Adenocarcinoma dell’ Esofago
E. Ancona SIC 2006
Cos’è ?
Cosa ha portato ?
Cosa porterà ?
E’ Fattibile ?
“Si”
 1992-1996 : Dallemagne, Cuscheri, Azagra, Gossot,
Collard, McAnena,De Paula, Akaishi, Dexter, Robertson,
Liu
 1997-2001 : Law, Kawahara, Smithers, Peracchia,
Swanstrom, Nguyen, Mafune, Luketich, Braghetto,
Watson
 2002-2006: Horgan, Osugi, Taguchi, Ikeda, Okushiba,
Shiozaki, Ide, Wong, Bonavina, Bresadola, Del Genio,
Kent, Van den Broeck, Martin, Van Hillegersberg,
Avital, Bernabe
Ma non c’è stata la esplosione tecnica della
colecistectomia, della Nissen o delle resezioni coliche
Outcomes After Esophagectomy With a Focus on Minimally
Invasive Esophagectomy and Quality of Life
This study is currently recruiting patients.
Verified by University of Pittsburgh September 2006
 Study start: May 1999
Enrollment: 300
Expected Total
 Assess short and long term outcomes after minimally
invasive esophagectomy(MIE) compared to open
esophagectomy. Measure standard observer derived
outcomes such as morbidity, mortality, tumor recurrence
and also patient derived outcomes, in particular quality of
life (QOL) using the MOS SF36 questionnaire. Evaluate
whether the SF36 will accurately reflect pre and
postoperative changes in clinical status in this patient
group.Compare the results of this global QOL instrument
(SF 36) to disease specific scales of dysphagia and reflux.
Assess the impact of adjuvant or neoadjuvant therapy on
QOL in this patient group and determine if any advantages
of MIE can be demonstrated.
 23 Centri negli USA partecipanti
Adenocarcinoma del cardias tipo 1 e 2
Problemi relativi all’intervento chirurgico
• estensione della resezione gastrica:
– resezione gastrica polare superiore per k di tipo
I e II o esogastrectomia totale
• linfoadenectomia (almeno 15 linfonodi):
– LN paracardiali, periesofagei medi e inferiori,
sottocarenali, paratracheali dx, piccola curva
gastrica, tripode celiaco, origine arteria epatica
e splenica
( linfoadenectomia D4: LN recurrenziali,
sovraclaveari, paraortici)
esophago-gastric resection
+ gastric pull-up
>6cm
total gastrectomy
+ Roux-en-Y esophago-jejunostomy
Adenocarcinoma of the esophagus &
esophago-gastric junction
Borderline location 
• spesso considerati insieme:
-
Tipo I &
Tipo II &
Tipo I &
ca esofago
Tipo II
Tipo III
Tipo II & Tipo III
& ca giunzione esofago-gastrica
• tipo II e’ stadiato a volte come ca esofageo
e a volte come ca gastrico
 Difficile valutare e confrontare i risultati ottenuti
con le diverse tecniche chirurgiche
Type II adenocarcinoma of the E-G junction
Esophago-gastric resection
& gastric pull-up
Peracchia 1987-1997
Ribet 1987
Sauvanet 1995
Launois 1993
Jakl 1995
Stark 1996
Stipa 1992 - 1996
Thomas 1997
Takeshita 1997
Harrison 1997
Fekete 1997
Fein 1998
Graham 1998
Harrison 1998
Adachi 1999
Parshad 1999
Ancona - Ruol 1999 -2000
Wijnhoven 1999
Stassen 2000
Van Sandick 2000
Volpe 2000
Dickson 2001
Collard 2001
Alexandrou – Wong 2002
Kobayashi 2002 (for T1 ca)
Hulscher 2002
Extended gastrectomy
& esophago-jejunostomy
Papachristou 1980
Husemann 1989
Holscher 1996
Soga 1996
Tachimori 1996
Akiyama 1997
Hsu 1997
Bozzetti 1997
Hsu 1997
Fein 1998
Guillem - Triboulet 1999
Maeta 1999
Nigro - DeMeester 1999
Bozzetti 2000
Siewert - Stein 1986-1998-2000-2002
Cordiano - DeManzoni 2001-2002-2003
Dresner 2001
Mattioli 2001
Monig 2001
Lekakos 2002
Monig - Holscher 2001-2002
Meyer 2002
Nakamura 2002
Mariette - Triboulet 2002 - 2003
Kobayashi 2002 (for T2-3-4 ca)
Gianotti – DiCarlo 2003
Ito 2004
Adenocarcinoma avanzato del cardias
Sopravvivenza in base al Tipo di intervento:
esogastrectomia totale (GT) vs. esogastroresezione
polare superiore (GRES) nella casistica 1980-1999
% 100
80
60
40
20
0
0
6
12
18
24
Res. R0
Res. R0
Res R1-2
Res R1-2
30
GT
GRES
GT
GRES
36
42
= 64 casi
= 169 casi
= 27 casi
= 74 casi
48
54
60
mesi
AdenoCa of the esophagus & esophago-gastric junction
problemi ancora controversi relativi all’ intervento chirurgico:
• volume di resezione esofagea:
– almeno 8-10 cm di esofago indenne a monte del tumore,
per via toracotomica dx (oppure sx)
– tutta la mucosa con metaplasia intestinale (Barrett)
– ? esofagectomia totale a torace chiuso
– ? resezione esofagea distale per via transiatale ( sec. Pinotti )
– ?? resezione esofago addominale per via laparotomica esclusiva
Paziente con adenoca Siewert 2 cui era stato proposto
in altra sede l’intervento per sola laparotomia
Tumore cardiale
Seconda
localizzazione
ESOPHAGEAL SECTION MARGIN
with microscopic tumor nests
in the submucosa
ANASTOMOTIC RECURRENCE
the safety resection margin proximal to the tumor (as measured
in vivo) should be at least 6 cm long, but preferably 8 cm long
Adenocarcinoma of the esophago-gastric junction
Microscopic evidence of cancer (R1) at the proximal
resection margin (in vivo measurements)
cm
proximal margin length
1-2
22/ 72
(30%)
2.1 - 4
26/174
(15%)
4.1 - 6
6/ 64
( 9%)
>6
0/ 21
( 0%)
Papachristou 1980
Adenocarcinoma of the esophago-gastric junction
Microscopic evidence of cancer (R1)
at a resection margin (on prefixed fresh specimen)
cm
proximal margin length
<2
2 -3.9
4 - 5.9
>6
Total
14/30 (47%)
1/ 9 (11%)
2/ 8 (25%)
distal margin length
3/ 8
2/17
(37.5%)
(12%)
0/37 (0%)
0/24 (0%)
23%
6%
Ito 2004
Centro Regionale Veneto Malattie dell’Esofago
Adenoca giunzione esofago-gastrica Tipo II
1980-2003: 267 resecati
n. pazienti
300
trancia
OK
250
200
3.8 %
0%
anastomosi superiore
anastomosi inferiore
150
100
50
0
trancia
con
tumore
Centro Regionale Veneto Malattie dell’Esofago
Adenoca giunzione esofago-gastrica Tipo II
1980-2003: 267 resecati
trancia di sezione prossimale positiva per tumore
Livello anastomosi Tranci
a
sup.
positiva
esofago cervicale
1/34
apice torace
1/28
sopra arco v. azigos
0/56
arco v. azigos
1/50
sotto arco v. azigos
4/35
vena polmonare inf.
2/35
2.9%
3.6%
0%
2%
11%
5.7%
sotto vena polmonare
inf.
1/22
4.5%
3/168 = 1.8%
10 / 260
= 3.8 %
7/92 = 7.6%
Centro Regionale Veneto Malattie dell’Esofago
Adenoca giunzione esofago-gastrica Tipo II
Sede recidiva
Trancia di sezione
con tumore, n=10
Trancia di sezione
indenne, n=235
anastomosi + locoreg.
1
7
anastomosi
1
3
locoregionale
2
26
Reci anastomosi
2/10 (20%)
Reci anastomosi
10/235 (4%)

Adenocarcinoma del cardias tipo 1 e 2
Problemi relativi all’intervento chirurgico
• estensione della resezione gastrica:
– resezione gastrica polare superiore per k di tipo
I e II o esogastrectomia totale
• linfoadenectomia (almeno 15 linfonodi):
– LN paracardiali, periesofagei medi e inferiori,
sottocarenali, paratracheali dx, piccola curva
gastrica, tripode celiaco, origine arteria epatica
e splenica
( linfoadenectomia D4: LN recurrenziali,
sovraclaveari, paraortici)
Stadio tumorale
eN+
1
pT1
44 pts
1
3
3
3
1
Stadio tumorale
eN+
1
1
pT2
43 pts
0
8
8
6
10
Stadio tumorale e
N+
2
7
pT3 171 pts
17
73
80
91
81
Main points of our typical
laparo-thoracotomic
Esophago-gastric
resection:
•Thin gastric tube to
resect all lesser curvature
nodes
•Mediastinal nodes
dissection up to the aortic
arc
•Anastomosis above the
Azygos vein
tripode celiaco
v. porta
art. epatica
art.
splenica
arco v. azigos
bronco dx
bronco sx
pericardio
30-day mortality after surgery for adenoCa
of the esophagus or esophagogastric
junction still today is
4,1 % (range 0-6)
144/3501 pts
Streitz -1991, Menke-Pluymers - 1992, Li - 1992, Lerut - 1993,
Holscher – 1995, Peracchia – 1999, Kodera – 1999, Siewert – 2000,
Collard – 2001, Hagen-DeMeester -2001, Alexandrou-Wong- 2002,
DeManzoni-Cordiano – 2002, Mariette-Triboulet - 2002,
Ancona-Ruol -1990-2002
Adenocarcinoma T2 T3 any N
Postoperative Morbidity in Specialized Center
1980-1990
R0-R1-R2
81/236
34%
1991-2005
R0-R1-R2
86/270
32 %
Padua University 2006
Adenocarcinoma T2 T3 any N
Postoperative Mortality in Specialized Center
1980-1990
R0-R1-R2
11/236
6%
1991-2005
R0-R1-R2
1/270
0,4 %
Padua University 2006
Adenoca Siewert I-II Stadio Patologico < 2B:
pazienti CT-RT trattati e non CT-RT trattati
1991-2005
% 100
p = 0.53
80
60
40
20
0
0
12
24
CT-RT (n=19/129 casi)
36
48
60
NO CT-RT (n=73)
mesi
Adenoca Siewert I-II, Stage pT2-T3 N0 vs N+
1991-2005: 204 pazients no CT/CT-RT, R0
Survival Rate
% 100
p < 0.0001
80
N0
60
40
N 1-2
20
0
0
12
24
T2-T3 N0 ( 58 pts)
36
48
60
mesi
T2-T3 N+ (146 pts)
Padua University 2006
Reliability of clinical stadiation of N +/230 cases observed in 1991-2005
T2 - T3 N0
124 cases
T2 – T3 N+
106 cases
N + 78
N – 51
N + 86
N - 20
62,9 %
37,1 %
81,1 %
18,9 %
Centro di Alta Specializzazione
della Regione Veneto per le
Malattie dell’Esofago
AdenoCa of the esophagus & E-G junction
Survival after R0 resection (hospital deaths included)
100
%
80
60
p<
0.0001
40
20
0
0
6 12 18 24 30 36 42 48 54 60 mos.
pStage 0 - Ia = 55 pts. (median surv. = 53 months)
pStage I b = 47 pts. (median surv. = 52 months)
pStage II
= 93 pts. (median surv. = 29 months)
pStage III-IV = 254 pts. (median surv. = 16 months) University of Padua, Italy
AdenoCa of the esophagus & esophago-gastric junction
Therapy
a multidisciplinary approach
( discussion & treatment planning )
for all patients with cancer of the esophagus &
esophago-gastric junction
is mandatory
to guarantee optimal quality of care
Neoadjuvant chemotherapy - Meta-analysis
Cochrane Database Syst Rev
2003; 4: CD001556 -
11 Randomized trials involving 2051 patients
- Pooled response rate to chemotherapy was about 36% with 3% pCR
- No difference in survival at 1 and 2 years
- Survival advantage starts at 3 yrs and reaches statistical significance at
5 yrs
Meta-analisis of randomized trials of neoadjuvant treatments
vs. surgery for resectable esophageal cancer
Absolute difference
improved 2-year survival of preoperative
Chemotherapy
4.4%
improved 2-year survival of preoperative
Chemo-Radiotherapy
6.4%
improved 2-year survival of neoadjuvant
treatments for Squamous Cell Cancer
6.1%
improved 2-year survival of neoadjuvant
treatments for Adenocarcinoma
6.4%
Urschel, Am J Surg 2003
Kaklamanos, Ann Surg Oncol 2003
Centro di Alta Specializzazione
della Regione Veneto per le Malattie dell’Esofago
1980-2004: cancers of the esophagus & EG-J
(4084 pts.) First line Chemo-Radiation
100
90
cervical
esoph.
%
80
70
SCC
thoracic
esoph.
60
50
40
30
adenoCa
esophagus &
E-G
junction
20
10
0
1980-87
1988-95
1996-99
2000-04
Neoadjuvant Chemotherapy
MAGIC Trial
Cunningham,
ASCO 2005 - N Engl J Med 2006
• Evaluate the efficacy of perioperative ECF
( preoperative & postoperative ) versus surgery alone
• 503 patients, stage II or greater
• Adenocarcinoma stomach / GE-junction / distal esophagus
• ECF was chosen secondary to high RR in two prior randomized trials for
locally advanced and metastatic gastric cancer
Webb JCO 1997; Ross JCO 2002
MAGIC randomized phase III trial
• Arm A (253 pts.): Surgery alone
(type of surgery & extent of nodal dissection left to discretion of surgeon)
• Arm B (250 pts.): ECF x 3  surgery  ECF x 3
Epirubicin (50mg/m2)
D1
Cisplatin (60mg/m2)
D1
Fluorouracil (200mg/m2) CIVI D1-21
Cycles q3weeks
MAGIC randomized phase III trial
• Toxicity:
< 12% severe Grade 3-4 toxicity
25% neutropenia
• Postoperative Morbidity : comparable
• Postoperative Mortality : comparable
(45% vs. 46%)
(5.9% vs. 5.6%)
• Only 55% of patients that underwent resection
commenced postoperative chemotherapy
• Only 42% completed postoperative chemotherapy
MAGIC Trial
Postoperative Staging
ECF
Surgery
p-value
Maximum
tumor
diameter
3cm (2-5)
5cm (3-7)
<0.001
T1/T2
T3/T4
52%
48%
38%
62%
0.009
N0/N1
N2/N3
84%
16%
71%
29%
0.01
MAGIC Trial
Survival Results
ECF
Surger
y
Benefit from
2-yr survival
50%
41%
9%
5-yr survival
36%
23%
13%
improvement
p=0.008
ECF
= 25% reduction of
risk of death
median survival
24 mo.
20 mo.
4 months
p=0.009
Results unchanged on multivariate analysis adjusted for age, gender, PS, site of disease
Sul trattamento dei tumori precoci su
Barrett è un fiorire di continue proposte
Which Therapy in presence of
Barrett’s Esophagus Cancerization ?
• No doubt on surgery in invasive cancer
• No doubt on neoadjuvant treatment in
•
locally advanced cancer
Only palliation in metastatic disease ?
• No agree on the best treatment of
HGD or early cancer
THE ENDOSCOPIC SURVEILLANCE OF BARRETT’S ESOPHAGUS
PERMITS TO DIAGNOSE HGD AND EARLY CANCER
sm
mm
tumor
m
Endoscopy and EUS images of a mucosal (T1a) esophageal carcinoma.
The esophageal wall, scanned at 20 MHz is displayed as a 5 layers structure.
A hypoechoic thickening of the second layer is recognizable (marks).
The third hyperechoic layer (i.e. submucosa) seems intact.
Clinical Stadiation in 495 pts observed
from 1991 to 2005
17%
24%
St.
St.
St.
St.
34%
25%
I
II
III
IV
Prevalence of early tumors among patients with resected
adenocarcinoma of the esophagus & esophago-gastric junction
%
35
30
25
20
15
10
5
0
1982-88
1989-95
1996-03
Stein 2004
Prevalence of early tumors among patients with resected
adenocarcinoma of the esophagus & esophago-gastric junction
%
30
25
20
15
10
5
0
1980-89
1990-99
2000-05
Ancona 2006
THE MANAGEMENT OF PATIENTS WITH HGD
IN BARRETT’S ESOPHAGUS IS CONTROVERSIAL
THERAPEUTIC OPTIONS :
 Intensive endoscopic biopsy surveillance
 Endoscopic Ablation Surgery: EMR, PDT, APC,
Laser
 Resection surgery: esophago-gastric resection
Which is the patient’s opinion ?
Survey results (20 patients)
15
frequent
endoscopy
esophagectomy
15
70
PDT
P = 0.0024
Endoscopic surveillance program
Drawbacks
• Fewer than 50% of BE patients are suitable for
surveillance
• Most BE patients under surveillance die of causes
other than esophageal adenocarcinoma
• Low patient compliance
• Heavy program workload and high cost of
surveillance
Case 1: Z.G., male, 71 years
Biennial
surveillance
1992: Diagnosis of BE
1999: Surgery (pT1N0M0) - alive & NED after 6
years
Case 2: B.B., male, 69 years
Refused
surveillance
1989: Diagnosis of BE
1999: Surgery (pT3N1M0) - died/recurrence,
15 mos.
Barrett’s adenocarcinoma
Influence of surveillance on survival
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
N=10 pts
N=49 pts
N=14 pts
0
6
12
18
24
30
36
42
48
54
60
months
Occasional finding
Unsurveilled Barrett's
Surveilled Barrett's
University of Padua, Italy
THE MANAGEMENT OF PATIENTS WITH HGD
IN BARRETT’S ESOPHAGUS IS CONTROVERSIAL
THERAPEUTIC OPTIONS :
 Intensive endoscopic biopsy surveillance
 Endoscopic Ablation Surgery: EMR, PDT, APC,
Laser
 Resection surgery: esophago-gastric resection
Endoscopic treatment of HGD or Early Cancer
in Barrett Esophagus
Papers collected in Medline
45
40
35
30
25
PDT
20
Mucosectomy
15
10
5
0
1990-94
1995-99
2000-04
IS THE PRESENCE OF BURIED BE
A CLINICALLY RELEVANT ISSUE ?
Several cases of invasive
adenocarcinoma developing from
“buried” Barrett’s epithelium have
already been reported after Barrett
mucosal ablation
(Bonavina, 1999 Van Laethem, 2000
Macey, 2001 Shand, 2001
Wolfsen, 2002 Overholt, 2003)
Endoscopic Mucosectomy Rational
The risk of lymph
node metastasis is
around 1.2% with
mucosal cancers and
19 % when
submucosa is
involved
(Stein HJ - Ann Surg 2000,
Van Sandick JW - Cancer
2000, Holscher AH - Br J Surg
1997, Ruol A - Dis Esoph
1997, Rice TW - Am Thor Surg
1998)
Diagnostic role of
Mucosectomy
In 25 patients
suspected of having
HGD or cancer, the
diagnosis was modified
in 40% of the cases
(Nijhawan, 2000)
A Larghi Gastroint Endosc 2005: EUS followed by EMR
in HGD and Early Cancer in Barrett’s Esophagus
A Larghi Gastroint Endosc 2005: EUS followed by EMR
in HGD and Early Cancer in Barrett’s Esophagus
A Larghi Gastroint Endosc 2005: EUS followed by EMR
in HGD and Early Cancer in Barrett’s Esophagus
C. Ell Gastroint Endosc 2007 : Curative endoscopic
resection of early Barrett’s cancer
667 pts with suspected HGD or EC
Not confirmed
80
More advanced
109
Early Barrett’s
Neoplasia 478
Low Risk BC 100
No Low Risk 229
HGIN
64
Post study 85
Low Risk Criteria: Types I, IIa, IIb, IIc; <20 mm; no lymph vessel
or vein invasion; G1 and G2
C.Ell Gastroint Endosc 2007 : Curative endoscopic
resection of early Barrett’s cancer. Results
• Median FU 33 m. No loss of FU
• Complete local remission (CLR) 99/100
• No major complication, minor compl. 11
• Metachronous lesions 11
• CLR after repeat ER 11/11
The Management Of Patients With HGD
in Barrett’s Esophagus is Controversial
THERAPEUTIC
OPTIONS :
 Intensive endoscopic biopsy surveillance
 Endoscopic ablation therapies:
EMR (PDT, APC, Laser)
 Resection surgery: esophagectomy
Barrett’s HGD or early Adenocarcinoma
The role of Surgery
Pros: is the only proven treatment that
 cures the condition
 completely eliminates the risk of recurrence
 prevents the development of incurable cancer
 excellent long-term survival for HGD or mucosal (pT1a)
cancer
 patients are free from lifelong endoscopic surveillance
Cons:
 significant postoperative morbidity: up to 45%
 surgical mortality not negligible:
0 – 6%
 several patients may not be candidates for surgery or
refuse surgery
Centro di Alta Specializzazione
della Regione Veneto per le Malattie dell’Esofago
A. Peracchia (1980-1992)
E. Ancona (1992-2005)
Postoperative = Hospital Deaths
(Any stage R0-1-2 resection)
period
adenocarcinoma of the lower
esophagus & es-gastric junction
1980 - 1984
1985 - 1989
9 / 117
4 / 180
( 7.7 % )
( 2.2 % )
1990 - 1994
4 / 106
( 3.7 % )
1995 - 1999
1 / 103
( 1.0 % )
2000 - 2005
0 / 169
(0%)
Prophylactic esophagectomy in
Barrett’s esophagus with HGD
• Incidence of occult invasive adenocarcinoma:
Tseng, 2003
30%
Fernando, 2002
Headrick, 2002
Zaninotto, 2000
Patti, 1999
Ferguson, 1997
Edwards, 1996
Peters, 1994
Rice, 1993
Pera, 1992
Altorki, 1991
39%
36%
33%
36%
53%
41%
55%
38%
50%
45%
1982-1994: 43%
1994-2001: 17%
( 61% pStage I )
( 100% pStage I )
range: 30-55%
pT1a:
5% pN+
pT1b: 18-31% pN+
Barrett’ HGD referred to us ( period: 1990-2005 )
late survival
31 patients with confirmed HGD
8 pts unfit for surgery
Endoscopic (EMR, PDT)
+ Medical therapy
Deaths 4/13
other causes at m. 15, 68, 61
for cancer at m. 43
23 pts fit for surgery
5 pts
refused
surgery
18 pts
resection
surgery
7/18 = 39% pT1 N0
3/18 = 17% pT0 N0
Deaths 5/18
other causes at
m. 3, 61, 79, 46, 40
Barrett’s T1 cancer referred to us ( period: 1990-2005 )
late survival
24 patients with confirmed T1
4 pts unfit for surgery
Radiotherapy, RT -Laser,
EMR
Deaths 2
other cause at m. 91
for cancer at m. 58, 25
One T1 recurrence after
EMR + Brachitherapy
20 pts fit for surgery
1 pt
refused
surgery
19 pts + 1
resection
surgery
Deaths 1
for cancer m.13 (pT3)
Survival in 38 EC p-T1N0M0 & p-HGD
100
80
60
40
-
20
0
0
1
2
3
T1N0M0 - HGD
4
5
year
Complication and mortality rate in
38 patients resected for HGD or E C (1990 -2005)
100%
80%
60%
40%
20%
0%
all patients
p T1
complication
HGD
none
p T0
Open questions in surgical resection of HGD or
Early Cancer in Barrett’s Esophagus
• The role of minimal resection (idest
Merendino jejunal interposition)
Less morbidity and less mortality rate
Survival in HD and EC surgical resection
Stein 2006
H J Stein M Feith
2005 Best Pract &
Research
Restare ancorati al solido passato
O lanciarsi nelle vie del futuro ?
Caso Clinico:D.G.C. 61 anni
ANAMNESI PATOLOGICA
1995 diagnosi di esofago di Barrett
1998 diagnosi di mielodisplasia con neutropenia
2000 sostituzione valvola aortica (bioprotesi
Hancock) e dell’aorta ascendente (protesi
vascolare di Hemashield) per steno-insufficienza
valvolare aortica ed aneurisma post-stenotico
dell’aorta ascendente
2004 novembre: in corso di follow up endoscopico
riscontro di irregolarità mucosa (a 25 cm)
positiva per adenocarcinoma
Endoscopia : esofago regolare fino a 25 cm ove si
osserva il limite della risalita della mucosa gastrica. In
tale sede, a livello della parete posteriore, nodulo
rigido di 1.5 cm
EUS: Nella zona descritta
ispessimento di mucosa e
sottomucosa. Non linfonodi
periesofagei patologici. Stadio T1
N0
TAC: Disomogeneamente ispessita la
parete esofagea che raggiunge
anche 25 mm a livello del cardias
con estensione cranio-caudale di
10 cm; in questo tratto ridotto il
calibro del lume esofageo. Alcune
nodularità linfonodali ascellari e
mediastinioche, la maggiore alla
carena di 11 mm di diametro
Iter terapeutico
•
17/01/05 mucosectomia della lesione nota a 25 cm.
All’esame istologico: adenoca ben differenziato dell’esofago,
infiltrante la sottomucosa. Stadio pTNM: T1NxMx
•
07/03/05 EGDS: a 26 cm, sede della linea Z, si osserva
piccolo nodulo, duro al contatto con la pinza bioptica (bio
multiple) con Barrett a fiamma che raggiunge i 24 cm. Esame
istologico: frammento con metaplasia intestinale ed HDG
•
Esegue trattamento di HDR Per la comparsa di substenosi a
28 cm (post HDR), esegue 6 dilatazioni con Savary (dal
21/07/05 al 05/09/05). Bio = ulcera di Barrett
•
(05/09/06) EGDS + EUS: a 28 cm ispessimento di mucosa e
sottomucosa come da esiti flogistici. Esame istologico :
adenoca ben differenziato.
Iter terapeutico
• Rivalutazione del rischio operatorio e proposizione
di eseguire la resezione esofagea in primo tempo
con ricostruzione dilazionata
• 30-10-06 Resezione esoago-gastrica ed
esoagogastroplastica in un tempo per laparotoracotomia destra. pT1N0Mx
• Decorso regolare
Il razionale del trattamento della
cancerizzazione dell’esofago di Barrett
scoperta in fase precoce consiste:
1 – nel completo possesso in egual maniera della tecnica
operatoria open e di quella della mucosectomia endoscopica
2 – nella precisa stadiazione EUS ed istopatologica (doppia
lettura)
3 – nel porre i casi in uno studio randomizzato della resezione
esofagogastrica vs mucosectomia endoscopica
4 – nel non perdere pazienti dal follow up