Trattamento chirurgico dell'esofago di Barrett - Gastrolearning®

La Chirurgia nell’esofago di Barrett

e nell’Adenocarcinoma

Carlo Castoro

USD Chirurgia Oncologica dell’Esofago

Istituto Oncologico Veneto

IOV-IRCCS

Padova

GASTRO-LEARNING 2014Secondo Modulo: Oncologia Gastrointestinale

Padova 16 giugno, 2014

The Natural History of Barrett’s Esophagus

Starts here…..

…..And ends here

Barrett’s esophagus Management

The management of patients with Barrett's esophagus involves three major components:

● Treatment of the associated GERD

● Endoscopic surveillance to detect dysplasia

● Treatment of dysplasia

The goal of therapy is to prevent cancer development

Meta-analysis of Incidence of AC in BE patients

Overall Incidence: 6.3/1000 pts year (95%c.i. 4.7-8.4)Heterogeneity: χ2= 238.2, p<.001)

Yousef F Am J Epidemiol 2008

Esofago di Barrett e Rischio di AdenocarcinomaE.B.R.A. Registry

• Standard endoscopic definition

• Standard pathologic report

• Definition of follow-up and outcomes

• Audit• Semestral meeting24 participant

centers

Prof G Zaninotto – Prof M Rugge

• Only index endoscopy: 439 pts (34%)

• Incident lesion at index endoscopy– 4 invasive cancer– 7 HG IEN

• Incident lesion (w/in 12 months) – 3 invasive cancer– 3 HG IEN

BE enrolled patients : 1297

Considered for

analysis:841

E.B.R.A. Registry. Results .1.

Median F-Up: 44.6 (24.7 – 60.5) months3083 Patient/years

23pts

Progression to HG-IEN/ACMultivariate Analysis

P-Value RR (95% CI)

Age 0.12 -

BE Length ( cm) 0.01 1.16 (1.03-1.30)

Hiatus Hernia(cm) 0.25 -

Nodularity/Ulceration (yes-no)

0.0002 7.60 (2.63-21.98)

LG –IEN (yes-no) 0.02 3.74 (1.22-11.43)

Barrett’s esophagus Dysplasia as a marker of

risk

— Endoscopic surveillance is performed primarily to detect dysplasia in Barrett's esophagus

- LGD ( LG NIN )

- HGD ( HG NIN )

The goal of therapy is to prevent cancer progression

Barrett’s esophagus Treatment of GERD

● Medical therapy: PPI

Reduces, does not eliminate, acid secretion and reflux

Eliminates symptoms

● Antireflux surgery


Intervento Antireflusso

Barrett’s Esophagus:Medical vs. Antireflux Surgery

• 89 patients (71 M 18 F, median age 58 yrs) • 45 pts Laparoscopic Nissen • 44 PPI• Follow-up 34 months (minimum F-up 12

months)

G Zaninotto JOGS, 2012

Symptoms: surgery vs medical therapy

* p<0.001

Before treatment

After treatment

* **

I.M. 1-30%

I.M. 31-100%

I.M. 1-30%

I.M. 31-100%

SSBE

LSBE

PRE POST

I.M. Score before and after treatment

p<0.001

No I.M.27%

12/44

Zaninotto G JOGS 2011

I.M. 1-30%

I.M. 31-100%

I.M. 1-30%

I.M. 31-100%

SSBE

PRE POST

I.M. Score before and after treatment

SSBE

Surgery

Medical Therapy

No I.M.

No I.M.

p<0.04

42%

16%

Effect of Antireflux Surgery on Barrett’s epithelium (Short and Long Segment)

Oelschlager 2001 30/54 (55%) 0/36 (0%) <0.001

Hofstetter 2001 8/20 (40%) 1/49 (2%) <0.001

Gurski 2003 11/32 (34%) 0/21 (0%) <0.001

Zaninotto 2005 6/11 (54%) 0/24 (0%) <0.001

Biertho 2006 23/59 (39%) 0/11 (0%) <0.001

Csendes* 2006 20/31 (64%) 26/42 (62%)

Author Year Regression

SSBE LSBEp

* Vagotomy, Partial Gastrectomy & Duodenal Diversion

Regression of LG NiN in BE: Multivariate Analysis

Medical 12/19 63.2 15.53 0.033

Surgery 15/16 93.8

< 60 13/16 77.2 1.02 0.407

> 60 14/19 76.9

Male 17/22 77.2 1.10 0.211

Female 10/13 76.9

SSBE 12/16 75 1.75 0.677

LSBE 15/19 78.9

Post-treatment regression (%) O.R. p

Rossi, Ann Surg 2006

Metanalysis: Probability of regression to lower grades of dysplasia, nondysplastic or non

metaplastic tissue between surgical and medical treated patients

Chang, Ann Surg 2007

Metanalysis: Probability of progression to more advanced grades of dysplasia between surgical

and medical treated patients

Chang, Ann Surg 2007

Comparison of pooled incidence rates of esophageal adenocarcinoma betwen surgically

and medically treated patients

Chang EY, Ann Surg 2007

Onset of HGD/Ca after medical (43 pts) or surgical therapy (58 pts) : long-term results

5% 3%

BE

Onset of HGD/Ca

Medical treatment Surgical treatment

No patients had cancer when surgery was effective!

Parrilla P et al. Ann Surg 2003

Participants 189 820

BMI 26.1 23.1 1.

s/p A.R Surgery 7 (3.7) 8 (1) 1

pts on antireflux medications 4 (57%) 0 0.026

Mean duration (years)of post-op A/R medications

10 = =

Esophageal Adenocarcinoma Control

sp

Barrett’s esophagus Treatment of GERD

Does aggressive treatment of reflux prevent progression to cancer?

— The primary goal of anti-reflux therapy for patients with Barrett's esophagus is to control their reflux symptoms

Available data suggest, but do not prove, that aggressive antireflux therapy might also prevent cancer in these patients.


http://www.uptodate.com/contents/management-of-barretts-esophagus/abstract/4



Does antireflux surgery prevent cancer?

Probably yes,....providing the dam can cope!

Barrett’s esophagus Treatment of LGD

ENDOSCOPIC ABLATION / MUCOSECTOMY AND ANTIREFLUX SURGERY ?

No Agreement


● For most patients with verified low-grade dysplasia after extensive biopsy sampling, we suggest surveillance endoscopy at intervals of 6 to 12 months

(Grade 2C). Extensive biopsy sampling involves taking four-quadrant biopsies at intervals of no more than 1 cm throughout the columnar-lined esophagus

AGA guidelines

http://www.uptodate.com/contents/grade/6?title=Grade%202C&topicKey=GAST/2236




● For most patients with verified low-grade dysplasia after extensive biopsy sampling, we suggest surveillance endoscopy at intervals of 6 to 12 months

(Grade 2C). Extensive biopsy sampling involves taking four-quadrant biopsies at intervals of no more than 1 cm throughout the columnar-lined esophagus

Radiofrequency ablation may be an appropriate therapy for verified low-grade dysplasia if an experienced provider is available

Antireflux surgery??AGA guidelines




No agreement

Barrett’s esophagus Treatment of HGD

TREATMENT OF HIGH-GRADE DYSPLASIA — For patients with verified high-grade dysplasia (also called intraepithelial neoplasia) in Barrett's esophagus, there are generally four proposed management options:

● Esophagectomy

● Endoscopic therapies that ablate the neoplastic tissue

● Endoscopic mucosal resection

● Intensive endoscopic surveillance in which invasive therapies are withheld until biopsy specimens reveal adenocarcinoma.???

No agreement



● Esophagectomy




No agreement



● Esophagectomy





● For most patients with Barrett's esophagus and high-grade dysplasia who are fit to undergo endoscopy, we suggest endoscopic eradication therapy rather than esophagectomy or intensive endoscopic surveillance

(Grade 2C). Endoscopic eradication therapy includes endoscopic mucosal resection for the removal and staging of visible lesions (if present), followed by radiofrequency ablation to ablate the remaining metaplastic epithelium.

AGA guidelines





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, 2000Macey, 2001 Shand, 2001Wolfsen, 2002 Overholt, 2003)

Courtesy E Ancona

EUS Stadiazione

Prophylactic esophagectomy in Barrett’s esophagus with HGD

• Incidence of occult invasive adenocarcinoma:

Tseng, 2003 30% 1982-1994: 43% ( 61% pStage I )1994-2001: 17% ( 100% pStage I )

Fernando, 2002 39% Headrick, 2002 36% Zaninotto, 2000 33% Patti, 1999 36% Ferguson, 1997 53% Edwards, 1996 41% Peters, 1994 55% Rice, 1993 38% Pera, 1992 50% Altorki, 1991 45%

range: 30-55%

pT1a: 5% pN+ pT1b: 18-31% pN+

Courtesy E Ancona

No agreement



● Esophagectomy





● Esophagectomy is the only therapy for high-grade dysplasia that clearly removes all of the neoplastic epithelium,

● rates of procedure-related mortality and long-term morbidity

● post-op quality of life impairment

Endoscopic eradication therapy is available, has proven efficacy (although long-term data are not yet available), and is relatively safe

DIVERTICOLO FARINGO-ESOFAGEO?

Attività 2010-2013 Chirurgia Oncologia dell’Esofago

INTERVENTI RESEZIONE ESOFAGEA: 216

Mortalità Postoperatoria: 2/216 (0.9%)

Fistole Anastomotiche: 6/216 (3.6%)

Open questions in surgical resection for HGD or Early Cancer in Barrett’s

Esophagus• The role of minimal resection (idest

Merendino jejunal interposition)

Courtesy E Ancona

Merendino jejunal interposition

Barrett’s esophagus The case for

esophagectomy

Multifocal HGD, not amenable of eradication with endoscopic mucosectomies

Confirmed diagnosis, 2 expert pathologists, repeated biopsies

Surgical risks acceptable

Lack of patient compliance to endoscopic follow up

The goal of therapy is to prevent cancer progression

No agreement

EGJ Adenocarcinoma Survival after R0 resection

Barrett’s adenocarcinomaInfluence of surveillance on survival

N=10 pts

N=49 pts

N=14 pts

G Zaninotto, E Ancona JOGS, 2012

Barrett’s esophagus Summary and Recommendations

Barrett’s – IM no dysplasia

- Treat GERD- Antireflux surgery in non responders to medical therapy

LGD

- Endoscopic ablation and antireflux surgery- Strict endoscopic followup

HGD

- Endoscopic mucosectomy and/or ablation and antireflux surgery- Esophagectomy if eradication fails or multifocal HGD

Oesophagectomy for cancer:

techniques and results

K Esofago Toracico (n = 2992)

K Esofago Cervicale (n = 717)K Cardias (n = 972)

Periodo: 1980 / 1994 - Pazienti: 3020

13%

65%

22%

Tecnica di esofagectomia per cancro

Esophageal and EG Junction Carcinoma1980-2011: 4179 pz


Esophageal and EG Junction Carcinoma1980-2011: 4179 pz

80-8

485

-89

90-9

495

-99

00-0

405

-11

0

20

40

60

80

100

SCC

Adeno

Altro

Achieving R0 resection should be the goal of surgery

(it is the most significant independent prognostic factor)

Key points

• surgical approach • esophageal resection• gastric resection

• extent of lymphadenectomy


Type II: Distal esophagectomy and proximal gastrectomy with paraesophageal and upper abdominal lymphadenectomy; resection extended to subtotal esophagectomy with proximal gastrectomy or total gastrectomy, or esophago-gastrectomy.

Adenocarcinoma of the esophagus & esophago-gastric junction

• Type I Esophago-gastric resection

& gastric pull-up

• Type II Esophago-gastric resection& gastric pull-up

Extended gastrectomy & esophago-jejunostomy

Limited resection for early cancer :short esophageal resection + proximal gastrectomy & Merendino jejunal interposition

• Type III Extended gastrectomy (D2)& esophago-jejunostomy

?


Trends in Management and Prognosis for Esophageal cancer

SurgeryTwenty-five Years of Experience at a Single Institution

Objective: To investigate trends in results of esophagectomies for carcinoma at a single

high-volume institution

Ruol A, Castoro C, et al. Arch Surg 2009; 144(3):247-254


1980-2004: 3493 carcinoma of the thoracic esophagus & EG-J type I-II

1978 consecutive surgical resections

years 1980-1987 1988-1995 1996-2004

N. patients % resections

p = 0.01

785/1438 54.6%

659/1178 55.9%

534/877 60.9%

R0 complete

resections p <

0.0001

585 74.5%

502 76%

481 90%

Ruol, Castoro et al. Arch Surg 2009;144(3):247-54

1978 esophagectomies for Cancer of the thoracic esophagus & EG-J - postoperative deaths

%

1.4% (7/495) after

gastric pull-up

64/785 8.2%

42/659 6.4%

14/534 2.6%

in-hospital deaths p < 0.0001



1980-1987 (n=785) 1988-1995 (n=659)1996-2004 (n=534)

Survival after resection surgery (R0-2), including postop. deaths

months

%

p<0.0001

43%

19%23%




New standards

• Early cancer T1a: endoscopic mucosectomy

• Neoadjuvant chemo-radiation (CROSS Trial)

• Minimally invasive oesophagectomy

• High volume centers multidisciplinary team

- Stadio potenzialmente operabile: CT, CT-RT,

Chirurgia?

- Terapia neoadiuvante: quando? quale ?

- Terapia definitiva: quando? quale CT-RT?

Carcinoma dell’esofago e del cardias:percorsi diagnostico-terapeutici

Padova, 9 Maggio 2014

Linee Guida: NCCN, ESMO, AIRO, AIOM

Courtesy H. van Laarhoven

To treat or not to treat neoadjuvantly?

That is not the question (anymore)

Courtesy H. van Laarhoven Ronellenfitch, Eur J Cancer 2013, 3149

Courtesy H. van LaarhovenSjoquist Lancet Oncol 2011

BJS 2014; 101: 321


Surgery(n=188)

N+ or T2/T3 oesophageal cancer

41.4Gy in 5 wkspaclitaxel 50 mg/m2 q wkCarboplatin AUC 2 q wk

Surgery(n=178)

CROSS: randomized phase III study

Van Hagen NEJM 2012

Courtesy H. van LaarhovenVan Hagen NEJM 2012

Courtesy H. van LaarhovenVan Hagen NEJM 2012


Neoadjuvant chemoradiation treatment of choice for oesphageal adenocarcinoma

How to make another substantial step forward?


Target therapy

Education

Trattamento chirurgico dell'esofago di Barrett - Gastrolearning®