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TERAPIA CHIRURGICA DELLA DISPLASIA GRAVE IN ESOFAGO DI BARRETT. Luigi Bonavina,MD Cattedra e U.O. Chirurgia Generale, Policlinico San Donato Università degli Studi di Milano. XXIV Congresso Nazionale A.C.O.I. Montecatini Terme, 27 Maggio 2005. Esophageal adenocarcinoma Melanoma

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Terapia chirurgica della displasia grave in esofago di barrett

TERAPIA CHIRURGICA DELLA DISPLASIA GRAVE IN ESOFAGO DI BARRETT

Luigi Bonavina,MD

Cattedra e U.O. Chirurgia Generale, Policlinico San Donato

Università degli Studi di Milano

XXIV Congresso Nazionale A.C.O.I. Montecatini Terme, 27 Maggio 2005


Terapia chirurgica della displasia grave in esofago di barrett

Esophageal adenocarcinoma BARRETT

Melanoma

Prostate Cancer

Breast Cancer

Lung Cancer

Colorectal Cancer

Rate ratio (relative to 1975)

Pohl H, J Natl Cancer Inst 2005


Terapia chirurgica della displasia grave in esofago di barrett

5-YR SURVIVAL RATES ACC. TO WALL INFILTRATION BARRETT

90%

80%

1 cm

70%

30%


Terapia chirurgica della displasia grave in esofago di barrett

PREVALENCE OF NODE+ ACC. TO WALL INFILTRATION BARRETT

%

Bonavina et al, WJS 2003


Terapia chirurgica della displasia grave in esofago di barrett

GASTROESOPHAGEAL REFLUX DISEASE BARRETT

Barrett’s metaplasia

Low grade dysplasia

High grade dysplasia

(in situ carcinoma)

Invasive carcinoma


Terapia chirurgica della displasia grave in esofago di barrett

MOLECULAR EVENTS IN THE SEQUENCE BARRETT

BARRETT’S ESOPHAGUS-ADENOCARCINOMA

Diploid cell

p53/p16 mutation

Clonal expansion and

multicentricity

Unpredictable molecular

alterations (5q,18q,13q)

Adenocarcinoma

Barrett M, Nature Genetics 1999


Terapia chirurgica della displasia grave in esofago di barrett

HIGH-GRADE DYSPLASIA BARRETT

Dysplasia is the histological expression of genetic alterations that favor cell growth and neoplasia. Glands show severe cytologic atypia, gland complexity with cribriform change and complete loss of nuclear polarity


Terapia chirurgica della displasia grave in esofago di barrett

CUMULATIVE CANCER INCIDENCE BARRETT

1.0

0.8

HGD

# Ca / n = 33/76

p < .001

Negative, Indefinite, LGD

# Ca / n = 9/251

0.6

Probability

0.4

0.2

0.0

0

6

12

2

4

8

10

14

Years

Reid et al, AJG 2000


Histologic changes after treatment of be median f u 5 yrs
HISTOLOGIC CHANGES AFTER TREATMENT OF BE BARRETT(median F/U > 5 yrs)

Parrilla et al, 2003


Terapia chirurgica della displasia grave in esofago di barrett

OUTCOME OF RESECTION ACC. TO SURVEILLANCE BARRETT

Cumulative survival %

p< 0.01

months

Incarbone et al, Surg Endosc 2002


Difficulties with the diagnosis of hgd
DIFFICULTIES WITH THE DIAGNOSIS OF HGD BARRETT

  • Interobserver agreement is 85% for distinguishing HGD from lesser lesions

  • There can be substantial disagreement when distinguishing HGD from intramucosal cancer

  • Dysplastic areas and foci of invasive cancer can be missed by 4-quadrant biopsy technique


Extent of hgd
EXTENT OF HGD BARRETT

  • FOCAL (histologic abnormalities confined to single focus involving up to 5 crypts)

  • DIFFUSE (abnormalities present in more than 5 crypts or in multiple biopsy specimen)

Buttar, 2001


Terapia chirurgica della displasia grave in esofago di barrett

EXTENT OF HGD AND CANCER RISK BARRETT

n=100

4-quadrant biopses every 2 cm

Focal4/33 (14%)

Diffuse28/67 (56%)

p<0.001

Buttar et al., Gastroenterology 2001


Reccomendation of practice parameters committee of a c g
RECCOMENDATION OF PRACTICE PARAMETERS COMMITTEE OF A.C.G. BARRETT

“…patients with focal HGD may be followed with intensive endoscopic surveillance (every 3 months), whereas intervention (e.g. endoscopic ablation or esophagectomy) should be considered for patients with diffuse HGD”

Sampliner et al, 2002


Terapia chirurgica della displasia grave in esofago di barrett
Can extent of high grade dysplasia in Barrett’s oesophagus predict the presence of adenocarcinoma at oesophagectomy?

  • Revision of preop biopsy specimen in 42 patients who had esophagectomy for HGD

  • Acc. to Cleveland Clinic criteria, 48% with focal and 67% with diffuse HGD had cancer (pNS)

  • Acc. to Mayo Clinic criteria, 72% with focal and 54% with diffuse HGD had cancer (pNS)

Dar et al, Gut 2003


Rate of occult invasive carcinoma in hgd
RATE OF “OCCULT” INVASIVE CARCINOMA IN HGD predict the presence of adenocarcinoma at oesophagectomy?


Terapia chirurgica della displasia grave in esofago di barrett

HIGH RATE OF OCCULT CARCINOMA predict the presence of adenocarcinoma at oesophagectomy?

  • Erroneous definition of HGD (missed intramucosal ADC)

  • Inclusion of patients with warning signs (presence of nodules/ulcers)

  • Failure to f/u closely during the first year (cancer missed at 1st endoscopy because of sampling error)


Treatment of high grade dysplasia
TREATMENT OF HIGH-GRADE DYSPLASIA predict the presence of adenocarcinoma at oesophagectomy?

  • Intensive surveillance

  • Endoscopic ablation

  • Endoscopic mucosectomy

  • Esophagectomy


Terapia chirurgica della displasia grave in esofago di barrett

ENDOSCOPIC MUCOSAL RESECTION FOR HGD/IM-Ca predict the presence of adenocarcinoma at oesophagectomy?

1.Area of Barrett’s < 20 mm in diameter

2. Cancers confined to the lamina propria

3. Involved peripheral or deep margins or extension

through muscularis mucosa require esophagectomy


Terapia chirurgica della displasia grave in esofago di barrett

S.B., male, 62 yr old: S/P endoscopic mucosectomy: invasive adenocarcinoma on the resected specimen


Terapia chirurgica della displasia grave in esofago di barrett

TIMING OF SURGERY AND SURVIVAL adenocarcinoma on the resected specimen

Prompt Attitude (n=20)

100

100%

80

Expectant Attitude (n=13)

60

Cancer-related survival (%)

52.5%

40

30

p = 0.0094

0

0

24

48

72

96

120

144

168

192

Romagnoli, JACS 2003


Terapia chirurgica della displasia grave in esofago di barrett

FREQUENCY OF ESOPHAGECTOMY AND HOSPITAL MORTALITY adenocarcinoma on the resected specimen

Mortality rate (%)

Case load/year

Metzger,Dis Esoph 2004


Terapia chirurgica della displasia grave in esofago di barrett

PARTIAL ESOPHAGECTOMY AND JEJUNAL INTERPOSITION adenocarcinoma on the resected specimen

  • Theoretical drawbacks

  • High mediastinal anastomosis

  • Incomplete Barrett’s ablation

  • Limited clinical experience (Siewert)


Terapia chirurgica della displasia grave in esofago di barrett

NERVE SPARING ESOPHAGECTOMY adenocarcinoma on the resected specimen


Terapia chirurgica della displasia grave in esofago di barrett

LAPAROSCOPIC + TRANS-CERVICAL adenocarcinoma on the resected specimen

VIDEOASSISTED MEDIASTINAL DISSECTION

Bonavina et al, J Lap Adv Surg Tech, 2004


University of milano department of surgery

ADENOCARCINOMA OF EGJ adenocarcinoma on the resected specimen

506 consecutive patients

(1992-2004)

University of Milano, Department of Surgery

(31%)


Patients referred for hgd n 30
PATIENTS REFERRED FOR HGD adenocarcinoma on the resected specimenn=30


Staging protocol
STAGING PROTOCOL adenocarcinoma on the resected specimen

  • Operative risk assessment

  • Repeat endoscopy + Lugol staining

  • Brushing cytology

  • 4-quadrant biopsies every cm

  • Look for nodules/ulcers

  • EUS/CT scan if doubtful

  • High-dose PPI if less than HGD

  • Repeat endoscopy (at 1-3 months)


Terapia chirurgica della displasia grave in esofago di barrett

RESULTS OF STAGING AND THERAPY (n=30) adenocarcinoma on the resected specimen

1st endoscopy:

7 invasive carcinoma (>surgery)

1 LGD

22 HGD (73%)

2nd endoscopy:

5 invasive carcinoma (>surgery)

1 LGD

17 HGD (57%)

15 surgery (9 TME, 6 TTE)

1 PDT

1 PPI therapy


Terapia chirurgica della displasia grave in esofago di barrett

RESULTS OF ESOPHAGECTOMY FOR HGD adenocarcinoma on the resected specimen

n=15

  • No operative mortality

  • Morbidity

  • 2 atelectasis

  • 1 chylothorax

  • Pathology

  • 1 LGD

  • 4 invasive carcinoma (27%)

  • 10 confirmed HGD


Terapia chirurgica della displasia grave in esofago di barrett

ESOPHAGECTOMY FOR HGD adenocarcinoma on the resected specimen

Actuarial survival (n=15)


Ongoing research protocols

ONGOING RESEARCH PROTOCOLS adenocarcinoma on the resected specimen

Endoscopic peritumoral ink injection

Laparoscopic nodal removal

Histopathological assessment

Tailored lymphadenectomy based on the sentinal node concept


Conclusions

CONCLUSIONS adenocarcinoma on the resected specimen

Prevalence of adenocarcinoma detected at endoscopy was 40% in patients referred with diagnosis of HGD

27% of patients with confirmed endoscopic diagnosis of HGD had cancer in the resected specimen

E.M.R. should be recommended only in patients with low likelihood of lymphatic spread

Videoassisted transmediastinal esophagectomy is the approach of choice in intramucosal tumors


Terapia chirurgica della displasia grave in esofago di barrett

“Surgery remains radical prophylaxis.…offering a massive macroscopic morbid solution for a microscopic mucosal problem”

Barr, Gut 2003; 52:14-5


Future scenario
FUTURE SCENARIO macroscopic morbid solution for a microscopic mucosal problem”

  • Improved reflux control by fundoplication

  • Barrett’s ablation and chemoprevention of genomic instability (Aspirin?)

  • Tailored surgical approach (vagal sparing procedures, sentinel node technology)