Dr. Paolo BocusDirettore U.O.C. di Gastroenterologia ed Endoscopia Digestiva

Ospedale Sacro Cuore – Don Calabria

Negrar (VR)

Endoscopia Diagnostica(Ecoendoscopia Diagnostica)

13 Dicembre 2016

Diagnosi endoscopica

Missed cancers 7,8%

2014

Missed cancers 7,2%

2004

• Studio retrospettivo inglese di coorte, basato sulla popolazione, ha identificato pazienti con diagnosi di cancro dell’esofago tra aprile 2011 e marzo 2012 utilizzando due database connessi (National Oesophago-Gastric Cancer Audit and Hospital Episode Statistics).

• Il main outcome era la percentuale di precedenti endoscopie nei 3 - 36 mesi prima della diagnosi di cancro.

• 6943 nuovi casi identificati, dei quali 7.8 % (95 % CI 7.1 - 8.4) erano stati sottoposti ad endoscopia nei 3 - 36 mesi precedenti la diagnosi.

• Stadio 0/1: 34.0 % endoscopia nei 3-36 mesi precedenti

• Stadio 2 10.0 %

• Stadio 3-4 4.5 %.

• Stadio 0/1 22.1 % diagnosticati dopo ≥ 3 endoscopie nei precedenti tre anni.

• Pazienti con un tumore dell’esofago cervicale sono stati sottoposti ad un numero maggiore di endoscopie nei 3 - 12 mesi precedenti (P = 0.040).

• La diagnosi più frequente è stata un’ulcera esofagea (48.2 % dei reperti).

• Il cancro dell’esofago può non essere individuato in circa il 7.8 % dei pazienti con successiva diagnosi di cancro.

Chadwick G, et al. Endoscopy 2014 Volume 46, Issue 7; Pages 553-60

Cancers Rarely Missed by Upper EndoscopyFrom Reuters Health Information

Cancers Rarely Missed by Upper GI EndoscopyBy Will Boggs, MD

NEW YORK (Reuters Health) Jan 29 - In Western populations, cancer is very rarely missed on esophagogastroduodenoscopy (EGD), say researchersfrom Australia in the American Journal of Gastroenterology.

"Although EGD remains an imperfect test, false-negative examinations are uncommon, particularly in those with a completely normal EGD," Dr. Spiro C. Raftopoulos from Sir Charles Gairdner Hospital, Perth, Western Australia, told Reuters Health in an email.

In an advance online article published January 12th, he and his colleagues note that in reports from Japan, rates of missed upper GI cancersare as high as 25%, but "these studies are not necessarily applicable to the West."

In their analysis of data on 28,064 EGDs done in Australia from 1990 to 2004, the researchers identified only 29 cases of missed cancer, 26 possible missed cancers (detected more than a year after EGD), and 75 latent cancers (diagnosed at least 3 years after a normalEGD).

Only 8 patients with a missed cancer had their EGD read as completely normal; most of those with missed cancers (72.4%) had an abnormalitydescribed at the site of the cancer. The missed cancer rate (i.e., the number of missed cancers divided by the total number of cancers diagnosedduring the study period) was 1.1% for normal EGDs and 3.5% for all EGDs.

The only significant factor associated with a missed cancer was an alarm symptom of either dysphagia or suspected bleeding.

The likelihood of missed or new cancer was independent of operator type or equipment used, the researchers note.

"Given that false-negatives do occur, this needs to be incorporated into the clinical decision making in patients with ongoingsymptoms after EGD, and where appropriate, they should undergo repeat examination to rule out a missed cancer," Dr. Raftopoulossaid.

"In particular, those patients with alarm symptoms (dysphagia, unintentional and sustained weight loss, suspected bleeding) who present for endoscopy, I now have a much lower threshold to biopsy any abnormality seen, and if symptoms are persistent, I follow these patients up with an early repeat endoscopy, and consider further investigations such as cross-sectional imaging (e.g., CT chest/thorax)," he added.

Am J Gastroenterol 2010

Cancro squamocellulare superficiale

Riconoscere la lesione

Definire i margini della lesione

Determinare il livello di infiltrazione della lesione ed ilrischio di interessamento linfonodale

Imparare a:

Imparare ad utilizzare:

Endoscopia ad alta risoluzione

Cromoendoscopia elettronica (NBI FICE I-Scan AFI)

Cromoendoscopia con coloranti vitali

Le classificazioni di

Parigi (lesioni visibili)

Praga (Barrett)

Inoue (Squamocellulare)

Siewert

I protocolli bioptici di

Seattle e Levine (e del registro del Barrett EBRA!)

NBI (Narrow Band Imaging)

FICE (spectral image processing technology for High Contrast Imaging)

I-Scan

AFI (Autofluorescence Imaging)

Paris Classification of Superficial Neoplastic Lesions in the Digestive Tract

Protocollo di Seattle

BSG Guidelines 2005

Wang KK AmJG 2008

Spechler SJ Gastroenterology 2011

Curves WL EUR J Gastro Hep 2008

Abrams JA Clin Gastro Hep 2009

Wani S Gastroenterology 2011

Time consuming

Risk of bleeding

Poor adherence

Costs

• Precedenti neoplasie capo-collo

• Forti fumatori, bevitori

• Regioni ad alto rischio

Anamnesi

Molta attenzione

Barrett “lungo” e bx con HGD su area rilevata Parigi IIa a 27 cm

Adenocarcinoma in Barrett

Pit Pattern

Pit Pattern

Ac Acetico in Barrett

Blu di Metilene in Barrett

Cromoendoscopia con Lugol in SCC

Cromoendoscopia con coloranti

Cromoendoscopia con Lugol in BE

Indaco Carminio

Trimodal endoscopy

Endoscopic tri-modal imaging is more effective than standard endoscopy in

identifying early-stage neoplasia in Barrett's esophagus.

Curvers WL et al. Gastroenterology. 2010 Oct;139(4):1106-14.

Trimodal endoscopy (TME) is a combination of autofluorescence endoscopy (AFI)

with high-magnification endoscopy (HME) and narrow-band imaging (NBI).

Coloranti Vitali

• Lugol

• Blu di metilene

• Cresyl violetto

• Blu di toluidina

Coloranti di contrasto• Indaco di Carminio

• Acido acetico

Coloranti reattivi• Rosso Congo

• Rosso Fenolo

Per Tatuaggio• Inchiostro di China

Classificazione dei coloranti

Colorante Azione Non colora Uso Clinico

Lugol Interagisce con i vacuoli di

glicogeno dell’ epitelio

malpighiano

Displasia

Cellule infiammatorie

Neoplasia squamosa

mucosa colonnare

Ca squamoso dell’esofago

Esofagite da reflusso

EB (delinea epitelio squamoso

da ep colonnare

Blu di

Metilene

Cellule di tipo intestinale

assorbenti

Epitelio squamoso e gastrico

Mucosa colonnare

Metaplasia intestinale gastrica

Barrett (colora l’epitelio

specializzato colonnare e non la

mucosa di tipo gastrico)

Indaco di

Carminio

Mette in rilievo la

superficie mucosa senza

essere assorbito.

Utile per rilevare le irregolarità

o nodularità di parete (es. polipi

piatti del colon)

Classificazione dei coloranti

Questo ci consente di porre diagnosi e di iniziare a stadiare la lesione:

Inoue H et al. Ann. Gastroenterol 2015 Jan-Mar;28(1):41-48.

IPCL: intraepithelial papillary capillary loop

IPCL: intraepithelial papillary capillary loop

Paris classification

Inoue classification

IPCL Tipo IV IPCL Tipo V 1 IPCL Tipo V n

Inoue H et al. Ann. Gastroenterol 2015 Jan-Mar;28(1):41-48.

Conclusions: The overall diagnostic

accuracy of both HR-E and HR-EUS with

a 20 MHz miniprobe in early

oesophageal cancer was high

(approximately 80%), with no significant

differences between the two techniques.

HR-E and HR-EUS provide a high level

of diagnostic accuracy for mucosal

tumours and submucosal tumours

located in the tubular part of the

oesophagus.

With submucosal tumours located at

the oesophagogastric junction or with

infiltration of the first third of the

submucosa however, the diagnostic

accuracy of both techniques is not yet

satisfactory.

la conoscenza dello stadio

della malattia è importante per

fornire al paziente delle cure il

più possibile appropriate, oltre

che per formulare una

probabile prognosi

(Wikipedia).

Stadiazione:

New TNM staging (7th ed., 2010)

Siewert Classification

Siewert Type I: adenocarcinoma of the lower esophagus with the center located within 1

cm to 5 cm above the anatomic EGJ.

Siewert Type II: true carcinoma of the cardia with the tumor center within 1 cm above and

2 cm below the EGJ.

Siewert Type III: subcardial carcinoma with the tumor center between 2 and 5 cm below

EGJ, which infiltrates the EGJ and lower esophagus from below.

Siewert type III lesions are considered

gastric cancers, and thus the NCCN

Guidelines for Gastric Cancer should be

followed. In some cases additional

esophageal resection may be needed in

order to obtain adequate margins.

To EUS or not EUS?

2013

Gerke H. Endoscopic mucosal resection for early esophageal cancer: skip EUS and cut to the chase. Gastrointest Endosc. 2011 Apr.

Pouw RE et al. Do we still need EUS in the workup of patients with early esophageal neoplasia? A retrospective analysis of 131 cases.

Gastrointest Endosc. 2011 Apr.

Savoy AD Wallace MB. J Clin Gastroenterol Volume 39, Number 4, April 2005

Routine use in patients with Barrett’s esophagus

without dysplasia or focal lesions cannot be

endorsed.

Its main use in Barrett’s esophagus appears to be in

the detection of more deeply invading tumors, and

metastatic lymph nodes, which would preclude the

appropriate use of endoscopic ablative therapies.

EGDS (zoom, NBI, FICE, etc)

EUS (+/- FNA)

EMR / ESD

CT/PET scan

Staging Strategies

2013

Complete staging of esophageal cancer has

traditionally involved EUS and FNA in conjunction

with cross-sectional imaging.

Numerous studies have demonstrated the

superiority of EUS in both local tumor (T) and

nodal (N) staging over CT.

Accuracy for T staging approaches 90% in

superficial

and partially obstructing esophageal cancers.

The accuracy of EUS for nodal staging based

solely on

these acoustic criteria approaches 80%.

FNA of lymph nodes increases nodal staging

accuracy to 92% to 98% by using pathologic

staging as the criterion standard.

2013

• Exclude the presence of advanced cancer that is not resectable by EMR or

ESD (>T1 disease)

• Distinguish between early cancer confined to the mucosa (T1a) and

submucosal invasion (T1b)

• Assess for lymph node metastasis

GOALS OF EUS IN BARRETT’S ESOPHAGUS WITH HGD AND CANCER

Mappaggio

+

EUS

EUS T1m Accuracy 75%

EUS staging of T1 Esophageal

Adenocarcinoma

19 studies with 1019 patients with

superficial adenocarcinoma of the

esophagus comparing EUS with surgical

or EMR pathology

–T1a: Sensitivity 85%, Specificity 87%

–T1b: Sensitivity 86%, Specificity 86 %

–Accuracy 85%

Thosami, N. et al. Gastrointest Endosc 2012;75:242-253

HFP-EUS staging of T1 Esophageal Adenocarcinoma

Seerden, T.C., et.al. Gastrointest Endo Clin N Am 21; 2011: 53-66

DIFFICULTIES IN STAGING T1/T2 LESIONS

Crypts and villi in BE are more heterogenous than layered architecture of

squamous epithelium

BE can be associated with inflammatory changes and presence of double

muscularis mucosae

Motility of Esophagus (HFP EUS)

BE lesions located in the distal esophagus/cardia EUS interpretation can be

difficult

Endoscopists experience/Technical difficulties

Dunbar KB, Spechler SJ. The Risk of Lymph-Node Metastases in Patients With High-Grade Dysplasia or Intramucosal Carcinoma in Barrett ’ s Esophagus: A Systematic Review. Am J Gastroenterol. 2012 Apr 10

RESULTS:

70 relevant reports that included 1,874 patients

who had esophagectomy performed for HGD or

intramucosal carcinoma in Barrett ’ s esophagus.

Lymph-node metastases were found in 26

patients (1.39 % , 95 % CI 0.86 – 1.92).

No metastases were found in the 524 patients

who had a final pathology diagnosis of HGD

26 had positive lymph nodes

(1.93 % , 95 % CI 1.19 – 2.66 % ) of the 1,350

patients with a final pathology diagnosis of

intramucosal carcinoma.

Raja et al. Esophageal submucosa: The watershed for esophageal cancer. The Journal of Thoracic and Cardiovascular Surgery 2011

Increasing depth of

submucosal invasion

is associated with a

disproportionately

increasing occurrence

of regional lymph node

metastases, leading to

decreasing survival.

A submucosal

cancer is not a

superficial

cancer!

sm1 sm2 sm3

RISK OF LN INVOLVEMENT IN ADENOCARCINOMA OF THE ESOPHAGUS

CORRELATING WITH T-STAGE

T-STAGE LN RISK OF MALIGNANCY

T1is/T1a (mucosa) <2 %

T1b (submucosa) >20%

Buskens, C.J., et. al. Gastrointest Endosc 2004; 60: 703-710

Incidence of lymph node metastases in superficial esophageal cancers according to depth of invasion

Shimada, H, et al. Prediction of lymph node status in patients with superficial esophageal carcinoma: analysis of 160 surgically resected cancers. Am J Surg 2006; 191:250.

Puli et al World J Gastroenterol 2008 May 21; 14(19): 3028-3037

NO FNA FNA

Puli et al World J Gastroenterol 2008 March 14; 14(10): 1479-1490

EUS-FNA of LN associated with Barrett’s with HGD and Intramucosal Adenocarcinoma

25 patients with HGD or Intramucosal Adenocarcinoma in Barrett’s referred for EUS staging

HGD in 12 patients, Intramucosal Adenocarcinoma 13 patients

5 patients had submucosal invasion by EUS

7 patients had suspicious LN. EUS-FNA confirmed malignancy in 5

Conclusion: EUS-FNA of suspicious LN changed management in 20% of patients

Shami, V.M. Endoscopy 2006; 38: 157-161

Neoplasie avanzate

Strutture adeguate

Accorgimenti tecnici

Miglior strumento disponibile (NBI, FICE, I-Scan, AFI, EUS ETC)

Cromoendoscopia con colorazioni

Optimal Setting (sedazione, adeguato tempo per l’indagine)

Punti di difficile valutazione (cervicale, jato, ernia)

Strumento pediatrico nelle lesioni avanzate

Valutare la eventuale necessità di dilatazione (Savary) nelle lesioni

avanzate

TAKE HOME POINTS

Segnalare nel referto:

Tipo di lesione secondo la classificazione di Parigi (morfologia e dimensioni)

La sede della neoformazione rispetto agli incisivi, allo sfintere esofageo superiore

ed inferiore

Grado di coinvolgimento circonferenziale e di ostruzione al passaggio

Posizione, lunghezza ed estensione dell’esofago di Barrett + noduli o altre lesioni

visibili (Class. di Praga)

Multiple biopsie da (6 a 8 sulle lesioni) e mappaggio con protocolli adeguati

(Seattle e o Levine)

Eventualmente pinze jumbo nel fu del Barrett

TAKE HOME POINTS

EUS nella stadiazione del Barrett con HGD o Early Adenocarcinoma e nelle

forme superficiali di SCC può essere utile per:

– Escludere l’invasione nella sottomucosa >T1a (o oltre T2)

– Valutare la presenza di linfonodi sospetti e/o malattia metastatica

– Eseguire la EUS-FNA dei linfonodi sospetti (se questo dato può cambiare il

management del paziente)

TAKE HOME POINTS