Endoscopy In Gastric Cancer: New Imaging Techinques, New Treatment .

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Endoscopy in gastric cancer: Newimaging techinques, new treatmentmodalities (EMR, ESD)Javier Sempere García-ArgüellesConsorcio Hospital General UniversitarioValencia. Spain

Disclosure of interest“No conflict of interests”

Role of endoscopy ingastric cancer:1. SCREENING2. DIAGNOSIS3. STAGING4. TREATMENTNew imaging techinques

New imaging techinques, new treatment modalities (EMR, ESD)1.Screening

Correa Modelof carcinogenesis

Preneoplasticconditions

Neoplasticlesions

“Early detectionand tratmentis the only way toreduce mortality”

Importance of nceNeoplasticlesions“Early stages”

SCREENING POPULATION?1ºscreeningPRENEOPLASTIC CONDITIONS?2ndsurveillanceNEOPLASTIC LESIONS?Screening and surveillance for gastric cancer in the United States: Is it needed? Kim. GH. GIE 2016

SCREENINGPOPULATIONInmigrants(high risk regions)Familiy History“Oportunisticscreening”(EGD onic Atrophic Gastritis (CAG)Gastrointestinal metaplasia (GIM)2ndsurveillanceNEOPLASTICLESIONSDisplasia (Intraepithelial neoplasia)AdenocarcinomaDetection of EGCwill improve the survivalrate of this cancer.Screening and surveillance for gastric cancer in the United States: Is it needed? Kim. GH. GIE 2016

SCREENINGPOPULATIONInmigrants(high risk regions)Familiy History“Oportunisticscreening”(EGD endoscopies)Eastern Countries (Japan,Korea): 60% of gastric screeningcancers are EGC (earlygastric cancer)PRENEOPLASTICCONDITIONS1ºChronic Atrophic Gastritis lmetaplasiathan 10%.2ndsurveillanceNEOPLASTICLESIONSDisplasia (Intraepithelial neoplasia)AdenocarcinomaIs time fornew imagingtechinques?Screening and surveillance for gastric cancer in the United States: Is it needed? Kim. GH. GIE 2016

first step: is high-quality endoscopy:Rutine Conventional With Light Endoscopy (WLE)SSS protocol 7 minutes Adequate preparation Insuflation Image documentation Avoid Blind Areas (SSS protocol)Performance measures for upper gastrointestinal endoscopy: A European Society of Gastrointestinal Endoscopy quality improvement initiative.Bisschops et al.2016

WHITE LIGHT ENDOSCOPY (WLE): Chronic atrophic gastritis Loss of gastric folds Mucosal pallor Increase visibility of mucosalvesselsATLAS OF CLINICAL GASTROINTESTINAL ENDOSCOPY Third edition C. Mel Wilcox

WITHE LIGHT ENDOSCOPY (WLE): GASTRIC INTESTINAL METAPLASIA (GIM) white plaquelike lesionswith a verrucousappearance

White light endoscopy in the diagnosis of Chronic atrophic gastitisand intestinal metaplasia Poor sensitivity and specificity Poor interobserver agreement Poor correlation with histologyCrhonic atrophic gastritisIntestinal metaplasiaWaddinham W. F1000Research 2018;Dinis-Ribeiro M, Endoscopy 2012

White light endoscopy in the diagnosis of Chronic atrophic gastirtisand intestinal metaplasiaThe diagnosis and risk stratification ofCrhonic atrophic gastritispremalignant changes in the stomach, such aschronic atrophic gastritis (CAG) and gastricintestinal metaplasia (GIM), are reliant onhistopathologyIntestinal metaplasiaWaddinham W. F1000Research 2018;Dinis-Ribeiro M, Endoscopy 2012

“Non-targetedbiopsies”Update Sidney SystemDixon MF, Am J Surg Pathol 1996

Staging CAG and GIM: OLGA and OLGIM systemCapelle LG, de Vries AC, Haringsma J, Ter Borg F, de Vries RA, Bruno MJ, van Dekken H, Meijer J, van Grieken NC, Kuipers EJ. The staging of gastritis with theOLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc. 2010;71(7):1150–8.

osix case–control studies and two cohortstudies,o2700 subjectsRELATIVE RISK: OLGIM,OLGA LOW STAGES (I/II) VS HIGH STAGES (III/IV)OLGIM III/IV: RR 3.99OLGA III/IV: RR 27,70

Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), EuropeanHelicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED) Dinis-Ribeiro M, Endoscopy 2012

Update Sidney SystemLimitations .o Low acurracy in WLE detection of CAG andGIMo “Non -targeted biopsies (blind)o Poor correlation endoscopy and biopsieso Poor interoberver agreement in histology(OLGA/OLGIM)Is it possible to improve the diagnosis of CAG and GIM?New advanced techiques? The era of “optic diagnosis”

Conventional endoscopyWhite light endoscopy(WLE)New advanced imaging tecnniques Dye-Based Image-Enhanced Endoscopy(Chromoendoscopy) image-enhancing endoscopy techniques(virtual Chromoendoscopy):Narrow Band Imaging (NBI)Others (FICE, iScan ) Magnifying Endoscopy:Magnifying Endoscopy ChromoendoscopyMagnifying Endoscopy NBI Confocal Laser endomicroscopy (CLE) Endoscopic ultrasound (EUS)

Conventional endoscopyWhite light endoscopy(WLE)New advanced imaging tecnniques Dye-Based Image-Enhanced Endoscopy(Chromoendoscopy) image-enhancing endoscopy techniques(virtual Chromoendoscopy):Narrow Band Imaging (NBI)Others (FICE, iScan ) Magnifying Endoscopy:-Magnifying Endoscopy Chromoendoscopy-Magnifying Endoscopy NBI Confocal Laser endomicroscopy (CLE) Endoscopic ultrasound (EUS)

Dye-Based Image-Enhanced Endoscopy(Chromoendoscopy)INDIGO CARMINE: morphologicalcharacteristics of the surface mucosaMETHYLENE BLUE: Stains gastric intestinalmetaplasia

Dye-Based Image-Enhanced Endoscopy(Chromoendoscopy) with WLECHRONIC ATROPHICGASTRITIS(Indigo carmine)Atrophic areas

image-enhancing endoscopy techniques (“virtualchromoendoscopy”): NARROW BAND IMAGING (NBI)blue and green narrowband lights(absorbed by hemoglobin)Vascular and surface architectureo superficial capillary networko Depht collecting vessels

NARROW BAND IMAGING (NBI)WLENBI“Normal gastric Body”

NARROW BAND IMAGING (NBI)WLENBINormal glands“Normal antrum”Colecting vessels

NARROW BAND IMAGING (NBI)“intestinal metaplasia”

Magnifying Endoscopy (ME)OPTIC ZOOM (x80)“Real-time Optic diagnostic”M-WLEME CHROMOENDOSCOPYMicrosurface mucosa structureME Narrow Band iImaging (NBI)Mucosal microvascular architectura

Magnifying Endoscopy (ME) Chromoendoscopy (indigo carmine)NORMAL BODYINTESTINAL METAPLASIA

Magnifying Endoscopy NBI (M-NBI)Normal corpusfundus mucosa

Magnifying Endoscopy NBI (M-NBI)Normal antralmucosa

Magnifying Endoscopy NBI (M-NBI)GASTRIC INTESTINALMETAPLASIA

NO WLEME-CHROMOENDOSCOPYOR NBIBiopsies should be taken

White Light Endoscopy- biopsiesVsNBI-Targeted biopsiesAccuracy, Sen, Spe NBI-targeted biopsies WLE-biopsiesPimentel-Nunes Pedro et al. NBI for the diagnosis of gastric lesions Endoscopy 2016; 48: 723–730

Importance of the “oportunistic screening in our “scenario” (low riskpopulation) with a high quality endoscopy New advanced imaging endoscopy (Magnification endoscopy withchromoendoscopy or Narrow Band Imaging with or withoutmagnification) sholud be offered to improve the detection ofprecancerous conditions (CAG and GIM)

New imaging techinques, new treatment modalities (EMR, ESD)2.Diagnosis

Advanced gastric cancerAtlas of Clinical Gastrointestinal Endoscopy . Third edition C. Mel Wilcox, MD, MSPH. Elsevier

early gastric cancer

SCREENINGPOPULATIONInmigrants(high risk regions)Familiy History“Oportunisticscreening”(EGD onic Atrophic Gastritis (CAG)Gastrointestinal metaplasia (GIM)surveillanceNEOPLASTICLESIONSDisplasia (Intraepithelial neoplasia)Adenocarcinoma2ndDetection of EGCwill improve the survivalrate of this cancer.Screening and surveillance for gastric cancer in the United States: Is it needed? Kim. GH. GIE 2016

EARLY GASTRIC CANCER (EGC) DEFINITION“EGC is a cancer in which tumor invasion is confined to the mucosa orsubmucosa (T1) regardless of the presence of lymph node metastasis”.IMPORTANCE OF EARLY DETECTIONo Good prognosiso Can be cured by minimallyinvasive approaches.Japanese Gastric Cancer Association, “Japanese classification of gastric carcinoma—2nd English edition,” Gastric Cancer, vol. 1, no. 1, pp. 10–24, 1998

9,4% of EGC are missedduring Uppergastrointestinal endoscopyIs time for new advanced imagingtechnology?Pimenta-Melo et al. Missing ratefor gastric cancer during upper gastrointestinal endoscopy: A systematic review and teta-analysis.Eur J Gastroenterol Hepatol 2016

EARLY GASTRIC CANCER (EGC) :WHITE LIGHT ENDOSCOPYImproving the Endoscopic Detection Rate in Patients with Early Gastric Cancer . Moon HS. 2015

EARLY GASTRIC CANCER (EGC) :WHITE LIGHT ENDOSCOPYImproving the Endoscopic Detection Rate in Patients with Early Gastric Cancer . Moon HS. 2015

EARLY GASTRIC CANCER (EGC) :Dye-based image endoscopyINDIGO CARMINE(0,2-0,4%):morphologicalcharacteristics of thesurface mucosa“Demarcation line”

EARLY GASTRIC CANCER (EGC) :ME- NBIClinical Application of Magnifying Endoscopy with Narrow-Band Imaging in the Stomach. Kenshi Yao Clin Endosc 2015;48:481-490

EARLY GASTRIC CANCER (EGC) :ME- NBINORMALCANCEROUS MUCOSANORMALCANCEROUS MUCOSAClinical Application of Magnifying Endoscopy with Narrow-Band Imaging in the Stomach. Kenshi Yao Clin Endosc 2015;48:481-490

White Light EndoscopyME-NBISEN: 48%SEN: 83%SP: 67%SP: 96% WLI has poor performance in the diagnosis of early gastric cancer. ME-NBI is an effective tool for real-time endoscopic diagnosis of earlygastric cancer

EARLY GASTRIC CANCER (EGC) :CONFOCAL LASER ENDOMICROSCOPY (CLE)X 1000 fold magnificationReal-time histology

EARLY GASTRIC CANCER (EGC) :CONFOCAL LASER ENDOMICROSCOPY (CLE)

sensibilitySpecificityGastric cancer89-93%98-100%Intestinal metaplasia92-93%93-99%Intraepithelial neoplasia77-84%87-100%Zhang 2016

Carefully inspection whit routine WLE should be done to detectsuspicious areas of malignancy especially in high risk patients (premalignant conditions) In superficial neoplasms, New advanced imaging endoscopy(Magnification endoscopy with chromoendoscopy or Narrow BandImaging, or CLE) is recomended to confirm the diagnosis anddelimitate the extension, especially when local endoscopic resection isplaned

New imaging techinques, new treatment modalities (EMR, ESD)3.Staging

CT (TAP) Rule out M Consider PET if CT-EUSUSE Locorregional staging/extentConsiderLAPAROSCOPY Exclude occult metastatic disease in some cases (pre or during surgery)

IMPORTANCE OF T- STAGING OF GASTRIC CANCERRisk of lymph node metastasisEndoscopic treatmentsurgery

EUS T-STAGING. NORMAL GASTRIC WALL

EUS T-STAGING. T1 (miniprobes 20 Hz)uT1auT1b

EUS T-STAGING. T2 (radial EUS)uT2Courtesy of Fernando Martinez de Juan. Insituto Valenciano de Oncología (IVI)

EUS T-STAGING. T3 (radial EUS)SubserosaCourtesy of Fernando Martinez de Juan. Insituto Valenciano de Oncología (IVI)

EUS T-STAGING. T4a (radial EUS)Invade SerosaCourtesy of Fernando Martinez de Juan. Insituto Valenciano de Oncología (IVI)

EUS T-STAGING. T4b (radial EUS)Invade pancreasCourtesy of Fernando Martinez de Juan. Insituto Valenciano de Oncología (IVI)

EUS IN N- STAGING OF GASTRIC CANCERN1PerigastricN2Branches coeliac axis

EUS IN N- STAGING OF GASTRIC CANCERN1N PerigastricD1N2M D2Branches coeliac axis

EUS IN N- STAGING OFGASTRIC CANCERMediastinumM 1-12N 13-16M

EUS IN N- STAGING OF GASTRIC CANCERM Techniques of imaging of nodal stations of gastric cancer by endoscopic ultrasound. Sharma M. eusjournal 2018

EUS IN M- STAGING OF GASTRIC CANCERLaparoscopyCourtesy of Fernando Martinez de Juan. Insituto Valenciano de Oncología (IVI)

EUS IN M- STAGING OF GASTRIC CANCERM

2015 meta-analysis, 66 studies, 7747 patientsT1-T2 vs T3-T4Se: 86%Sp: 90%T1 vs T2Se: 85%Sp: 90%Mocellin 2015

2015 meta-analysis, 66 studies, 7747 patientsT1a vs T1bS: 87%E: 75%

N vs N-S: 83%E: 67%

EUS N-STAGING: RELIABILITY OF BIOPSYFNA Lymph nodes:o Specificity for adenocarcinoma isconsidered around of 100%.o Sensitivity varies from 87 to 100%IS IT NECESSARY TO PUNCTUREALL THE LYMPH NODES?

EUS N-STAGING: RELIABILITY OF BIOPSYooIn patient with gastric cancer, the mainutility ofsampling.EUS-guided sampling is to avoidNo rutine EUS-guideunnecessary surgery, demonstratinglymph nodesor others lesionsOnly if impact indistantstreatmentdecisionsindicating the patient for palliation(ESMO-ESSO-ESTRO)(prognosis)

EUS N-STAGING: RELIABILITY OF BIOPSYo Mortensen et al: Prospective study of 62patients. Therapeutic changed in 8% of thepatients after exclusion of suspectedmetastasis lesions on CT-scano Hassan et al: retrospective study of 234patients. Therapeutic managementchanged in 15% of the patientso Araujo et al: Retrospective study of 115patients. Therapeutic management changesin 23% of the patientsEUS staging, looking for distant lesionswill change your therapeuticmanagement in 8 to 23% finding lesionwhich will change the status of thepatient (local disease to metastaticdisease)Mortensen Mb et al . Endoscopy, 2001;Hassan C et al GIE, 2010;Araujo J et al. Ends Ultrasound, 2014;Dumonceau JM et al. Endoscopy 2011.

EUS N-STAGING: ELASTOSONOGRAPHYNormal LNinflammatory LNMalignantMalignant(central necrosis)(homogeneus)

EUS N-STAGING: ELASTOSONOGRAPHYELASTOGRAPHYSEN: 83,6%SPE: 95%VS CONVENTIONAL B-MODE :SEN: 78.6%;SPE: 50%US elastography is superior compared to conventional B-modeimaging and appears to be able to distinguish benign from malignantlymph nodesBut .EUS elastography is not considered a modality that can replacebiopsy. it should be considered as complementary to other imagingtechniques rather than a replacement for tissue confirmationEUS-e has the potential to be useful for target selection prior toendosonographic guided tissue samplingEndoscopic ultrasound elastography for evaluation of lymph nodes and pancreatic masses: A multicenter study. Giovannini M. 2009Endoscopic ultrasound elastography: current status and future perspectives Xin-Wu Cui. 2015

EUS N-STAGING: ELASTOSONOGRAPHYELASTOGRAPHYSEN: 83,6%SPE: 95%VS CONVENTIONAL B-MODE :SEN: 78.6%;SPE: 50%Endoscopic ultrasound elastography for evaluation of lymph nodes and pancreatic masses: A multicenter study. Giovannini M. 2009Endoscopic ultrasound elastography: current status and future perspectives Xin-Wu Cui, Jian-Min Chang, Quan-Cheng Kan, Liliana Chiorean, AndreIgnee, Christoph F Dietrich 2015

o EUS staging is more reliable than others techniques to differentiate T1 from T2 andsuperficial versus advanced gastric tumors but has a moderate/low sensibility andspecificity to differentiate between mucosal and submucosal in T1 cancers or inlymph node involvemento EUS staging will not change the therapeutic management in most cases.Neoadjuvant chemotherapy is already decided.o But EUS staging, looking for distant lesions will change the therapeuticmanagement in 8 to 23% finding lesion which will change the status of the patient(local disease to metastatic disease)

New imaging techinques, new treatment modalities (EMR, ESD)4.Treatment

An endoscopictreatment is a localtreatment for lesionwithout lymph nodesmetastasis

Endoscopy in gastric cancer: new treatment modalities (EMR, ESD)INDICATIONS FORENCOSCOPICRESECTION?ESGE recommends endoscopic resection for thetreatment of gastric superficial neoplastic lesionsthat possess a very low risk of lymph node metastasis

Endoscopy in gastric cancer: new treatment modalities (EMR, ESD)INDICATIONS FORENCOSCOPICRESECTION?ESGE recommends endoscopic resection for thetreatment of gastric superficial neoplastic lesionsthat possess a very low risk of lymph node metastasisTumor-related factorsTechnique-related factorso Grade of difererentiation(diferentiated/diffuse)o Size (horizontal expansion)o Resection (“en bloc” vs piecemeal)o Margins (free)o Depth (vertical invasion)o Morphology (ulcerated/non-ulcerated)o Lympho-Vascular invasion ( /-)Final Objetive:Negligible Risk of lymph node methastasis after resection

ABSOLUTE INDICATIONS Macroscopically intramucosal (cT1a)differentiated carcinomas measuringless than 2cmEXPANDED INDICATIONS Macroscopically intramucosal (cT1a) UL-,differentiated carcinomas 2cm, LV Macroscopically intramucosal (cT1a) UL ,differentiated carcinomas 3cm, LV Macroscopically intramucosal (cT1a) UL-,undifferentiated carcinomas 2cm, LVDifferentiated-type adenocarcinoma withsuperficial submucosal invasion (sm1 500μm), and size 3cmPreoperative diagnosisHistopathological diagnosisCurative resection (R0)

EVALUATION BEFORE RESECTION(PREOPERATIVE DIAGNOSIS)IS ESD OR EMR INDICATED?Inspectión: MorphologyJAPANESE CLASSIFICATION90-95% SM 80-85% IE

EVALUATION BEFORE RESECTION(PREOPERATIVE DIAGNOSIS)IS ESD OR EMR INDICATED?DEPTH OF INVASIONT1aT1b“Determination of the depth of invasion by EGC is generally carried outusing conventional endoscopy with additional indigo-carmine dye sprayingbeing recommended”Guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer. Ono 2015

DEPTH OF INVASIONCharacteristic endoscopic features of mucosal cancero Smooth surface protrusiono Shallow and evendepressiono slight marginal elevationGuidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer. Ono 2015

DEPTH OF INVASIONCharacteristic endoscopic features of submucosalinvasive cancerIrregular/nodular surface protrusionFusion of converging foldsAbrupt cutting of converging foldsClubbing of converging folds.Deep ulcer with marked marginal elevationGuidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer. Ono 2015

EVALUATION BEFORE RESECTION(PREOPERATIVE DIAGNOSIS)IS ESD OR EMR INDICATED?3) DEPTH OF INVASIONT1aT1bo High quality endoscopy ideallywith contrast or digitalchromoendoscopy (NBI)o Experienced endoscopist

EVALUATION BEFORE RESECTION(PREOPERATIVE DIAGNOSIS)IS ESD OR EMR INDICATED?DEPTH OF INVASION

EVALUATION BEFORE RESECTION(PREOPERATIVE DIAGNOSIS)IS ESD OR EMR INDICATED?DEPTH OF INVASIONROLE FOR EUS?T1aT1bComparison of endoscopic ultrasonography and conventional endoscopy for prediction of depth of tumor invasion in early gastric cancer Choi 2010 Endoscopy

EVALUATION BEFORE RESECTION(PREOPERATIVE DIAGNOSIS)IS ESD OR EMR INDICATED?DEPTH OF INVASIONROLE FOR USE?T1a (m) vs T1b (Sbm)T1aT1bS: 87%E: 75%“Over and under diagnosis”Mocellin S 2015

EVALUATION BEFORE RESECTION(PREOPERATIVE DIAGNOSIS)IS ESD OR EMR INDICATED?3) DEPTH OF INVASIONROLE FOR EUS?USE in EGC is not neccessary .Only for selected cases When difficulties are encountered indetermining the depth of invasion usingconventional endoscopy alone, endoscopicultrasonography may be useful as anadditional diagnostic modalityEUS in EGC may not be necessary routinely

EVALUATION BEFORE RESECTION(PREOPERATIVE DIAGNOSIS)IS ESD OR EMR INDICATED?3) DEPTH OF INVASIONT1aT1bBut .histopathological analysis of endoscopically resectedspecimens is the gold standard reference for tumor stagingMocellin S 2015

ENDOSCOPICAL MUCOSAL RESECTION (EMR)VSENDOSCOPICAL SUBMUCOSAL DISECTION (ESD)ESDEMR

ENDOSCOPIC MUCOSAL RESECTION: TECHNIQUESTANDAR

ENDOSCOPIC SUBMUCOSAL DISSECTIONCourtesy of Dr juan Carlos Marín (H.12 Octubre Madrid)

EMR/ESD: DURATION OF THE PROCEDUREESDVSEMREMR

EMR/ESD: “EN BLOC RESECTION RATE”EMRVSESDESD

EMR/ESD: COMPLETE HISTOLOGIC RESECTION RATEEMRVSESDESD

EMR/ESD: LOCAL RECURRENCE RATEEMRVSESDESD

EMR/ESD: COMPLICATION RATEPerforation rateESDVSEMREMRFavours EMR but most fo perforations in ESD group are managedconservatory without the need of surgery

EMR/ESD: COMPLICATION RATEBleeding rateESDVSEMREMRFavours EMR but non significant difference

ResectionR0 RESECTION RATERECURRENCE RATEEMR54%15%ESD91%4%But . no differences in survivalPimentel-Nunes Endoscopy 2014

EMR 10-15mm Low probability ofadvanced histology (0-IIa)ESDTreatment ofchoice

The risk of incomplete resection is high when using EMR for lesionswith expanded indications, so ESD should be carried out instead ofEMR for these lesions (evidence level V, grade of recommendationC1).EMR 10 mm Absolute indications (nonESDTreatment ofchoiceexpanded)“ESD should be the first-line therapy for all potentially endoscopically resectablesuperficial gastric neoplasia. Surgery can be reserved and used as a rescue therapy”

ATLAS OF CLINICAL GASTROINTESTINAL ENDOSCOPY Third edition C. Mel Wilcox . Japanese classification of gastric carcinoma—2nd English edition, Gastric ancer, vol. 1, no. 1, pp. 10-24, 1998 o Good prognosis . New advanced imaging endoscopy (Magnification endoscopy with chromoendoscopy or Narrow Band Imaging, .

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