ENDOSCOPY IN GASTRIC CANCER: NEW IMAGING TECHNIQUES, NEW TREATMENT MODALITIES (EMR, ESD)

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1 ENDOSCOPY IN GASTRIC CANCER: NEW IMAGING TECHNIQUES, NEW TREATMENT MODALITIES (EMR, ESD) Fabrice Caillol Paoli Calmettes Institute, Marseille, France June 10th, Prague, Czech Republic

2 EUS AND STAGING 1980: beginning of EUS No EUS gastric EAC: Mac Donald protocol 2006: MAGIC protocol All USt included Pretherapeutic EUS localization: gastric, oesocardial junction, lower part of the oesophagus 2011:FNLCC and FFCD protocol optional EUS staging In these studies EUS does not have therapeutic impact on the decision to perform chemotherapy, although most of team began to perform EUS for gastric ECA staging Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001; 345: Smalley SR, et al. J Clin Oncol Cunningham et al. NEJM, 2006 Ychou M et al. JCO, 2011

3 EUS STAGING Unclear data about EUS staging. Downstaging is described, although the main argument is the lower incidence of advanced pt/pn on pathology report in the chemotherapy groups and not the EUS staging. meta-analysis of 14 studies about neoadjuvant chemotherapy Ronellenfittsch et al, Eur T od Cancer, 2013

4 EUS STAGING T1+T2 VS T3-T4 SENITIVITY SPECIFICITY PPV NPV ACCURACY 86% 91% 98% 65% 89% meta-analysis, 54 studies, 5601 patients Mocelli et al, GIE 2011

5 LYMPH NODE INVASION AND EUS Sensitivity= 83% Specificity= 67% Accuracy of lymph node status is lower than T staging Heterogenicity of studies needs to consider carefully results of EUS Metanalysis of 44 studies Mocellin S, Pasquali S. Diagnostic accuracy of endoscopic ultrasonography (EUS) for the preoperative locoregional staging of primary gastric cancer. Cochrane Database, 2015

6 EUS STAGING: POTENTIAL COMPLICATIONS Needle tract seeding: only 3 cases reported. Exceptional. Perforation: 0,03% Infectious adverse event: 0 to 8% Bleeding: 4%. 2 cases with clinically significant bleeding ESGE guideline ASGE guideline

7 EUS STAGING: RELIABILITY OF BIOPSY Lymph nodes: Specificity for adenocarcinoma is considered around of100%. Sensitivity varies from 87 to 100%. A prospective study with pathological findings found sensitivity of 83% and specificity of only 93% for oesophageal cancer. Dumonceau JM, Polkowski M, Larghi A et al. Indications, results, and clinical impact of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European society of gastrointestinal endoscopy (ESGE) clinical guideline. Endoscopy Vazquez-Sequeiros E, Norton ID, Clain JE et al. Impact of EUS-guided fine-needle aspiration on lymph node staging on therapy of esophageal carcinoma. Gastroenterology 2003.

8 EUS staging TNM 2010 French thesaurus M+ N+ M+

9 EUS STAGING: DISTANT LESIONS carcinosis lymph nodes EUS-FNA can change therapeutic management in 8-23% Mortensen et al: Prospective study of 62 patients. Therapeutic changed in 8% of the patients after exclusion of suspected metastasis lesions on CT-scan Hassan et al: retrospective study of 234 patients. Therapeutic management changed in 15% of the patients Araujo et al: Retrospective study of 115 patients. Therapeutic management changes in 23% of the patients Metastases of left liver lobe was diagnosed in 3-5% of the patients for esophageal cancer with 100% specificity. Mortensen MB, Pless T, Durup J et al. Clinical impact of endoscopic ultrasound-guided fine needle aspiration biopsy in patients with upper gastrointestinal tract malignancy. A prospective study. Endoscopy, 2001 Hassan C, Vilmann P, Sharma P et al. Impact of EUS-guided FNA on management of gastric carcinoma. GIE, 2010 Araujo J, Bories E, Caillol F et al. Distant lymph nodes metastases in gastroesophageal junction adenocarcinoma: impact of endoscopic ultrasoundguided fine-needle aspiration. Ends Ultrasound, 2014 Dumonceau JM, Polkowski M, Larghi A et al. Indications, results, and clinical impact of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European society of gastrointestinal endoscopy (ESGE) clinical guideline. Endoscopy 2011.

10 How to improve the LN Staging? Sonovue ELASTOSONOGRAPHY Distortion FNA Colorisation Hard Soft

11 CONTRAST ENHANCEMENT inflammatory lymph nodes: centrifugal and homogenous pattern Carcinoma: heterogenous enhancement, focal cortical thickening, focal contrast enhancement lymphoma: variable contrast enhancement, intense homogeneous enhancement most of time Cui XW, Jenssen C Saftoiu A et al. New ultrasound techniques for lymph node evaluation. WJG, 2013

12 SCC ADK sarcoidosis

13 RATIO-ELASTOGRAPHY

14 EUS ELASTOGRAPHY cut-off=10 Cervical Mediast. Celiac Perirectal 101 PATIENTS with lymph nodes AdenoCa SCC NET Melanoma Lymphoma Benign MULTICENTRE PROSPECTIVE STUDY ON EUS ELASTOGRAPHY. Giovannini et al: WJG,2009

15 EUS ELASTOGRAPHY METANALYSIS : EUS elastography & LN * Differentiation Benign vs Malignant 368 Pts including 431 LN Pooled Sensitivity = 88% Pooled Specificity = 85% *Xu W. et al : GIE, 2011, 74(5),

16 EUS ELASTOGRAPHY: GOOD RESULTS BUT VARIABLE CUT-OFF 50 patients, 53 lymph nodes EUS-guided elastography of lymph nodes was performed before EUS-FNAB. Standard EUS characteristics were also described. Elastography strain ratio: sensitivity 83%, specificity 96%, positive predictive value 95%, and negative predictive value 86% for distinguishing between malignant and benign nodes. The overall accuracy of elastography strain ratio was 90% (Ratio Cut-off = 7.5). Elastography was more sensitive and specific in determining malignant nodal disease than standard EUS criteria. PATERSON ET AL; :ENDOSCOPIC ULTRASOUND-GUIDED ELASTOGRAPHY IN THE NODAL STAGING OF OESOPHAGEAL CANCER WJG 2012

17 LYMPH NODES STUDIES AND BENCHMARK HISTOLOGY An essential limitation of lymph nodes evaluation is the lack of benchmark histology in most of the studies. Only surgical piece can be a real gold standard for pathology. In the study lead by Mortensen et al, a reliable benchmark histology decreases in the final results sensitivity and specificity. We probably have to be cautious in the diagnosis of begnin/malignancy for lymph nodes given by literature data. sensitivity= 55% specificity= 82% 31% of the patients are excluded in this study. Larsen MH, Frstrup C, Hansen TP et al. Endoscopic ultrasound, endoscopic sonoelastography, and strain ratio evaluation of lymph nodes with histology as gold standard. Endoscopy 2012

18 TRYING TO IMPROVE ACCURACY OF LN-STAGING AQ-flex 19G probe Endomicroscopy, CLE needle Caillol et al, UEGW 2012

19 TRYING TO IMPROVE ACCURACY OF LN-STAGING NORMAL LYMPH NODE Reticular pattern Lymphocytes

20 METASTASIS GASTRIC ADENOCARCINOMA Irregular distribution of cells with fibers Irregular distribution of cells Glands

21 Tumoral lymph nodes Normal lymph nodes

22 GASTRIC CANCER Endoscopic aspect Ct -Distant LN Mediastinum, Aortico-caval -liver metastasis -carcinosis -Biopsy+++++ CHEMOTHERAPY TUMOR M0 EUS Endoscopic aspect T1N0 T 2-3/N0-1 SURGERY + NEOADJUVANT CT ENDOSCOPIC TREATMENT SURGERY

23 ENDOSCOPIC TREATMENT Why endoscopic treatment is an oncoligical treatment? N+

24 ENDOSCOPIC TREATMENT ESD technique EMR technique image from medscape

25 EMR/ESD: COMPLICATION RATE ESD EMR Bleeding perforation Park YMI, Cho E, Kang HY, Kim JM. The effectiveness and safety of endoscopic submucosal dissection compared with endoscopic mucosal resection for early gastric cancer: a systematic review and metaanalysis. Surg Endosc (2011) 25:

26 EMR/ESD: DURATION OF THE PROCEDURE ESD EMR Park YMI, Cho E, Kang HY, Kim JM. The effectiveness and safety of endoscopic submucosal dissection compared with endoscopic mucosal resection for early gastric cancer: a systematic review and metaanalysis. Surg Endosc (2011) 25:

27 EMR/ESD: COMPLETE RESECTION RATE EMR ESD Park YMI, Cho E, Kang HY, Kim JM. The effectiveness and safety of endoscopic submucosal dissection compared with endoscopic mucosal resection for early gastric cancer: a systematic review and metaanalysis. Surg Endosc (2011) 25:

28 EMR/ESD: CURATIVE RESECTION RATE EMR ESD Park YMI, Cho E, Kang HY, Kim JM. The effectiveness and safety of endoscopic submucosal dissection compared with endoscopic mucosal resection for early gastric cancer: a systematic review and metaanalysis. Surg Endosc (2011) 25:

29 EMR/ESD: LOCAL RECURRENCE RATE EMR ESD Park YMI, Cho E, Kang HY, Kim JM. The effectiveness and safety of endoscopic submucosal dissection compared with endoscopic mucosal resection for early gastric cancer: a systematic review and metaanalysis. Surg Endosc (2011) 25:

30 ENDOSCOPIC TREATMENT: EVALUATION BEFORE RESECTION

31 ENDOSCOPIC TREATMENT: EVALUATION BEFORE RESECTION Videoendoscopy exploration is mandatory. Risk of metachronous lesions exists. The cumulative 3-years risk is 5.9%. EUS is not always mandatory Nb Patients EUS Accuracy Endoscopy Acc. p Choi,2010 * ,9% 81,4% 0,052 Song, ,4% 73,7% <0,001 Nakajima T, Oda I, Gotoda T et al. Metachronous gastric cancers after endoscopic resection: How effective is annual endoscopic surveillance? Gastric Cancer 2006:9:93-8

32 ENDOSCOPIC TREATMENT: EVALUATION BEFORE RESECTION ESGE suggests that a strategy of precise endoscopic evaluation of these lesions is sufficient for predicting resectability, with EUS reserved only for selected cases. Pimentel-Nunes P, Dinis-Ribeiro M, Ponchon T et al. Endoscopic submucosal dissection: European society of gastrintintestinal endoscopy (ESGE) guidelines. Endoscopy 2015;47:

33 ENDOSCOPIC FINDINGS: JAPANESE CLASSIFICATION TYPE IIA TYPE I IIB TYPE III IIC 90-95% SM % IE

34 IIC IIA IIB+ IIC

35 JAPONESE GUIDELINE Indication for endotherapy: Expanded Criteria Macroscopically intramucosal (ct1a) differentiated carcinomas measuring less than 2cm UL-, differentiated carcinomas> 2cm, LV- +++ UL+, differentiated carcinomas< 3cm, LV- +++ UL-, undifferentiated carcinomas< 2cm, LV- +++ Lymph nodes metastatic risk is for expanded criteria is 0.4% (2678 patients) Choi KK, Bae JM, Kim SM et al. The risk of lymph node metastases in 3951 surgically resected mucosal gastric cancers: implications for endoscopic resection. GIE 2016;83(5): Ono H, Yao K, Fujishiro M, Oda I, Nimura S, Yahagi N, Lishi H, Oka M, Ajioka, Ichinose M, Matsui T. Guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer. Dig Endosc 2016; 28:3-15

36 Size in expanded criteria: Superficial carcinoma, follow-up size out of expanded criteria: time of resection: 6h Histopathology: Sm3

37 ENDOSCOPIC TREATMENT: DETECTION OF EGC IS ESSENTIAL Only less than 10% of gastric carcinoma are EGC (early gastric cancer) in western countries/ 60% in Eastern countries. 10% of EGC are misdiagnosed as gastritis, erosion or ulcers. With experienced endoscopist the diagnosis of EGC in patients referred for dyspepsia can increase from 1% to 26% in a united kingdom registry As a result, video-endoscopy with high definition is also a new imaging in the management of gastric cancer. Detection of EGC will improve the survival rate of this cancer. Caillol F, Bories E, Guiramand J et al. Can we resect EGC with signet ring cells in Europe? J Gastrointest Cancer, 2013

38 CONCLUSION EUS is essential to detect distant lymph nodes, carcinosis, left lobe liver metastasis and these lesions need to be punctured. Endoscopic resection is the first line therapy for early gastric tumours. Strict criteria of resection have to be applied.

39 GASTRIC CANCER Endoscopic aspect Ct -Distant LN Mediastinum, Aortico-caval -liver metastasis -carcinomes -Biopsy+++++ CHEMOTHERAPY TUMOR M0 EUS Endoscopic aspect T1N0 T 2-3/N0-1 SURGERY + NEOADJUVANT CT ENDOSCOPIC TREATMENT SURGERY