How good is EUS in the diagnosis of submucosal mass lesion

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1 How good is EUS in the diagnosis of submucosal mass lesion Dr. Yuk Tong LEE MBChB, MD(CUHK), FRCP (Edin), FRCP(Lond), FHKCP, FHKAM Specialist in Gastroenterology and Hepatology

2 Submucosal tumour, SMT Subepithelial tumour, SET Incidence of gastric SET 0.36% in a Swedish routine endoscopy study ~ 3% in another Japan study Different layers in the GI wall mucosa, muscularis mucosae, submucosa, circular and longitudinal muscularis propria, and serosa. It is difficult to be differentiated by ordinary endoscopy. Hedenbro JL, Surg Endosc 1991; Kawaguchi M, 2001

3 SET Non-tumour lesion - ectopic pancreas, inflammatory fibroid polyp, submucosal cyst and ectopic glands. Non-epithelial neoplasia - gastrointestinal stromal tumour (GIST), leiomyoma, leiomyosarcoma, and neurogenic tumour, vascular tumours, lipoma, liposarcoma, malignant lymphoma malignant melanoma Epithelial neoplasia mimicking SET carcinoid, carcinoma and metastatic carcinoma.

4 Endoscopic diagnosis Effective in diagnosing mucosal lesion Cannot differentiate submucosal lesion i.e. mural or extramural lesion Sensitivity 29% - 89%; specificity 64% - 98% Hwang JH, Gastrointest Endosc 2005; Rosch T, Scand J Gastroenterol 2002

5 Endoscopic ultrasonography, EUS Combined endoscopic and ultrasound examination in one High frequency ultrasound probe higher resolution Bring close to the disease origin Accurate in diagnosing mural and extramural diseases close to GI tract. Accurate in differentiating the nature of SET, predicting the growth and malignant change. Can perform fine needle aspiration and biopsy No radiation, can do repeated examination, but invasive.

6 Radial endoscopic ultrasound

7 Miniprobe EUS Pass through the regular endoscope channel New 3D reconstruction

8 Layered structure under EUS

9 Histopathological classification of GI SET Wiech T. Endoscopy 2005

10 EUS differentiating SET Hwang JH, Gastroenterology 2012

11 Benign features Tumour size up to 3cm (up to 2cm in the small bowel), Smooth outer contour Uniform and homogenous echo pattern Specific layer location or echotexture (e.g. lipoma) No signs of infiltration No lymph node enlargement Elastography - typically shows a homogenously intermediate elasticity At follow up - no significant increase in size (e.g. >1cm or 50% increase) No texture change and no new tumour related symptoms. SET lesions may develop degenerative changes that result in anechoic or hyperechoic areas; they may also develop an irregular shape that makes it difficult if not impossible to determine their nature

12 SET: OGD vs CT vs EUS 3/2009-6/2011, OGD found 93 suspected gastric SET. EUS revealed possibly malignant SET in 60 cases (64.5%). Others benign or mimic lesion only. 55 lesions also had CT done. 32 possibly malignant SET was suspected by CT. Sensitivity and specificity of CT was 80.6% and 84.2%. The mean size of possibly malignant SET detected and not detected by CT was 27.4 and 11.0 mm (p = ). Goto O, Abdom Imaging 2012

13 Current status of endoscopic ultrasound (EUS) for the upper gastrointestinal tract in Asia Questionnaire survey of 10 institutes in Asia Is EUS useful for the differential diagnosis of SET Many investigators have described the appearance of SMT of the upper GI tract Differential diagnosis of a hypoechoic within the 3rd and 4th layer lesion is difficult. The diagnostic accuracy of EUS imaging alone as low as 43% Yoshinaga S, Dig Endosc. 2014

14 10 year retrospective review of EUS image and final pathology Four variables, including location, shape, layer of origin and echogenicity of the tumour N=226, 69 (30.5%) had GIST, 68 (30.1%) had ectopic pancreas and 35 (15.5%) had leiomyoma Seo SW, J Dig Dis 2013

15 0 1 2 Location Cardia Fundus Body Originating layer muscularis mucosa muscularis propira submucosa Echogenicity hypoechoic mixed hyperechoic Shape irregular round oval Score range of 0 1 for leiomyoma, 2 3 for GIST, 4 6 for ectopic pancreas and 7 8 for lipoma Sensitivity and specificity were 75.8% and 85.4% for GIST, 84.6% and 73.1% for ectopic pancreas, 75.9% and 99.5% for leiomyoma and 91.7% and 96.7% for lipoma, respectively. Seo SW, J Dig Dis 2013

16 Ectopic pancreas Well developed and normally organized pancreatic tissue outside the pancreas, without anatomic or vascular connections with the true pancreas. Autopsies series - 0.6% %. Sites: stomach 25-38% (antrum 85%-95%), duodenum 17%-36%, jejunum 15%-21.7% Rarely - oesophagus, GB, CBD, spleen, mesentery, mediastinum and fallopian tube. Kim JH, Gastrointest Endosc 2012

17 Ectopic pancreas Asymptomatic Nausea, epigastric pain, weight loss, hematemesis, gastric outlet obstruction, obstructive jaundice and intussusceptions. Rarely malignant change

18 Endoscopic and EUS features Endoscopic - firm round or oval SET with a central depression (34.6% in a 26 patients series). EUS - indistinct borders, heterogeneous echogenicity, the presence of an anechoic area and location within the second, third and /or fourth layers. Park SH, J Gastroenterol Hepatol 2011

19 EUS vs EMR pathological study of gastric SET 22 patients Accuracy of EUS for final diagnosis - 10/22 (45.5%) Accuracy rate differentiate between neoplastic (30.8%) and nonneoplastic (66.7%) Karaca C, Gastrointest Endosc 2010

20 Contrast enhanced harmonic EUS (CEH-EUS) for GIST 29 resected GIST, high grade (n=16) and low grade (n=13) Aloka prosound a-10 Bolus infusion of contrast agent (15µL/kg Sonazoid), Vascular structure second (vessel image) and second (perfusion image). Digital recording. Identify irregular vessels Sensitivity Specificity Accuracy CE-CT 31% Power Doppler EUS 63% CEH-EUS 100% 63% 83% Sakamoto H, Gastrointest Endosc 2011

21 EUS elastography Still in investigational phase C.F. Dietrich, Eur J Radiol. 2014

22 Linear endoscopic ultrasound Can perform FNA to confirm diagnosis

23 EUS - FNA for gastric SET 141 patients, EUS-FNA 1-5 passes Diagnostic 43.3%, suggestive 39%, non-diagnostic 17.7% 69 had final diagnosis, 41(59.4%) GISTs, 9 (13%) leiomyomas, 7 gastric wall carcinomas, 6 extragastric lesions (3 pancreatic tumors, 2 abdominal lymph nodes, and 1 peritoneal desmoid tumor), 2 glomus tumors, 2 schwannomas, 1 gastric inflammatory granuloma, and 1 lipoma. 53 / 69 SMTs (76.8%) were proven finally to be malignant lesions or potentially malignant lesions. EUS-FNA accuracy rate 66/69 (95.6%) EUS -FNA differentiate benign from potentially malignant lesions with a sensitivity of 92.4%, specificity 100%, PPV 100%, NPV 80% and accuracy 94.2% Mekky MA, Gastrointest Endosc 2010

24 EUS FNA and trucut for SET 40 patients Final diagnosis - GIST (27), carcinoma (2), leiomyoma (1), schwannoma (1), no diagnosis (9). EUS-TCB - 6 failure Diagnostic accuracy EUS-FNA: 52% vs EUS-TCB : 55% Immunohistochemistry study (IHS) - EUS-FNA 74% and EUS-TCB 55% Fernandez-Esparrach G, Endoscopy 2010

25 EUS trucut for SET ³ 2cm 65 patients 9 failure to puncture, 19 insufficient tissue, 37 (57%) obtained diagnostic result. Change of treatment in 18/65 (27.2%) patients Lee JH, Gastrointest Endosc 2011

26 EUS FNA with 19G needle 4 years multicentre prospective study, N = 100 SET 71 gastric SET > 1cm Only 46 FNA could be performed. In 46/71 cases (65%) with one to four needle passes Definite diagnosis (52%), suspected histological diagnosis (7%). Not informative (41%) Immunohistochemistry was possible in 91% of cases with sufficient amounts of tissue; 30% were GIST. Self-limited, mild hemorrhage occurred in 22%; one patient developed a fatal abscess (large necrotic tumour). Eckardt AJ, Eur J Gastroenterol Hepatol 2012

27 Prospective database, N = 90, EUS-FNA for hypoechoic SET < 2cm. Compared with surgery (n=44), and/or clinical follow-up (n=46) using OGD, CT, and/or US. Additionally, immunophenotyping of specimens obtained by EUS-FNA and surgical resection specimens were compared. Akahoshi K, J Gastrointestin Liver Dis 2014

28 Diagnostic rate of EUS-FNA - 73% (66/90). EUS-FNA showed 47 (52%) malignant SET (44 GISTs, 1 glomus tumor, 1 SET like cancer, and 1 malignant lymphoma) 19 (21%) benign SET (14 leiomyomas, 4 ectopic pancreas, and 1 neurinoma) 24 (27%) indeterminate SET In 44 surgically resected cases, the diagnostic accuracy of EUS-FNA using IHS was 98% (43/44). No complications Appropriate management was performed in 65 out of 66 SET (98%) diagnosed by definitive EUS-FNA. After surgery, there was no recurrence of malignant SET. Akahoshi K, J Gastrointestin Liver Dis 2014

29 EUS FNA for GIST 16 years retrospective study, 84 cases of GIST, 67 were resected surgically after EUS Tumour size was < 20 mm (n = 19), 20 mm (n = 48). EUS-FNA for the diagnosis of 20 mm GIST Sensitivity 80.6% and PPV 100% EUS-FNA for <20mm GIST Sensitivity 81.3% and PPV 100% Sekine M, Dig Endosc 2014

30 Factors affecting the EUS-FNA result 170 EUS-FNA in 158 patients with upper GI SET or extraluminal solid lesions. The overall accuracy of EUS-FNA was 86.5% (147/170). The accuracy of EUS-FNA for SET was 85.2% 3.0 or more needle passes and combined cytologic-histologic analysis enhance the diagnostic accuracy of EUS-FNA Rong L, Dig Endosc 2012

31 Forward viewing EUS for FNA of SET Retrospective study of 121 consecutive patients (13 in the esophagus, 96 in the stomach, 10 in the duodenum, 2 in the rectum) All successful but one. No complication Full histological assessment including immunostaining could be completed in 93.4% (113/121) of the patients. Considering neoplastic vs. non-neoplastic diseases, the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were 92.8%, 100%, infinity, and 0.07 Larghi A, Endoscopy 2014

32 Forward viewing EUS for FNA of SET Larghi A, Endoscopy 2014

33 EUS FNA of colonic lesion is possible by forward viewing echoendoscope a 68 years old patient with ileal neuroendocrine tumour confirmed by EUS-FNA Galasso D, Endoscopy 2014

34 EUS guided treatment of SET Monitoring Guided therapy - Biopsy Mucosectomy ESD Submucosal tunneling endoscopic resection (STER)

35 Retrospective study, 100 SMT patients underwent surgery. 23 (13M, 10F, incidentally found SMT) with size enlargement during observation period. Median age of 54 (41 71). Tumours size 1.8 ( ) cm, enlarged up to 3.2 ( ) cm at the operation during 63.0 ( ) months. Laparoscopic partial gastrectomy (78.3%). GIST (n=21) and schwannoma (n=2). 16 / 21 GISTs - very low (n=1), low (n=13), intermediate (n=5) and high (n=2) risk. No recurrences / metastases were noted in 23.2 (0.9 87) months of postoperative follow-up. European Journal of Cancer 2013

36 GIST new cases / year in USA Estimated incidence of 1.5/ /year Age % - 30% malignant Presence of KIT or PDGFRA mutation, 5% KIT -ve. Micro-GIST (1-10mm) detected in 22.5% of the autopsy series in patient > 50 years old. Sites: Stomach (60%), small bowel (30%), duodenum (5%) and colorectum (<5%). Rarely - mesentery, omentum, retroperitoneum.

37 GIST AGA guideline - SET <3cm can be followed by periodic endoscopic or EUS exam NCCN guideline - GIST >2cm - resected, incidental tumour <2cm - resection or surveillance Patient compliance, cost-effectiveness, risk of repeated endoscopic examination, delayed diagnosis of malignancy. Hwang JH, Gastroenterology 2006; Demetri GD, J Natl Compr Canc Netw 2010

38 EUS may predict the enlargement of GIST 74 patients with GIST Features sought to predict the tumour growth: mucosal ulceration, irregular shape, irregular border, intrenal hyperechoic spot, heterogeneity, hypoechoic area and anechoic area. Large tumour size: heterogeneity (p=0.016) and anechoic area (P = 0.003) Increased growth: hypoechoic area (OR 5.38, P=0.03) Onishi M, Gastrointest Endosc 2012

39 EUS guided single-incision needle-knife biopsy (SINK biopsy) 14 patients with upper GI SETs 13 had histological diagnosis (diagnostic yield 92.8%) Allow for immunohistochemical analysis, mitotic index assessment. Serna-Higuera C, Gastrointest Endosc 2011

40 Unroofing technique for SET biopsy 16 patients Diagnostic yield 93.7% - leiomyoma (7), GIST (6), ectopic pancreas (1), well-differentiated NET (1) Minor complication - oozing, 56%, controlled by APC. Lee CK, Gastrointest Endosc 2010

41 ESD method for SET biopsy Lee HL, Gastrointest Endosc 2011

42 EUS for the diagnosis and selecting treatment of oesophageal leiomyoma 229 patients with oesophageal leiomyoma 118 endoscopic resection, 7 surgical resection. EUS sensitivity 99.1%, specificity 48.3%, PPV 88%, NPV 93.3%, accuracy 88.6%. No recurrence. Xu GQ, J Gastroenterol Hepatol 2012

43 EUS guided resection of oesophageal leiomyoma

44 EUS predicts complete ESD resection of SET 37 patients Median tumour diameter 25mm. R0 resection 81.1% - submucosa 100%, muscularis propria 68.2%. Perforation 5.4%, one require surgery. Median follow up 21 months. EUS features - no, or only narrow, tumour connection with the underlying muscle layer predict R0 resection (OR 35.0, P=0.001) Bialek A, Gastrointest Endosc 2012

45 85 SETs, oesophagus (60), cardia (16), stomach (9). STER - 100% success rate The mean tumor size mm. The mean procedure time min. Pathology - leiomyoma (65), GIST (19), calcifying fibrous Complication - 8 developed pneumothorax, subcutaneous emphysema, and/or pneumoperitoneum. These patients recovered after conservative treatment. More in lesion at deeper MP layer (70 %) than in the superficial MP layer (1.3 %; p < 0.001). More in GIST than (26.3%) than leiomyomas (4.6%), (P < 0.05). No residual or recurrent tumors were detected during the follow-up period (median: 8 months). Ye LP, Surg Endosc 2013

46 Submucosal tunneling endoscopic resection (STER) Ye LP, Surg Endosc 2013

47 DDW 2014

48 AGA recommendation (2006) AGA Medical position Statement on the Management of Gastric subepithelial mases. Gastroenterology 2006

49 Conclusion EUS imaging is still useful in detecting and differentiating SET / SMT Improved EUS technology such as contrast study may help to differentiate benign from malignant lesion EUS FNA can provide tissue diagnosis and for IHS, with varying successful rate EUS is helpful in selecting appropriate treatment for SET / SMT