Endoscopic and surgical management of gastric and duodenal NETS - PowerPoint PPT Presentation

The 2018 Gastrointestinal Oncology Conference 2nd November 2018, Arlington WA Endoscopic and surgical management of gastric and duodenal NETS Sebastian Maasberg Med. Dep. Of Gastroenterology and Hepatology University Medicine Charité Berlin U N I V E R S I T Ä T S M E D I Z I N B E R L I N

Epidemiology of neuroendocrine neoplasia 5.25 6.98 1.09 1.09 Lung Small Intestine Rektum Stomach Yao J et al,., JCO 2008 Dasari A et al, JAMA Oncol 2017

Primary tumor localization in population-based studies Austria 25.0% 22.8% 20.7% 20.0% 15.4% 15.4% 15.0% 11.6% 10.0% 7.0% 5.6% 5.0% 1.7% 0.0% s h m x m m n P c i a o U d u u u e a l C n e n o t r m c c e l e C i e n o - p d o R a t p o S n P u A u D j e J Niederle et al, Endocr Rel Cancer 2010

Phenotyp of gastric NET Small & multiple Mucosa: atrophic Small & solitary Mucosa: atrophic Small & multiple Large & solitary Mucosa: hypertrophic Mucosa: normal

Phenotyp of gastric NET T ype 1 T ype 2 T ype 3 T ype 4 Proportion of 70 - 80 5–6 10-20 <5 Gastric-NEN [%] solitary, frequently solitary, mostly Mostly small (< 1-2 Mostly small (<1–2 large (>2cm), large (>2cm), Characteristic cm), in 65% multipel, cm) and multipel, polypoid & polypoid & mostly in 78% polypoid polypoid sometimes ulcerated ulcerated chronic atrophic Gastrinoma & ZES Association none none gastritis (CAG) in MEN1 Pathology G1/2-NET G1/2-NET mostly G2-NET G3-NEC Serum-Gastrin normal normal ↑ ↑↑ Stomach-pH ↑↑ ↓↓ normal normal Metastasis [%] 2-5 5-15 30-80 50-100 Tumor-associated 0 <10 25-30 60-95 deaths [%] ZES = Zollinger-Ellison-Syndrom Klöppel et al Yale J Biol Med 1996

Prognostic factors in gastric NEN Stage I Type 1/2 St. II Type 3 St. III Type 4 & MANEC St. IV G1 Prognosis depends on: Ø Type of gastric-NEN G2 G3 Ø TNM-Staging Ø Ki67-Grading La Rosa et al Hum Pathol 2011

Staging in gastroduodenal NEN • Endoscopy including biopsy or polypectomy of the largest polyp and mucosal biopsies of antrum (2x) and corpus & fundus (min. 4x each) Ø EUS in gastric polyps > 1-2cm and in duodenal NEN • Laboratory: Chromogranin A, Gastrin (Type 1/2 gNET, dNET), Vitamin B12 and anti-parietal cell Ab (type 1), H. pylori (type I) • MEN-1 diagnostic in type II gastric NET and gastrinoma dNEN • CT/MRI in type 2-4 gastric NEN and duodenal NEN • Somatostatin-receptor imaging in metastatic g/d NEN

Therapeutic Management of gastric NETs Type 1/2 Type 1 or 2 (>T2 or incomplete resection ) Gastric NET and Type 3 or 4 <1cm 1- 2 cm T1 T1 >2 cm Surgery (partial or total Endoscopic Therapy Endoscopic gastrectomy) (PE by Forceps, Therapy EMR) (EMR, ESD) Regular Follow: CT/MRI/Sonography + Endoscopy + possibly Endoscopic Follow up: SRS/Ga68 oder FDG- Type 1 every 1-2 Year PET/CT Type 2 every Year Adapted from Delle Favre et al, Neuroendocrinology 2012 & 2016

NANETS Guidelines on Gastric NEN Indvidualized therapeutic approach: endoscopic-assisted laparoscopic resection in gastric NET Kunz P et al, Pancreas 2013 Maasberg et al, Der Chirurg 2016

recurrence rate and risk factors for metastases in type I gastric NET median recurrence free survival 8 months Merola E et al, Neuroendocrinology 2012 Grozinsky-Glasberg et al, WCG 2013

Classification of duodenal NET Typ 1 Typ 2 Typ 3 Typ 4 Typ 5 Characteristic Gastrin Somatostatin Gangliocytic Gastrin- Poorly Secretion Secretion Paraganglioma /Serotoin- differentiated /Calcitonin Expression w/out Symptoms Associated ZES/MEN-1 NF-1 None None None Disease Localization Proximal Periampullary Periampullary/ Proximal Periampullary Duodenum /ampullary ampullary Duodenum /ampullary Size 77% <1cm, 15-23mm 10-25mm 10-15mm Mean 25mm Mean 9,3mm (8-40mm) Histology NET -G1 NET -G1/G2 NET -G1/G2 NET -G1/G2 NEC-G3 Adapted from Maasberg et al., Der Chirurg 2016

Disease specific survival of duodenal NET Vanoli et al, Neuroendocrinology 2017

ENETS Guidelines – Therapy of Duodenal NET Delle Favre et al, Neuroendocrinology 2016

Outcome of endoscopic treatment in dNET

Outcome of EMR vs ESD Endoscopic mucosal resection (EMR) Endoscopic submucosal dissection (ESD) Masumoto S. et al, WJG 2014 Kim GH et al, J Gastroenterol Hepatol 2014

To conclude: • Management of localized gastric NEN comprises: – Endoscopic therapy in type I/II NET with polyps <2cm and absence of submucosal invasion – Type III/IV and TNM-Stage >T2 need surgical resections • In localized duodenal NEN management consists of: – Endoscopic treatment in non-periampullar polyps <1cm – Polyps between 1-2cm can be treated by endoscopy or surgery – Larger polyps (>2cm) and polyps located periampullary need a surgical treatment approach

Thank you for your attention

Interactive Question No 1: What treatment strategy would you recommend in type I gastric NET with >10 polyps of differented sizes (<2cm) and without submucosal infiltration or locoregional/distant metastasis ? 1.) endoscopic resection of all polyps 2.) endoscopic resection of every polyp >1cm 3.) surgery 4.) treatment with somatostatin analogue 5.) antrectomy to suppress hypergastrinemia

Interactive Question No 2: What treatment strategy would you recommend in a non ampullary NET of the duodenum 1.1cm in size but and without submucosal infiltration or locoregional/distant metastasis ? 1.) endoscopic resection with EMR 2.) endoscopic resection with ESD 3.) local resection 4.) pancreaticduodenectomy