BONNETZentrum 17.10.2017 „Surgical treatment of upper GI neuroendocrine tumors ” Philipp Lingohr Jana Enderes Cyrus Wix

What are neuroendocrine tumors? Introduction What are neuroendocrine tumors? Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. Many are benign, while some are malignant. They most commonly occur in the intestine, where they are often called carcinoid tumors, but they are also found in the pancreas, lung and the rest of the body. NETs are believed to arise from various neuroendocrine cells whose normal function is to serve at the neuroendocrine interface. Neuroendocrine cells are present not only in endocrine glands throughout the body that produce hormones, but are found in all body tissues. https://en.wikipedia.org/wiki/Neuroendocrine_tumor 2

Yordanova et al. 2017, Horm Met Res Classification Weisst Du noch woher das Bild ist!?! Quelle!?! Steht unter dem Bild und das ist nicht nur für Magen Yordanova et al. 2017, Horm Met Res 3

Incidence Incidence: 2,5-5 /100 000 /y 50-70 y; m=f 4 Yao et al. 2008, Journal of clinical oncology Hallet et al. 2015, Cancer 4

Symptoms Vinik A. et al. 2009, Pancreas 5

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Therapy 68Ga-DOTATOC & 68Ga-DOTATATE (sst2 receptor specific) 68Ga-DOTANOC (sst2,3,5 receptor specific) Pavel et al. Systemic Therapeutic Options for Carcinoid. Semin Oncol 40:84-99 © 2013 Elsevier Inc. 7

Curative treatment Palliative treatment Chemotherapy SSA SSA + PRRT For example: Temozolomid (+PRRT) SSA SSA + PRRT Ki-67 > 10%, high hepatic tumour burden G3 NEC: chemotherapy Everolimus G1/G2 Curative surgery Resection of the primary tumour and/or resection of the metastases PRRT (+ SSA) Palliative surgery NO YES OR Progress? Re-PRRT Locoregional Therapy TACE/TAE/SIRT If predominant hepatic tumour load Yordanova et al. 2017, Horm Met Res 8

NET data UKB 1997-2017 112 patients 65 NECs 47 NETs 9

NET data UKB 1997-2017 upper GI 76 (32 NECs, 34 NETs) surgery 1 7 surgery 10 no surgery 14 upper GI 76 (32 NECs, 34 NETs) NECs NETs 3 surgery 4 no surgery 3 21 surgery 27 no surgery 7 No surgery = Radiopeptid, other chemotherapy, EMR, rejected surgical treatment 10

NET data UKB 1997-2017 mid gut 33 (27 NECs, 6 NETs) surgery 30 surgery 3 NECs NETs No surgery = Radiopeptid, other chemotherapy, EMR, rejected surgical treatment 11

NET data UKB 1997-2017 lower GI 13 (6 NECs, 7 NETs) No surgery = Radiopeptid, other chemotherapy, EMR, rejected surgical treatment surgery 6 no surgery 7 12

Case report 1 Case 1: 62-year-old male patient presenting with incidentally detected NET of the stomach Krajak, Andreas 26.11.1953 13

Case report 1 Medical history diabetes mellitus (insulin-dependent) diabetic polyneuropathy s/p gastritis (H.p. negative) urosepsis Bei Herrn Krajak wurde im Rahmen einer Urosepsis inzidentell ein gastraler neuroendokriner Tumor mittels Computertomographie und endoskopischer Biopsie gesichert (das wollte ich eigentlich mit dem Pfeil von der Urosepsis zum CT-Befund darstellen) 14

Case report 1 Diagnostics DOTATOC-PET/CT: neuroendocrine tumor of the stomach, somatostatin-receptor-positive local lymphogenic metastasis possible haematogenic metastasis liver (segment VI) CIO-Tumorboardbeschluss 05/2015: Indikation zur Operation, in Lebersegment VI fraglicher Befund, falls dieser intraoperativ tumorverdächtig ist, wird dieser auch reseziert 15

Case report 1 Therapy Exploratory laparotomy, total gastrectomy with D2 lymphadenectomy and Y-Roux-reconstruction atypical resection of liver segment II and III Explorative Laparotomie, totale Gastrektomie mit D2-Lymphadenektomie und Rekonstruktion nach Y-Roux, atypische Leberresektion Seg 2, Seg 3 caudal und Seg 3 dorsal nach intraoperative Sonographie der Leber (hier muss ich mir morgen früh nochmal den OP-Bericht studieren, warum nun Segment II und III reseziert wurden und nicht Segment VI, ich vermute aufgrund des intraoperativem Schallbefundes) A. Hirner, J.C. Kalff, M. Overhaus: Magenkarzinom Herbst-Symposium Onkologie 2008 Siriwardena AK et al. Nat Rev Onc, 2014 16

Case report 1 Result Neuroendocrine tumor of the stomach pT2, pN1 (4/17, ece+), R0, L1, V0, M1 (HEP), G2 KI67: 4% Biotherapy with somatuline Letztendlich konnte der Befund in Segment II nicht komplett reseziert werden, daher Therapie mit Somatuline 17

Case report 1 Follow-up 5 months post surgery MRI of the liver: multiple unspecific lesions follow up 8 months post surgery MRI of the liver: suspicious lesions in segment II and VI Relaparotomy and atypical resection of liver segment II and VI simultaneous cholecystectomy Continuation of biotherapy with somatuline and start with palliative chemotherapy with capecitabin and temozolomid (in total 13 cycles ; diffuse metastasis of liver) 18

Case report 1 Follow-up 14 months post surgery MRI of the liver: new suspicious lesion in segment VI and VII 17 months post surgery MRI of the liver: suspicious lesion in segment VI and VII stable in size follow-up 24 months post surgery MRI of the liver: suspicious lesion in segment VI and VII stable in size follow-up 19

Case report 2 Case 2: 42-year-old female patient presenting with suspected liver metastasis of breast cancer/malignant melanoma Heckers, Martina 14.04.1966 20

Case report 2 Medical history s/p breast cancer, left side, pT1b, pN0 (0/9), M0, G3, Her2neu negative, Ki67 50% s/p DCIS, right side (2006) bilateral mastectomy and reconstruction chemotherapy (6 cycles of 5-Fluorouracil/Epirubicin/Cyclophosphamid) radiotherapy s/p malignant melanoma right thigh (1997) - radical excision 21

Case report 2 Diagnostics CT abdomen: 1. suspicious lesion (12,5 x 6,7 x 9 cm) left liver lobe (segment II, III and infiltration of segment IVa/b) 2. suspicious lymph node retrosternally Vorstellung über die chirurgische Ambulanz, nachdem in einer auswärtig angefertigten CT-Abdomen eine malignomsuspekte Raumforderung (12,5 x 6,7 x 9 cm) im linken Leberlappen aufgefallen war. Verdachtsdiagnose: metastatische Absiedelung in der Leber nach Mammakarzinom sowie nach Malignem Melanom FDG-PET/CT: 1. suspicious FDG uptake within left liver lobe 2. suspicious FDG uptake retrosternally 3. suspicious FDG uptake in the duodenum 22

Case report 2 Therapy Instantaneous section analysis of lesion in liver: malignancy liver resection of left liver lobe Instantaneous section analysis of lesion in head of pancreas: malignancy Kausch-Whipple procedure Siriwardena AK et al. Nat Rev Onc, 2014 MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH 23

Case report 2 Result Poorly differentiated large-cell carcinoma of the pancreas - pT2 (m), R1, L1, V1, pN1 (2/11), pM1 (HEP), G3 - chromogranin A positive - synaptophysin positive - NSE positive - KI67 80-90% Chemotherapy (over the next 4 months) 10 cycles of Carboplatin and Etoposid 24

Case report 2 Follow-up FDG-PET/CT (3 months after last cycle of chemotherapy): regression of retrosternal lymph node metastasis new axillary lymph node metastasis on right side new metastasis of the right adrenal gland (8 x 3,5 x 3,5 cm) lymph node exstirpation (instantaneous section: metastasis of NET) chemotherapy ACOII protocol (Adriamycin/Cyclophosphamid/Vincristin) 25

Case report 2 Follow-up 2 months later patient presents with a tendency to fall new diffuse metastasis in both hemispheres one prominent metastasis in the cerebellar vermis (symptoms!) Patientin wechselte mehrmals die Kliniken, beispielsweise Radiatio im Uniklinikum Köln. Aktueller Status gab es daher glaube ich nicht, schaue ich morgen aber nochmal nach. Habe zu Hause bekanntlich kein Zugriff aufs KAS… after 20 cycles of radiotherapy with 40 Gy symptoms diminished chemotherapy with Temozolomid and Thalidomid 26

Thank you for your attention! 27