Challenges in gastric, appendiceal and rectal NETs Leuven,
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1 Challenges in gastric, appendiceal and rectal NETs Leuven, Prof. Dr. Chris Verslype, Leuven Prof. Dr. Aurel Perren, Bern
2 Menue Challenges: 1. Gastric NET 2. Appendiceal NET 3. Rectal NET
3 SEER, U.S.A.
4 Incidence by stage: localized regional Lawrence et al, Endocrinol Metab Clin N Am
5 Gastric NET 23% of GI- NET (Austria) Type 1 Type 2 Type 3 NEC (Type 4) Background CAG MEN-1 sporadic sporadic Multifocality yes, stomach yes, stomach, duodenum etc. no no Surrounding mucosa LK-Meta if >1cm Atroph Hyperplastic Normal Normal 5% 30% 70% Allways?
6 Pathogenesis of gastric NET type 1 CAG associated
7
8
9 Gastric NET G1, type 1 BENIGN Corpus Antrum VMAT2 ICC
10 Pathogenesis of gastric NET type 1 MEN1/ZES associated MEN1-Keimbahnmutation ZES MEN1 germline mutation
11 Gastric NET G1, type 2 Corpus Antrum MEN1 and ZES
12 Gastric NET type 3 sporadic > Sporadic solitary ECLoma > EComa (serotonin producing) wdnet > Gastrinoma > Poorly differentiated (small cell) pdnec neuroendocrine Carcinoma
13 Treatment Endoscopic follow-up (1/yr) + endoscopic resection Risk of leaving lesions < 1 cm in place? Lesions > 1 cm: EUS and EMR (surgery) Delle Fave, Neuroendocrinology 2012
14 Treatment Local excision Delle Fave, Neuroendocrinology 2012
15 Treatment Treat as adenocarcinoma Delle Fave, Neuroendocrinology 2012
16 Conclusions: gastric NEN s Increasingly recognized due to expanding indications of upper endoscopy Management of gastric NEN s is driven by the subtype Type 1 and type 2: carefull endoscopic and pathological mapping place/extent of surgery not well defined Type 3: same approach as for gastric adenocarcinoma
17 Neuroendocrine neoplasms of the rectum Chris Verslype MD PhD U.Z. Leuven, Belgium
18
19 SEER, U.S.A.
20 SEER, U.S.A.
21 Epidemiology and prognosis Rapidly increasing incidence due to colonoscopy screening Asian > African > Caucasian Metastatic potential: < 1 cm: 2% 1-2 cm: 10-15% > 2 cm: 60-80% Mani and Modlin, J Am Coll Surg 1994
22 Epidemiology and prognosis localized disease: 90 % 5 year survival rate (5-YSR) regional disease: 62 % 5-YSR metastatic disease: 24 % 5-YSR Yao et al. JCO 2008
23 Clinical presentation Incidental finding Age: 56 No serotonin production
24 Rectal NEN Morphology Small round/yellow polyps Small pseudoglands, cell nests Frequently T1, cured after endoscopic resection Well differentiated (G1, MIB1<2%) Paul Komminoth Soga, J., Carcinoids of the colon and ileocecal region: a statistical evaluation of 363 cases collected from the literature. J Exp Clin Cancer Res, (2): p
25 Rectal NEN Immunohistochemistry Positive for NE markers Synaptophysin, Chromogrannin A often negative Serotonin negative, GLP, PP positive (L-cells) Shunsuke Tsukamoto, J. Int J Colorectal Dis p
26 Rectal NEN Differential diagnosis No problem Think of it Immunohistochemistry in small samples of well differentiated infiltrating tumor with artefacts!
27 Staging Endoscopic ultrasound Lesions > T1 MRI
28
29 Weinstock et al. Neuroendocrinology 2013
30 Weinstock et al. Neuroendocrinology 2013
31 Treatment NEN < 1 cm : Endoscopic resection (EMR, ESD) In case of T1a lesion, and low grade (G1), no invasion of muscularis mucosae or lymphovascular invasion: no follow-up
32 Treatment NEN 1-2 cm : G2, lymphatic invasion: surgery probably the best option No invasive/ aggressive features: endoscopic resection
33 Treatment NEN > 2 cm: Treatment as rectal adenocarcinoma
34 Conclusions Increasing incidcence Size/ invasion/ grade: determinants of prognosis Lesions between 1-2 cm: challenge (endosocpy, minimal invasive surgery ) Multidisciplinary discussion
35 Rectal NET SEER Japan LN-metastasis < 5 mm n.a. 3.7 % < 10 mm 3 % 9.7 % > mm % 27.6 % > 20 mm % n.a. <1cm, L0, pt1: No metastases! In Austria: 60% <1cm, 20% 1-2cm 35
36 Colonic NEN Different tumors! rare Frequently malignant Frequently G3 (NEC) or mixed (MANEC) Niederle M: ERC,
37 Appendix NET 50-77% of appendiceal neoplasms 19% of all NET Inzidence 0.15/ /Jahr 1/300 appendectomies More frequently in women (2:1)
38 Appendix NET prognosis > local disease: % 5 year survival rate (5-YSR) > regional disease: % 5-YSR > metastatic disease: 12-28% 5-YSR > overall % 5-YSR
39 Appendix NET prognosis <1cm: (allmost) never metastases >2cm: Relevantes Metastase-Risiko (21-44%) Moertel 1987: 150 patients 127 <2cm no LN meta 3/14 2-3cm LN meta (21%) 4/9 >3cm LN meta (44%) Bamboat Patienten <2cm: no Meta Anderson Patienten <2cm: 2 Meta (1.3%) Syracuse Patienten <1cm: 2 Meta (2.1%)
40 Staging > ONLY for tumours > 1cm > Imaging: CT or MRI SRS (tumours > 2 cm) > Blood tests: Chromogranin A (M+)
41 TNM-Appendix UICC 2010: T1a (<1cm), T1b 1-2cm ENETS T1 (<1cm) T2 (2 4cm) T3 (>4cm, Invasion Ileum) identical? T2 (<2cm <3mm Mesoappendix) T3 (> 2cm, > 3mm Mesoappendix) T4 (Invasion Peritoneum andere Organe) T4 (Invasion Peritoneum andere Organe)
42
43 65-85% of appendiceal NEN 100% cure No follow-up No additional work-up
44 <10% of appendiceal NEN M+ in 25-40% Radical resection Long term follow-up
45 5-25% of appendiceal NEN M+ in 0-10% Type of resection? Long term follow-up?
46 B01_19800
47 B01_19800_Mesenteriolon
48 LKmeta in eins von 15
49 699 pts < 20 years T >2 cm: 4% Invasion mesoappendix: 30,5% Further resection: 11,6% Recurrence/death: 0 Kim et al. 2014
50 Treatment NEN < 1 cm (ENETS stage 1, UICC 1a): Appendectomy when location at the base of the appendix, meso-appendix > 3 mm: discuss right hemicolectomy (very rare...)
51 Treatment NEN > 2 cm (ENETS stage 3, UICC 2): Right hemicolectomy
52 Treatment NEN 1-2 cm (ENETS stage 2, UICC 1b): Base of the appendix, R1 resection, Young age, Meso-appendix > 3 mm: Right hemicolectomy Additionnal criteria: G2 grade, angioinvasion?
53 Goblet cell carcinoid/carcinoma A subset of the MANEC type RARE! Eminence -based medecine
54 Goblet cell carcinoid/carcinoma TNM staging is the same as for adenocarcinoma of the appendix Treatment is right hemicolectomy, rapidly after diagnostic appendectomy Surgery of liver metastases? No data.. Chemotherapy: 5-FU based (FOLFOX), 50% SD for 8-12 months.
55 Questions
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