Transcript ΝΕΥΡΟΕΝΔΟΚΡΙΝΕΙΣ ΟΓΚΟΙ ΣΤΟΜΑΧΟΥ

ΠΑΡΟΥΣΙΑΣΗ ΕΝΔΙΑΦΕΡΟΝΤΩΝ
ΠΕΡΙΣΤΑΤΙΚΩΝ GIΝΕΥΡΟΕΝΔΟΚΡΙΝΩΝ ΟΓΚΩΝ
ΝΕΤ ΟΡΘΟΥ
Γεώργιος Αλεξανδράκης
Διευθυντής
Γαστρεντερολογική Κλινική ΝΙΜΤΣ
ΝΕΤ MASTERCLASS
Γαστρεντερικοί Νευροενδοκρινικοί όγκοι (GI-NETs). Πρόσφατες εξελίξεις και χαρακτηριστικά κλινικά περιστατικά
Ίδρυμα Ευγενίδου, Αθήνα, Σάββατο 5 Ιουλίου 2014
INCIDENCE
Increasing incidence
• 0.2/100.000 (1973)
• 0.86/100.000 (2004)
 Awareness
Screening colonoscopy
Genuine increase
• 27% of GI NETs
Modlin I et al. Lancet Oncol 2008; 9: 61-72
EPIDEMIOLOGY
Distribution of 35.825 ΝΕΤ according to location
Liver 0,8%
Appendix
3%
Cecum 3,2%
Duodenum 3,8%
Colon
4%
Stomach
6%
Pancreas
6,4%
Jejunum/Ileum
13,4%
Rectum
17,2%
0,0
5,0
10,0
15,0
20,0
Yao JC, Hassan M, Phan A et al. J Clin Oncol. 2008;26(18):3063-3072
CLASSIFICATION
WHO (1980)
WHO (2000)
WHO (2010)
I. Carcinoid
1. Well-differentiated endocrine
tumor (WDET)*
2.Well-differentiatedendocrine
carcinoma (WDEC)*
3. Poorly differentiated endocrine
carinoma/small cell carcinoma
(PDEC)
1.
2.
3.
II. Mucocarcinoid
III. Mixed forms carcinoidadenocarcinoma
4. Mixed exocrine-endocrine
carcinoma (MEEC)
4. Mixed adenoneuroendocrine
carcinoma (MANEC)
NET G1 (carcinoid)
NETG2*
NEC G3
large-cell or small-cell type
NET, neuroendocrine tumor―well differentiated; NEC, neuroendocrine carcinoma―poorly differentiated;
G, Grade (G1<2/10hpf and/or Ki67≤2%, G2 2-20/10hpf and/or Ki67 3-20%, G3>20/10hpf and/or Ki67>20%
*If the Ki67 index exceeds 20%, this NET may be labeled G3.
Rindi G, et al: Nomenclature and classification of neuroendocrine neoplasms of the digestive system; in Bosman FT, Carneiro F, Hruban RH,
Theise ND (eds): WHO Classification of Tumours of the Digestive System, ed 4. Lyon, IARC, 2010, pp 13–14.
DIAGNOSIS
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Mean age at diagnosis of 56.2 years
Small polypoid/submucosal lesions
Solitary
Incidental finding
Change in bowel habits, blood per
rectum, anorectal symptoms or
asymptomatic
Non functioning
Rarely metastatic (Distant metastasis
at diagnosis 2-8%)
Endoscopy (colonoscopy/EUS)
CT/MRI
Octreoscan/PET
CgA
Neuroendocrinology 2012; 95:88-97
PROGNOSTIC FACTORS
Factors favoring metastatic behaviour [1]
Size>2cm
Angiogenesis
G3/high grade
Neural/lymphatic/vascular invasion
Poorly differentiated
Increased tumor proliferation index
Muscularis propria invasion
Endoscopic/EUS features
Prognostic Factor
75.2 - 88.3%
Tumor size > 14 mm [2]
Overall 5-year
survival
Mitotic index ≥ 2 /10 HPF [2]
Localized disease
290 months
Lymphovascular invasion [2]
Regional disease
90 months
Muscularis layer invasion [3]
Distant disease
22 months
[1] Neuroendocrinology 2012;95:88-97
[2] ParkCH et al.Criteria for decision making after endoscopic resection of well-differentiated rectal carcinoids with regard to potential lymphatic spread.
Endoscopy 2011; 43: 790 – 795
[3] Wang M, et al. Prognostic analysis for carcinoid tumors of the rectum: a single institutional analysis of 106 patients. Colorectal Dis 2011; 13: 150 – 153
TREATMENT ALGORITHM
Neuroendocrinology 2012; 95:88-97
ENDOSCOPIC RESECTION
Placement of an
asymmetric snare into
the inner rim of the cap
Saline injection into
the submucosa to
create a voluminous
submucosal swelling
beneath the lesion.
Endoscopic appearance after resection.
de Mestier Louis et al. Endoscopy 2013; 45: 1039–1046
ENDOSCOPIC RESECTION
Endoscopic submucosal dissection of
a residual rectal
neuroendocrine
tumor after primary
polypectomy.
Directly visualized
dissection along the
submucosal plane, using the
dual knife.
First circumferential
incision along the
outer perimeter of
the marking dots,
after saline injection.
Endoscopic
appearance after
dissection
de Mestier Louis et al. Endoscopy 2013; 45: 1039–1046
CASE REPORT 1
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Female 83 years old
History of ovarian cancer – hysterectomy + Chemo (1998)
Occasional bleeding per rectum
Colonoscopy revealed a 1,2 cm polypoid lesion, 6 cm from the
anal verge – Biopsies were taken
Pathology report: “neoplastic cells with mild to moderate
nuclear atypia”. “The histologic type cannot be accurately
assessed”.
CASE REPORT 1
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07/2012 transanal surgical excision
Pathology report : “Colonic mucosa with invasion of a
neuroendocrine tumor of mean diameter 1.2 cm, grade 2 (Ki67
≈12%, <2/10hpf), extending into the excision margins.”
Stage???
Chest CT/Abdominal-Pelvic MRI : Negative
CgA = 3.1 nmol/l
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Rectal NET G2, T1bN0M0
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CASE REPORT 1
Incomplete
resection
Surgery
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Annual follow up
Endoscopy : No recurrence
Abdominal/PelvicMRI :
Negative
CgA : 1.80 nmol/l
CASE REPORT 2
CASE REPORT2
■ Male 50 years old
■ Mild rectal bleeding for the last 5 days and changes in bowel habits last month
■ COLONOSCOPY : ulcerative mass of 6cm in length, at 8 cm from the anal verge
■ BIOPSIES: Poorly differentiated NEC, (Chrom. A +, Synaprt. A +)
Ki-67 : 80% , diffuse stained
Cytocheratines 5/6 : negatives
■ CT scan of the abdomen : pathological enlarged mesorectal Ln
chest CT scan : normal
■ TREATMENT : Low anterior resection with total mesorectal resection and Ln dissection
with free macroscopic surgical margins
Resected 24 Ln , 4 + and neoplastic emboli in lymphatics and vessels
■ Histology – immunohistichemical : poorly differentiated large cell NEC
AND
Squamouse cell carcinoma g representing 5-10% of tumor population
Mitotic rate : > 20 HPF,
Ki-67 : 80%
G3 , pT3 N1 M0
Neuroendocrine Rectal Tumors (NRTs): 7.2 – 27% of all NETs
WHO classification : neuroendocrine tumors (NETs) ,
well differentiated, carcinoids , grade G1 or G2
neuroendcrine carcinomas (NTCs)
poorly differentiated, small and large, high grade G3
mixed neuroendocrine carcinomas (MANEC) , G3 , and
when : both neuroendocrine and non-neuroendocrine
each component exceeds 30%
This case is NOT - MANEC , because we have G3 large cell NEC
BUT
the squamous component represent only the 5 – 10% of tumors cells
Li et al. analyzed 87 cases of MANEC
- no one in the rectum
- 56% in the right colon
- 41% in the left colon
- 12% squamous cell carcinomas with glandular epithelial component
MIXED G3 large cell NEC with Squamous carcinoma of the rectum is
extremely rare
CASE REPORT 3
CASE REPORT 3
■ Male 62-year old
■ One month history of intermittent, voluminous bleedings per rectum
( single, short-lasting syncope before bleeding)
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COLONOSCOPY: rectal tumor (8-13cm from anal verge),in a hemiannular
fashion
HISTOLOGY : poorly differentiated small cell carcinoma
Immunohistochemical : positivity for neurofilaments
complete absence of cytokeratins
Synaptophysine (+)
Chromogranine A (-)
Ki-67 : heterogeneous expression
■ MRI : extensive growth into pelvic
multiple Ln metastasis within – outside mesorectum
■ MRI – CT – U/S : multiple metastases in the liver
Chest CT – scan : normal
■ LAB : normal
■ DIAGNOSIS : extensive small – cell carcinomas of the intestinal tract
TREATMENT
Both clinical and radiological assessment revealed a locally advanced rectal
cancer that cannot be completely removed by surgery alone
■ CHEMOTHERAPY : highly sensitive
4 week cycles
- at the beginning good response
4th cycle : septicemia -klebsiella pneumoniae
bleeding from the rectum
pulmonary embolization
bone marrow toxicity
■ RADIOTHERAPY
Highly sensitive to radiotherapy (paliative treatment )
Clinical improvement
BUT
with opioid medication , the patient developed attention disturbance and cognitive
disability - DELIRIUM caused by disturbances in brain metabolism
SUMMARIES
1) Early detection
2) EUS is the most accurate for pre-therapeutic determination of the invasion
depth
3) Low risk rectal carcinoids : endoscopic resection ( ESMR-L , ESD )
4) High risk : surgical excision if it is possible
In local excision with incomplete resection margins
TEN (trananal resection or radical surgery )
5) This tumors have substantial off relapse and / or spreading,
and must be followed for at least 5 years
Thank you for your attention