Neuroendocrine Tumour of Small Bowel Kai-Hong Yue, Ivan Kwong Wah Hospital.
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Transcript of Neuroendocrine Tumour of Small Bowel Kai-Hong Yue, Ivan Kwong Wah Hospital.
Neuroendocrine Tumour of Small BowelKai-Hong Yue, Ivan
Kwong Wah Hospital
Outline
Neuroendocrine tumour Distribution and Classification Morphology Presentation and Diagnosis Treatment and survival Take home message
Neuroendocrine Tumour
Oberndorfer, 1907: used Karzinoide to represent the carcinoma-like appearance and the relative indolent nature
Neuroendocrine cells throughout the entire GI tract, bronchopulmonary systems, and urogenital tract
Secrets vasoactive substances
Controversies about terminology and staging WHO 2010 classification
1. Lubarsch O. Uber den pimaeren krebs des ileum nebst Bemerkungen ueber das gleichzeitige Vorkommen von krebs und Tuberculos. Virchows Arch 1888;11:280–317.
2. Oberndorfer S. Karzinoide tumoren des dunndarms. Frankf Z Pathol 1907;1:425–429.
Distribution
Site Occurrence (%)
Extragastrointestinal (Lung, ovary, uterus)
~30
Oesophagus <1
Stomach 4-8
Duodenum/ pancreas < 2
Small intestine 25-30
Appendix 6
Colon 10
Rectum 15
Kenneth J. . Current management of gastrointestinal carcinoid tumors .Journal of Gastrointestinal Surgery. 2004, Volume 8, Issue 6, pp 742-756
WHO 1980 WHO 2000 WHO 2010
Carcinoid Highly differentiated neuroendocrine tumor
Neuroendocrine tumor Grade 1 (carcinoid)
Grade 2
Highly differentiated neuroendocrine carcinoma
Poorly differentiated (small-cell) neuroendocrine carcinoma
Neuroendocrine carcinoma Grade 3(Small- or large-cell)
Mucocarcinoid mixed carcinoid-adenocarcinoma
Mixed endocrine-exocrine carcinoma
Mixed adenoneuroendocrine carcinoma
Bosman FT, et al. WHO Classification of Tumours of the Digestive System. Lyon, France: IARC Press; 2010.
Small Bowel Neuroendocrine Tumours
Midgut/ Jejuno-ileal NETs “classical” midgut carcinoids serotonin (5-hydroxytryptamine [5-HT])
immunoreactivity 30% of NETs 25% of small-bowel neoplasms Average age of diagnosis: 65 year-old Slight male predominance
Modlin, I.M., Kidd, M., Latich, I., et al. Current status of gastrointestinal carcinoids. Gastroenterology 2005; 128: 1717-1751.
Morphological Features
Most common: terminal ileum Small (usually <1cm), flat and fibrotic
submucosal tumour, central navelling
Mesenteric metastases Typically conspicuously larger than primary
tumour
Incidence: 70-90% in patient subjected to surgery
Marked desmoplastic reaction with fibrosis
Conglomerate of mesenteric lymph gland metastases
Surgical treatment of midgut carcinoid tumours. World J Surg 1990;14:377-385
Evers BM, Townsend CM Jr, ThompsonJC. Small intestine. In Schwartz SI, ed. Principles of Surgery.New York: McGraw-Hill, 1999, pp 1217–1263.http://www.webpathology.com/image.asp?case=209&n=2
Mesenteric metastases Partial or complete small-intestinal
obstruction by kinking and fibrotic entrapment Fibrosis may tether the mesenteric root to the
retroperitoneum/ duodenum
Mesenteric vessels encased or occluded Venous stasis/ congestion, or arterial
deficiency
Vascular elastosis: specific angiopathy marked thickening of mesenteric vessel
walls due to elastic tissue proliferation in the adventitia
Surgical treatment of midgut carcinoid tumours. World J Surg 1990;14:377-385
Distant Metastases
Most common: liver Bilateral, diffusely spread; 10%
dominant lesion Carcinoid syndrome
Skeleton (spine, orbital framing) Lungs, CNS, peripheral
lymphnodes, ovaries, breast, skin
Surgical treatment of midgut carcinoid tumours. World J Surg 1990;14:377-385
Clinical Presentation
Slow growing tumour Long periods of prodromal symptoms Episodic abdominal pain; features of
carcinoid syndrome Intestinal bleeding: rare, late
Moderate size, submucosal location
Mesenteric metastases invasion
Venous stasis
Modlin, I.M., Kidd, M., Latich, I., et al. Current status of gastrointestinal carcinoids. Gastroenterology 2005; 128: 1717-1751.
Carcinoid Syndrome 20% of patient with jejuno-ileal NETs Release of vasoactive peptides:
Serotonin, bradykinin, tachykinins (substance P, neuropeptide K), prostaglandins and growth factors, e.g. platelet-derived growth factor (PDGF), noradrenaline
Implication: Hepatic metastasis Impaired monoamine oxidase activity for
detoxification
Symptoms: Secretory Diarrhoea, Cutaneous Flushing, Heart valve fibrosis, Bronchial constriction
Modlin, I.M., Kidd, M., Latich, I., et al. Current status of gastrointestinal carcinoids. Gastroenterology 2005; 128: 1717-1751.
Diagnosis
Biochemistry Radiology Histology
Biochemistry
Sensitive, reflect tumour load, as indicator of treatment response, non specific
Serotonin metabolite: (5-hydroxyindoleacetic acid ) 5-HIAA
Chromogranin A
24-hour urine sample Plasma
Specific Sensitive
advanced disease, liver metastases
Reflect tumour load, Indicator of treatment response, non specific
Radiology Contrast CT
Sensitivity 50-100% “circumscribed mesenteric mass with radiating
densities”
Somatostatin receptor scintigraphy - OctreoScan Sensitivity 43%–86%
indium-111. Somatostain receptors type 2 and 5
PET Sensitivity 90% - 97%
fluorine 18 (18F) FDG is less useful . Low proliferative rate
Gallium; 68Ga DOTA octreotate
Midgut Neuroendocrine Tumors: Imaging Assessment for Surgical ResectionWoodbridge et al. RadioGraphics 2014 34:2, 413-426
Woolbridge et al. Midgut Neuroendocrine Tumors: Imaging Assessment for Surgical Resection. RadioGraphics 2014 34:2, 413-426
Histology
Insular, glandular, mixed growth pattern
Immunocytochemistry staining Chromogranin A Synaptophysin Ki67 antibody: proliferation rate
grade 1 < 3%, grade 2 = 3–20%, and grade 3 > 20%
Treatment
Surgery Primary tumour and mesenteric
metastases Resection
Medical treatment and prophylaxis against carcinoid crisis
Primary tumour
Surgical resection Active strategy with early prophylactic locoregional
tumor removal
to prevent or delay abdominal complications from the growth of the mesenteric tumor disease
Resection of the primary tumor reduces symptoms and improves survival, even though inoperable mesenteric lymph node and liver metastases are present
Inoperable Involvement of origins of proximal jejunal arteries,
median colic artery or extending retroperitoneally
Hellman et al. Effect of Surgery on the Outcome of Midgut Carcinoid Disease with Lymph Node and Liver Metastases. World J. Surg. 26, 991–997, 2002
Medical Treatment
Palliation of symptoms Somatostatin analogues
Octreotide, lanreotide
Binding to somatostatin receptors types 2 and 5 Reduce the release of bioactive peptides
Inhibit tumour growth, induce apoptosis
Long-acting formulations (Monthly) Octreotide-LAR, lanreotide-PR
Interferon-α (IFN - α) Reduces hormone secretion and stimulates
natural killer cells
Prophylaxis Against Carcinoid Crisis
Carcinoid crisis Hyperthermia, shock, arrhythmia, excessive
flush or bronchial obstruction
Octreotide 500 microgram in 500ml NS,
50 microgram/hr infusion for prophylaxis
100 microgram/ hr infusion for carcinoid crisis
ENETS Consensus guidelines for the standards of care in neuroendocrine tumors: pre- and perioperative therapy in patients with neuroendocrine tumors. Neuroendocrinology 2009;90: 203-208.
Survival Age-adjusted overall 5-year survival:
67% Median survival 8.4 year Inoperable liver metastases: 50% 5-
year survival Inoperable liver and mesenteric lymph
node metastases: 42% 5-year survival
Long-Term Results of Surgery for Small Intestinal Neuroendocrine Tumors at a Tertiary Referral Center. World J Surg (2012) 36:1419–1431
Take Home Message
Rare, Slow growing tumour, long periods of prodromal symptoms
Intestinal obstruction Carcinoid syndrome uncommon Locoregional resection improves
survival even in presence of liver metastases
Medical treatment improves symptoms