2018年5月25日金曜日

Carcinoid tumors, neuroendocrine tumors, カルチノイド, 神経内分泌腫瘍

カルチノイド、神経内分泌腫瘍のまとめです。

・Am Fam Physician 2006;74:429-34.
・CMAJ 2017 March 13;189:E398-404
・Am J Med May 2017Volume 130, Issue 5, Pages e177–e180
の3文献のまとめです。

日本ではクロモグラニンAの測定は高価であり、ルーチンでの検査は難しいところです。
_________________________

rare
slow-growing neuroendocrine neoplasms
often indolent

1-2 /100,000 from Am Fam Physician
2.48-5.86/100,000 from CAMJ

forgot carcinoid tumors in lungs, bronchi or stomach
midgut carcinoid tumors in small intestine, appendix, or proximal large bowel
hindgut carcinoid tumors in distal colon or rectum

most common site: appendix, followed by rectum, ileum, lungs, bronchi, stomach
GI tract 48%, lung 25%, pancreas 9%

Carcinoid syndrome: 10% with carcinoid tumors, often associated with midgut tumors
vasoactive substance: 5-HT (serotonin), prostaglandins, histamine, bradykinin, fibroblast-proliferative properties (tachykinins: substance P, neurokinin A, neuropeptide K)

Differential Diagnosis of Carcinoid Syndrome
・ Flushing
Menopausal syndrome; pheochromocytoma; mastocytosis; benign cutaneous flushing; medullary carcinomas of the thyroid; ingestants (e.g., food, drugs)
・Wheezing
Asthma; anaphylaxis; pulmonary edema; bronchial foreign body
・Diarrhea
Gastroenteritis; inflammatory bowel disease; infectious colitis; laxative abuse
・Heart valve symptoms
Rheumatic heart disease; subacute bacterial endocarditis; dilated cardiomyopathy; ischemic heart disease with papillary muscle dysfunction

Dx
with vasoactive symptoms, measuring urine 5-HIAA in 24hr sample (sensitivity 35-73%) & serum chromogranin A(glycoprotein secreted by neuroendocrine tumors, sensitivity 80% (53-91%), specificity 95% (< 50% from CMAJ), false positive rate 40% with MM, false elevations in PPI, renal insufficiency, adenocarcinomas, severe arterial hypertension)
with bowel dys-motility, CT and MRI

serum serotonin

urine 5-HIAA
24hr sample
lack sensitivity and specificity; may not be elevated in atypical carcinoids, can elevated other condition (tropical sprue, celiac disease, Whipple Dx, small bowel obstruction, serotonin rich food, certain medications

111In-labelled pentetreotide somatostatin receptor scintigraphic imaging
a sensitivity of 46%–100% for abdominal NETs, 46%–83% for pancreatic NETs and 71% for bronchial NETs

endoscopic imaging
pancreatic NETs: sensitivity 82-93%
particularly useful for identifying < 2cm and localization of insulinoma

Tx
Carcinoid tumor
incidental finding of metastatic low-grade carcinoid tumor wit asymptomatic and hormonally non-functional → observation & repeat imaging several times each year to determine whether progress or not (from MKSAP 17)
Surgical resection if possible:
Hepatic metastases dominant: long-acting somatostatin analogues (octerotide)for positive radio labeled octerotide scan & low-grade; hepatic artery embolization or ligation with or without interferon, with or without chemotherapy
Systemic spread: chemotherapy (platinum-based chemotherapy for high-grade) or interferon or long-acting somatostatin analogues

Carcinoid syndrome
Systematic progression through treatment options:
Valvular Heart disease: diuretics, long-acting somatostatin analogues, occasional valvular replacement
Flushing: avoid precipitating food and alcohol; 5-HT3-receptor antagonist; long-acting somatostatinanalogues; interferon; hepatic artery embolization or ligation with or without interferon, with or without chemotherapy
Diarrhea: antidiarrheal agents; 5-HT3-receptor antagonist; long-acting somatostatin analogues; interferon; hepatic artery embolization or ligation with or without interferon, with or without chemotherapy
Wheezing: selective bronchodilators; long-acting somatostatin analogues; interferon; hepatic artery embolization or ligation with or without interferon, with or without chemotherapy

Carcinoid crisis
acute life-threatening go carcinoid syndrome
profound flushing, bronchospasm, rapidly fluctuating BP

Px
metastatic liver disease arising from a small bowel carcinoid tumor → uniformly poor
median survival with grade 1 124 mon
median survival with grade 2 64 mon
median survival with grade 3 10 mon