-
BACKGROUND
Neuroendocrine neoplasms (NENs) of the gallbladder (GB),
extrahepatic bile duct (EHBD), and ampulla of Vater (AoV) are very
rare.1 Biliary NENsaccount for less than 1 percent of all
gastrointestinal NENs.1 According to the Surveillance,
Epidemiology, and End Results (SEER) program andEuropean studies,
the incidence of NENs is increasing due to greater awareness and
improved diagnostic tools.2,3 The clinicopathology andprognosis of
patients with different types of biliary NENs remain unclear. In
this study, we tried to evaluate clinicopathology of biliary NENs
andidentify factors related to prognosis in affected patients.
PATIENTS
The Korean Gastroenteropancreatic Neuroendocrine Tumor Study
Group of the Korean Society of Gastrointestinal Cancer conducted a
multicenterretrospective study between 2005 and 2014. A total of 43
patients with biliary NENs were finally enrolled from 7 tertiary
hospitals. The biliary NENswere in the GB (n=11), EHBD (n=5), or
AoV (n=27). We compared the clinicopathology and outcome of
patients with NENs in these different locations.
WHO CLASSFICATION
The 2010 WHO classification was used to classify tumors as:
neuroendocrine tumor (NET) G1 (mitotic count 20per 10 HPFs and/or
>20% Ki- 67 index); or mixed adenoneuroendocrine carcinoma.4
STATISTICAL ANALYSIS
Categorical variables and continuous variables were compared by
Fisher’s exact test and the Mann- Whitney U- test, respectively.
Progression freesurvival and overall survival rates were compared
by the log- rank test. Multiple Cox regression analysis was used to
evaluate factors related to theoverall survival. A p- value of 0.05
was considered statistically significant. All statistical analyses
were performed using SPSS version 12.0 forWindows (SPSS Inc.
Chicago, IL, USA).
Authors Kyong Joo Lee1, Jae Hee Cho, Sang Hyub Lee, Kwang Hyuk
Lee, Byung Kyu Park, Jun Kyu Lee, Sang Myung Woo, Ji KonRyu, Jong
Kyun Lee, Yeon Suk Kim, Jae Woo Kim, Woo Jin Lee
E- mail [email protected]
Institute 1Department of Internal Medicine, Yonsei University
Wonju College of Medicine
City/Nationality Wonju, Korea
Category Review
Case
Upper GI Lower GI Pancreatobiliary tract Others
Title of Article
Clinicopathological characteristics of biliary neuroendocrine
neoplasmamulticenter study
RESULTS
We examined the records of 43 patients with biliary NENs (Table
1). The median age was 62 years (range: 29- 84 years) and there
were 25 males(58.1%) and 18 females (41.9%). The most common
symptoms at diagnosis were abdominal pain and jaundice. There were
incidental diagnosesduring regular check- ups in 2 patients (18.2%)
who had GB NENs and in 9 patients (33.3%) who had AoV NENs. The
most common metastatic sitewas the liver. According to the WHO
classification, all of patients with GB NENs had NEC G3 and 37.1%
of patients with AoV NENs were classified asNEC G3.
-
In conclusion, our multivariate analysis indicated that patients
with biliary NENs classified as G3 by the 2010 WHO classification
had poor prognosesirrespective of the tumor site and metastasis. In
addition, because most AoV NENs are classified as G1 or G2,
patients with these tumors have morefavorable prognoses. Further
prospective studies are needed to establish the prognostic factors
for patients with biliary NENs.
< Lee KJ, Cho JH, Lee SH, Lee KH, Park BK, Lee JK, et al.
Scand J Gastroenterol 2017;52(4):437-441.
FIGURE
FIGURE 1 Kaplan- Meier survival curves of progression free
survival between patients with GB NENs an
FIGURE 2 Kaplan- Meier survival curves of overall survival
between patients with GB NENs and AoV NE
-
TABLETABLE 1 Clinicopathological features of biliary
neuroendocrine neoplasms
Gallbladder EHBD Ampulla of Vater
(n=11) (n=5) (n=27)
Median age, years 62 (range, 31- 84) 74 (range, 54- 84) 60
(range, 29- 77)
Sex
Male 6 (54.5%) 4 (80%) 15 (55.6%)
Female 5 (45.5%) 1 (20%) 12 (44.4%)
Symptoms
Abdominal pain 8 (72.7%) 2 (40%) 7 (25.9%)
Jaundice 2 (18.2%) 2 (40%) 7 (25.9%)
Weight loss 1 (9.1%) 0 1 (3.7%)
Incidental diagnosis 2 (18.2%) 1 (20%) 9 (33.3%)
Coexistence
Diabetes mellitus 1 (9.1%) 0 2 (7.4%)
Gallbladder stone 0 0 1 (3.7%)
Choledocholithiasis 1 (9.1%) 0 0
Initial metastasis
Liver 7 (73.6%) 0 5 (18.5%)
Lymph nodes 2 (18.2%) 0 1 (3.7%)
WHO classification (2010)
NEN G1 0 1 (20%) 13 (48.1%)
NEN G2 0 0 4 (14.8%)
NEC G3 11 (100%) 4 (80%) 10 (37.1%)
Initial treatment
Operation 7 (63.6%) 5 (100%) 21 (77.8%)
Endoscopic resection 0 0 3 (11.1%)
Chemotherapy 3 (27.3%) 0 1 (3.7%)
Conservative care 1 (9.1%) 0 2 (7.4%)
Curative resection (R0) 3 (27.3%) 3 (60%) 16 (59.3%)
EHBD, extrahepatic bile duct; WHO, World Health Organization;
NEN, neuroendocrine neoplasm; NEC, neuroendocrine carcinoma
-
Characteristic HR P- value* HR 95% CI P- value**
Age
-
REFERENCES
01 Modlin IM, Lye KD, Kidd M. A 5- decade analysis of 13,715
carcinoid tumors. Cancer. 2003;97(4):934- 959.
02 Hauso O, Gustafsson BI, Kidd M, et al. Neuroendocrine tumor
epidemiology: contrasting Norway and North America.
Cancer.2008;113(10):2655- 2664.
03 Lawrence B, Gustafsson BI, Chan A, Svejda B, Kidd M, Modlin
IM. The epidemiology of gastroenteropancreatic neuroendocrine
tumors.Endocrinol Metab Clin North Am. 2011;40(1):1- 18.
04 Rindi G, Klimstra DS, Arnold R. Nomenclature and
classification of neuroendocrine neoplasms of the digestive system.
In: Bosman F,Carneiro F, R.H. H, Theise ND, editors. WHO
classfication of tumors of the digestive system; World Health
Organization of Tumors. 4thed. IARC, Lyon. 2010:13- 14.
05 Dumitrascu T, Dima S, Herlea V, Tomulescu V, Ionescu M,
Popescu I. Neuroendocrine tumours of the ampulla of Vater:
clinico-pathological features, surgical approach and assessment of
prognosis. Langenbecks Arch Surg. 2012;397(6):933- 943.
06 Kloppel G. Tumour biology and histopathology of
neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab.
2007;21(1):15- 31.
07 Modlin IM, Shapiro MD, Kidd M. An analysis of rare carcinoid
tumors: clarifying these clinical conundrums. World J
Surg.2005;29(1):92- 101.
08 Michalopoulos N, Papavramidis TS, Karayannopoulou G, Pliakos
I, Papavramidis ST, Kanellos I. Neuroendocrine tumors of
extrahepaticbiliary tract. Pathol Oncol Res. 2014;20(4):765-
775.
09Henson DE, Albores- Saavedra J, Compton CC. Protocol for the
examination of specimens from patients with carcinomas of
theextrahepatic bile ducts, exclusive of sarcomas and carcinoid
tumors: a basis for checklists. Cancer Committee of the College
ofAmerican Pathologists. Arch Pathol Lab Med. 2000;124(1):26-
29.
10 Malaguarnera G, Paladina I, Giordano M, Malaguamera M,
Bertino G, Berretta M. Serum markers of intrahepatic
cholangiocarcinoma.Dis Markers. 2013;34(4):219- 228.
11 Emory RE Jr, Emory TS, Goellner JR, Grant CS, Nagorney DM.
Neuroendocrine ampullary tumors: spectrum of disease including the
firstreport of a neuroendocrine carcinoma of non- small cell type.
Surgery. 1994;115(6):762- 766.
12 Hartel M, Wente MN, Sido B, Friess H, Buchler MW. Carcinoid
of the ampulla of Vater. J Gastroenterol Hepatol. 2005;20(5):676-
681.
13 Kim J, Lee WJ, Lee SH, et al. Clinical features of 20
patients with curatively resected biliary neuroendocrine tumours.
Dig Liver Dis.2011;43(12):965- 970.
14 Todoroki T, Sano T, Yamada S, et al. Clear cell carcinoid
tumor of the distal common bile duct. World J Surg Oncol.
2007;5:6.
15 Chamberlain RS, Blumgart LH. Carcinoid tumors of the
extrahepatic bile duct. A rare cause of malignant biliary
obstruction. Cancer.1999;86(10):1959- 1965.
16 Hatzitheoklitos E, Buchler MW, Friess H, et al. Carcinoid of
the ampulla of Vater. Clinical characteristics and morphologic
features.Cancer. 1994;73(6):1580- 1588.
17 Fazio N, Milione M. Heterogeneity of grade 3
gastroenteropancreatic neuroendocrine carcinomas: New insights and
treatmentimplications. Cancer Treat Rev. 2016;50:61- 67.
18Milione M, Maisonneuve P, Spada F, et al. The
Clinicopathologic Heterogeneity of Grade 3 Gastroenteropancreatic
NeuroendocrineNeoplasms: Morphological Differentiation and
Proliferation Identify Different Prognostic Categories.
Neuroendocrinology.2017;104(1):85- 93.
19 Avisse C, Flament JB, Delattre JF. Ampulla of Vater.
Anatomic, embryologic, and surgical aspects. Surg Clin North Am.
2000;80(1):201-212.
koreaArticle_01koreaArticle_03koreaArticle_04koreaArticle_05koreaArticle_06