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 <2 per 10 high power fields [HPFs]and/or ≤2% Ki- 67 index); NET G2 (mitotic count 2- 20 per 10 HPFs and/or 3- 20% Ki- 67 index); neuroendocrine carcinoma (NEC) G3 (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 smild123@yonsei.ac.kr

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

    <60 1 1

    ≥60 0.65 0.418 0.82 0.26- 2.56 0.738

Sex

    Female 1 1

    Male 2.57 0.041 2.07 0.57- 7.47 0.264

Tumor location

Ampulla of Vater 1 1

Extrahepatic bile duct 5.11 0.001 1.94 0.45- 8.31 0.368

Gallbladder 3.77 0.033 2.86 0.72- 11.36 0.136

Presence of metastasis

    No 1 1

    Yes 2.46 0.039 2.2 0.53- 9.03 0.274

WHO classification (2010)

    NEN G1 & G2 1 1

    NEC G3 34.17 0.001 27.1 2.81- 260.68 0.004

Curative resection (R0)

    No 1 1

    Yes 0.79 0.575 0.38 0.07- 1.88 0.235

Chemotherapy

    No 1 1

    Yes 0.299 0.006 1.19 0.27- 5.2 0.813

*Univariate analysis, **Multivariate analysis were used.

WHO, World Health Organization; NEN, neuroendocrine neoplasm; NEC, neuroendocrine carcinoma; HR, hazard ratio; CI, confidence interval

TABLE 2 Prognostic factors affecting overall survival in biliary neuroendocrine neoplasms

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