Title of Article Clinicopathological characteristics of biliary...

5
B A C K G R O U N D Neuroendocrine neoplasms (NENs) of the gallbladder (GB), extrahepatic bile duct (EHBD), and ampulla of Vater (AoV) are very rare. 1 Biliary NENs account for less than 1 percent of all gastrointestinal NENs. 1 According to the Surveillance, Epidemiology, and End Results (SEER) program and European studies, the incidence of NENs is increasing due to greater awareness and improved diagnostic tools. 2,3 The clinicopathology and prognosis of patients with different types of biliary NENs remain unclear. In this study, we tried to evaluate clinicopathology of biliary NENs and identify factors related to prognosis in affected patients. P A T I E N T S The Korean Gastroenteropancreatic Neuroendocrine Tumor Study Group of the Korean Society of Gastrointestinal Cancer conducted a multicenter retrospective study between 2005 and 2014. A total of 43 patients with biliary NENs were nally enrolled from 7 tertiary hospitals. The biliary NENs were 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. W H O C L A S S F I C A T I O N The 2010 WHO classi cation was used to classify tumors as: neuroendocrine tumor (NET) G1 (mitotic count <2 per 10 high power elds [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 >20 per 10 HPFs and/or >20% Ki- 67 index); or mixed adenoneuroendocrine carcinoma. 4 S T A T I S T I C A L A N A L Y S I S Categorical variables and continuous variables were compared by Fisher’s exact test and the Mann- Whitney U- test, respectively. Progression free survival and overall survival rates were compared by the log- rank test. Multiple Cox regression analysis was used to evaluate factors related to the overall survival. A p- value of 0.05 was considered statistically signi cant. All statistical analyses were performed using SPSS version 12.0 for Windows (SPSS Inc. Chicago, IL, USA). A u t h o r s Kyong Joo Lee 1 , Jae Hee Cho, Sang Hyub Lee, Kwang Hyuk Lee, Byung Kyu Park, Jun Kyu Lee, Sang Myung Woo, Ji Kon Ryu, Jong Kyun Lee, Yeon Suk Kim, Jae Woo Kim, Woo Jin Lee E - m a i l [email protected] I n s t i t u t e 1 Department of Internal Medicine, Yonsei University Wonju College of Medicine C i t y / N a t i o n a l i t y Wonju, Korea C a t e g o r y Review Case Upper GI Lower GI Pancreatobiliary tract Others Title of Article C l i n i c o p a t h o l o g i c a l c h a r a c t e r i s t i c s o f b i l i a r y n e u r o e n d o c r i n e n e o p l a s m a m u l t i c e n t e r s t u d y R E S U L T S We examined the records of 43 patients with biliary NENs (T a b l e 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 diagnoses during 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 site was the liver. According to the WHO classi cation, all of patients with GB NENs had NEC G3 and 37.1% of patients with AoV NENs were classi ed as NEC G3.

Transcript of Title of Article Clinicopathological characteristics of biliary...

  • 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