An intraductal papillary component is associated with prolonged survival after hepatic resection for intrahepatic cholangiocarcinoma

Tajima, Yoshitsugu; Kuroki, Tamotsu; Fukuda, Kenzo; Tsuneoka, Noritsugu; Furui, Junichiro; Kanematsu, Takashi

doi:10.1002/bjs.4366

Cited by 57 publications

(51 citation statements)

References 33 publications

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“…1,5,14,15 The mean survival of patients with IPNL types 3 and 4 and non-IG-ICC was 55.5 Ϯ 17.1 months, 36.9 Ϯ 6.3 months, and 15.8 Ϯ 1.8 months, respectively. The survival of patients with IPNL types 3 and 4 was similar (log-rank test, P ϭ .12).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Intrahepatic Cholangiocarcinoma of the Intraductal Growth-Type and Its Precursor Lesions *

et al. 2005

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A cohort of patients with intraductal growth-type intrahepatic cholangiocarcinoma (IG-ICC) and its precursor lesions, collectively termed intraductal papillary neoplasm of the liver (IPNL), was characterized with respect to demographics, clinical manifestations, perioperative management, long-term survival, and molecular features associated with carcinogenesis. A total of 122 patients with IPNL types 1 through 4, 108 patients with non-IG-ICC and 210 patients with hepatolithiasis alone were studied. Expression of CDX2, TFF1, MUC1, MUC2, MUC5AC, EGFR, and p53 was determined by using immunohistochemistry. Females predominated in those with hepatolithiasis alone and IPNL. The mean age of patients with hepatolithiasis alone was 6 to 8 years younger than that of those with IPNL. The association with hepatolithiasis in patients with IPNL types 1 and 2, IPNL types 3 and 4, and non-IG-ICC was 100%, 79%, and 64%, respectively. Mucobilia, anemia, and elevated serum carcinoembryonic antigen levels were helpful in distinguishing IG-ICC and its precursor lesions. The mean survival of patients with IPNL type 3, IPNL type 4, and non-IG-ICC was 55.5 months, 36.9 months, and 15.8 months, respectively. The incidence of expression of CDX2 and TFF1 was maximal in IPNL type 3. Expression and cellular distribution of MUC2 and CDX2 were similar. MUC5AC was strongly expressed in all patients with IPNL; EGFR and p53 were rarely expressed in patients with IPNL. In conclusion, hepatolithiasis appears to be a precipitating factor in the development of IPNL. Signs of mucobilia were specific for the diagnosis of IPNL. Expression of CDX2 and MUC2 are helpful in differentiating IPNL and non-IG-ICC. Significant differences in survival associated with the various lesions studied warrants a more aggressive surgical strategy in their management. ( I ntrahepatic cholangiocarcinoma (ICC) is a primary adenocarcinoma originating from the second or higher order branches of hepatic bile ducts. The incidence of ICC exhibits wide geographical variations that range from 5% to 30% of primary liver cancers. 1 Various predisposing factors, including liver fluke infestation, hepatolithiasis, primary sclerosing cholangitis, choledochocyst, and Caroli's disease, have been implicated. [1][2][3] In Taiwan, ICC was found in 5% to 10% of patients with hepatolithiasis. 3,4 Based on gross morphology, ICC can be divided into three types (mass-forming, periductalinfiltrating, and intraductal growth [IG]-type). 1 The IG-ICC is the least common type but is associated with the most favorable outcome. 1,5 Biliary papillomatosis, intraductal growth-type cholangiocarcinoma (IG-ICC), and mucin-producing ICC constitute essentially the same disease entity. [5][6][7] This category of papillary biliary neoplasm resembles intraductal papillary mucinous neoplasm of the pancreas histologically. 8 We recently proposed the term intraductal papillary neoplasm of the liver (IPNL) for such lesions, which include both IG-ICC and its precursor lesions. 6,9 Phenotypes of gastrointestinal meta...

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Section: Discussionmentioning

confidence: 99%

Characterization of Intrahepatic Cholangiocarcinoma of the Intraductal Growth-Type and Its Precursor Lesions *

et al. 2005

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“…Recently, we showed that MMP-7 and MT1-MMP were commonly expressed in invasive ICC with BilIN, but not non-invasive lesions (BilIN-1, -2, -3), suggesting that the expression of MMP-7 and MT1-MMP was closely associated with invasive growth of the BilIN lineage [25] . In contrast, the IPNB lineage was only occasionally and weakly positive for these molecules, reflecting its favorable prognosis [3,45,46] .…”

Section: Matrix Metalloproteinases (Mmps)mentioning

confidence: 98%

Multistep carcinogenesis of perihilar cholangiocarcinoma arising in the intrahepatic large bile ducts

Nakanuma

Sasaki²,

Sato³

et al. 2009

WJH

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Flat-type "biliary intraepithelial neoplasia (BilIN)" and papillary-type "intraductal papillary neoplasm of the bile duct (IPN-B)" are proposed as precursors of invasive, perihilar intrahepatic cholangiocarcinoma (ICC). Three carcinogenetic pathways are proposed: BilIN progressing to tubular adenocarcinoma, and IPN-B progressing to tubular adenocarcinoma or to colloid carcinoma. Carcinogenesis via BilIN was characterized by mucin core protein 2-/cytokeratin 20-(MUC2-/CK20-) with MUC1 expression, while carcinogenesis via IPN-B leading to tubular adenocarcinoma was associated with MUC1 expression or that to colloid carcinoma with MUC1-negativity. In both the BilIN and IPNB series, the expression of p21, p53, and cyclin D1 was upregulated with histological progression. Interestingly, p53 expression was upregulated at the invasive stage of BilIN, but was low in noninvasive BilIN, while p53 expression was upregulated in IPN-B1 and reached a plateau in IPN-B2 and invasive ICC. Expression of p16INK4a , which was frequent in BilIN1, was decreased in BilIN-2/3 and invasive carcinoma. EZH2 expression showed a stepwise increase from BilIN to invasive carcinoma. Membranous expression of β-catenin and E-cadherin was more markedly decreased in ICC with BilIN than in ICC with IPNB. Interestingly, disruption of the membranous distribution of β-catenin

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“…Patients without distant metastasis and eligible for surgery should be considered for surgical resection. The prognosis of patients with IPNB has been reported to be better than conventional bile duct cholangiocarcinomas (13). Our patient was also referred to surgery and resection was performed.…”

Section: Answer: Intraductal Papillary Neoplasia Of the Bile Duct (Ipnb)mentioning

confidence: 71%

A polypoid mass in the common bile duct

Asıl

Dertli²,

Bıyık³

et al. 2016

Turk J Gastroenterol

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A polypoid mass in the common bile duct Question:A 73-year-old woman with a prior history of cholecystectomy operation due to cholelithiasis was admitted to our clinic with complaints of abdominal pain in the epigastrium and right upper quadrant. Laboratory studies were unremarkable: Hb: 14.2 g/dL, hematocrit: 42.8%, WBC: 6000 /μL, platelet: 167000/μL, AST: 14 U/L, ALT: 16 U/L, ALP: 69 U/L, GGT: 42 U/L, total bilirubin: 0.57 mg/dL, and direct bilirubin: 0.32 mg/dL. Abdominal ultrasound examination showed dilatation of intrahepatic bile ducts. Endoscopic ultrasound (EUS) (Figure 1) and endoscopic retrograde cholangiopancreatography (ERCP) were then performed ( Figure 2). During ERCP, the common bile duct was explored with a stone extraction balloon and a polypoid mass of 0.5 cm (Figure 3) came out of the common bile duct lumen, which was retrieved using a netted snare and sent to the pathology laboratory for histological examination ( Figure 4). Intraductal papillary neoplasia of the bile duct (IPNB) is a very rare tumor of the biliary tract characterized by exophytic growth of tumor cells into the biliary tree forming papillary structures. Various nomenclatures such as biliary papillomatosis, mucinproducing cholangiocarcinoma, mucin-producing bile duct tumor, and mucin-hypersecreting bile duct tumor have been used in the literature to define IPNB (1-5). In the 2010 World Health Organization Classification of biliary tumors, IPNB was included as a separate clinical entity covering intraductal papillary cholangiocarcinoma and its precursor lesions (6). IPNB may be associated with mucin secretion, and similar to other mucin-producing tumors, it also has a premalignant potential. Papillary cholangiocarcinoma is the malignant counterpart of IPNB. IPNB is considered as the biliary variant of intraductal papillary mucinous neoplasia (IPMN) of the pancreas, and both share common microscopic, macroscopic, and clinical characteristics. Four different subtypes of IPNB have been defined: gastric, pancreato-biliary, intestinal, and oncocytic (7). IPNB can occur anywhere along the biliary tract; however, extra-hepatic IPNB has been reported to be more frequent (8). In studies from Eastern countries, IPNB has been shown to be associated with hepatolithiasis and clonorchiasis; however, such an association has not been reported from Western countries.Intraductal papillary neoplasia of the bile duct is derived from the biliary epithelium. It progresses from low-grade, intermediate, and high-grade intraepithelial neoplasia to invasive carcinoma. TP53, p16, KRAS, and SMAD4 mutations have been shown to be associated with the carcinogenesis sequence of IPNB (9). Because both the bile ducts and pancreas develop from the ventral endoderm of the foregut, it has been suggested that similar genetic and molecular oncologic pathways are involved in IPNB and IPMN (10).Although some patients can be totally asymptomatic, the majority of patients with IPNB present with signs and symptoms related to biliary obstruction. Abdominal pain, repea...

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An intraductal papillary component is associated with prolonged survival after hepatic resection for intrahepatic cholangiocarcinoma

Abstract: An IDPCC in the tumour resulted in long-term survival after hepatic resection for ICC.

Cited by 57 publications

References 33 publications

Characterization of Intrahepatic Cholangiocarcinoma of the Intraductal Growth-Type and Its Precursor Lesions *

Characterization of Intrahepatic Cholangiocarcinoma of the Intraductal Growth-Type and Its Precursor Lesions *

Multistep carcinogenesis of perihilar cholangiocarcinoma arising in the intrahepatic large bile ducts

A polypoid mass in the common bile duct

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