Long-term survival and prognostic factors in the surgical treatment of mass-forming type cholangiocarcinoma

Inoue, Kazuto; Makuuchi, Masatoshi; Takayama, Tadatoshi; Torzilli, Guido; Yamamoto, Junji; Shimada, Kazuaki; Kosuge, Tomoo; Yamasaki, Susumu; Konishi, Masaru; Kinoshita, Taira; Miyagawa, Shinichi; Kawasaki, Seiji

doi:10.1067/msy.2000.104673

Cited by 178 publications

(146 citation statements)

References 31 publications

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…[1][2][3][4][5][6] In the present study, the frequency of extrahepatic metastasis within 2 years after surgery in patients with CK19-positive HCC was also significantly higher than in those with CK19-negative HCC. Lymph nodes were the preferred site of metastasis, with a significantly (P<0.01) higher frequency in cases of CK19-positive HCC.…”

Section: Discussionmentioning

confidence: 53%

“…atients with intrahepatic cholangiocarcinoma (ICC), including combined hepatocellular and cholangiocarcinoma (cHCC-CC), exhibit poorer postoperative prognosis than those with hepatocellular carcinoma (HCC) due to more aggressive invasion and higher frequency of extrahepatic metastasis. [1][2][3][4][5][6] Thus, it is important for surgeons to take into account the presence of CC components within hepatic tumors in selecting a surgical strategy. 6) Cytokeratins (CK) are cytoskeletal intermediate filaments present in both normal and malignant epithelial cells.…”

mentioning

confidence: 99%

“…[1][2][3][4][5][6] Thus, it is important for surgeons to take into account the presence of CC components within hepatic tumors in selecting a surgical strategy. 6) Cytokeratins (CK) are cytoskeletal intermediate filaments present in both normal and malignant epithelial cells.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence

et al. 2003

View full text Add to dashboard Cite

. Semiquantitative analysis of expression levels demonstrated a significant correlation between CK7 and CK19 expression. Of various clinicopathologic parameters, tumor differentiation exhibited a significant correlation with CK7 and CK19 expression. All 15 patients with CK19-positive HCC also had anti-HBc. Log-rank test revealed that CK7 expression, CK19 expression, high aspartate aminotransferase (AST) activity, low albumin concentration, portal invasion, intrahepatic metastasis, and severe fibrosis (cirrhosis) reduced the tumor-free survival rate. Multivariate analysis demonstrated that CK19 expression, intrahepatic metastasis, and severe fibrosis were independent predictors of postoperative recurrence, while CK7 expression was not. Twelve of 15 patients with CK19-positive HCC had tumor recurrence within 2 years after surgery, a significantly higher incidence of early recurrence than for CK19-negative HCC. The incidence of extrahepatic disease, especially lymph node metastasis, was significantly higher for patients with CK19-positive HCC. These findings indicate that CK19 expression is a predictor of early postoperative recurrence due to increased invasiveness. atients with intrahepatic cholangiocarcinoma (ICC), including combined hepatocellular and cholangiocarcinoma (cHCC-CC), exhibit poorer postoperative prognosis than those with hepatocellular carcinoma (HCC) due to more aggressive invasion and higher frequency of extrahepatic metastasis. [1][2][3][4][5][6] Thus, it is important for surgeons to take into account the presence of CC components within hepatic tumors in selecting a surgical strategy. 6) Cytokeratins (CK) are cytoskeletal intermediate filaments present in both normal and malignant epithelial cells.7) Characteristic combinations of CK polypeptides are expressed in different epithelia depending on the organ and/or type of differentiation. 7,8) In normal human liver, hepatocytes express CK8 and CK18, while bile duct cells also contain CK7 and CK19. [8][9][10][11] Since this CK pattern has been believed to be preserved during neoplastic transformation, HCC would be expected to express CK8 and CK18, but not CK7 or CK19. [8][9][10][11] Thus, expression of biliary-specific CK (CK7 and CK19) is widely used to distinguish ICC from HCC. 6,[8][9][10][11][12] Maeda et al. 6) recommended that HCC with "suggestive" CC components (incomplete gland formation without mucin production) should be categorized as cHCC-CC when "suggestive" CC components are positive for biliary markers. However, some HCCs have been reported to express biliary markers even with typical HCC growth pattern and morphologic appearance, [13][14][15][16][17] although the histogenesis of such biliary marker-positive HCC is not wellunderstood. A previous report indicated that without treatment, the prognosis is poorer for patients with biliary differentiation marker [AE1-AE3, cytokeratin (CK) 19]-positive HCC than for those without it.16) There have, however, been no studies on the clinical usefulness of biliary marker expression by HC...

show abstract

Section: Discussionmentioning

confidence: 53%

mentioning

confidence: 99%

See 1 more Smart Citation

Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence

et al. 2003

View full text Add to dashboard Cite

show abstract

“…30 One of the major hallmark of cholangiocarcinoma is its lymph node metastasis. The lymphatic invasion and lymph node involvement are important prognostic indicators for intrahepatic cholangiocarcinoma; [31][32][33][34] however, lymph node metastasis and lymphangiogenesis at the mechanistic level in intrahepatic cholangiocarcinoma are poorly understood.…”

mentioning

confidence: 99%

Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma

et al. 2008

View full text Add to dashboard Cite

Lymph node metastasis via lymphatic vessels is related with an adverse outcome in many tumors. It is unclear whether lymphatic spread needs the development of the new lymphatic vessels or the expression of lymphangiogenetic factor in intrahepatic cholangiocarcinoma. The aim of this study was to assess the role of lymphangiogenesis, vascular endothelial growth factor-C (VEGF-C) expression, and D2-40-positive myofibroblastic cells for lymphatic spread and patient outcome in 88 cases of intrahepatic cholangiocarcinoma. We also assessed VEGF-C expression in 15 cases of metastatic lymph nodes. There was a significant correlation between lower lymphatic vessel density in the tumor center and positive lymphatic invasion (P ¼ 0.0100). Poorly differentiated cholangiocarcinoma showed higher lymphatic vessel density in the tumor periphery and in the peritumoral area (P ¼ 0.0315 and P ¼ 0.0360, respectively). Lymphatic invasion was observed higher in the peritumoral area (63%, 24/38) and in the tumor periphery (79%, 30/38) than in the tumor center (27%, 9/ 38). There was no significant correlation between the proliferative lymphatic vessels and pathologic features; however, lymphatic invasion was significantly associated with VEGF-C expression (P ¼ 0.0006), and the VEGF-C expression was seen in 12 of 15 cases (80%) of metastatic lymph node. Nodal metastasis was correlated with D2-40-positive myofibroblasts (P ¼ 0.0161). VEGF-C expression was an independent prognostic factor by multivariate survival analysis (P ¼ 0.0131). Our findings suggest that VEGF-C has an important role in lymphatic invasion via the preexisting lymphatic vessels in the tumor margin, and that lymphangiogenesis does not play a direct role in lymphatic metastasis. D2-40-positive myofibroblasts may contribute to lymphatic metastasis.

show abstract

“…The activation of VEGFR3 induces lymphatic endothelial cell proliferation in vitro and new lymphatic vessel formation in vivo (14)(15)(16)(17). Lymphatic invasion and node metastasis are important prognostic factors for intrahepatic CCA (18,19). Although the original location of VEGFR3 is the cell membrane, it can also be present in serum.…”

Section: Introductionmentioning

confidence: 99%

Roles of serum and biliary CEA, CA19-9, VEGFR3, and TAC in differentiating between malignant and benign biliary obstructions

İnce

Yıldız²,

Baysal³

et al. 2014

Turk J Gastroenterol

View full text Add to dashboard Cite

Background/Aims: Despite the presence of many diagnostic methods, the differential diagnosis between benign and malignant biliary obstructions is still not easy. We aimed to evaluate the role of serum/biliary carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), vascular endothelial growth factor receptor-3(VEGFR-3), and total antioxidant capacity (TAC) tests in this differential diagnosis. Materials and Methods: Patients (n:225; 110♂, 115♀) with diagnosis of malignant (n:96) or benign (n:129) biliary obstruction were included in this cross-sectional study. Serum and biliary CEA, CA 19-9, VEGFR-3, and TAC tests were analyzed, statistics were obtained, and significance was defined as p<0.05. Results: Mean age was 54.9±16.4 for the benign and 54.2±19.6 for the malignant group (p=0.89). Head of pancreas cancer (18.2%), cholangiocarcinoma (11.4%) and choledochal stone (48%) were the most common etiologies. The area under the curve (AUC)s by ROC analysis of serum/biliary CA 19-9, VEGFR-3, and TAC and serum CEA were 0.701/0.616, 0.622/0.663, 0.602/0.581, and 0713, respectively. Serum TAC had higher sensitivity (61.1%) and CEA had lower sensitivity (42.7%), whereas CEA had higher specificity (89.9%) and TAC had lower specificity (60.5%). In biliary tumor markers, CA 19-9 had higher sensitivity (74%) and VEGFR-3 had lower sensitivity (56.2%); however, VEGFR-3 had higher specificity (79.1%) and CA 19-9 had lower specificity (34.1%). Additionally, combination of serum CEA (p<0.001), CA 19-9 (p<0.001), VEGFR-3 (p<0.001), and biliary CA 19-9 (p=0.028) markers achieved 95% estimation probability, and the sensitivity, specificity, and accuracy were 88.5%, 45.7%, and 64%, respectively. Conclusion: Serum and biliary CEA, CA 19-9, VEGFR-3, and TAC tests would not be useful in the differentiation between malignant and benign biliary obstructions.

show abstract

Long-term survival and prognostic factors in the surgical treatment of mass-forming type cholangiocarcinoma

Cited by 178 publications

References 31 publications

Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence

Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence

Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma

Roles of serum and biliary CEA, CA19-9, VEGFR3, and TAC in differentiating between malignant and benign biliary obstructions

Contact Info

Product

Resources

About