Mass-forming Type Intrahepatic Cholangiocarcinoma Research Articles

Effect of surgical margin width after R0 resection for intrahepatic cholangiocarcinoma: A nationwide survey of the Liver Cancer Study Group of Japan

BackgroundData are inconsistent regarding the effects of a wide surgical margin for intrahepatic cholangiocarcinoma on recurrence-free survival and overall survival. This study was performed to investigate the effect of surgical margin width in patients undergoing R0 resection for intrahepatic cholangiocarcinoma, using a nationwide database in Japan. MethodsIn total, 635 patients with intrahepatic cholangiocarcinoma who were treated by an R0 resection from 2000 to 2007 were identified from the database of a Japanese nationwide survey. Patients were divided into quartiles of the surgical margin width as follows: marginal (<1 mm), narrow (1–4 mm), intermediate (5–9 mm), and wide groups (≥10 mm). Multivariable Cox regression models for recurrence-free survival and overall survival were constructed with adjustment for preoperative and postoperative clinicopathologic factors. ResultsCompared with the marginal group, the risk-adjusted hazard ratios (95% confidence intervals) in the narrow, intermediate, and wide groups for recurrence-free survival were 0.92 (0.62–1.37), 0.91 (0.61–1.37), and 0.81 (0.56–1.17), and those for overall survival were 0.79 (0.51–1.24), 0.93 (0.59–1.47), and 0.70 (0.46–1.08), respectively. In 398 patients without lymph node metastasis, the hazard ratios for overall survival were 0.62 (0.34–1.11), 0.63 (0.34–1.17), and 0.51 (0.29–0.90), and those of mass-forming type intrahepatic cholangiocarcinoma were 0.48 (0.21–1.08), 0.43 (0.19–0.96), and 0.40 (0.19–0.82), respectively. ConclusionSurgical margin width appears to have a limited effect on the prognosis of intrahepatic cholangiocarcinoma except in patients without lymph node metastasis, where a wide surgical margin is associated with favorable outcomes. This survival benefit of a wide surgical margin is especially apparent for the mass-forming type intrahepatic cholangiocarcinoma.

Long-term survival after surgical resection for recurrent hepatic and pulmonary metastases of intrahepatic cholangiocarcinoma: a case report

BackgroundA few reports to date have described the effectiveness of surgical resection for recurrent intrahepatic cholangiocarcinoma (ICC). We report in this study a patient who achieved long-term survival after surgical resection for recurrent hepatic and pulmonary metastases of ICC.Case presentationA 62-year-old man was referred to our hospital for examination of a tumor in the left lobe of the liver. Computed tomography (CT) scans of the abdomen revealed a hypovascularized tumor, 30 mm in hepatic segment 2 (S2). The patient was diagnosed with a mass-forming type of ICC. A left lateral sectionectomy with regional lymph node dissection was performed. Histopathological examination showed moderately differentiated adenocarcinoma in the hepatic S2 with lymph node metastasis. There were two intrahepatic metastases around the main tumor. The pathological stage of the ICC was pT2pN1M0pStageIIIB. The patient did not receive adjuvant chemotherapy after surgery. Twelve months after surgery, liver lesions in S4/S8 and S7 were detected on CT scans. A partial hepatectomy was performed. The histopathological features were similar to those of the previous ICC. The patient did not receive adjuvant chemotherapy after the repeat hepatectomy. Four years and four months after this repeat hepatectomy, CT scans showed multiple nodes in S4 and S10 of the left lung and in S1 of the right lung. Wedge resection of the left upper lobe and sectionectomy in S10 of the left lung were performed. Histopathological findings of the resected lung nodules were compatible with metastatic ICC. The nodule in S1 of the right lung was too small to be diagnosed as metastasis; therefore, it was not resected. After pulmonary resection, the patient was treated with gemcitabine and cisplatin for 6 months. After chemotherapy, the size of the nodule in S1 increased gradually. One year and ten months after the pulmonary resection, we performed wedge resection of S1 of the right lung, and the histopathological findings were compatible with metastatic ICC. The patient is alive without evidence of disease 8 years after the initial surgery and 8 months after the last pulmonary resection.ConclusionsICC with poor prognostic factors can frequently recur; however, surgical resection for recurrent ICC might, for selected patients, enable long-term survival.

β4 and β6 Integrin Expression Is Associated with the Subclassification and Clinicopathological Features of Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a heterogeneous group of cancers of the intrahepatic biliary tract. However, few studies have evaluated integrin expression according to an ICC subgroup. We immunohistochemically investigated α6β4 (β4) and αvβ6 (β6) integrin expressions in 48 ICCs, and evaluated their relationship with clinical and pathological parameters and ligand expression, as well as transforming growth factor (TGF)-β1. β4 and β6 expressions were detected in 46 (96%) and 35 (73%) ICC cases, respectively. We classified ICC into negative, low (β4, 29 cases; β6, 36 cases), or high (β4, 19 cases; β6, 12 cases) integrin expression groups. β4 and β6 integrin levels were higher in the non-peripheral central localization type ICC than in the peripheral localization type; they were also higher in the periductal-infiltrating or intraductal-growth types than in the mass-forming type ICC; lastly, they were higher in the well-differentiated type than in the poorly-differentiated type ICC. High expression was related to bile duct invasion. In addition, β4 and β6 expressions were associated with mucin production and the expression of cytoplasmic epithelial membrane antigen, laminin-5, and tenascin-C. TGF-β1 was correlated with β6 expression and poor overall survival. These results suggest that integrin expression is associated with subclassification and clinicopathological features of ICC through the coincident expression of their ligands and TGF-β1.

Macroscopic types of intrahepatic cholangiocarcinoma and the eighth edition of AJCC/UICC TNM staging system.

The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is undefined among the different macroscopic types. This study evaluated the viability of the American Joint Committee on Cancer (AJCC) 8th edition staging classification for different macroscopic types. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled a total of 2,679 eligible patients with an estimated 199 periductal infiltrating type of ICC (ICC-PI) patients and 2,480 mass-forming type of ICC (ICC-MF) patients. After conducting a multivariate Cox analysis, we found that the AJCC 8th edition staging system was suitable for ICC-MF patients but not for ICC-PI patients according to cancer-specific survival (CSS) and overall survival (OS). The main reason was the similar hazard ratio (HR) between the ICC-PI patients with stage I and stage II disease according to CSS (HR:0.969, P = 0.949) and OS (HR:0.832, P = 0.703). Moreover, we found that ICC-PI patients in AJCC stage I had a similar HR as ICC-MF patients in AJCC stage II according to CSS (HR: 1.208, P = 0.475) and OS (HR:1.206, P = 0.456). Therefore, we suggested that ICC-PI patients may be defined as T2, which is classified as stage II disease. This suggestion for the AJCC 8th edition staging system would be more suitable for different macroscopic types of ICC but requires further verification in prospective clinical trials.

Low Incidence of Lymph Node Metastasis After Resection of Hepatitis Virus-Related Intrahepatic Cholangiocarcinoma.

We determined the rates of initial lymph node metastasis following curative resection of mass-forming type-intrahepatic cholangiocarcinoma (ICC) in patients with and without hepatitis virus infection. We enrolled 87 patients between January 2000 and December 2013 with ICC without preoperative lymph node metastasis and without lymph node dissection. Patients included 32 who were seropositive for hepatitis B or C virus (virus group) and 55 who had no evidence of hepatitis virus infection (nonvirus group). Postsurgical outcomes and initial recurrence of the groups were compared, and we identified the risk factors for lymph node metastasis as initial recurrence. Platelet counts and prothrombin activities were significantly lower in the virus group compared with those of the nonvirus group. The number of patients with chronic hepatitis or liver cirrhosis was significantly higher in the virus group compared with the nonvirus group as well as their respective rates of recurrence-free survival. One patient (3%) in the virus group and 14 patients (25%) in the nonvirus group had lymph node metastasis as initial recurrence (p=0.007). Multivariate analysis revealed that the absence of hepatitis virus infection as an independent risk factor (p=0.047). Hepatitis virus-associated mass-forming-type ICC confers a low risk of lymph node metastasis as initial postoperative recurrence.

The role of diffusion-weighted imaging in differentiation of hepatic alveolar echinococcosis and intrahepatic cholangiocarcinoma

ObjectiveA technique is proposed for evaluating the utility of apparent diffusion coefficient (ADC) measurements in the differentiation of type 4 hepatic alveolar echinococcosis (HAE) from the mass-forming type of intrahepatic cholangiocarcinoma (IHCC), using diffusion-weighted magnetic resonance imaging (DW-MRI). MethodsThis study, conducted from November 2013 to January 2015, was approved by the ethics committee of First Affiliated Hospital of Xinjiang Medical University. All patients were given written informed consent. A total of 11 patients underwent T1WI, T2 fat-saturation, and a respiratory triggered DWI sequence by a 1.5T MR imaging system. An experienced radiologist measured the ADC in both alveolar echinococcosis and cholangiocarcinoma lesions. DWI was performed with a b-value gradient of 0 and 600. The mean ADC values of type 4 hepatic alveolar echinococcosis were compared with those of mass-forming type cholangiocarcinoma, in order to determine variations between the two. Differences in ADC between lesion types were determined by using an independent samples t-test and a statistically significant (P < 0.05) difference was observed. ResultsMean ADC values for IHCC were 1.24 ± 0.23 × 10−3 mm2/s, which was significantly lower than the 1.71 ± 0.23 × 10−3 mm2/s observed for HAE. These results supported the use of this technique as a mechanism for lesion differentiation. ConclusionsLower ADC in DW-MRI represents restricted diffusion. Due to multicellularity being higher in IHCC than HAE, the mean ADC values for IHCC were lower than for HAE.

The favorable prognosis after operative resection of hypervascular intrahepatic cholangiocarcinoma: A clinicopathologic and immunohistochemical study

The aim of this study was to clarify the clinicopathologic characteristics of hypervascular intrahepatic cholangiocarcinoma (ICC). Seventy patients with a mass-forming type ICC underwent hepatectomy between 2003 and 2013. These patients were divided into 2 groups and compared based on findings during the late arterial phase of computed tomography: hypervascular ICC (the mean computed tomography value of the tumor≥that of the nontumorous liver parenchyma, n=21), and hypovascular ICC (n=49). The overall survival of the hypervascular group was better than that of the hypovascular group (5-year survival: 63% vs 35%, respectively, P=.046). Pathologic examinations showed less lymph node metastasis (0% vs 39%), lymphatic invasion (14% vs 57%), mucin secretion (19% vs 61%), tumor necrosis (24% vs 57%), and combined periductal infiltration (0% vs 27%), P≤.01 each, in the hypervascular group. The microscopic bile ductular feature was more frequent in the hypervascular group (57% vs 29%, P=.023). Immunohistochemical analysis revealed that the hypervascular group had greater immunoreactivity to neural cell adhesion molecule (71% vs 37%, P=.008) and a lesser S100P immunoreactivity (33% vs 73%, P=.002). Multivariate analysis revealed that neural cell adhesion molecule reactivity (P=.018) was independently associated with the hypervascular group. Tumor vascularity predicts the aggressiveness of ICC. In most patients with hypervascular ICC, the tumor has a less invasive nature. Furthermore, the prognosis after resection in patients with hypervascular ICC is significantly better than in patients with hypovascular ICC.

Evaluation of mass-forming intrahepatic cholangiocarcinoma with viral hepatitis.

The correlation between the mass-forming type of intrahepatic cholangiocarcinoma (ICC) and the infection of the hepatitis B virus and hepatitis C virus are poorly understood. In this study, the clinical features of 34 patients with the mass-forming type ICC were reviewed to evaluate prognostic determinants. Between January 1997 and December 2007, 34 patients underwent surgical resection for the mass-forming type of ICC in Kumamoto University Hospital. The significance of 14 clinicopathological factors consisting of age, gender, CA19-9 levels, CEA levels, size, intrahepatic metastases, portal vein invasion, bile duct invasion, histological differentiation, lymph node involvement, type B or C hepatitis, lymph node dissection, Sirius Red score of the tumor and platelet count in peripheral blood were analyzed, with regard to prognostic aspect. Univariate analysis showed that significant risk factors for poor survival included age =65 years, CEA levels =1.6ng/mL and pathological lymph node involvement. Multivariate analysis revealed that age, CEA levels and lymph node involvement were independent and significant poor prognostic factors. It was concluded that age, CEA levels and lymph node involvement were significantly poor prognostic factors. However, the infection with type B or C hepatitis was not a prognostic factor of the mass forming type ICC.

Long-term survival after resection of mass-forming type intrahepatic cholangiocarcinoma directly infiltrating the transverse colon and sequential brain metastasis: Report of a case

MUC1 expression in cholangiocarcinoma is considered to be correlated with patient survival. We report a case of mass-forming type intrahepatic cholangiocarcinoma (ICC) with direct infiltration of the transverse colon and sequential brain metastasis. The patient was treated by curative right hepatectomy with right hemicolectomy followed by resection of the brain metastasis; there has been no evidence of recurrence in the 7 years since the hepatic resection. Thus, surgical resection may improve the prognosis of ICC involving the adjacent organs, even with brain metastasis. Immunohistochemical staining was performed for MUC1, MUC2, and MUC5AC. Although MUC1 expression was found in the liver tumor and metastatic brain tumor, the correlation between MUC1 expression and the prognosis of this patient was unclear. To clarify the correlation between immunohistochemical characteristics and prognosis, further studies on a greater number of cases of long-term survival of mass-forming type ICC are needed.

Mass‐forming intrahepatic cholangiocarcinoma with marked enhancement on arterial‐phase computed tomography reflects favorable surgical outcomes

Outcomes after hepatectomy in patients with mass-forming (MF) type intrahepatic cholangiocarcinoma (ICC) with marked enhancement within the tumor on arterial-phase computed tomography (CT) scans have not been clarified in detail. We retrospectively studied 140 patients with MF type ICC who underwent hepatectomy from 1989 through 2008. Surgical outcomes were compared between 25 patients with MF type ICC with marked enhancement within the tumor (hypervascular ICC) and 109 patients without enhancement within the tumor (hypovascular ICC) on arterial-phase CT scans. Portal invasion and intrahepatic metastasis were significantly lower in patients with hypervascular ICC than in those with hypovascular ICC. The 5-year survival rate was significantly higher in patients with hypervascular ICC (86%) than in patients with hypovascular ICC (27%, P < 0.0001). Multivariate analysis showed hypervascular ICC on arterial-phase CT scans, normal level of cancer-associated carbohydrate antigen 19-9, absence of portal invasion, and absence of intrahepatic metastasis of ICC to be significant independent prognostic factors for overall survival in patients with MF type ICC. MF type ICC with marked enhancement within the tumor on arterial CT scans showed a favorable surgical outcome due to its less invasive histopathologic characteristics in patients with MF type ICC.

Clinicopathological Prognostic Factors After Hepatectomy for Patients with Mass-Forming Type Intrahepatic Cholangiocarcinoma: Relevance of the Lymphatic Invasion Index

The present study was conducted to clarify the pathological factors in patients who underwent surgery for mass-forming type intrahepatic cholangiocarcinoma (IHC). From 1982 to July 2004, a total of 60 liver resections for mass-forming type IHC were performed at Kyushu University and its affiliated institutions. Portal venous, lymphatic, hepatic venous, and serosal invasion was examined by univariate and multivariate analyses for their prognostic value. The portal venous (PV) invasion index was defined as follows: PV0, portal venous invasion (-) and intrahepatic metastasis (-); PV1, portal venous invasion (+) or intrahepatic metastasis (+); PV2, portal venous invasion (+) and intrahepatic metastasis (+). The lymphatic invasion (LI) index was defined as follows: LI0, lymphatic duct invasion (-) and lymph node metastasis (-); LI1, intrahepatic lymphatic duct invasion (+) or lymph node metastasis (+); LI2, intrahepatic lymphatic duct invasion (+) and lymph node metastasis (+). In univariate analysis, statistically significant prognostic factors for poor outcome were tumor size (>5 cm), serosal invasion (+), PV1 or PV2, LI1 or LI2, histological grade (moderate and poor), hepatic venous invasion (+) and noncurative resection. After multivariate analysis, the lymphatic invasion index and histological grade were statistically independent prognostic factors for overall survival and recurrence-free survival. In patients with mass-forming type IHC, lymphatic invasion is the most important invasion pathway, compared with serosal and portal and hepatic venous invasion. Stratification of the lymphatic invasion pathway by lymphatic invasion, including intrahepatic lymphatic duct invasion and lymph node metastasis, is a good predictor for prognosis in patients after hepatectomy for mass-forming type IHC.

Intrahepatic cholangiocarcinoma with micrometastasis in the portal tract of the liver.

Intrahepatic metastasis of intrahepatic cholangiocarcinoma (ICC) has not been evaluated in detail. We report a case of mass-forming type ICC with micrometastasis to the distant portal tract in a 40-year-old woman. In 2006, she was given a diagnosis of mass-forming type ICC, 4cm in diameter, and right hepatectomy with lymph node dissection was performed. Macroscopic findings showed an irregular white mass-forming type lesion with two small daughter lesions and portal vein invasion in the S5 subsegment. Microscopically, other cancer cells within vessels had proliferated in the peripheral portal tract of the S8 subsegment, and these cancer cells in the portal tract had invaded the vessel wall. The endothelial cells of the vessels around the cancer cells were positive for CD34, but negative for D2-40 and CK19 on immunohistochemical analysis. Therefore, intrahepatic metastasis of cancer cells through the portal vein was diagnosed. Intrahepatic metastasis of cancer cells through the portal vein was demonstrated in a patient with mass-forming ICC.

Therapeutic value of lymph node dissection during hepatectomy in patients with intrahepatic cholangiocellular carcinoma with negative lymph node involvement

Routine and radical lymph node dissection is a clinical concern for improving the surgical outcome in patients with intrahepatic cholangiocarcinoma (ICC). The therapeutic value of the procedure during hepatectomy has, however, not been evaluated. Between January 1990 and December 2004, 104 patients with ICC undergoing macroscopic curative resections were investigated retrospectively with special reference to lymph node status. The role of lymph node dissection was evaluated according to macroscopic type: mass-forming (MF) type (n = 68) and MF plus periductal infiltration (PI) type (n = 36) of ICC. Lymph node involvement and intrahepatic metastases were an independent, unfavorable prognostic factor in the MF type of ICC. Negative lymph node involvement provided a favorable survival rate in the 41 patients without intrahepatic metastases (P < .0001). Among the 29 patients without lymph node involvement and intrahepatic metastases, there was no difference according to the use of lymph node dissection (P = .8071). Also, no difference was seen with lymph node involvement in the 24 patients with the MF plus PI type of ICC who had no intrahepatic metastases (P = .6620). For purpose of diagnostic staging and exclusion of positive regional lymph nodes, lymph node dissections might be useful in patients with the MF type and the MF plus PI type of ICC; however, routine use of lymph node dissection in patients with the MF type of ICC is not recommended, because no difference in survival was observed in the patients with negative lymph node metastases, irrespective of the use of lymph node dissection.

Clinicopathological features, diagnosis and surgical treatment of mass-forming type intrahepatic cholangiocarcinoma: a study of 104 cases

目的 分析外科手术治疗后的肝内胆管细胞癌病人临床病理特征与生存时间的相关性.方法从1996年11月至2000年5月共有104例肝内胆管细胞癌病人接受手术治疗.对其临床资料进行归纳,并随访调查.成功回访79例(76.0%).对16个临床病理因素(年龄、性别、慢性肝病史、HBsAg携带、手术方式、辅助治疗、腹水、淋巴结转移、邻近器官侵犯、肿瘤大小、肿瘤坏死、肿瘤包膜、肝内转移、TNM分期、组织学分级、肝硬化)进行了单因素和多因素相关分析,以了解它们对治疗预后的影响.结果 79例病人的1,3,5年生存率分别为49.4%,17.3%和9.6%.单因素相关分析显示性别(P=0.0221),HBsAg携带(P=0.0115),手术方式(P=0.0042),辅助治疗(P=0.0389),腹水(P=0.0001),临近器官侵犯(P=0.0220),肝内转移(P=0.0000),TNM分期(P=0.0001)与生存时间相关.多因素分析表明HBsAg携带、腹水和TNM分期与预后显著相关.结论早期诊断和早期治疗以及规则性肝切除是改善肝内胆管细胞癌外科治疗效果的关键因素。