Cholangiocarcinoma (CCA) is a rare and aggressive cancer, mostly diagnosed at advanced or metastatic stage, at which point systemic treatment represents the only therapeutic option. Chemotherapy has been the backbone of advanced CCA treatment. More recently, immunotherapy has changed the therapeutic landscape, as immune checkpoint inhibitors have yielded the first improvement in survival and currently, the addition of either durvalumab or pembrolizumab to standard of care cisplatin plus gemcitabine represents the new first-line treatment option. However, the use of immunotherapy in subsequent lines has not demonstrated its efficacy and therefore, it is not approved, except for pembrolizumab in the selected microsatellite instability-high population. In addition, advances in comprehensive genomic profiling have led to the identification of targetable genetic alterations, such as isocitrate dehydrogenase 1 (IDH1), fibroblast growth factor receptor 2 (FGFR2), human epidermal growth factor receptor 2 (HER2), proto-oncogene B-Raf (BRAF), neurotrophic tropomyosin receptor kinase (NTRK), rearranged during transfection (RET), Kirsten rat sarcoma virus (KRAS), and mouse double minute 2 homolog (MDM2), thus favoring the development of a precision medicine approach in previously treated patients. Despite these advances, the use of molecularly driven agents is limited to a subgroup of patients. This review aims to provide an overview of the newly approved systemic therapies, the ongoing studies, and future research challenges in advanced CCA management.
Citations
Citations to this article as recorded by
Genomic and transcriptomic signatures of sequential carcinogenesis from papillary neoplasm to biliary tract cancer Taek Chung, Seungho Oh, Jeongsoo Won, Jiho Park, Jeong Eun Yoo, Ho Kyoung Hwang, Gi Hong Choi, Chang Moo Kang, Dai Hoon Han, Sangwoo Kim, Young Nyun Park Journal of Hepatology.2025;[Epub] CrossRef
Is 26S proteasome non-ATPase regulatory subunit 6 a potential molecular target for intrahepatic cholangiocarcinoma? Yong-Zhi Zhuang, Li-Quan Tong, Xue-Ying Sun World Journal of Hepatology.2024; 16(11): 1219. CrossRef
Imaging findings of intrahepatic cholangiocarcinoma for prognosis
prediction and treatment decision-making: a narrative review Jun Gu Kang, Taek Chung, Dong Kyu Kim, Hyungjin Rhee The Ewha Medical Journal.2024;[Epub] CrossRef
Resectability and survival outcome in real world practice of 720 cholangiocarcinoma patients: intrahepatic, perihilar and distal cholangiocarcinoma. Poowanai Sarkhampee, Weeris Ouransatien, Nithi Lertsawatvicha, Satsawat Chansitthichock, Paiwan Wattanarath World Journal of Surgical Oncology.2024;[Epub] CrossRef
Cholangiocarcinoma is a biliary carcinoma with a wide spectrum of imaging, histological, and clinical features. In immunocompromised patients, pyogenic abscesses are relatively common and an echinococcal hepatic cysts are very rare. The authors experienced a very rare case of cholangiocarcinoma showing multiple hypodense masses with wall enhancement mimicking pyogenic liver abscess, echinococcal hepatic cyst, and cystic metastases. An 83-year-old man, complaining of fatigue and poor oral intake, presented to our outpatient clinic. Abdominal computed tomography (CT) revealed multiple, variable-sized hypodense masses with peripheral rim enhancement throughout the liver. Dynamic liver magnetic resonance images also showed findings similar to those of a CT scan. We performed ultrasound-guided biopsy of the mass which revealed cholangiocarcinoma.
Citations
Citations to this article as recorded by
Primary Cholangiocarcinoma of the Liver Presenting as a Complicated Hepatic Cyst: A Diagnostic Challenge Chang Won Ha, Sang Deok Shin, Myung Ji Goh, Byeong Geun Song, Wonseok Kang, Dong Hyun Sinn, Geum-Youn Gwak, Yong-Han Paik, Moon Seok Choi, Joon Hyeok Lee The Korean Journal of Gastroenterology.2025; 85(1): 83. CrossRef
Surgical strategy for incidental intrahepatic cholangiocarcinoma in terms of lymph node dissection Sung Hyun Kim, Dai Hoon Han, Gi Hong Choi, Jin Sub Choi, Kyung Sik Kim Journal of Gastrointestinal Surgery.2024; 28(6): 910. CrossRef
Background/Aims To investigative the potential role of postoperative chemoradiotherapy (CCRT) after R1 resection of intrahepatic cholangiocarcinoma (IHCC). Methods Between January 2000 and December 2012, medical records of 18 patients who underwent curative surgery with R1 resection for IHCC were retrospectively reviewed. Results Median age was 68 years and 12 patients (66.7%) were male. Median tumor size was 5.0 cm (range, 2.2-11.0) and 12 patients (66.7%) had T3 or higher disease. Lymph nodes were involved in four patients (22.2%). Vascular invasion and perineural invasion were present in 10
(55.6%) and 12 patients (66.7%), respectively. Postoperative CCRT given with 5-fluorouracil or gemcitabine were delivered to 7 patients (38.9%). Median radiation dose was 50.4 Gy (range, 45-54). Univariate analysis showed that median loco-regional recurrence-free survival (LRRFS), progression-free survival (PFS) and overall survival (OS) were prolonged for patients treated with CCRT (median LRRFS; 5.6 months vs. not reached, P<0.001, median PFS; 5.6 vs. 8.3 months,
P=0.047, median OS; 15.0 vs. 26.6 months, P=0.064). Conclusions Postoperative CCRT improved the loco-regional control and PFS in IHCC patients with R1 resection. Further study is warranted to validate the role of postoperative CCRT for these patients.
Citations
Citations to this article as recorded by
Prognostic Evaluation and Survival Prediction for Combined Hepatocellular-Cholangiocarcinoma Following Hepatectomy Seok-Joo Chun, Yu Jung Jung, YoungRok Choi, Nam-Joon Yi, Kwang-Woong Lee, Kyung-Suk Suh, Kyoung Bun Lee, Hyun-Cheol Kang, Eui Kyu Chie, Kyung Su Kim Cancer Research and Treatment.2025; 57(1): 229. CrossRef
Precision therapy for intrahepatic cholangiocarcinoma: A case report on adjuvant treatment in a recurrent patient after surgery and literature review Bao Ying, Tao Tang, Li-Xing Zhang, Jian-Wei Xiong, Kai-Feng Zhao, Jia-Wei Li, Guo Wu Oncology Letters.2023;[Epub] CrossRef
Stereotactic radiotherapy for intrahepatic cholangiocarcinoma Aditya Borakati, Farid Froghi, Ricky H Bhogal, Vasileios K Mavroeidis World Journal of Gastrointestinal Oncology.2022; 14(8): 1478. CrossRef
Heterogeneous features of liver cancer can mimic liver abscess. Therefore it is essential to doublecheck
tumor markers in the diagnosis of liver abscess. Herein, we report a case of combined
hepatocellular-cholangiocarcinoma (cHC) occurred in an unrecognized chronic hepatitis B patient
initially misdiagnosed as liver abscess. A 49-year old male initially presented with chill, right
upper quadrant pain, and a liver mass. Mass showed peripheral enhancement in arterial phase
of computed tomography, which was not typical for hepatocellular carcinoma (HCC). Strikingly
elevated alpha-fetoprotein and fine needle aspirated pathology revealed HCC. Despite discordant
image findings he was treated with transarterial chemoembolization. He was treated with
sorafenib due to metastatic retrocaval lymphadenopathy afterwards. The mass presumed to be
HCC progressed with sorafenib. It was surgically resected and he was finally confirmed as cHC.
Discordant tumor markers with presumptive image findings should prompt the suspicion of rare
type of primary liver cancer, the cHC.
Intrahepatic sarcomatoid carcinoma is a rare tumor with poor prognosis due to its highly invasive
and metastatic nature and difficulty for early detection. The most common form of intrahepatic
sarcomatoid carcinoma is the sarcomatoid hepatocellular carcinoma, the development of which is
usually associated with previous treatment for hepatocellular carcinoma. In contrast, sarcomatoid
cholangiocarcinoma is extremely rare and results from spontaneous sarcomatoid transformation
during the development of tumor. Here, we report a case of sarcomatoid cholangiocarcinoma,
in a 58-year-old male, which developed at the site of previous treatment for hepatocellular
carcinoma. A 9 × 7 cm sized tumor which had not been detected in the computed tomography
exam 3 months before diagnosis was newly observed. The tumor rapidly progressed and the
patient died only 31 days after the diagnosis.
Sarcomatoid carcinoma arising from intrahepatic cholangiocyte, an extremely rare primary liver
cancer, has highly invasive and metastatic potential. The pathogenesis of this tumor is unclear,
although histogenetic mechanisms, such as transdifferentiation/dedifferentiation (epithelialmesenchymal
transition or metaplastic transformation), biphasic differentiation (combination
and collision), and redifferentiation, might be suggested to explain the simultaneous coexistence
of carcinoma and sarcoma components in the same tumor. Immunohistochemical
staining might be necessary to differentiate whether sarcomatous component is originated from
hepatocyte or cholangiocyte. We report a case of sarcomatoid intrahepatic cholangiocarcinoma
in a 58 year-old man presenting as an incidentally detected liver mass on regular health
examination, which was diagnosed by an application of immunohistochemical methods
after surgical resection, with a review of the literature based on 9 cases reported in Korea.
Citations
Citations to this article as recorded by
Pathologic features and clinical treatment of sarcomatoid intrahepatic cholangiocarcinoma Xiaoli Xie, Nannan Lai, Yuanyuan Yang, Jinwei Zhang, Jianmin Qin, Xia Sheng Intractable & Rare Diseases Research.2023; 12(4): 267. CrossRef
Clinical diagnosis and treatment strategies for sarcomatoid intrahepatic cholangiocarcinoma Xia Sheng, Jian-Min Qin World Chinese Journal of Digestology.2022; 30(14): 614. CrossRef
Analysis of intrahepatic sarcomatoid cholangiocarcinoma: Experience from 11 cases within 17 years Dong Kyun Kim, Bo Ra Kim, Jin Sook Jeong, Yang Hyun Baek World Journal of Gastroenterology.2019; 25(5): 608. CrossRef
Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are major primary liver cancers in adults, comprising liver
cancer spectrum. The existence of combined hepatocellular-cholangiocarcinoma (CHC), a histopathologic intermediate form
between HCC and CC, suggests phenotypic overlap between these tumors. By applying an integrative oncogenomic approach,
we identified a novel HCC subtype, i.e., cholangiocarcinoma-like HCC (CLHCC), which expressed cholangiocarcinoma-like
traits (CC signature). In addition, we found that CLHCC coexpressed embryonic stem cell–like expression traits (ES signature)
suggesting its derivation from bipotent hepatic progenitor cells. Further histopathological evaluation revealed a variant HCC with
fibrous stromal component, i.e. scirrhous HCC, has CC-like genomic features, suggesting that the fibrous stromal component in
HCC may contribute to the acquisition of CC-like gene expression trait in HCC. Our integrative analysis combining
histopathological and genomic data would be a powerful approach to delineate the tumor heterogeneity.
Gene Hyun Bok, Soung Won Jeong, Jae Young Jang, Kwang Yeun Shim, Sae Hwan Lee, Sang Gyune Kim, Young Seok Kim, Hong Soo Kim, Boo Sung Kim, So Young Jin, Sung Sook Hong, Yong Jae Kim
Journal of the Korean Liver Cancer Study Group. 2012;12(1):23-27. Published online February 28, 2012
Morphologically, intrahepatic cholangiocarcinoma (ICC) presents as a parenchymal mass, and it is occasionally resectable and
potentially curable. In some cases, differentiation from other hepatic neoplasms such as metastatic lesions and hepatocellular
carcinoma (HCC) can be extremely difficult, both clinically and histologically, and definitive diagnosis often needs correlation
with clinical and radiologic finding.Contrasted computed tomography (CT) is useful in the diagnosis of ICC and in determining
the extent of tumor involvement. Although the majority of liver tumors can be diagnosed by modern imaging modalities such as
contrast CT, some cases of ICC show tumor enhancement in the arterial phase the same as that in HCC, or a biliary dilatation
without stenosis by intraductal tumor growth. Differences in these patterns of tumor enhancement and status of the bile ducts in
ICC may also reflect differences in cellular characteristics, clinical features, and prognosis after treatment. We present a case of a
small ICC showing similar clinical and radiologic characteristics to HCC.
C. sinensis induces adenomatous hyperplasia of the epithelium of the bile ducts, and the epithelium of the bile duct persistently
exposed to biochemically altered bile may undergo the sequence, hyperplasia-metaplaisa-dysplasia-carcinoma. Cholangiocarcinomas
were developed in most hamsters treated with an N-nitroso compound and then infected with C. sinensis. In the patients with
intrahepatic duct stones, bile usually infected with bacteria. Mechanical stimuli due to stones, long-lasting bile stasis, and bacterial
infection are considered to be the other significant causative factors in cholangiocarcinogenesis. Radiological examinations are
essential in the diagnosis and treatment of biliary tree diseases including clonorchiasis, biliary stone disease, and cholangiocarcinoma.
As both C. sinensis and intrahepatic duct stones are common, radiological and clinical findings should be attentively investigated for
the possible presence of cholangiocarcinoma in patients with clonorchiasis or intrahepatic duct stones.
Combined hepatocellular-cholangiocarcinoma (CHC) is an extremely rare form of primary liver cancer having
features of both hepatocellular and biliary epithelial differentiation. The incidence of CHC was 1.0-6.3% of all
primary liver cancers.
Since Allen and LIsa first described the features of this tumor in 1949, Allen’s classification has been widely
used. This classification includes: type A, double cancer of HCC and CC, with HCC and CC present at different
sites without contact; type B, HCC and CC are present at adjacent sites and mingle with continued growth; and
type C, HCC and CC are mixed, growing within the same tumor. CHC are often confused with pseudoglandular
growth pattern in HCC, but this has led to the mistaken impression that CHC are common. Histologically, only
type C displays the characteristic of genuine mixture of both HCC and CC elements, and only Allen’s type C was
included and regarded as true CHC in many published studies of CHC. With regard to the tumorigensis of CHC,
the following possibilities have been proposed: 1st, the CC component arises from the main HCC tumor, and 2nd,
the entire cancer arises from a stem cell potentially differentiating into hepatocytes and bile duct epithelium.
In this review, I will describe the tumorigenesis of CHC and introduce the hepatic stem cell, such as hepatic
progenitor cells.
Combined hepatocellular-cholangiocarcinoma (HCC-CC) is a rare tumor showing histological evidence of both
hepatocellular and biliary epithelial differentiation. Because of its rarity, there have been few reports about the
imaging findings of this tumor. The CT findings of the combined HCC-CC include well-defined tumor with signs
of malignancy such as hepatic hypervascularity, biliary obstruction, satellite nodules, and lymphadenopathy. Some
portions may show hypoattenuation on arterial phase, whereas other portions show delayed persistent
enhancement. The signal intensity of this tumor on magnetic resonance (MR) imaging is not specific. However,
when the tumor resembles cholangiocarcinoma on gross pathologic exam, it shows peripheral rim-like
enhancement, infiltrative margin, and portal vein invasion in patients with liver cirrhosis. On the other hand, when
the tumor has gross appearance of HCC, imaging findings are not helpful for diagnosis. Cross-sectional imagings
are helpful for predicting the predominant component of the combined HCC-CC and determining the treatment
strategy.
Combined hepatocellular and cholangiocarcinoma (HCC-CC) is an uncommon form of primary liver cancer
(PLC) with features of hepatocellular and biliary epithelial differentiation. According to publishing records
HCC-CC accounts for 0.4% to 14.2% of all PLC cases. Large number of HCC-CC is associated with chronic viral
hepatitis or cirrhosis, especially in asian countries. The tumor markers of HCC-CC (AFP, CA19-9) shows the
intermediate level between hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). The clinical features of
HCC-CC resembled with HCC but its post operative result and metastatic pattens are similar to that of CC.
Surgical results of this tumor can yield results that are intermediate between HCC and CC in characteristics. But
complete resection is the only effective therapy and can result in long term survival. And there are hot debates
for the additional hilar lymph node dissection. The survival rate of HCC-CC is higher than CC but lower than
HCC. The recurrence after resection has been frequently reported. Most of them are intrahepatic recurrences as
HCCs but extrahepatic recurrences are much more frequent like CC. The CC component of HCC-CC seem to
determine the prognosis. So more effective approaches for treating recurrent disease, such as local ablation
therapy and or combination systemic chemotherapy and neoadjuvant chemoradiation, should be applied for long
term and better results.
Jung Hyun Kwon, Si Hyun Bae, Jung Pil Suh, Ho Sung Park, Chan Ran You, Jong Young Choi, Seung Kew Yoon, Dong Hoon Lee, Ho Jong Chun, Byung Gil Choi, Chan Kwon Chung, Eun Sun Jung, Mi Ryung Ryu
Journal of the Korean Liver Cancer Study Group. 2007;7(1):49-54. Published online June 30, 2007
A 43 year-old-women patient was admitted for one month of jaundice. She was diagnosed hepatitis B carrier
17 years ago and has not done a routine check. Abdominal CT showed a large ill defined mass in left hepatic lobe
with inhomogenous enhancement in arterial and delayed phase. The result of biopsy including the
immunohistochemical stains showed the combined hepatocellular and cholangiocarcinoma (stage IVa, type C by
Allen and Lisa). With the radiation therapy (3,910 cGy), six times of transarterial chemo-lipiodolization and two
times of percutaneous ethanol injection, huge mass was markedly decreased in size and no stain in hepatic
angiogram. She underwent left lobectomy.
Combined hepatocellular and cholangiocarcinoma (cHCC-CC) is an uncommon form of primary liver cancer
having features of both hepatocellular and billiary epithelial differentiation. We report a case of cHCC-CC in a
patient who was serologically positive for hepatitis B virus. A 39-year-old male was diagnosed by
ultrasonography with an asymptomatic tumor in the left lobe of the liver. Based on radiologic and serologic
findings of elevated serum alpha-fetoprotein level, a preoperative diagnosis of hepatocellular carcinoma was made,
but differential diagnosis included focal nodular hyperplasia, because tumor was enhanced in delayed phase in
Godolinium MRI scan. A final diagnosis of cHCC-CC was made after operation.
Woo Jin Chung, Sang Hun Jeon, Dong Choon Kim, Ju Yup Lee, Kyung In Lee, Hye Jin Seo, Byung Kuk Jang, Kyung Sik Park, Kwang Bum Cho, Jae Seok Hwang, Sung Hoon Ahn, Ku Jeong Kang, Young Hoon Kim, Jung Hyeok Kweon, Young Hwan Kim, Yu Na Kang
Journal of the Korean Liver Cancer Study Group. 2007;7(1):59-61. Published online June 30, 2007
A 51 years-old man who had postnecrotic liver cirrhosis due to chronic hepatitis B had elevated serum alpha
fetoprotein level. According to computed tomographic findings, about 2.4cm sized mass was noted at segment 7
and he underwent segmentectomy. After 9 months later, multicentric recurrence was detected at segment 5-6, So,
he underwent transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection therapy. After
22 months later, marginal recurrence was noted again at segment 6. So, he underwent 2nd TACE and he was
following up over 30 months until now.