Cholangiocarcinoma as an Indication for Liver Transplantation in the Era of Transplant Oncology

Gringeri, Enrico; Gambato, Martina; Ivanics, Tommy; Lynch, Erica Nicola; Mescoli, Claudia; Burra, Patrizia; Cillo, U.; Russo, Francesco Paolo

doi:10.3390/jcm9051353

Cited by 13 publications

(29 citation statements)

References 126 publications

(141 reference statements)

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“…PHCCA is the most common type (50%), followed by DCCA (40%) and IHCCA (10%)[ 10 ]. According to its pattern of growth and macroscopic appearance, CCA may present in three different types: Mass-forming (which presents with a mass), periductal-infiltrating (growing along the wall of the bile duct) and intraductal-growing (with intraluminal growth)[ 117 , 118 ]. The mass-forming type is by far the most frequent[ 118 ](Figure 2 ).…”

Section: Anatomical Location and Macroscopic Morphology Of Ccamentioning

confidence: 99%

Review of incidence and outcomes of treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis

Saffioti

Mavroeidis

2021

WJGO

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Primary sclerosing cholangitis (PSC) is a premalignant condition and a well-documented risk factor for cholangiocarcinoma (CCA) which is the most common malignancy in this setting and the leading cause of deaths in the recent years, with an increasing incidence. PSC-associated CCA has a geographical distribution that follows the incidence of PSC, with an observed ascending gradient from the Eastern to the Western and from the Southern to the Northern countries. It may arise at any location along the biliary tree but is most common in the perihilar area. Patients with PSC and intrahepatic or perihilar CCA are typically not suitable for liver resection, which is otherwise the treatment of choice with curative intent in patients with resectable tumours, providing a radical resection with clear margins can be achieved. This largely relates to the commonly advanced stage of liver disease at presentation, which allows consideration for liver resection only for a very limited number of suitable patients with PSC. On the other hand, remarkable progress has been reached in the last decades with the implementation of a protocol combining neoadjuvant chemoradiation and orthotopic liver transplantation (OLT) for the treatment of perihilar CCA, within specific criteria. Excellent results have been achieved particularly for PSC patients with this cancer, who seem to benefit the most from this treatment, having converted this into an accepted indication for transplantation and the standard of care in several experienced centres. Intrahepatic CCA as an indication for OLT remains controversial and has not been accepted given disappointing previous results. However, as recent studies have shown favourable outcomes in early intrahepatic CCA, it may be that under defined criteria, OLT may play a more prominent role in the future. Distal CCA in the context of PSC requires aggressive surgical treatment with curative intent, when feasible. This review provides insight about particular features of CCA in the setting of PSC, with a main focus on its incidence, considerations relating to its anatomical location and implications to treatment and outcomes, through the viewpoint of historical evolution of management, and future perspectives.

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Section: Anatomical Location and Macroscopic Morphology Of Ccamentioning

confidence: 99%

Review of incidence and outcomes of treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis

Saffioti

Mavroeidis

2021

WJGO

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“…Recently, the liver transplantation option has been considered in some specific disease conditions. For example, liver transplantation in unresectable pCCA preceded by neoadjuvant chemoradiotherapy showed admirable long-term disease-free survival rates [ 17 , 18 ]. Recently it has been demonstrated that very early iCCA patients after liver transplantation present good oncologic and survival outcome, although more confirmations are needed, such as the clarification of the systemic neoadjuvant regimens to be associated [ 19 , 20 ].…”

Section: Current Therapeutic Intervention In Cholangiocarcinomamentioning

confidence: 99%

The Role of the Hedgehog Pathway in Cholangiocarcinoma

Anichini

Carrassa

Stecca

et al. 2021

Cancers

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Cholangiocarcinoma (CCA) is a poorly treatable type of cancer and, along with hepatocellular carcinoma (HCC), is the predominant type of primitive liver cancer in adults. The lack of understanding of CCA biology has slowed down the identification of novel targets and the development of effective treatments. While tumors share some general characteristics, detailed knowledge of specific features is essential for the development of effectively tailored therapeutic approaches. The Hedgehog (HH) signaling cascade regulates stemness biology, embryonal development, tissue homeostasis, and cell proliferation and differentiation. Its aberrant activation has been associated with a variety of solid and hematological human malignancies. Several HH-inhibiting compounds have been indeed developed as potential anticancer agents in different types of tumors, with Smoothened and GLI inhibitors showing the most promising results. Beside its well-established function in other tumors, findings regarding the HH signaling in CCA are still controversial. Here we will give an overview of the most important clinical and molecular features of cholangiocarcinoma, and we will discuss the available evidence of the crosstalk between the HH signaling pathway and the cholangiocarcinoma cell biology.

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“…200 The second most common hepatic liver cancer after HCC is cholangiocellular carcinoma (CCC), which arises from the malignant growth of cholangiocytes, the biliary tract epithelium, and accounts for approximately 10 to 15% of all hepatobiliary malignancies. 201,202 Current screening methods include ultrasound, computerized tomography, magnetic resonance imaging, serum biomarker assessment, and biopsy analysis 203,204 ; however, positive diagnosis can often be difficult through medical imaging and biomarker methods, 205 while a biopsy sample may misrepresent the liver due to the heterogeneity of tumor growth. 206 After diagnosis, treatments for liver cancer include transarterial chemoembolization, ablation, chemotherapy and radiation therapy, molecularly targeted therapies, surgical resection, or orthotopic liver transplantation.…”

Section: Liver Cancermentioning

confidence: 99%

Bioengineered Liver Models for Investigating Disease Pathogenesis and Regenerative Medicine

Kukla

Khetani

2021

Semin Liver Dis

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Owing to species-specific differences in liver pathways, in vitro human liver models are utilized for elucidating mechanisms underlying disease pathogenesis, drug development, and regenerative medicine. To mitigate limitations with de-differentiated cultures, bioengineers have developed advanced techniques/platforms, including micropatterned cocultures, spheroids/organoids, bioprinting, and microfluidic devices, for perfusing cell cultures and liver slices. Such techniques improve mature functions and culture lifetime of primary and stem-cell human liver cells. Furthermore, bioengineered liver models display several features of liver diseases including infections with pathogens (e.g., malaria, hepatitis C/B viruses, Zika, dengue, yellow fever), alcoholic/nonalcoholic fatty liver disease, and cancer. Here, we discuss features of bioengineered human liver models, their uses for modeling aforementioned diseases, and how such models are being augmented/adapted for fabricating implantable human liver tissues for clinical therapy. Ultimately, continued advances in bioengineered human liver models have the potential to aid the development of novel, safe, and efficacious therapies for liver disease.

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Cholangiocarcinoma as an Indication for Liver Transplantation in the Era of Transplant Oncology

Cited by 13 publications

References 126 publications

Review of incidence and outcomes of treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis

Review of incidence and outcomes of treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis

The Role of the Hedgehog Pathway in Cholangiocarcinoma

Bioengineered Liver Models for Investigating Disease Pathogenesis and Regenerative Medicine

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