Colorectal cancer (CRC), gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN), and cholangiocarcinoma (CCA) exhibit high rates of morbidity and mortality once metastasized to the liver. Liver transplantation (LT) is a viable therapeutic approach for these cancers in highly selected patients; however, their invasive nature at late stages causes many patients to be delisted from transplantation or to require further downstaging. Immunotherapy with immune checkpoint modulators has revolutionized cancer research. Immune checkpoint inhibitors (ICI) leverage the chronic inflammatory state and the overexpression of cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) by malignant cells and regulatory T cells, to block immune checkpoints and counteract tumor's ability to evade the immune system. However, the interaction between allograft PD-L1 and PD-1 on infiltrating T cells functions as a means of graft tolerance in cases of LT. Therefore, the application of ICIs might block this protective effect and induce graft rejection, a phenomenon particularly observed in PD-1/PD-L1 inhibiting ICIs. The risk of post-LT graft rejection can be mitigated by applying advanced biomarkers and specifying certain mutations that enhance patient selection criteria for pre-LT ICI use. Furthermore, the determination of optimal intervals of ICI administration pre- and post-LT, identification of ICI indications in de novo malignancies occurring after LT, and investigation of biomarkers for early rejection detection, pave the way for more promising LT outcomes in patients with CRC, GEP-NEN, or CCA. Therefore, this review aims to illustrate a comprehensive overview of the role of ICI therapy in the management of non-hepatocellular carcinoma transplant oncology cancers by demonstrating the potential for its application in both pre-and post-LT states, and pathways to reduce or timely detect ICI-associated graft rejection.

Biliary tract cancers (BTCs) are a histologically and molecularly diverse group of malignancies arising from the gallbladder and the ductal epithelium of the biliary tree. Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver malignancy in the United States. Surgical resection with negative margins is the only recognized curative treatment option for iCCA; however, most patients will present with advanced or unresectable disease. The clinical presentation is largely non-specific, with the characteristic symptoms of biliary malignancies being less frequent than extrahepatic cholangiocarcinoma. Clinical management in iCCA is heavily influenced by the molecular profile of individual tumors. Hence, pathologists must exercise caution to prevent tissue exhaustion during the diagnostic workup of iCCA and ensure the availability of tissue samples for molecular testing. Establishing standardized procedures for obtaining adequate tissue and using molecular testing is vital. Circulating tumor DNA (ctDNA) offers a potential alternative to tissue-based analysis, especially in cases with insufficient tissue samples. Drugs targeting alterations in NTRK, IDH1, BRAF, FGFR2, and HER2 are commonly utilized. Targeting the MDM2-p53 pathway represents an avenue for future investigations in advanced BTCs. Liver transplantation and locoregional therapies are treatment modalities that may represent curative intent treatments for patients with unresectable disease, and larger explorations are warranted. Akin to HCC, a multidisciplinary team-based approach is essential for patients with BTCs. Through this narrative review of literature, we provide an overview of the current management of iCCA with perspectives regarding future directions in the clinical management of iCCA. We also present patient perspectives regarding the importance of patient advocacy and access to advances in clinical research for patients with BTCs.

Liver transplant (LT) for transplant oncology (TO) indications is being slowly adopted worldwide and has been recommended to be incorporated cautiously due to concerns about mid-long-term survival and its impact on the waiting list.

We conducted 4 systematic reviews of all series on TO indications (intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma [phCC]) and liver metastases from neuroendocrine tumors (NETs) and colorectal cancer (CRLM) and compared them using patient-level meta-analyses to data obtained from the United Network for Organ Sharing (UNOS) database considering conventional daily-practice indications. Secondary analyses were done for specific selection criteria (Mayo-like protocols for phCC, SECA-2 for CRLM, and Milan criteria for NET). A total of 112,014 LT were analyzed from 2005 to 2020 from the UNOS databases and compared with 345, 721, 494, and 103 patients obtained from meta-analyses on intrahepatic cholangiocarcinoma and phCC, and liver metastases from NET and CRLM, respectively. Five-year overall survival was 53.3%, 56.4%, 68.6%, and 53.8%, respectively. In Mantel-Cox one-to-one comparisons, survival of TO indications was superior to combined LT, second, and third LT and not statistically significantly different from LT in recipients >70 years and high BMI.

Liver transplantation for TO indications has adequate 5-year survival rates, mostly when performed under the selection criteria available in the literature (Mayo-like protocols for phCC, SECA-2 for CRLM, and Milan for NET). Despite concerns about its impact on the waiting list, some other LT indications are being performed with lower survival rates. These oncological patients should be given the opportunity to have a definitive curative therapy within validated criteria.

Biliary tract cancers comprise a heterogeneous collection of malignancies usually described as cholangiocarcinoma of the intra- or extrahepatic bile duct, including perihilar cholangiocarcinoma and gallbladder cancer.

A review of pertinent parts of the ESSO core curriculum for the UEMS diploma targets (Fellowships exam, EBSQ), based on updated and available guidelines for diagnosis, surgical treatment and oncological management of cholangiocarcinoma.

Following the outline from the ESSO core curriculum we present the epidemiology and risk factors for cholangiocarcinoma, as well as the rationale for the current diagnosis, staging, (neo-)adjuvant treatment, surgical management, and short- and long-term outcomes. The available guidelines and consensus reports (i.e. NCCN, BGS and ESMO guidelines) are referred to. Recognition of biliary tract cancers as separate entities of the intrahepatic biliary ducts, the perihilar and distal bile duct as well as the gallbladder is important for proper management, as they each provide distinct clinical, molecular and treatment profiles to consider.

Core competencies in knowledge to the diagnosis, management and outcomes of biliary tract cancers are presented.

Liver transplantation (LT) provides the best long-term survival outcomes for patients with liver cancer. As a result, the field of transplant oncology has grown greatly over the past few decades, and many centers have expanded their criteria to allow increased access to LT for liver malignancies. Center-level guidelines and practices in transplant oncology significantly vary across the world, leading to debate regarding the best course of treatment for this patient population. An international consensus conference was convened by the International Liver Transplantation Society and the International Liver Cancer Association on February 1-2, 2024, in Valencia, Spain to establish a more universal consensus regarding LT for oncologic indications. The conference followed the Delphi process, followed by an external expert review. Consensus statements were accepted regarding patient assessment and waitlisting criteria, pretransplant treatment (including immunotherapy) and downstaging, living donor LT, post-LT patient management, and patient- and caregiver-related outcomes. The multidisciplinary participants in the consensus conference provided up-to-date recommendations regarding the selection and management of patients with liver cancer being considered for LT. Although participants deferred to center protocols in many cases, there was great interest in safely expanding access to LT for patients with larger tumor burden and biologically amenable lesions.

Liver transplantation for cancer indications has gained momentum in recent years. This review is intended to optimize the care setting of liver transplant candidates by highlighting current indications, technical aspects and barriers with available solutions to facilitate the guidance of available strategies for healthcare professionals in specialized centres.

A review of the most recent relevant literature was conducted for all the cancer indications of liver transplantation including colorectal cancer liver metastases, hilar cholangiocarcinoma, intrahepatic cholangiocarcinoma, neuroendocrine tumours, hepatocellular carcinoma and hepatic epitheloid haemangioendothelioma.

Transplant benefit from the best available evidence, including SECA I, SECA II, TRANSMET studies for colorectal liver metastases, various preoperative protocols for cholangiocarcinoma patients, standard, extended selection criteria for hepatocellular carcinoma and neuroendocrine tumours, are discussed. Innovative approaches to deal with organ shortages, including machine-perfused deceased grafts, living donor liver transplantation and RAPID procedures, are also explored.

Cancer indications for liver transplantation are here to stay, and the selection criteria among all cancer groups are likely to evolve further with improved prognostication of tumour biology using adjuncts such as radiomics, cancer genomics, and circulating DNA and RNA status. International prospective registry-based studies could overcome the limitations of smaller patient cohorts and lack of level 1 evidence.

Despite the growing interest in liver transplantation for cholangiocarcinomas (CCA), conclusive evidence is lacking. We sought to evaluate the outcomes of liver transplantation for intrahepatic cholangiocarcinoma in Brazil.

Retrospective database analysis of patients undergoing liver transplantation for hepatocellular carcinoma (HCC) within Milan criteria in São Paulo, Brazil. Anatomopathological examination of the explanted liver with the presence of intrahepatic cholangiocarcinoma (iCCA) or combined hepatocellular-cholangiocarcinoma (cHCC-CCA) comprised the study group (50 patients). They were compared to a 1:3 HCC-matched cohort.

Study group had lower survival rates than HCC controls (survival at 1, 3, and 5 years, 70.0 %, 57.5 %, and 57.5 % versus 78.7 %, 71.4 %, and 66.6 %, p = 0.019). 5-year survival rates of the control group, cHCC-CCA, and iCCA group were 66.6 %, 59.6 %, and 50.0 % (p = 0.017). There was no statistically significant difference in survival for study group patients with tumors up to 3 cm compared to their controls (p = 0.086).

Patients with CCA had worse outcomes after liver transplantation than those with HCC. Interesting results were found in the more individualized analyses, but because of the limited number of patients, caution should be taken when analyzing them.

Hepatocellular carcinoma (HCC) and cholangiocarcinoma are the primary hepatic malignancies with established pathways to transplantation and model for end-stage liver disease (MELD) exception points. Other tumors managed with liver transplantation (LT) include hepatic epithelioid hemangioendothelioma and fibrolamellar HCC. LT for metastatic neuroendocrine tumor has been established with patient selection criteria and a path to MELD exception points. Additionally, recent data on LT for patients with unresectable hepatic colorectal metastases demonstrate increasingly encouraging initial results.

Primary and secondary liver cancers are frequently unresectable at the time of diagnosis. Historically, these patients were treated with palliative therapy and no hope for curative resection. While liver transplant has been the standard of care for unresectable hepatocellular carcinoma (HCC), its indications have expanded to other oncologic indications based on promising data from select centers. This review focuses on the utilization of liver transplant for HCC, cholangiocarcinoma, and colorectal liver metastasis.

In the realm of HCC, immunotherapy is an emerging treatment that has the potential for use in the advanced and neoadjuvant setting. It can benefit patients by downstaging them to resectable or transplantable disease burden. Regarding cholangiocarcinoma, better molecular profiling and targeted therapies have benefited patients, and ongoing studies in the United States and internationally will help further delineate the patients with cholangiocarcinoma who benefit from transplantation. Finally, there is emerging evidence that liver transplant for colorectal liver metastases can be safe and effective. While there is promising data showing survival benefit of liver transplantation (LT) for CRLM, standardized guidelines and recommendations in coordination with multidisciplinary oncology teams will be essential for establishing best practices.

Similar to the evolution of LT becoming the standard of care for well selected patients with HCC, the evolution of the role for LT for other hepatobiliary malignancies is quickly progressing as centers in Europe, Asia, and North America gain experience and develop protocols for selected patients with favorable tumor biology. Optimal oncology treatment requires multidisciplinary tumor board and case-by-case approaches which are essential for providing these patients with the best chance at optimal survival.

The purpose of this review is to summarize the current knowledge of cholangiocarcinoma molecular biology and to suggest a framework for implementation of next-generation sequencing in all stages of liver transplantation. This is timely as recent guidelines recommend increased use of these technologies with promising results.

The main themes covered here address germline and somatic genetic alterations recently discovered in cholangiocarcinoma, particularly those associated with prognosis and treatment responses, and nascent efforts to translate these into contemporary practice in the peri-liver transplantation period.

Early efforts to translate molecular profiling to cholangiocarcinoma care demonstrate a growing number of potentially actionable alterations. Still lacking is a consensus on what biomarkers and technologies to adopt, at what scale and cost, and how to integrate them most effectively into care with the ambition of increasing the number of patients eligible for liver transplantation and improving their long-term outcomes.

Perihilar cholangiocarcinoma (phCCA) has excellent outcomes following liver transplantation (LT). Neoadjuvant radiation-based locoregional therapy is standard-of-care. Gemcitabine and cisplatin (gem/cis) combination systemic therapies have improved outcomes in advanced settings, but their efficacy pre-LT has not been studied.

We review our experience following neoadjuvant gem/cis alone versus radiation-based approaches. Patients with phCCA undergoing LT at a single center between January 2008 and February 2023 were identified retrospectively. Neoadjuvant therapy was categorized as gem/cis systemic therapy (ST) alone, or any ST and radiotherapy (RT). Outcomes were posttransplant overall survival (OS), recurrence-free survival (RFS), waitlist time, and pathologic tumor response.

During study period, 27 phCCA patients underwent LT. One patient decompensated with neoadjuvant therapy and was excluded. Median age was 61 y (interquartile range, 53-68 y) and 14 (54%) were male. Of 26 patients, 12 (46%) received ST and 14 (54%) RT. Six RT patients received gem/cis ST. Median waitlist time was 199 d (interquartile range, 98-405 d) and did not differ by neoadjuvant regimen. Explanted tumors were predominantly T1 stage, without lymphovascular invasion or nodal involvement. Neither pathologic features nor percent tumor necrosis differed by regimen. OS probabilities at 1 and 3 y were 84% and 55% for the cohort. There was no significant difference in OS and RFS when stratified by regimen.

Post-LT OS, RFS, waitlist time, and tumor response were similar in the 2 groups. Patients with phCCA who do not undergo RT may still be considered for LT under appropriate institution-based protocols that adhere to other established criteria.

Cholangiocarcinoma (CCA) has rising incidence and mortality rates. Outcomes from combination systemic, loco-regional therapy (LRT) and liver transplantation (LT) are improving, but more granular data are needed to inform evidence-based management, including patient selection and immunosuppression.

Patients with peri-hilar (PH) and intrahepatic (IH) CCA who underwent LT at a single center between January 2008 and February 2023 were reviewed retrospectively. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS) with significance determined by Cox proportional hazards model.

During the study period, 53 patients underwent LT for either PH (n = 27), or IH (26). Cohort had mean age 58.5 years old (IQR, 47.0-63.0), body mass index (BMI) 25.9 (IQR, 22.9-30.0) kg/m2, and mean biologic MELD 9 (IQR, 7-17). Most frequent etiology was PSC (n = 12, 22.6%). Forty-nine patients (92.5%) received neoadjuvant therapy, including systemic (n = 48, 90.6%) and locoregional therapy (LRT) (n = 22, 41.5%), to which PH tumors were both most and least responsive (P = .03). On explant pathology, tumor were a median size of 3.5 cm and lympho-vascular invasion (LVI) was present in 13 (24.5%) cases. Median follow-up post-transplant was 910 days (IQR, 407-1509). Probabilities of OS and RFS at 3-years post-LT were 69.2% (95% CI, 56.9%-84.2%) and 57.4% (95% CI, 43.7%-75.4%). In multivariable analysis, OS was associated with tumor type and LVI, and RFS with age, BMI, PSC and LRT. After a median post-LT period of 38 days (IQR, 27-79.5), 39 (71.7%) patients started mTOR inhibition with lowered tacrolimus goal. Cox proportional hazard model showed significant association of OS with mTOR inhibition, though this was not validated by a time-dependent co-variate approach.

In this single center cohort of CCA, post-LT outcomes were significantly greater for patients with IH tumors and no LVI. Immunosuppression with mTOR inhibition was not consistently associated with outcomes.

Intrahepatic and peri-hilar cholangiocarcinoma are life threatening disease with poor outcomes despite optimal treatment currently available (5-year overall survival following resection 20-35%, and <10% cured at 10-years post resection). The insidious onset makes diagnosis difficult, the majority do not have a resection option and the high recurrence rate post-resection suggests that occult metastatic disease is frequently present. Advances in perioperative management, such as ipsilateral portal vein (and hepatic vein) embolisation methods to increase the future liver remnant volume, genomic profiling, and (neo)adjuvant therapies demonstrate great potential in improving outcomes. However multiple areas of controversy exist. Surgical resection rate and outcomes vary between centres with no global consensus on how 'resectable' disease is defined - molecular profiling and genomic analysis could potentially identify patients unlikely to benefit from resection or likely to benefit from targeted therapies. FDG-PET scanning has also improved the ability to detect metastatic disease preoperatively and avoid futile resection. However tumours frequently invade major vasculo-biliary structures, with resection and reconstruction associated with significant morbidity and mortality even in specialist centres. Liver transplantation has been investigated for very selected patients for the last decade and yet the selection algorithm, surgical approach and both value of both neoadjuvant and adjuvant therapies remain to be clarified. In this review, we discuss the contemporary management of intrahepatic and peri-hilar cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a rare neoplasm, with high mortality, originating in the bile ducts. Its incidence is higher in Eastern countries due to the endemic prevalence of liver parasites. Factors such as metabolic syndrome, smoking, and pro-inflammatory conditions are also linked to the disease. Clinical features include asthenia, abdominal pain, cholestasis, and increased serum levels of CEA and CA19-9.

The aim of this study was to evaluate CCA prevalence, survival, and potential prognostic and therapeutic implications in a patient cohort and assess correlations with clinical laboratory data and possible associated risk factors.

This is a retrospective study of the clinical and histological data of patients diagnosed with CCA at Santa Casa de Misericórdia in Porto Alegre, Brazil, between 2016 and 2021.

There was a 56% prevalence of CCA in women, with intrahepatic localization in 55.4% of cases and unifocality in 85.6% of patients. The mean age of the patients was 63 years (26-89 years), with a mean tumor size of 5.5 cm. The median survival time was 7 months (0 to >50). CA19-9 was altered in 81% of patients, whereas GOT/GPT was altered in 62.5% and gamma-glutamyl transferase/alkaline phosphatase/bilirubin in 69.1% of patients. Mortality was higher among patients with extrahepatic CCA.

Risk factors such as smoking, cholecystectomy, cirrhosis, intrahepatic lithiasis, and transplantation should be considered individually by the attending physician for radiological monitoring and incidental discovery of the neoplasm. Lack of timely identification by the attending physician can delay diagnosis, increasing mortality.

Intrahepatic cholangiocarcinoma (iCCA) was considered a contraindication for liver transplantation. However, recent studies have shown that highly selected cases of patients with a good response to neoadjuvant therapy may achieve acceptable survival rates when following liver transplantation.

To present two cases of patients with iCCA, without extrahepatic disease, who underwent living donor liver transplantation after receiving neoadjuvant chemotherapy.

Two cases of patients with histopathological diagnosis of locally advanced iCCA, ineligible for resection and without evidence of extrahepatic disease, are presented.

These patients underwent at least nine sessions of neoadjuvant chemotherapy, including Gemcitabine and Cisplatin, with or without the addition of immunobiological agents, resulting in a radiological tumor response. They subsequently underwent living donor liver transplantation. The average follow-up time was 15 months, with no clinical or radiological signs of disease.

In well-selected patients without extrahepatic disease, living donor liver transplantation represents a potential therapeutic option for iCCA.

Hepatocellular carcinoma (HCC) and biliary tract cancers (BTC) pose significant diagnostic and therapeutic challenges. Magnetic resonance imaging (MRI) and multiphase computed tomography (CT) have been the preferred imaging modalities for diagnosis, staging, and surveillance of patients with these malignancies. The best clinical outcomes depend on the appropriate selection of treatment options from the tools available in neo-adjuvant therapy, surgical resection, locoregional therapy, liver transplantation, and adjuvant therapy. While not a part of the routine diagnostic work-up or follow-up, F-18 fluorodeoxyglucose positron emission tomography (FDG PET/CT) can inform therapeutic decision making and help avoid futile surgeries by detecting unsuspected distant metastases. Additionally, metabolic information obtained with FDG PET/CT has prognostic value, predicting treatment response and survival. In patients with HCC metabolic parameters obtained by FDG PET/CT have been shown to correlate with microvascular invasion and predict recurrence in orthotopic transplant recipients. This article will highlight studies that have evaluated the role of FDG PET/CT in diagnosis, staging and therapeutic response assessment in patients with hepatobiliary cancers.

Liver transplantation (LT) is an established life-saving procedure. The field of LT has changed in the past 10 years from several perspectives, with the expansion of indications, transplantation of patients with acute-on-chronic liver failure, evolution of transplant oncology, the use of donations after cardiac death, new surgical techniques, and prioritisation of recipients on the waiting list. In addition, the advent of organ perfusion machines, the recognition of new forms of rejection, and the attention paid to the transition from paediatric to adult patients, have all improved the management of LT recipients. The purpose of the EASL guidelines presented here is not to cover all aspects of LT but to focus on developments since the previous EASL guidelines published in 2016.

Cholangiocarcinoma is a rare and heterogeneous disease that often requires multimodal treatment. The role of liver transplantation in these tumors has been controversial due to historically poor prognosis and higher recurrence rates. However, in recent years, scientific evidence has challenged this notion. We report the case of a 49-year-old woman with locally advanced intrahepatic cholangiocarcinoma. The therapeutic approach for this patient was complex, involving locoregional and systemic therapies. Despite the tumor's characteristics, namely, large size, multifocality, and vascular involvement, the good response to the treatment allowed a liver transplant 57 months after diagnosis.

Liver transplantation (LT) is a potentially curative experimental treatment for unresectable intrahepatic cholangiocarcinoma (iCC). Pre-transplant downstaging may help defining tumor aggressiveness and drive patient selection. We report the preliminary results of LT for liver-limited unresectable iCC after sequential downstaging with systemic chemotherapy and radioembolization (SYS-TARE). In case of sustained disease stability after SYS-TARE, patients underwent surgical nodal sampling and, if negative, were listed for LT. In this study, 13 patients with unresectable iCC underwent downstaging with SYS-TARE. The median age was 70 years and 77% were female. All had single bulky lesions at diagnosis. After SYS-TARE, 9 (69%) dropped out: 3 due to progressive disease after TARE with no response to second-line, 4 due to extrahepatic disease development and 2 due to positive nodal disease at pre-listing abdominal exploration. The median OS after dropout was 11.5 months. Four (31%) were successfully listed and transplanted. At pathology, viable tumor ranged from 30% to less than 5%. All four patients are alive and disease-free at 73, 40, 12, and 8 months from LT. LT for unresectable iCC after downstaging with SYS-TARE appears to select suitable patients for LT, achieving optimal oncological outcomes in case of response to therapy and no lymphnodal spread.

Advances in surgical procedures and immunosuppressive therapies have considerably improved the outcomes of patients who have undergone liver transplantation in the past few decades. In 2020, the Italian Liver Transplant Working Group published practice-oriented algorithms for immunosuppressive therapy (IT) in adult liver transplant (LT) recipients. Due to the rapidly evolving LT field, regular updates to the recommendations are required. This review presents a consensus- and evidence-based update of the 2020 recommendations.

The Italian Liver Transplant Working Group set out to address new IT issues, which were discussed based on supporting literature and the specialists' personal experiences. The panel deliberated on and graded each statement before consensus was reached.

A series of consensus statements were formulated and finalized on: (i) oncologic indications for LT; (ii) management of chronic LT rejection; (iii) combined liver-kidney transplantation; (iv) immunosuppression for transplantation with an organ donated after circulatory death; (v) transplantation in the presence of frailty and sarcopenia; and (vi) ABO blood group incompatibility between donor and recipient. Algorithms were updated in the following LT groups: standard patients, critical patients, oncology patients, patients with specific etiology, and patients at high immunologic risk. A steroid-free approach was generally recommended, except for patients with autoimmune liver disease and those at high immunologic risk.

The updated consensus- and evidence-based 2024 recommendations for immunosuppression regimens in adult patients with ABO-compatible LT address a range of clinical variables that should be considered to optimize the choice of the immunosuppression treatment in clinical practice in Italy.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common malignant primary liver cancer. iCCA may develop on an underlying chronic liver disease and its incidence is growing in relation with the epidemics of obesity and metabolic diseases. In contrast, perihilar cholangiocarcinoma (pCCA) may follow a history of chronic inflammatory diseases of the biliary tract. The initial management of CCAs is often complex and requires multidisciplinary expertise. The French Association for the Study of the Liver wished to organize guidelines in order to summarize the best evidence available about several key points in iCCA and pCCA. These guidelines have been elaborated based on the level of evidence available in the literature and each recommendation has been analysed, discussed and voted by the panel of experts. They describe the epidemiology of CCA as well as how patients with iCCA or pCCA should be managed from diagnosis to treatment. The most recent developments of personalized medicine and use of targeted therapies are also highlighted.

Liver transplantation is known to generate significant inflammation in the entire organ based on the metabolic profile and the tissue's ability to recover from the ischemia-reperfusion injury (IRI). This cascade contributes to post-transplant complications, affecting both the synthetic liver function (immediate) and the scar development in the biliary tree. The new occurrence of biliary strictures, and the recurrence of malignant and benign liver diseases, such as cholangiocarcinoma (CCA) and primary sclerosing cholangitis (PSC), are direct consequences linked to this inflammation. The accumulation of toxic metabolites, such as succinate, causes undirected electron flows, triggering the releases of reactive oxygen species (ROS) from a severely dysfunctional mitochondrial complex 1. This initiates the inflammatory IRI cascade, with subsequent ischemic biliary stricturing, and the upregulation of pro-tumorigenic signaling. Such inflammation is both local and systemic, promoting an immunocompromised status that can lead to the recurrence of underlying liver disease, both malignant and benign in nature. The traditional treatment for CCA was resection, when possible, followed by cytotoxic chemotherapy. Liver transplant oncology is increasingly recognized as a potentially curative approach for patients with intrahepatic (iCCA) and perihilar (pCCA) cholangiocarcinoma. The link between IRI and disease recurrence is increasingly recognized in transplant oncology for hepatocellular carcinoma. However, smaller numbers have prevented similar analyses for CCA. The mechanistic link may be even more critical in this disease, as IRI causes the most profound damage to the intrahepatic bile ducts. This article reviews the underlying mechanisms associated with biliary inflammation and biliary pathology after liver transplantation. One main focus is on the link between transplant-related IRI-associated inflammation and the recurrence of cholangiocarcinoma and benign liver diseases of the biliary tree. Risk factors and protective strategies are highlighted.

Tumor entities represent an increasing indication for liver transplantation (LT). This review addresses the most contentious indications of LT in transplant oncology.

Patient selection based on tumor biology in LT for colorectal cancer liver metastases (CRLM) demonstrated promising long-term outcomes and preserved quality of life despite high recurrence rates. In selected cases, LT for intrahepatic cholangiocarcinoma (iCCA) is feasible, with acceptable survival even in high-burden cases responsive to chemotherapy. LT following a strict neoadjuvant protocol for perihilar cholangiocarcinoma (pCCA) resulted in long-term outcomes consistently surpassing benchmark values, and potentially outperforming liver resection.

While preliminary results are promising, prospective trials are crucial to define applications in routine clinical practice. Molecular profiling and targeted therapies pave the way for personalized approaches, requiring evolving allocation systems for equitable LT access.

Conditional survival analysis can serve as a dynamic prognostic metric, which helps to estimate the real-time survival probability over time. The present study conducted a conditional recurrence-free survival (CRFS) analysis for locally advanced intrahepatic cholangiocarcinoma (ICC) after R0 hepatectomy from an inflammatory-nutritional perspective using the competing risk method.

We extracted the medical data of 164 locally advanced ICC patients after R0 resection from Sun Yat-sen University Cancer Center. The calculation formula of the CRFS rate is CRFS(y/x) = RFS(y + x)/RFS(x). Univariable and multivariable COX regression analysis and competing risk analysis were conducted to identify RFS indicators.

Considering death before recurrence as a competing risk factor, the conditional RFS rates every 6 months gradually increased over time. The 24-month RFS rate increased from 29.2 % to 49.9 %, 68.5 %, and 85.1 % given 6, 12, and 18-month already recurrence-free survival, respectively. Both in multivariate COX regression analysis and competing risk analysis, tumor diameter and number, lymph node metastasis, aggregate systemic inflammation index score (AISI), and albumin-bilirubin score (ALBI) all remained significant. For both AISI and ALBI variables, the CRFS rates in the low-value set were higher than those of the high-value set.

Conditional RFS rates of locally advanced ICC after R0 hepatectomy dynamically increased over time, which contributed to reducing survivors' psychological distress and facilitating personalized follow-up schedules. In addition, a person's inflammatory and nutritional status significantly impact the recurrence risk. Oncologists should consider the role of inflammation-nutritional status when making decisions for patients with locally advanced ICC.

Cholangiocarcinoma (CCA), or bile duct cancer, is the second most common liver malignancy, with an increasing incidence in Western countries. The lack of effective treatments associated with the absence of early symptoms highlights the need to search for new therapeutic targets for CCA. Sulfatides (STs), a type of sulfoglycosphingolipids, have been found in the biliary tract, with increased levels in CCA and other types of cancer. STs are involved in protein trafficking and cell adhesion as part of the lipid rafts of the plasma membrane. We aimed to study the role of STs in CCA by the genetic targeting of GAL3ST1, an enzyme involved in ST synthesis. We used the CRISPR-Cas9 system to generate GAL3ST1-deficient TFK1 cells. GAL3ST1 KO cells showed lower proliferation and clonogenic activity and reduced glycolytic activity compared to TFK1 cells. Polarized TFK1 GAL3ST1 KO cells displayed increased transepithelial resistance and reduced permeability compared to TFK1 wt cells. The loss of GAL3ST1 showed a negative effect on growth in 30 out of 34 biliary tract cancer cell lines from the DepMap database. GAL3ST1 deficiency partially restored epithelial identity and barrier function and reduced proliferative activity in CCA cells. Sulfatide synthesis may provide a novel therapeutic target for CCA.

Biliary tract cancers (BTCs) are rare and aggressive malignancies with an increasing incidence and poor prognosis. The standard systemic treatment for BTCs has evolved to include immune checkpoint inhibitors associated with gemcitabine-cisplatin as first-line therapies. However, survival rates remain low, highlighting the critical need for personalized treatment strategies based on molecular profiling. Currently, significant advancements have been made in the molecular characterization of BTCs, where genetic alterations, such as IDH1 mutations and FGFR2 fusions, provide targets for therapy. Molecular profiling is crucial early in the management process to identify potential candidates for clinical trials and guide treatment strategy. The integration of these molecular insights into clinical practice has allowed for the development of targeted therapies, although many of them are still in the phase 2 trial stage without definitive survival benefits demonstrated in phase 3 trials. This integration of comprehensive molecular profile insights with traditional treatment approaches offers a new horizon in the personalized medicine landscape for BTCs, with the aim of significantly improving patient outcomes through precision oncology.