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Summary Background Chemotherapy with gemcitabine and cisplatin is the current standard for patients with unresectable cholangiocarcinoma. Local photodynamic therapy has also demonstrated benefit in patients with extrahepatic cholangiocarcinoma. Aim To evaluate the benefit of photodynamic therapy in combination with systemic chemotherapy in advanced extrahepatic cholangiocarcinoma. Methods Three hundred and fifty‐three patients diagnosed with cholangiocarcinoma between 2004 and 2016 were treated at the University Hospital of Bonn, Germany. Of these, 96 suffering from unresectable extrahepatic cholangiocarcinoma were included. Patients were stratified according to treatment: combination photodynamic therapy and chemotherapy (36 patients), photodynamic therapy alone (34 patients), and chemotherapy alone (26 patients). Results Combined photodynamic therapy with chemotherapy resulted in significantly longer overall survival than chemotherapy alone (P = 0.022). Median survival was 20 months in the combination group (95% CI: 16.38‐23.62), 15 months in the photodynamic alone group (95% CI: 10.02‐19.98) and 10 months in the chemotherapy alone group (95% CI: 8.45‐11.55). In multivariate analysis, combination therapy and photodynamic therapy alone (HR: 0.41, 95% CI: 0.22‐0.77, P = 0.006), metal stenting, and radiofrequency ablation were independent predictors of longer survival. Conclusions Combination photodynamic therapy and chemotherapy was well tolerated and resulted in significantly longer survival than chemotherapy alone. Application of photodynamic therapy significantly correlated with longer survival, demonstrating benefit in advanced cholangiocarcinoma. Thus, photodynamic therapy should be considered during therapeutic decision making in advanced cholangiocarcinoma.

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The liver is endowed with an amazing regenerative capacity that allows it to withstand an enormous amount of damage. Nevertheless, it is precisely this highly regenerative capacity that renders it susceptible to dysplasia and liver cancer. Liver cancer is not only one of the most common cancers but also one of the deadliest. Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for up to 70%-90% of all cases, but treatment options for advanced stages remain scarce. Therefore, a great deal of effort has gone into identifying early diagnostic markers as well as novel therapies, both local and systemic, for the treatment of this deadly disease. In this review, we aim to shed light into the current therapeutic landscape of HCC with an emphasis on the available treatments, ranging from surgical and local-ablative therapy for early and intermediate stages of the disease to systemic therapies for advanced cancer treatments. We will also address the molecular mechanisms and limitations of currently available systemic therapies and the causes of treatment resistance and finally summarize the emerging future avenues and novel concepts that are promising.

Therefore, aging of the liver in HIV may play a much more pivotal role in the future considering age-related effects, coinfection with hepatotropic viruses and the toxicity of long-term antiviral treatment. Thus, adequate monitoring of liver disease and development of management algorithms are clearly needed to optimize outcome and care of the aging liver in an HIV-infected individual.

Hepatocellular Carcinoma (HCC) is a highly prevalent malignancy that develops in patients with chronic liver diseases and dysregulated systemic and hepatic immunity. The tumor microenvironment (TME) contains tumor-associated macrophages (TAM), cancer-associated fibroblasts (CAF), regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) and is central to mediating immune evasion and resistance to therapy. The interplay between these cells types often leads to insufficient antigen presentation, preventing effective anti-tumor immune responses. In situ vaccines harness the tumor as the source of antigens and implement sequential immunomodulation to generate systemic and lasting antitumor immunity. Thus, in situ vaccines hold the promise to induce a switch from an immunosuppressive environment where HCC cells evade antigen presentation and suppress T cell responses towards an immunostimulatory environment enriched for activated cytotoxic cells. Pivotal steps of in situ vaccination include the induction of immunogenic cell death of tumor cells, a recruitment of antigen-presenting cells with a focus on dendritic cells, their loading and maturation and a subsequent cross-priming of CD8+ T cells to ensure cytotoxic activity against tumor cells. Several in situ vaccine approaches have been suggested, with vaccine regimens including oncolytic viruses, Flt3L, GM-CSF and TLR agonists. Moreover, combinations with checkpoint inhibitors have been suggested in HCC and other tumor entities. This review will give an overview of various in situ vaccine strategies for HCC, highlighting the potentials and pitfalls of in situ vaccines to treat liver cancer.

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