Risks and benefits of TIPS in HCC and other liver malignancies: a literature review.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a well-validated treatment option for clinically significant portal hypertension (CSPH) in the context of liver cirrhosis. Its high efficacy and safety in the management of treatment-refractory ascites and variceal bleeding have been extensively proven. Contraindications for TIPS include severe right heart failure, hepatic encephalopathy, and sepsis. However, the role of liver malignancy in TIPS is debatable. Mostly, primary liver malignancies such as hepatocellular carcinoma (HCC) emerge from advanced liver diseases. Coexisting portal hypertension in HCC often results in limited treatment options and a poor prognosis. Previous studies have shown that TIPS implantation in patients with HCC is technically feasible and is usually not associated with major adverse events. Furthermore, TIPS may help in bridging the time to liver transplantation in early HCC and allow for locoregional treatment in advanced HCC. However, several studies suggest that seeding tumour cells to the lungs by TIPS placement might worsen the prognosis. CONCLUSIONS: TIPS placement in patients with coexisting liver malignancy remains a case-by-case decision, and there is no profound evidence allowing general recommendations. This review aims to provide a state-of-the-art overview of the potential risks and benefits of TIPS placement in patients with liver malignancies.

Pembrolizumab-induced acute exacerbation of hepatitis D.

A 55-year-old man was treated with combined immunochemotherapy (pembrolizumab, carboplatin and pemetrexed) because of non-small cell lung cancer (NSCLC). In addition, the patient had a medical history of chronic hepatitis B/D virus infection and cystic echinococosis. The viral hepatitis co-infection was treated with pegylated interferon (IFN)-alpha and tenofovir in the past (non-response after treatment), followed by maintenance therapy with tenofovir. Since the echinococosis was inactive, there was no need for specific treatment. The therapy for NSCLC had to be stopped after three weeks due to rising liver enzymes. HDV-RNA could be detected as high as 107 GE/mL in the serum, HBV-DNA was not detected. A liver biopsy was performed. Histological analysis showed a chronic and partly active hepatitis, but its aetiology remained unclear. Because of the stable viral load after the first administration of pembrolizumab, an autoimmune-induced liver injury was suspected. Thus, a prednisolone-treatment was initiated. Yet, the liver enzyme levels did not decline, so bulevirtide (2 mg/d s.c.) was added to the ongoing antiviral treatment with tenofovir. This new treatment combination led to a restitution of the elevated enzymes; HDV-RNA was below detection limit. Finally, the therapy for NSCLC could be continued. The antiviral therapy could improve the patient´s prognosis significantly. To our knowledge, this is the first reported case of a pembrolizumab-induced exacerbation of hepatitis D and a successful management by application of bulevirtide in the context of cancer.

Delineation of Subregions in the Early Postnatal Human Cerebellum for Design-Based Stereologic Studies.

Recent design-based stereologic studies have shown that the early postnatal (<1 year of age) human cerebellum is characterized by very high plasticity and may thus be very sensitive to external and internal influences during the first year of life. A potential weakness of these studies is that they were not separately performed on functionally relevant subregions of the cerebellum, as was the case in a few design-based stereologic studies on the adult human cerebellum. The aim of the present study was to assess whether it is possible to identify unequivocally the primary, superior posterior, horizontal, ansoparamedian, and posterolateral fissures in the early postnatal human cerebellum, based on which functionally relevant subregions could be delineated. This was tested in 20 human post mortem cerebellar halves from subjects aged between 1 day and 11 months by means of a combined macroscopic and microscopic approach. We found that the superior posterior, horizontal, and posterolateral fissures can be reliably identified on all of the specimens. However, reliable and reproducible identification of the primary and ansoparamedian fissures was not possible. Accordingly, it appears feasible to perform subregion-specific investigations in the early postnatal human cerebellum when the identification of subregions is restricted to crus I (bordered by the superior posterior and horizontal fissures) and the flocculus (bordered by the posterolateral fissure). As such, it is recommended to define the entire cerebellar cortex as the region of interest in design-based stereologic studies on the early postnatal human cerebellum to guarantee reproducibility of results.