Filip Kohutek

Systemic oncological treatment may cause drug‑induced liver injury (DILI). Therefore, there is a pressing need for an active drug able to accelerate liver regeneration. Silymarin mitigates oxidative stress, and inhibits pro‑inflammatory and pro‑apoptotic cytokines and the fibrotic transformation of liver tissue. Currently, there are a lack of data regarding the optimal dosage of silymarin and its efficacy. Thus, the present retrospective study aimed to determine the optimal dose of silymarin for use in oncological DILI treatment. For this purpose, 180 patients with solid malignancies treated with systemic oncological therapy and silymarin between January, 2015 and November, 2021 were enrolled in the study. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (Bil) levels, as well as the dose of silymarin were assessed at the initiation of silymarin treatment, after 3‑6 weeks and after 6‑12 weeks. Pearson's correlation analysis was performed to evaluate the correlation between the initial dose of silymarin (IDoS), and the ALT, AST and Bil levels. The effects of four independent variables, namely IDoS, the initial dose reduction of systemic treatment, the systemic treatment dose reduction at first assessment (DR1M) and the elevation of the silymarin dose at first control on the ALT, AST and Bil levels were evaluated using regression analysis. The median IDoS was 450 mg. A decrease in or the stabilization of the ALT, AST and Bil levels after 6‑12 weeks were observed in 68.63, 65.85 and 53.25% of patients, respectively. There was a weak correlation between IDoS and the decrease in ALT and AST levels after 6‑12 weeks (correlation coefficient, R=0.361 and 0.277 respectively, P<0.001). No significant correlation between the IDoS and a decrease in Bil levels was observed. DR1M was a negative predictor for a decrease in Bil levels in patients with liver tumors. On the whole, the present study demonstrates that silymarin appears to be efficient in alleviating DILI at a dose of 300‑450 mg. A further increase in the dose of silymarin may not lead to an adequate increase in its efficacy.

Merkel cell carcinoma (MCC) is a rare skin neuroendocrine tumor presumably arising from Merkel cells in the basal layer of epidermis. It is an aggressive tumor predominantly found on the head and neck area of elderly people, with a mortality rate around 41% for all stages. Complete spontaneous regression of MCC is seldom observed, mostly in elderly women. We describe complete spontaneous regression of large, histologically confirmed MCC in an elderly woman after biopsy, which occurred incidentally, while waiting for radical surgery with skin flap. Next-generation sequencing with SOPHiA Solid Tumor Plus Solution did not reveal any relevant gene mutations or rearrangements. An update of literature for these very rare cases is provided.

Hypotension can be a symptom of paraneoplastic autonomic neuropathy (PAN). Onconeural antibodies (OA) provide strong evidence for the paraneoplastic origin of neurological syndromes. Our goal was to assess the frequency of PAN among patients with advanced malignancies and hypotension using OA. Patients with advanced malignancies and hypotension were screened and enrolled as per protocol. Plasma levels of six classical OAs were assessed in these patients. We prospectively evaluated other symptoms of PAN in these patients. 31 patients out of 740 screened met the criteria of this cross-sectional study. OAs were present in 4 patients (12.9%). Anti-amphiphysin was found in 1 patient (3.23%), anti- CV2 (anti-CRPM5, anti- collapsin- response mediator protein) was present in 1 patient (3.23%), 1 patient (3.23%) was positive for anti-Hu and anti-Ma2 was present in 1 patient (3.23%). No patient was positive for 2 or more OAs. Normalization of blood pressure in concordance with partial remission occurred in 5 patients. The most used criteria for PAN were fulfilled in 9 patients. The frequency of PAN may be underestimated in a busy oncology clinic. Assessing OAs may aid in the differential diagnosis of hypotension of unknown origin.

Primary angiosarcoma of the spleen is a rare diagnosis with poor prognosis. Morphologically, it demonstrates conventional blood vessel differentiation. We present a case of 65-year-old female who underwent radical splenectomy for primary angiosarcoma of the spleen. After three-year disease-free interval, she was diagnosed with bone-only metastatic disease. Palliative radiotherapy and bisphosphonates kept her disease reasonably stable for another four years. After development of lung metastases, six cycles of single agent doxorubicin kept her progression-free for six years. Upon further progression in lungs, thirteen years after original diagnosis, lung biopsy confirmed metastatic splenic angiosarcoma in the lungs. She started weekly paclitaxel chemotherapy. Although splenic angiosarcoma generally carries grave prognosis, some patients may enjoy prolonged periods of disease stabilization. Durable benefit can be achieved in some patients with multimodality management. We review the literature focusing on systemic treatment for this rare tumor.