Fatal myocarditis after the first dose of nivolumab.

BACKGROUND: Thymic carcinoma (TC) is a rare subtype of thymic epithelial malignancy. Surgical resection is a mainstay in the treatment of TC, while radiotherapy and chemotherapy are modalities used in adjuvant or palliative setting. Immune checkpoint inhibitors (ICI) including anti-PD-1 (programmed cell death 1) antibodies represent an emerging treatment modality in TC; however, their administration could be associated with life-threatening toxicity. CASE: We present a case of a 59-year-old female with grade III TC, who had received neoadjuvant chemotherapy followed by surgery and subsequent adjuvant radio-immunotherapy with an ICI, nivolumab. We provide our experience with the toxicity of an administered treatment. RESULTS: Fourteen days after the first dose of nivolumab and on 21st day after starting of radiotherapy (total dose of 40 Gy), the patient developed fulminant myocarditis with subsequent heart failure. Despite immunosuppressive therapy with high-dose glucocorticoids and mycophenolate mofetil and intensive support, the patient died within 6 days after the onset of first symptoms. CONCLUSION: Physicians should be aware of these extremely rare, but potentially fatal complications of immunotherapy.

The Chest Wall Tumor as a Rare Clinical Presentation of Hepatocellular Carcinoma Metastasis.

BACKGROUND: Extrahepatic metastatic spread of hepatocellular carcinoma is present at the time of diagnosis in 5-15% of hepatocellular carcinoma patients. The most common site of metastastic spread is the lungs, bones, lymph nodes. Isolated chest wall localization is extremely rare. CASE: We report a 58-year-old patient with large, synchronous chest wall hepatocellular carcinoma metastasis with solitary primary hepatocellular carcinoma. He underwent a radical, surgical en bloc metastasectomy and subsequent anatomic liver resection. Removal of this metastasis further led to aggressive dissemination to different sites during the course of the disease and subsequently the patient was treated with antiangiogenic therapy and, after failure, with systemic chemotherapy. Combined multimodality treatment in this case led to overall survival of 22-months. We suggest that the initial huge presentation of chest wall metastasis and consecutive aggressive dissemination after surgical removal could be explained by the biological process called "tumor self-seeding" by circulating tumor cells. CONCLUSION: The chest wall hepatocellular carcinoma metastasis is a rare entity associated with poor prognosis. Radical surgical approach is limited to a minority of patients and may be justified for the treatment of extrahepatic metastases on a case by case basis.Key words: hepatocellular carcinoma - chest wall metastasis - metastasectomy - ciculating tumor cells.

[Agressive fibromatosis: genetic and biological correlations]. / Agresívna fibromatóza: geneticko-biologické korelácie.

Aggressive fibromatosis, also known as desmoid tumor, is specific and relatively rarely occuring disease. It belongs to heterogenous group of soft tissue tumors. Originally, it arises from fibroblasts with monoclonal proliferation derived from fibro-aponeurotic tissue with typical local invasive spreading without metastatic tendency. Increased amount of knowledge about the role of the APC gene and its protein product in FAP play an important role in revealing the molecular nature of desmoid tumors. In general, we can conclude that the ß-catenin dysregulation is the key player of the FAP associated desmoid tumor onset. The Wingless/Wnt cascade plays a crucial role in the pathogenesis of aggressive fibromatosis. However, it has not been definitely proven that the mutations of APC or ß-catenin genes are the trigger mechanisms. The research outcome can pave the way for using target biological therapy in routine practice in patients with aggressive fibromatosis in the future.

[Aggressive fibromatosis: clinical aspects]. / Agresívna fibromatóza: klinické aspekty.

The clinical picture of desmoids is unpredictable, which is a feature of different tumor specific associations. Anatomic location, age, sex, association with FAP as well as other factors determine biological behavior of the tumor. Negative prognosis is linked with the intraabdominal area and as many as 80% of desmoids are associated with FAP. Currently, biological targeting therapy is used in the treatment of many cancer diseases. It is only the question of time when and by which of these therapies we will be able to treat the patients with aggressive fibromatosis as well. A disadvantage is heterogenity and rare occurrence of desmoids. The efficacy of tailoring treatment still depends on knowledge and study of particular disease biological markers, which is currently the most important issue. .