Hepatic Injury Induced by a Single Dose of Nivolumab - a Case Report and Literature Review.

BACKGROUND: The use of nivolumab in the treatment of metastatic melanoma has become well established during past years. Despite its undeniable efficacy, immune-related side effects may occur, including acute liver injury. Liver toxicity caused by nivolumab is usually observed as liver enzyme elevation with mild or no symptoms; further, there is limited information regarding any histopathological findings. CASE: We report a case of a 38-year-old woman with metastatic melanoma who developed unusual nivolumab-induced hepatic injury after a single dose of nivolumab. A liver biopsy was performed to assess the aetiology of hepatic lesions as no other analysis concerning biochemistry, virology, autoantibodies, nor imaging studies revealed any pathology. The histopathological analysis showed an oedema in the portal fields and mixed inflammation consisting of eosinophilic and neutrophilic granulocytes. The major finding was a prominent, predominantly intracellular, cholestasis. CONCLUSION: To our knowledge, no such histopathological pattern of liver injury has been described in relation to nivolumab therapy elsewhere. This type of liver injury shows higher resistance to corticosteroids, which may warrant upfront high-dose corticotherapy combined with other immunosuppressive agents, including mycophenolate mofetil. This case highlights a necessary awareness regarding immunotherapy-related adverse events, which could be severe and potentially life-threatening.

[Non-specific immunotherapy inhibits angiogenesis - results of the monitoring of serum levels of vascular endothelial growth factor and matrix metalloproteinase 8 in patients with malignant melanoma receiving adjuvant high-dose interferon therapy]. / Nespecifická imunoterapie inhibuje angiogenezi - výsledky monitorování sérových hladin vaskulárního endotelového rustového faktoru a matrixmetaloproteinázy 8 v prubehu adjuvantní lécby vysokodávkovaným interferonem u pacientu s maligním melanomem.

OBJECTIVE: Interestingly, evidence is currently emerging that the activation of angiogenesis leads to immunomodulatory/immunosuppressive effects both at the local and systemic levels. These are very complex and interconnected processes. In this study, our aim was to establish interferon alpha-2b as an anti-angiogenic agent and show the complexity of angiogenesis and immunomodulation through the serum levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 8 (MMP-8) in high-risk resected malignant melanoma before and after adjuvant therapy with high-dose interferon alpha-2b (HDI). Clinical outcomes of patients were also evaluated. MATERIAL AND METHODS: We prospectively measured the serum levels of VEGF and MMP-8 by ELISA in 29 patients with high-risk resected malignant melanoma receiving adjuvant HDI. Blood samples were collected before and within one week after the treatment. RESULTS: To see the results clearly, we divided our patients into two groups. The first group of patients whose VEGF serum level decreased after HDI (66%) showed long-term complete remission. The mean VEGF serum level in these patients decreased from 779.4 pg/ml to 446.2 pg/ml. This downward trend in VEGF was statistically significant. The second group of patients who did not show a decrease in VEGF serum level after HDI (34%) had no clinical benefit from the treatment. The mean VEGF serum levels in group 2 patients were 408 pg/ml before the treatment and 500 pg/ml after HDI. Results for MMP-8 were ambivalent. CONCLUSIONS: Non-specific immunotherapy with interferons reduces angiogenesis. Our results are in line with the current view of the interconnection and complexity of angiogenesis and immunomodulation/immunosuppression. Non-specific immunotherapy with interferons disrupts the immunosup-pressive effect of the angiogenesis on the development of immune response against tumours and supports anti-tumour response in both direct and indirect way. The interference of HDI with the activation of angiogenesis and tumour progression could explain good clinical outcomes of patients with a decrease in serum VEGF. The outcomes of MMP-8 are inconclusive, its role remain unclear, and MMP-8 does not seem to function as a tumour suppressor.

[Changes in immune reactivity in cancer patients]. / Zmeny imunologické reaktivity u onkologických pacientu

It appears that the long-accepted paradigm that cytostatic and radiation therapy cause only immunosuppression, is not so clearly true. With regard to new knowledge in cancer immunology field, it seems that not only cytostatic and radiation therapy plays an important role in the alteration of immune system. There are many other factors influencing immunity like tumour environment itself, the use of immunomodulatory drugs or even the mental condition of cancer patients. The aim of review is to familiarize physicians with possible alterations of the immune system in cancer patients.

[Palliative cancer care within the Hradec Králové Region Health Care System: own experience]. / Paliativní onkologická péce v systému poskytování zdravotní péce v Královéhradeckém kraji: vlastní zkusenosti.

Palliative cancer care is an active treatment and nursing intervention in patients in whom cancer therapy has been withdrawn due to untreatable progression of the cancer disease. The main aim of palliative cancer care is to ensure the best possible quality of life of a cancer patient and the patient's family members. Palliative cancer care is provided in two basic forms, general and specialized. In the present paper, the authors discuss palliative cancer care and its implementation into clinical practice with reference to their own experience in providing this care.

Malignant thymoma as etiology of bilateral, biventricular cardiac failure.

The authors report on a case of a 60-year-old female admitted to hospital with symptoms of bilateral cardiac failure. Upon ultrasonic examination of the heart, a massive pericardial exudate was diagnosed. Pericardial drainage was done to find the cause of pericardial effusion. Cells of malignant lymphoma were detected cytologically while immunophenotypization demonstrated a malignant lymphoma exudate. A computed tomography (CT) examination of the thorax disclosed a mediastinal tumour with infiltration of both lungs, vascular structures and dissemination on the chest wall. A CT-guided tumour biopsy was performed to confirm or exclude a lymphoproliferative process. Histopathologically, an invasive cortical thymoma was verified. The tumour was evaluated as stage III thymoma according to Masaoka. This case report highlights a rare malignant thymoma, its clinical symptoms, diagnosis, therapy and prognosis (Fig. 2, Ref. 10).

Tamoxifen/norfloxacin interaction leading to QT interval prolongation in a female patient with extracranial meningioma.

The authors report on a case of tamoxifen/norfloxacin interaction leading to QT interval prolongation in an 83-year-old female patient with extracranial meningioma treated with radiation and hormonal therapy (with Tamoxifen). This case report highlights the potential risk of tamoxifen causing depression of electrical impulse in sinoatrial node, leading to symptomatic sinus bradycardia with prolonged QT interval. At the same time it indicates the need to be on the look out for drug interactions (in our case between tamoxifen and norfloxacin), as well as to be aware of other drugs possibly inducing QT interval prolongation (Fig. 2, Ref. 7).

Sexual dysfunction in females treated with peripheral blood progenitor cell transplantation: review of literature.

BACKGROUND: Peripheral blood progenitor cell transplantation (PBPCT) is a therapeutic modality used in the anti-tumorous treatment of hemato-oncological diseases and solid tumors. Apart of that, it is also used in therapy of non-malignant and hereditary diseases. AIM: As is the case with other treatments, PBPCT also affects not only the disease process but also the quality of life (QoL). MATERIALS AND METHODS: In the last decade of 20th century, several QoL studies among patients treated with PBPCT were undertaken and an influence on particular dimensions of QoL was observed. One of closely watched aspects was sexuality in patients treated with PBPCT. RESULTS: Sexuality and its expression belong to very important aspects of human behavior. It is also a very sensitive and sensible aspect, so with no doubts it is affected by the diagnosis of neoplasm and cancer treatment. CONCLUSION: Physical and psychosocial factors of PBPCT do affect patient's sexuality and sexual functioning as part of QoL. They remain in focus because of the complex care of patients treated with PBPCT (Fig. 2, Ref. 21).

Screening for depression in survivors of metastatic ovarian cancer in a programme of palliative cancer care.

BACKGROUND: Depression is seen in many cancer patients. It occurs in approximately 25% of palliative care patients. MATERIALS AND METHODS: This study was local, prospective and cross-sectional. It was carried at Department of Clinical Oncology and Radiation Therapy of Charles University Hospital and Faculty of Medicine in Hradec Králové, Czech Republic. RESULTS: The incidence of depression was 83.3% (25 of all 30 survivors). The relevance of depression is characterized: severely depressed was proved in 9 of all 30 survivors, the moderately depressed in 5 of all 30 survivors, the mildly depressed in 11 of all 30 survivors and normal range in 5 of all 30 survivors. The statistical evaluation not presents statistically significant dependence of ZSRDS on smoking abuse, marital status, age, number of associated diseases and type of palliative cancer care. CONCLUSION: The results of the pilot depression study showed that subsist clear association between metastatic ovarian cancer and depression (Fig. 2, Ref. 30). Full Text (Free, PDF) www.bmj.sk.

Depression symptoms and health-related quality of life among patients with metastatic breast cancer in programme of palliative cancer care.

Depression is seen in many cancer patients. It occurs in approximately 25% of palliative care patients. The quality of life term contains the information on an individual's physical social and spiritual condition. The study evaluated incidence and relevance of depression symptoms and level of health-related quality of life (HRQoL) among patients with metastatic breast cancer in programme of palliative cancer care. This study was local prospective and cross-sectional. It was carried at Department of Clinical Oncology and Radiation Therapy of Charles University Hospital in Hrader Králové, Czech Republic. Dates were obtained during year 2008 among 41 patients with metastatic breast cancer in programme of palliative cancer care. The mean age for all 41 subjects was 58 years old (aged 41 - 80 years old). The Czech version of Zung self-rating depression scale was performed for evaluation of depression symptoms. The Czech version of genetic EuroQol questionnaire EQ-5D was performed for evaluation of level of HRQoL. The statistical evaluation presents that mean ZSDS (Zung self-rating depression score) certifies the presence of signs of moderately depression symptoms among patients with metastatic breast cancer (ZSDS range was 60-69). The mean ZSDS in all patients was 60,6. The mean ZSDS is group of healthy females was 38,9 (normal range of ZSDS). The incidence of depression was 61% (25 of all 41 subjects). The relevance of depression is characterized: severely depressed was proved in 5 of all 25 subjects, the moderately depressed in 10 subjects of all 25 subjects and mildly depressed in 10 of all 25 subjects. The statistical evaluation not presents statistically significant dependence of ZSDS on age, number of associated diseases and type of palliative cancer care. The HRQoL among patients with metastatic breast cancer is on very low level. The mean EQ-5D score (dimension of quality of life) was 55%. The mean EQ-5D VAS (subjective health condition) was 59,2%. The mean EQ-5D score in group of healthy female was 78,4% and the mean EQ-5D VAS was 85% (both QoL parameters show very good of QoL level). The statistical evaluation not presents statistically significant dependence of EQ-5D score and EQ-5D VAS on age, number of associated diseases and type of palliative cancer care. The results showed that subsist clear association between metastatic breast cancer in programme of palliative cancer care and depression. Also, the results showed that subsist low level of HRQoL of patients with metastatic breast cancer.

[Tumor stem cells and "niche"--a limiting factors of the carcinogenesis]. / Nádorové kmenové bunky a "niche"--jako limitující faktor karcinogeneze.

Presently, the view of tumor development is increasingly linked up with disorders of stem cells, no matter whether they are normal tissue stem cells or early progenitor cells. There is much evidence now that microenvironment regulates tissue specificity, reparation process as well as process of carcinogenesis. The aim of this paper is to enlarge the basic knowledge of carcinogenesis and show the role of stem cells and tumor stem cells as potential primary source of tumor development. We support the view that tumor may be considered an abnormal "organ" where the growth of tumor cells is controlled by a rare subpopulation of tumor stem cells giving rise to both greater number of tumor cells and non-tumorigenic tumor cells. This all is complementary and in connection with microenvironment we can speak about limiting factors of carcinogenesis. This insight into the tumor biology shows the shortcomings of recent tumor therapy. Therefore, most likely for effectual tumor therapy, attention should be given to both tumor stem cells and microenvironment. Consequently, this complementary relationship should be considered a limiting factor for understanding of carcinogenesis and also for further therapeutic strategy--homing therapy (tailored therapy) with the use of stem cells.

Cancer and depression: a prospective study.

Cancer diagnosis and treatment often produce psychologic stresses resulting from the actual symptoms of the disease, as well as from perceptions of the disease and its stigma. Depression is seen in many cancer patients. Depression occurs in approximately 25% of palliative care patients. It is widely recognised by clinicians that depression is a difficult symptom to identify amongst patients with advanced illness. The study is aimed for screening of depression among palliative care female patients. This study was local, prospective and cross-sectional. It was carried at Department of Clinical Oncology and Radiation Therapy of Charles University Hospital in Hradec Kralove, Czech Republic. Dates were obtained during year 2007 - 2008 in 64 palliative care female patients. The mean age for all 64 subjects was 60,5 years old (aged 29 - 88 years old). The Czech version of Zung self-rating depression scale was performed. The statistical evaluation presents that mean SDS (self-rating depression score) certifies the presence of signs of mildly depression among palliative care female patients (SDS range was 50-59). The mean SDS in all subjects was 56. The mean SDS in group of healthy females was 38,9 (normal range). The incidence of depression is 71,8% (46 of all 64 subjects). The relevance of depression is characterized: severely depressed was proved in 8 of all 46 subjects, the moderately depressed in 21 subjects of all 46 subjects and mildly depressed in 17 of all 46 subjects. The statistical evaluation not presents statistically significant dependence of SDS on smoking abuse, marital status, age, number of associated diseases and type of palliative care. The statistical evaluation presents that patients with cancer of lung, with cancer of endometrium, with cancer of gallbladder and with melanomas are moderately depressed (SDS 60-69), patients with cancer of ovary, with cancer of breast, with primary brain tumour, with cancer of ventricle, with cancer of pancreas head and with cancer of bucall cavity are mildly depressed (SDS 50-59). The results show that subsists clear association between oncological disease in palliative care and depression.