Duška Petranović

Serum IL-6, IL-8, IL-10 and beta2-microglobulin in association with International Prognostic Index in diffuse large B cell lymphoma.

Aims and Background Diffuse large B-cell lymphoma displays striking heterogeneity at clinical, genetic and molecular levels. The International Prognostic Index is useful to predict the outcome of diffuse large B-cell lymphoma patients. However, patients with identical International Prognostic Index values in clinical practice exhibit marked variability in survival, suggesting the presence of significant residual heterogeneity within each category. Since cytokines such as interleukin-6, -8 and -10 play important roles in the pathogenesis of lymphomas, and plasma level of beta2-microglobulin is associated with the outcome of patients with diffuse large B-cell lymphoma, the aim of the present study was to determine whether these parameters combined with the International Prognostic Index would better stratify these patients to predict their prognosis. Patients and Methods The study included 46 untreated diffuse large B-cell lymphoma patients. Results All study parameters (International Prognostic Index, Ann Arbor stage, extra-nodal involvement, performance status, lactate dehydrogenase, beta2-microglobulin, interleukin-6 and -10, and response to therapy) except for patient age and serum interleukin-8 level were associated with overall survival. In addition, the International Prognostic Index was strongly correlated with beta2-microglobulin, interleukin-6, -8 and -10, and when combined these parameters significantly better stratified patients according to survival. On multivariate analysis, therapeutic response to the primary treatment, elevated interleukin-6 and -10 levels, and the International Prognostic Index were significant predictors of overall survival. Conclusions Our data imply that interleukins and beta2-microglobulin evaluation should be used in association with the International Prognostic Index to define prognostic subgroups in diffuse large B-cell lymphoma patients.

Pityriasis rubra pilaris in association with laryngeal carcinoma

Pityriasis rubra pilaris (PRP) is a rare group of hyperkeratotic, papulosquamous diseases that can be acquired or inherited. Cases of PRP associated with malignancy have been rarely reported. We report a case of 46‐year‐old man who presented with rapidly progressing PRP as a possible initial cutaneous symptom of a previously undiagnosed laryngeal carcinoma. Microlaryngoscopy was performed because of the patient’s hoarseness, and this revealed leucoplakia on the left vocal cord. Histopathological examination led to the diagnosis of squamous cell carcinoma in situ. After surgical treatment, the clinical signs of PRP began to resolve, and the patient was free of skin lesions at follow‐up. This case represents a rare coexistence of PRP with malignancy, and indicates that PRP can occur as paraneoplastic dermatosis associated with laryngeal cancer.

Prophylactic broad spectrum antibiotics as a new anti-myeloma therapy

Multiple myeloma is a common, yet incurable, haematological neoplasm. The reciprocal communication between malignant plasma cells, other cell types, and the extracellular matrix in the bone marrow micro-eco system is mediated by cell-cell and cell-matrix adhesion, as well as the production of different soluble factors, and is crucial for tumour growth and drug resistance. Inflammation and pro-inflammatory cytokines contribute to the clonal expansion of neoplastic plasmacytes. This extremely complex pathogenesis of multiple myeloma gives us the opportunity to promote numerous novel drugs and approaches based on the paradigm of targeted therapy. Immune dysfunction is a hallmark of multiple myeloma. Intrinsic and therapy-related immunosuppression leads to an increased risk of recurrent infection, the major cause of mortality. However, little data is available regarding the possible influence of infection on the biology and progression of multiple myeloma. Some authors have shown that pathogenic microorganisms can activate tool-like receptors on myeloma cells, as well as the robust production of pro-inflammatory cytokines; together these factors can contribute to myeloma growth, survival, and progression. Therefore, we proposed a simple, inexpensive, and new approach for anti-myeloma therapy that, to the best of our knowledge, is the first one concerning the prophylactic, long-term use of broad-spectrum antibiotics during the course of disease regardless of the chosen concomitant regimens. Prophylactic treatment with antibiotics should suppress the pro-inflammatory milieu produced during recurrent bacterial infections and prevent the activation of tool-like receptors on tumour cells, which are important factors responsible for tumour growth and survival in patients with multiple myeloma.

Perforin- and granulysin-mediated cytotoxicity and interleukin 15 play roles in neurocognitive impairment in patients with acute lymphoblastic leukaemia

Acute lymphoblastic leukaemia (ALL) is an aggressive disease. The course of disease is regulated by pro-inflammatory agents, and malignant cell infiltration of tissues plays a deleterious role in disease progression, greatly impacting quality of life, especially in the cognitive domains. Our hypothesis is that significant serum concentrations of interleukin 15 (IL-15) are responsible for higher expression of adhesion molecules on endothelial cells of blood-brain barrier (BBB) which allow leukaemia cells and/or normal lymphocytes the infiltration into the brain. In brain tissue these cells could be stimulated to release perforin and granulysin causing induction of apoptosis in brain cells that are involved in complex neural signalling mediated by neurotransmitters, and consequent fine cognitive impairment. Such changes could be detected early, even before notable clinical psycho-neurological or radiological changes in patients with ALL. To evaluate this hypothesis we propose measuring cognitive function using Complex Reactiometer Drenovac (CRD) scores in patients with ALL. The expression of different adhesion molecules on BBB as well as presence and distribution of different lymphocytes in brain tissue will be analyzed. We will then correlate CRD scores with levels of IL-15 and the percentages of T cells, natural killer T cells, and natural killer cells expressing perforin and/or granulysin proteins. CRD is a scientifically recognised and highly sensitive psychometric laboratory test based on the complex chronometric mathematical measuring of speed of reaction to various stimuli. It provides an objective assessment of cognitive functions from the most complex mental activities to the simplest reaction reflexes. Early recognition of cognitive dysfunction might be important when selecting the most appropriate chemotherapy and/or radiotherapy regimens, and could allow for the implementation of preventive measures against further deterioration in cognitive function and quality of life in patients with ALL.

Primary gastric mantle cell lymphoma

Mantle cell lymphoma represents 2.5–7% all of non Hodgkins lymphomas. Stomach is the most common site of extranodal lymphoma. However, that is not the case with mantle cell lymphoma, which is extremely rare. We present a case of 71-year-old woman admitted to the Internal Clinic of the University Clinical Hospital Center Rijeka, because of stomach discomfort and melena. Endoscopy and computed tomography revealed a polyp in gastric antrum. Histopathologic, immunohistochemic and genetic methods were also performed and the results were consistent with primary gastric mantle cell lymphoma without periepigastric and/or local or distant abdominal lymph node involvement.

Endogenous erythropoietin and erythropoietin receptors in colorectal cancer; can we answer the questions?

Erythropoietin (Epo) is glycoprotein hormone which binds on erythropoietin receptors (EpoR) promoting proliferation and differentiation. Studies have shown that EpoR, apart from erythrocyte precursors, is expressed on no hematopoietic tissue and various tumor cells. Despite the progress in modern medicine, colorectal carcinoma (CRC) is still the leading cause of increased morbidity and mortality between oncology patients worldwide. Its precursors are benign villous adenomas, which in certain percentage progress to cancer. Anemia of chronic disease is common finding in CRC patients. Some of them are treated with Epo. Epo/EpoR seems to correlate with tumor progression and metastasizing. Therefore, the identification of at-risk group remains a clinical challenge. Vascular endothelial growth factor (VEGF) is a signal protein that stimulates angiogenesis and concentration of VEGF is positive correlated with tumor growth in numerous tumors. The importance of Epo in tumor pathogenesis has led to a growing interest in the potential prognostic value. By our point of view there are many open questions about role of Epo/EpoR in CRC.