The impact of the patient's condition, diagnostic procedures and treatment on the survival of carcinoma of unknown primary site patients.

INTRODUCTION: Carcinoma of unknown primary site (CUP) refers to 1-5% of all head and neck neoplasms. Very often, the primary site remains difficult to determine. Squamous cell carcinoma is the most frequent histopathological type diagnosed in the head and neck region. According to statistics, a primary site is usually located in the oropharynx. STUDY OBJECTIVE: The study presents diagnostic difficulties and the methods of diagnosing and the therapy of CUP and primary sites in patients treated in the region of Lower Silesia and Silesia. The aim of the study was to show a retrospective analysis of 233 CUP patients to assess how clinical features, diagnosis and treatment affect the survival of patients. MATERIAL AND METHODS: The diagnostics of patients included panendoscopy with specimen collection (nasoendoscopy, laryngoscopy, esophagoscopy, brochoscopy), computed tomography examination of the neck, chest, abdomen and pelvis minor, as well as positron emission tomography examination. Tonsilletomy was performed in 37 patients. Neck dissection was carried out in 109 subjects and 165 patients were treated bt radiotherapy, and 135 by chemotherapy. CONCLUSIONS: Tonsillectomy is required in CUP patients with the negative results of biopsy and imaging tests. It gives a possibility of detecting the primary site and improves the results of treatment and survival of CUP patients.Combination therapy, including surgical treatment and chemoradiotherapy, gives the best therapeutic results in CUP patients. The general condition of patient and younger age have an impact on prognosis and survival.

Dysregulated expression of both the costimulatory CD28 and inhibitory CTLA-4 molecules in PB T cells of advanced cervical cancer patients suggests systemic immunosuppression related to disease progression.

UNLABELLED: Cervical cancer (CC) occurs more frequently in women who are immunosuppressed, suggesting that both local and systemic immune abnormalities may be involved in the evolution of the disease. Costimulatory CD28 and inhibitory CTLA-4 molecules expressed in T cells play a key role in the balanced immune responses. There has been demonstrated a relation between CD28, CTLA-4, and IFN genes in susceptibility to CC, suggesting their importance in CC development. Therefore, we assessed the pattern of CD28 and CTLA-4 expression in T cells from PB of CC patients with advanced CC (stages III and IV according to FIGO) compared to controls. We also examined the ability of PBMCs to secrete IFN-gamma. We found lower frequencies of freshly isolated and ex vivo stimulated CD4 + CD28+ and CD8 + CD28+ T cells in CC patients than in controls. Loss of CD28 expression was more pronounced in the CD8+ T subset. Markedly increased proportions of CTLA-4+ T cells in CC patients before and after culture compared to controls were also observed. In addition, patients' T cells exhibited abnormal kinetics of surface CTLA-4 expression, with the peak at 24 h of stimulation, which was in contrast to corresponding normal T cells, revealing maximum CTLA-4 expression at 72 h of stimulation. Of note, markedly higher IFN-gamma concentrations were shown in supernatants of stimulated PBMCs from CC patients. CONCLUSIONS: Our report shows the dysregulated CD28 and CTLA-4 expression in PB T cells of CC patients, which may lead to impaired function of these lymphocytes and systemic immunosuppression related to disease progression.

Influence of CTLA-4/CD28/ICOS gene polymorphisms on the susceptibility to cervical squamous cell carcinoma and stage of differentiation in the Polish population.

Abnormal expressions of the costimulatory molecules CD28, "inducible co-stimulator" (ICOS), and inhibitory molecule cytotoxic T-lymphocyte antigen-4 (CTLA-4) lead to disturbances of immune response and entail an increased risk of cancer. This study was undertaken to evaluate the association between the polymorphisms CTLA-4c.49A>G, CTLA-4g.319C>T, CTLA-4g.*642AT(8_33), CTLA-4g.*6230G>A (CT60), CD28c.17+3T>C, and ICOSc.1554+4GT(8_15), and susceptibility to CSCC. The association between CTLA-4g.319C>T[T] allele and [TT+CT] genotype and susceptibility to CSCC was observed (OR = 1.99, p = 0.003, and OR = 2.07, p = 0.005, respectively). The CTLA-4g.319C>T[T] allele and [TT+CT] genotype increased the risk of well-differentiated CSCC by a factor of 3.84 and 4.44 (p = 0.00001, and p = 0.00001, respectively). In patients with moderately differentiated CSCC, a trend toward increased frequency of CTLA-4g.319C>T[T] allele and CTLA-4g.319C>T[TT+CT] genotype was noticed (OR = 1.68, p = 0.09, and OR = 1.75, p = 0.09, respectively), whereas in low differentiated CSCC such relation was not observed. Both CTLA-4g.*642AT(8_33) [(AT)(8)]/[(AT)(8)] homozygote and [(AT)(8)] allele were overrepresented in CSCC patients in comparison with healthy women (p = 0.004, OR = 1.93, and p = 0.03, OR = 1.41, respectively) but this polymorphism was not related to histologic grade of tumor. CD28c.17+3T>C polymorphism was not associated with susceptibility to CSCC in whole group of patients, but CD28c.17+3T>C[C] allele and CD28c.17+3T>C[CC+TC] genotype were more frequently observed among well differentiated CSCC patients compared with controls (OR = 1.89, p = 0.05, and OR = 2.05, p = 0.05, respectively). Other studied polymorphisms were not associated with susceptibility to CSCC and with histologic grade of CSCC. Our results suggest that the CTLA-4 gene is susceptibility gene to CSCC especially to well-differentiated tumor, while association between CD28 gene polymorphism and disease is restricted only to the well-differentiated CSCC.

[Assessment of hematopoiesis regeneration in patients with solid tumors after radiotherapy]. / Ocena regeneracji ukladu krwiotwórczego u chorych na nowotwory lite leczonych promieniowaniem jonizujacym.

The myelotoxicity is one of the most severe adverse events of radiotherapy. Increase of CD34+ cells level in peripheral blood as result of raised output of granulocyte colony stimulating factor (G-CSF) can be result of hematopoiesis regeneration after radiotherapy. The aim of this study was to determine the hematopoiesis regeneration using analysis of CD34+ cells level in peripheral blood and serum concentration of G-CSF in patients treated with radiotherapy according to irradiated body region and irradiation field size. Two groups of irradiated patients were examined. Group I consisted of 11 patients (mean age 56) with gynecological malignancies (teletherapy dose 40-50 Gy for pelvic area and brachytherapy with Cs). Group II consisted of 10 patients (mean age 58) with head and neck malignancies (teletherapy only 50-70 Gy). Every patient was evaluated 3 times: before radiotherapy, in the day of ending and 14 days after therapy. 3 ml of blood for CD34 and serum for G-CSF estimation were collected. Blood cells were stained with monoclonal antibody specific for CD34 antigen and analysed by flow cytometry. G-CSF level was estimated by ELISA. After radiotherapy in both groups statistically significant leukopenia (p < 0.001) was observed. There was no difference between two groups in levels of CD34+ cells before and in the last day of therapy but there was significant increase of CD34+ cells in group I compared with group II 14 days after treatment (p < 0.01). Decrease of CD34+ cells during radiotherapy and after its ending in all patients was observed but only in group II was statistically significant. Positive correlation between amount of leukocytes and CD34+ cells percentage was stated. There were no statistically significant differences in serum G-CSF concentration within particular groups and between group I and II. Our results indicate that evaluation of CD34+ cells level in peripheral blood is useful in prediction of hematopoiesis regeneration after radiotherapy. G-CSF serum concentration is not prognostic factor in these groups of patients.