Glottic and supraglottic pT3 squamous cell carcinoma: outcomes with transoral laser microsurgery.

Patients diagnosed with T3 squamous cell laryngeal carcinomas are nowadays offered either organ-preserving surgical or non-surgical treatment, with the optimum approach remaining undefined. No direct comparison of organ-preserving therapeutical options, stratified by anatomical subsites is available in the literature. The aim of this study is to present institutional treatment outcomes for laser-assisted microsurgery (TLM) of laryngeal T3 squamous cell carcinomas and review the relevant literature. Sixty-four consecutive, previously untreated patients were evaluated. Twenty-four supraglottic and 19 glottic patients were treated with TLM and neck dissection, tumor exposure and postoperative upstaging of the tumors through pathology evaluation of the specimens being the only exclusion criteria. Five-year disease-specific survival and organ preservation rates for supraglottic carcinomas were both 91.7 %. The respective values for glottic carcinomas were 63.2 and 73.3 %. TLM-treated T3 supraglottic tumors seem to attribute better outcomes than T3 glottic tumors in terms of recurrence-free survival, organ preservation and local control (p = 0.01, <0.0001 and 0.01, respectively). The results of this study suggest that TLM-treated T3 supraglottic tumors have a good prognosis, substantially better than that of glottic tumors. A literature review, on the other hand, attributes to chemo-radiation-treated T3 supraglottic tumors a considerably poorer prognosis. Further studies of homogenous populations in terms of anatomical subsites are needed in order to reach a consensus regarding treatment of T3 laryngeal tumors.

Serum Levels of Vascular Endothelial Growth Factor and Insulin-like Growth Factor Binding Protein-3 in Obstructive Sleep Apnea Patients: Effect of Continuous Positive Airway Pressure Treatment.

BACKGROUND AND AIM: Hypoxia, a major feature of obstructive sleep apnea (OSA), modifies Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) levels, which contribute to atherogenesis and occurrence of cardiovascular (CV) events. We assessed and compared serum levels of VEGF and IGFBP-3 in newly diagnosed OSA patients and controls, to explore associations with anthropometric and sleep parameters and to study the effect of continuous positive airway pressure (CPAP) treatment on these levels. MATERIALS AND METHODS: Serum levels of VEGF and IGFBP-3 were measured in 65 OSA patients and 31 age- and body mass index- matched controls. In OSA patients, measurements were repeated after 6 months of CPAP therapy. All participants were non-smokers, without any comorbidities or systemic medication use. RESULTS: At baseline, serum VEGF levels in OSA patients were higher compared with controls (p<0.001), while IGFBP-3 levels were lower (1.41±0.56 vs. 1.61±0.38 µg/ml, p=0.039). VEGF levels correlated with apnea-hypopnea index (r=0.336, p=0.001) and oxygen desaturation index (r=0.282, p=0.007). After 6 months on CPAP treatment, VEGF levels decreased in OSA patients (p<0.001), while IGFBP-3 levels increased (p<0.001). CONCLUSION: In newly diagnosed OSA patients, serum levels of VEGF are elevated, while IGFBP-3 levels are low. After 6 months of CPAP treatment these levels change. These results may reflect an increased CV risk in untreated OSA patients, which is ameliorated after CPAP therapy.

Immunomodifiers in combination with conventional chemotherapy in small cell lung cancer: a phase II, randomized study.

PURPOSE: To evaluate the effect of immunotherapy on response, survival, and certain immune markers in patients with small cell lung cancer (SCLC) who are receiving chemotherapy. PATIENTS AND METHODS: Patients with SCLC (n = 164) were assigned to receive either chemotherapy alone (group A) or a combination of chemotherapy and immunotherapy as follows: interferon α (IFN-α; 3 million IU) 3 times per week (group B); IFN-γ (3 million IU) 3 times per week (group C); and IFN-α and IFN-γ (1.5 million IU of each) 3 times per week (group D). Chemotherapy was the same for all groups and consisted of eight cycles with carboplatin 5.5 mg/m(2) intravenously on day 1, ifosfamide 3.5 mg/m(2) intravenously on day 1, and etoposide 200 mg/m(2) total dose taken orally on days 1 through 3, every 28 days. Patients completing chemotherapy were restaged, and those who were found to have limited disease received primary site and prophylactic cranial irradiation. Immunotherapy was continued throughout these treatments and during the follow-up period. Blood was taken before each course of chemotherapy and during follow-up to measure CD3+ lymphocytes, CD3+CD4+ lymphocytes, CD3+CD8+ lymphocytes, natural killer cells, and natural killer T cells. RESULTS: Differences in response and survival were not significantly different when all patients were considered. However, among patients with limited disease, Kaplan-Meier analysis disclosed a survival benefit for group B (P , 0.05). The analysis of immunologic measurements revealed that the improvement of immune markers was always accompanied by clinical improvement, whereas deterioration of all markers was accompanied by disease progression (result not statistically significant except for group C; P , 0.05). CONCLUSION: Among cytokines used in the study, only IFN-α seems to confer a survival benefit to patients with SCLC with limited disease. However, immunotherapy remains a challenge in the treatment of lung neoplasms and should be further explored.

Potential prognostic value of intracellular cytokine detection by flow cytometry in pulmonary sarcoidosis.

In pulmonary sarcoidosis, differential cytokine production in the lungs could be related to variable prognosis of patients at different stages of disease. Twenty patients with pulmonary sarcoidosis (10 at radiographic stage I and 10 at stages II-IV), as well as 10 age-matched healthy volunteers participated in the study. A 4-colour flow cytometric technique was used to measure interferon-γ (IFN-γ), interleukin (IL)-2, tumour necrosis factor-α (TNF-α), IL-4, and IL-13 production in phorbol myristate acetate (PMA)/ionomycin-stimulated CD4+ and CD8+ T cells from bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) of patients, and PB of control subjects. CD4+ T cells from patients showed higher expression of IFN-γ in BALF than in PB. Significant correlations were observed between the percentages of BALF CD4+ and CD8+ T cells expressing intracellular IFN-γ, IL-2, and TNF-α. Stage I patients had lower percentages of IFN-γ-producing CD4+ and CD8+ T cells, as well as TNF-α-producing CD8+ T cells, in BALF (but not in PB) than stage II-IV patients. A decreased TH1 and TC1 response was demonstrated in BALF of patients at stage I of disease, which could explain their anticipated better prognosis.

Inflammatory markers in middle-aged obese subjects: does obstructive sleep apnea syndrome play a role?

BACKGROUND: Obstructive Sleep Apnea Syndrome (OSAS) is associated with inflammation, but obesity may be a confounding factor. Thus, the aim of this study was to explore differences in serum levels of inflammation markers between obese individuals with or without OSAS. METHODS: Healthy individuals (n = 61) from an outpatient obesity clinic were examined by polysomnography and blood analysis, for measurement of TNF-alpha, IL-6, CRP, and fibrinogen levels. According to Apnea-Hypopnea Index (AHI), participants were divided into two BMI-matched groups: controls (AHI < 15/h, n = 23) and OSAS patients (AHI > or = 15/h, n = 38). RESULTS: OSAS patients had significantly higher TNF-alpha levels (P < .001) while no other difference in the examined inflammation markers was recorded between groups. Overall, TNF-alpha levels were correlated with neck circumference (P < .001), AHI (P = .002), and Oxygen Desaturation Index (P = .002). CONCLUSIONS: Obese OSAS patients have elevated TNF-alpha levels compared to BMI-matched controls, suggesting a role of OSAS in promoting inflammation, possibly mediated by TNF-a.

Reduction of serum retinol-binding protein-4 levels in nondiabetic obstructive sleep apnea patients under continuous positive airway pressure treatment.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with impaired glucose metabolism and insulin resistance. Retinol-binding protein-4 (RBP-4) is an adipokine, hypothesized to induce insulin resistance. OBJECTIVES: The aim of the study was to explore the association between serum RBP-4 levels and OSAS severity in nondiabetic, adherent to therapy OSAS patients and to investigate the role of continuous positive airway pressure (CPAP) in the alteration of RBP-4 levels. METHODS: OSAS patients (n = 62) without comorbidities or medication use were included. Fasting RBP-4, glucose and insulin levels, HbA(1c), homeostatic model assessment of insulin resistance index and lipid profile were measured at baseline and after 6 months of CPAP use. Patients were divided into group A (with fasting glucose levels <110 mg/dl, n = 47), and group B (with impaired fasting glucose (IFG), i.e. fasting glucose levels ≥110 mg/dl, n = 15). RESULTS: RBP-4 levels were not associated with apnea-related indices, anthropometric characteristics or markers of glycemic control, insulin resistance or lipid profile. In group A (but not in group B), a significant reduction was observed in RBP-4 (p = 0.046), HbA(1c) (p = 0.005), LDL cholesterol (p = 0.034), and high-sensitivity C-reactive protein (hs-CRP, p = 0.033) levels after 6 months of CPAP use. CONCLUSIONS: RBP-4 levels were not correlated with sleep, anthropometric characteristics, markers of glycemic control and insulin sensitivity. OSAS patients without IFG respond well to CPAP use as evidenced by the significant reduction in RBP-4, HbA(1c) and, additionally, hs-CRP and LDL- cholesterol levels. This treatment effect is not observed in patients with IFG.

Long-term effect of continuous positive airway pressure therapy on inflammation markers of patients with obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Several lines of evidence suggest immune system derangement in obstructive sleep apnea syndrome (OSAS) patients. However, no data exist on the long-term effect of continuous positive airway pressure (CPAP) treatment on systemic immunity. Hence, we sought to evaluate this effect on various immunological parameters in OSAS patients. DESIGN: Prospective case series. SETTING: Sleep unit of a general hospital. PATIENTS: Newly-diagnosed, nonsmoking, otherwise healthy OSAS male patients (n = 52) were evaluated on diagnosis and 6 months after CPAP treatment. According to compliance to CPAP use at 6-month follow-up, they were divided into 2 groups: group A (n = 32): good compliance (mean CPAP use > or = 4 h/night); and group B (n = 20): poor compliance (mean CPAP use < 4 h/night). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Blood samples were obtained at baseline and at the 6-month follow-up. Percentage and absolute count of lymphocyte subsets (by flow cytometry), serum TNF-alpha, IL-6, and uric acid levels were measured. No differences were recorded regarding the baseline anthropometric or sleep characteristics of the 2 groups. In group A, a significant decrease in the absolute count of total lymphocytes (P = 0.003), and of CD4+ cells (P = 0.001), and a decrease in TNF-alpha levels (P = 0.001) and uric acid levels (P < 0.001) was observed after CPAP application. On the contrary, no alterations occurred in any of the tested parameters in group B patients. CONCLUSIONS: The selective reduction of soluble and cellular immune response factors only in those OSAS patients who exhibited good compliance to CPAP therapy provides further evidence for an ongoing systemic immune process in OSAS.

Effect of iron loading on peripheral blood lymphocyte subsets and on circulating cytokine levels in iron-depleted hemodialysis patients receiving erythropoietin.

BACKGROUND/AIMS: High doses of iron are recommended intravenously in iron-depleted hemodialysis (HD) patients receiving recombinant erythropoietin (EPO). Iron deficiency and mainly iron overload impair cellular and humoral immune response mechanisms. Imbalances in T cell subsets are common findings in disorders of iron metabolism. The aim of this study was to evaluate the effect of iron load on peripheral blood lymphocytes subsets and on circulating cytokine levels in HD iron depleted patients, treated with EPO. METHODS: We studied 19 stable adult HD patients, 12 males, with a mean age 59 +/- 11 years and mean HD duration 24 +/- 14 months. All patients were iron deficient and were treated with unchanged EPO dose for the last 4 months before entering the study. The administered dose of iron was infused intravenously (1,000 mg iron sucrose) in 10 doses, during 10 consecutive HD sessions. Patients were screened before the commencement of the HD session on two occasions, once prior to the first dose of iron and 2 days after the 10th dose. Hematocrit (Ht), hemoglobin (Hb), iron, serum ferritin, transferrin saturation, interleukin (IL)-2, IL-4, IL-10, interferon-gamma and tumor necrosis factor-alpha were measured. Major lymphocyte subsets (CD3+, CD19+, CD4+, CD8+, CD16+/56+, CD3+CD16+CD56+) and the ratio CD4+/CD8+ were also determined by two-color immunofluorescent analysis using flow cytometry. RESULTS: Hb, transferrin saturation and ferritin increased significantly at the end of the study 11.2 +/- 0.9 to 11.6 +/- 0.8 g/dl, p < 0.005, 17.5 +/- 6.9 to 23.0 +/- 10.8 %, p < 0.05, and 70 +/- 43 to 349 +/- 194 microg/l, p < 0.005, respectively. IL-2 also increased significantly 27.8 +/- 15.2 to 38.9 +/- 12.8 pg/ml, p < 0.05. After iron load there was no significant change to the major lymphocyte subsets examined but a significant increase of the percentage and number of T lymphocytes with positive natural killer receptors (NKR+ T) cells was observed, 5.1 +/- 3.7% to 6.3 +/- 3.46%, p < 0.05, and 76.4 +/- 40 to 101.5 +/- 48 cells/microl, p < 0.005, respectively. CONCLUSION: Iron load in iron-deficient EPO-treated HD patients did not produce any changes in major lymphocyte subsets in peripheral blood, but it resulted in a significant increase of NKR+ T cells, a subpopulation important for local immune responses. Iron load for a relatively short period improved anemia of HD patients and influenced the levels of the circulating IL-2, which may regulate factors affecting the survival of patients.