Klotho expression and nodal involvement as predictive factors for large cell lung carcinoma.

INTRODUCTION: Klotho has been recently described as a carcinogenesis suppressor. Large cell neuroendocrine lung carcinoma (LCNEC) is a rare, highly malignant neoplasm. In the light of increasing incidence of neuroendocrine tumours, biomarkers predicting survival are needed. We consider that Klotho might be one. MATERIAL AND METHODS: We analysed records of all patients diagnosed with LCNEC, atypical carcinoid and typical carcinoid operated on in our institution between 2007 and 2015. Initially, we found 134 cases. Forty-six specimens were unattainable and thus excluded from research. All patients diagnosed with LCNEC according to the WHO classification were included in the study. Immunohistochemical staining for Klotho was performed. We retrospectively reviewed patient charts and analysed multiple variables. RESULTS: Positive staining for Klotho was present in 36 tissue specimens, while 12 patients were Klotho-negative. Survival length was significantly higher in Klotho-positive cases (p = 0.024), while advanced nodal status (N1 and N2) represented a marker of poor outcome (p = 0.011). In multivariate analysis, both Klotho presence (p = 0.015; HR = 0.37; 95% CI: 0.17-0.86) and nodal involvement (p = 0.007; HR = 3.04; 95% CI: 1.37-6.82) were independent prognostic factors. Tumour vessel invasion and visceral pleura infiltration were not associated with worse treatment results. Klotho presence predicted a favourable prognosis in these groups (p = 0.018; p = 0.007). CONCLUSIONS: Our results suggest that Klotho might be a positive factor for predicting survival in LCNEC and nodal involvement a negative one. Thus, these two markers may assist in the selection of subjects with unfavourable prognosis and to personalise therapy regimens.

Association of total, acylated and unacylated ghrelin with apolipoprotein A1 and insulin concentrations in acromegalic patients.

BACKGROUND: Ghrelin is a hormone that occurs in acylated (AG) or unacylated (UG) form. Ghrelin strongly stimulates growth hormone (GH) secretion from anterior pituitary, as well as regulates the energy balance and various metabolic parameters. Increased consideration is given to UG, thought to be inactive. OBJECTIVES: We aimed to evaluate the levels of total ghrelin, AG and UG in medically naive and treated patients with biochemically active acromegaly, with respect to variables of lipid and glucose metabolism. MATERIAL AND METHODS: We studied total ghrelin, AG and calculated UG levels in a group of 24 patients with active acromegaly and 15 healthy controls. Plasma levels of GH, insulin-like growth factor 1 (IGF-1), insulin, glucose, total cholesterol (TC), high-density lipoprotein (HDL) cholesterol and calculated low-density lipoprotein (LDL) cholesterol, triglycerides (TG), apolipoproteins A1 (APO A1), and B-100 (APO B-100) were measured. RESULTS: Patients with acromegaly revealed lower levels of total ghrelin than healthy controls. In pooled data of all subgroups, simple linear regression analysis revealed that total ghrelin concentration was significantly associated with APO A1 concentration (ß = 0.8087; p = 0.0315) and AG concentration was significantly associated with fasting insulin concentration (ß = 15.5183; p = 0.011). There was an inverse association between UG and the patients' age, and positive association between UG and APO A1. CONCLUSIONS: Our results suggest that ghrelin may influence metabolic disturbances in acromegaly. It seems that the assessment of AG and UG is superior to total ghrelin measurement. Mechanisms regulating ghrelin acylation and function of each form need elucidation in order to improve diagnostics and treatment of metabolic disturbances, not only acromegaly.

18F-FDG PET/CT and nestin expression as prognostic tools in pulmonary neuroendocrine tumours.

OBJECTIVES: The aim of this study was to investigate the fluorine-18-fluorodeoxyglucose (F-FDG) uptake on integrated PET [PET/computed tomography (CT)] images and its correlation with nestin expression in a series of neuroendocrine lung tumours. As the incidence of neuroendocrine lung tumours is rising, tools predicting diagnosis, outcome and assisting in the selection of treatment regimens are needed. PATIENTS AND METHODS: We reviewed records of patients diagnosed with large cell neuroendocrine lung carcinoma, atypical carcinoid and typical carcinoid who were operated upon in our institution. Into the study, we included those who underwent F-FDG PET/CT before the operation. Immunohistochemical staining for nestin was performed. We retrospectively reviewed patient charts and analyzed multiple variables. RESULTS: Maximal standardized uptake value (SUVmax) was significantly higher in poorly differentiated than in well-differentiated tumours (P<0.001). The estimated SUVmax cut-off value, which distinguishes large cell neuroendocrine lung carcinoma from carcinoid with the highest sensitivity and specificity (88.6%; 85%), was 6.3. Positivity of the tumour on F-FDG PET/CT was associated with shorter survival of the patient (P=0.0057). Multivariate analysis showed that nodal involvement and SUVmax were predictors of adverse outcome. Nestin expression did not correlate with lymph node metastases (P=0.97), SUVmax (P=0.9), maximal size of the lesion (P=0.49) or Ki-67 (P=0.93). Nestin expression did not influence survival on multivariate analysis. CONCLUSION: The study revealed a comparable expression of nestin in tumours with different activity of glucose metabolism measured by F-FDG uptake at PET/CT. It did not show any significant influence of nestin expression on survival. The study confirmed that F-FDG PET/CT is useful in the preoperative evaluation of patients with pulmonary neuroendocrine tumours.

Anti-thyroidal peroxidase antibodies are associated with thyrotropin levels in hypothyroid patients and in euthyroid individuals.

OBJECTIVE: The study was designed to evaluate the relationship between thyroid antibodies and gland dysfunction, with the aim of finding a clinically useful threshold value of thyreoperoxidase antibodies, which could prove to be predictive for thyroid failure. MATERIAL AND METHODS: The study was conducted on 99 women, ages ranging from 18-91 years (mean age: 45.5 ±17.0), were treated as outpatients in the Department of Endocrinology, Metabolism and Internal Medicine. Analysis of serum samples for TSH concentration and anti-TPO titers was conducted. RESULTS: The most common disorder was hypothyroidism. Anti-TPO titers above reference range values were observed in 35 patients (35.4%): 21 (60%) were hypothyroid and 11 (31.4 %) were euthyroid. The anti-TPO and TSH serum levels correlated both in patients with high thyroid antibody titers, and in the anti-TPO negative groups. To find the threshold value of anti- TPO that would help predict hypothyroidism, receiver operating curves were used. With this approach, TPO antibody titers over 17 IU/ml indicated hypothyroidism with a 90% sensitivity and 75% sensibility. CONCLUSIONS: It can be postulated that the cutoff values of anti-TPO in the general population should be decreased in order to improve autoimmune thyroid disorder screening. Obviously, using that margin may lead initially to the detection of some false positive subjects. However, with lower cut-off values, more patients can be enrolled into thyroid follow-up groups. In this way, many people could avoid complications of undiagnosed, insidious thyroid failure.

Clinical significance of nestin and its association with survival in neuroendocrine lung tumours.

Nestin is considered to be a cancer stem cell marker. Nestin expression in neuroendocrine tumours might be useful to predict prognosis and facilitate treatment planning. 88 patients with neuroendocrine lung tumours operated in the Department of Thoracic Surgery from 2007 to 2015 were included into the study. Immunohistochemical staining for nestin was performed. Clinicopathological and survival data were retrospectively analyzed. Nestin expression was detected in 15 (17%) specimens. Multivariate analysis showed that lymph node metastases (p = 0.0001; hazard ratio (HR) = 3.93; confidence interval (CI) 95%: 1.96-7.87), nestin expression (p = 0.034; HR = 2.30; CI 95%: 1.06-4.99) and patient's age (p = 0.024; HR = 1.04; CI 95%: 1.00-1.09) were independent negative prognostic factors. Nestin expression was significantly higher in large cell neuroendocrine carcinoma when compared with carcinoids (p = 0.001). Collected data support the thesis that nestin can be regarded as a biomarker in patients with neuroendocrine lung tumours.

The prevalence of thyroid nodular disease in patients with increased titers of anti-thyroidal peroxidase antibodies.

OBJECTIVES: The aim of our study was to evaluate the possible association between autoimmunity and thyroid nodular disease (TND). DESIGN AND SETTING: We conducted a study on 58 patients who were treated in outpatient setting at the Department of Endocrinology, Metabolism and Internal Medicine. Serum samples were analyzed for TSH concentration and anti-TPO antibodies titers. Thyroid ultrasonography was performed in each subject in order to evaluate volume of the gland, and the number and size of nodules. RESULTS: TND occurred in 70% of anti-TPO positive subjects and in 57.9% of anti-TPO negative subjects, but statistical analysis did not demonstrate a significant concordance between the presence of anti-TPO antibodies and prevalence of TND (p>0.05). We showed that the mean (0.82 vs 0.75; p=0.49), minimal (0.2 vs 0.3; p=0.89) and maximal (2.7 vs 2.4; p=0.49) diameters of a nodule were similar in both groups. Solely in anti-TPO positive patients, anti-TPO titers positively correlated with the number of nodules (p=0.04). CONCLUSION: Our results favor the role of autoimmunity in TND development although associations between thyroid nodules and thyroid autoimmunity are complicated and may be the subject of much controversy. Increased anti-TPO may influence the number of nodules rather than the presence of TND itself.