MGMT immunoexpression in growth hormone-secreting pituitary adenomas and its correlation with Ki-67 labeling index and cytokeratin distribution pattern

Recent publications suggest the utility of temozolomide (TMZ) in the management of aggressive pituitary adenomas and carcinomas, resistant to conventional treatments. The response to TMZ is inversely correlated with tumoral expression of O-6 methylguanine DNA methyl transferase (MGMT). Therefore, we aimed to assess MGMT immunoexpression in pure GH-secreting pituitary adenomas, in an effort to predict the likelihood of response to TMZ, and to correlate MGMT immunoexpression with Ki-67 LI and cytokeratin (CK) distribution pattern. Our material consisted of 36 GH-secreting pituitary adenomas (21 female,15 male, mean age 42.5±10.5), operated at our center between 2003 and 2010. Immunostaining for MGMT, Ki-67, and CK was performed using avidin-biotin-peroxidase complex method. Immunoreactivity for MGMT and Ki-67 was evaluated microscopically and recorded as percentages of positive nuclear immunostaining. CK distribution pattern was also evaluated microscopically and assoreted into dot-like and nondot-like pattern subtypes. MGMT immunoexpression scored as 0=none, 1=<10%, 2=<25%, 3=<50%, and 4=>50%. Staining for MGMT was <10% (score 1) in 30 (83.3%), 10-25% (score 2) in 3 (8.3%), 25-50% (score 3) in 2 (5.6%) and >50% (score 4) in 1 (2.8%) of the tumors, respectively. There was no correlation between Ki-67 LI and CK distribution pattern with MGMT immunoreactivity (P>0.05). Data from the current study suggest a large proportion of GH-secreting adenomas, including those with dot-like CK distribution pattern and high Ki-67 LI, demonstrate negative/low MGMT immunoreactivity and could be treated with TMZ, if conventional treatment fails.     

Acromegaly is associated with a distinct oral and gut microbiota

Pituitary - Our aim was to investigate the changes in the composition of oral and gut microbiota in patients with newly diagnosed acromegaly and their relationship with IGF-1 levels. Oral and fecal...     

National implementation of a pragmatic quality improvement skills curriculum for urology residents in the UK: Application and results of ‘theory-of-change’ methodology

BackgroundThere is global momentum to establish scalable Quality Improvement (QI) skills training curricula. We report development of an implementation plan for national scale-up of the ‘Education in Quality Improvement’ program (EQUIP) in UK urology residencies.Materials & methodsTheory-of-Change (ToC) methodology was used, which engaged EQUIP stakeholders in developing a single-page implementation ‘Logic Model’ in 4 study phases (2 stakeholder workshops (N = 20); 10 stakeholder interviews). The framework method was used for analysis.ResultsCore elements of the EQUIP Logic Model include: (i) QI curriculum integration into national surgical curricula; (ii) resident-led, modular, team-based QI projects; (iii) development of a national web-platform as QI projects library; (iv) a train-the-trainers module to develop attendings as QI mentors; and (v) knowledge transfer activities (e.g., peer-reviewed publications of residents’ QI projects).ConclusionsToC methodology was useful in developing a stakeholder-driven, actionable implementation plan for the national scale-up of EQUIP in the UK.     

Relationship Among Pulmonary Hypertension,Autoimmunity, Thyroid Hormones and Dyspnea in Patients With Hyperthyroidism

Objective

Previous studies have reported conflicting results regarding the mechanisms underlying the pathophysiology of pulmonary hypertension (PHT) in patients with hyperthyroidism. Therefore, in this study, we investigated the association between PHT and thyroid-stimulating hormone (TSH) receptor antibody, thyroid peroxidase antibody, thyroglobulin antibody, TSH, fT3, fT4 and dyspnea during daily activities in a large population of patients with hyperthyroidism.

Survival in progressive systemic sclerosis with pulmonary involvement: a single-center experience in Istanbul, Turkey

The objective of the current study was to determine survival and factors that affect survival in progressive systemic sclerosis (SSc) with pulmonary involvement. A total of 102 SSc patients with pulmonary involvement, diagnosed between 1994 and 2008, enrolled into the study. Pulmonary involvement was defined based on the presence of interstitial changes on high-resolution CT (HRCT). Demographical, clinical, radiological, and laboratory data of the patients were found from patient records and were used for the evaluation of survival. The mean age of the patients at diagnosis was 50?±?12?years. In follow-up, 22 (21.5%) patients were deceased. The mean age of the patients at death was 55?±?12?years. Seventy-eight percent of known causes of mortality were related to pulmonary complications. After any initial systemic manifestation of disease, the mean survival was 447?±?27?months and 5, 10, 15, and 20?year survival rates were 99, 92, 83, and 72%, respectively. The mean survival after initial pulmonary manifestation was 269?±?23?months and 5, 10 and 15?year survival rates were 91, 73 and 57%, respectively. Mean survival was 113?±?5?months, and 5- and 10-year survival rates after the lung involvement detected with HRCT were 85 and 66%, respectively. Pulmonary artery hypertension, disease onset after the age of 40, and honeycombing on HRCT were associated with poor survival. Our data suggest that pulmonary involvement is the most important determinant factor for poor prognosis in patients with SSc. Therefore, echocardiography, pulmonary function tests, and HRCT should be performed in early stages of the disease for early diagnosis of pulmonary artery hypertension and lung involvement before irreversible vascular and interstitial changes exist.     

MGMT immunoexpression in adamantinomatous craniopharyngiomas

At present, no effective medical treatment exists for recurrent and aggressive craniopharyngiomas that are resistant to conventional therapies, including surgery and adjuvant radiotherapy. Temozolomide is an alkylating chemotherapeutic agent used routinely in the management of high grade gliomas. The response to temozolomide is suggested to be dependent on the tumoral expression of O-6 methylguanine DNA methyltransferase (MGMT). Evidence supports that low MGMT immunoexpression correlates with positive response to temozolomide. Therefore, we aimed to assess MGMT immunoexpression in adamantinomatous craniopharyngiomas, in an effort to predict the likelihood of response to temozolomide. The MGMT immunostaining was performed on 23 adamantinomatous craniofaryngiomas operated at the Sisli Etfal Training and Research Hospital and identified by histological analysis. Paraffin embedded tissue sections were immunostained for MGMT and were evaluated semi-quantitatively. Of the 23 cases evaluated, 22 (96%) demonstrated negative (<10%) and 1 (4%) demonstrated low (10%) MGMT immunoexpression. Data from this study suggest a high proportion of adamantinomatous craniopharyngiomas exhibit negative/low MGMT immunoreactivity and could be treated with temozolomide, if conventional therapy fails.     

Is the measurement of inferior thyroid artery blood flow velocity by color-flow Doppler ultrasonography useful for differential diagnosis between gestational transient thyrotoxicosis and Graves' disease? A prospective study

OBJECTIVE:

To determine the role of peak systolic velocity, end-diastolic velocity and resistance indices of both the right and left inferior thyroid arteries measured by color-flow Doppler ultrasonography for a differential diagnosis between gestational transient thyrotoxicosis and Graves'' disease during pregnancy.

METHODS:

The right and left inferior thyroid artery-peak systolic velocity, end-diastolic velocity and resistance indices of 96 patients with thyrotoxicosis (41 with gestational transient thyrotoxicosis, 31 age-matched pregnant patients with Graves'' disease and 24 age- and sex-matched non-pregnant patients with Graves'' disease) and 25 age- and sex-matched healthy euthyroid subjects were assessed with color-flow Doppler ultrasonography.

RESULTS:

The right and left inferior thyroid artery-peak systolic and end-diastolic velocities in patients with gestational transient thyrotoxicosis were found to be significantly lower than those of pregnant patients with Graves'' disease and higher than those of healthy euthyroid subjects. However, the right and left inferior thyroid artery peak systolic and end-diastolic velocities in pregnant patients with Graves'' disease were significantly lower than those of non-pregnant patients with Graves'' disease. The right and left inferior thyroid artery peak systolic and end-diastolic velocities were positively correlated with TSH-receptor antibody levels. We found an overlap between the inferior thyroid artery-blood flow velocities in a considerable number of patients with gestational transient thyrotoxicosis and pregnant patients with Graves'' disease.

CONCLUSIONS:

This study suggests that the measurement of inferior thyroid artery-blood flow velocities with color-flow Doppler ultrasonography does not have sufficient sensitivity and specificity to be recommended as an initial diagnostic test for a differential diagnosis between gestational transient thyrotoxicosis and Graves'' disease during pregnancy.     

A comparison of antineutrophil cytoplasmic antibody prevalence in patients treated and untreated for hyperthyroidism

We aimed to compare the prevalence of antineutrophil cytoplasmic antibody (ANCA) and its subgroups between on-treatment (with anti-thyroid drugs; propylthiouracil, methimazole) and untreated patients with hyperthyroidism in our unit. Overall 78 consecutive patients were enrolled in the study; 45 patients were on-treatment (female/male 31:14) and 33 were newly diagnosed (female/male 20:13). We have studied ANCA, perinuclear-ANCA (p-ANCA), cytoplasmic-ANCA (c-ANCA), myeloperoxidase-ANCA (mpo-ANCA), and proteinase 3-ANCA (pr3-ANCA) in sera of all the patients. The data about clinical status, laboratory tests, and physical examination and mean duration of treatment in treated group were recorded. There was no statistically significant difference between the two groups for ANCA, c-ANCA, and pr3-ANCA (P=0.13, P=0.07, and P=0.63 respectively). p-ANCA and mpo-ANCA prevalences were significantly higher in on-treatment group than in untreated group (P=0.04 and P=0.01, respectively). The mean duration of treatment was 17 months in on-treatment group. The use of antithyroid drugs (propylthiouracil, methimazole) seems to be correlated with increased prevalence of ANCA. These drugs may especially increase p-ANCA and mpo-ANCA positivity.