Brain Metastasis and Renal Cell Carcinoma: Prognostic Scores Assessment in the Era of Targeted Therapies.

AIM: This study aimed at exploring several brain metastatic prognostic scores in patients with renal cell carcinoma. PATIENTS AND METHODS: We retrospectively analyzed data of 93 metastatic renal cell carcinoma patients who were diagnosed with brain metastases between October 2005 and July 2016 who received targeted therapy. Potential prognostic factors (RTOG RPA, BS-BM, and a newly developed score CERENAL) were analyzed. RESULTS: A total of 75 patients received targeted therapy. All scores showed prognostic value in progression-free survival after first-line treatment with CERENAL being the sole independent prognostic factor associated with improved duration of first-line treatment. Both RTOG RPA and CERENAL were potential prognosticators for overall survival, whereas only the CERENAL score was associated with prolonged disease-specific survival. CONCLUSION: Several prognostic scores can be useful to predict survival of patients with brain metastases from renal cancer, especially the newly developed CERENAL score.

Anti-livin antibodies: novel markers of malignant gastrointestinal cancers.

INTRODUCTION: Livin represents apoptosis inhibitors and may be important in cancer. OBJECTIVES: The aim of the study was to develop an anti-livin auto antibody assay and investigate its usefulness in the clinical practice in relation to gastrointestinal cancers (GIC). PATIENTS AND METHODS: We studied sera obtained from 36 patients with GIC and 59 healthy controls. A solid-phase radioimmunoassay to detect anti-livin antibodies in serum was developed. Polipropylene tubes were coated with recombinant human livin, and 100-fold dilutions of sera were incubated in these tubes. On the next day, the tubes were decanted, washed and labeled 125-I protein A was added. After 2-hour incubation, the tubes were washed and radioactivity was measured using the gamma counter. RESULTS: We observed a statistically significant difference between the presence and levels of anti-livin antibodies in sera of patients with GIC and in control subjects. Anti-livin auto antibodies were detected in 9 patients with GIC. Of note, the level of anti-livin antibodies was significantly elevated in 25% of GIC patients. The presence of anti-livin antibodies was confirmed with sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting. CONCLUSIONS: A high prevalence of anti-livin antibodies in patients with GIC indicates that they may be useful in the diagnosis of these malignancies.

A jejunal stromal tumour in a patient with metastatic neuroendocrine cancer of unknown origin; a rare coexistence, diagnostic and therapeutic challenge.

A 59-year-old woman presented to the Department of Gastroenterology complaining of progressing weight loss, unexplained diarrhoea, and, as revealed by abdominal ultrasound, numerous hyperechogenic foci in the liver. The immunohistochemical evaluations of the specimens from biopsy revealed well-differentiated hepatic neuroendocrine metastases. The biochemical marker levels, including serum chromogranin A (CGA) and urine 5-hydroxyindolacetic acid (5-HIAA) 24-hour excretion, were significantly elevated. Whole body somatostatin receptor scintigraphy showed tracer accumulation in the liver lesions, with no extrahepatic tumour, possibly the primary origin. Long-term somatostatin analog therapy was initiated and a peptide-receptor targeted radionuclide therapy decision was made parallel to this treatment. Therefore, a followed-up CT scan of the abdomen showed, as well as the metastatic changes within the liver, a wellvascularised jejunal tumour suspected to be the primary focus of the disseminated neuroendocrine neoplasm. Unexpectedly, the pathological examination revealed a positive cell reaction for CD 117, confirming the diagnosis of a rare jejunal stromal tumour. Two months later peptide-receptor therapy with 90Y/77Lu-DOTA-TATE was commenced.

Circulating resistin levels are lower in hypothyroid women but independent from thyroid hormones concentrations.

OBJECTIVES: Although resistin is involved in metabolism, its role in humans is unclear. Since thyroid status influences metabolism, and since only few studies have evaluated the associations between resistin and thyroid status with inconclusive results, we investigated serum serum resistin levels and their correlations with TSH, FT4 and FT3 in hypothyroid and euthyroid women. DESIGN AND METHODS: Study group consisted of 22 women with a history of total thyroidectomy and radioiodine ablation performed for thyroid cancer. Controls were 22 healthy euthyroid women matched for age and BMI. After six-weeks of thyroxine withdrawal, subjects were admitted to the Department of Endocrinology of the Poznan University of Medical Sciences to perform this study. RESULTS: Serum resistin concentrations were lower in hypothyroid patients, 12.40 +/- 5.197 vs. 18.01 +/- 7.31, p=0.0065. In hypothyroid subjects, correlations were as follows: r of -0.2636 and p of 0.248, r of 0.0336 and p of 0.885, and r of 0.3080 and P of 0.174 for resistin and FT4, resistin and FT3, and resistin and TSH, respectively. In controls: r of 0.0311 and p of 0.8908, r of -0.0986 and p of 0.6625, and r of 0.1605 and p of 0.4754 for resistin and FT4, resistin and FT3, and resistin and TSH, respectively. CONCLUSIONS: Short-term profound hypothyroidism decreased resistin levels. However, no significant correlations between the levels of circulating resistin and thyroid hormones and TSH were shown.

Serum insulin levels and the degree of thyroid dysfunction in hypothyroid women.

OBJECTIVES: Among the peripheral effects of thyroid hormone action, their influence on insulin is of great interest and conflicting data on this subject are available. Despite various studies already performed, of concern is whether insulin levels change in line with a deterioration of thyroid function. In this study, we investigated serum serum insulin levels and their correlations with thyroid-stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) in hypothyroid women. DESIGN AND METHODS: Study group consisted of 22 women with a history of total thyroidectomy and radioiodine ablation performed for thyroid cancer, without diabetes or glucose intolerance. After six-weeks of thyroxine withdrawal, subjects were admitted to the Department of Endocrinology of the Poznan University of Medical Sciences to perform this study. RESULTS: Plasma glucose and insulin were respectively: 4.76+/-0.47 mmol/L and 7.19+/-4.22 microU/mL. Serum TSH, FT4 and FT3 were respectively: 91.66+/-58.59 microU/mL, 2.65+/-2.19 pmol/L, and 1.53+/-1.00 pmol/L. Correlations were: r of -0. 4381 and P of 0.0414, r of -0.2368 and P of 0.2887, and r of 0.3954 and P of 0.0686 for insulin and FT4, insulin and FT3, and insulin and TSH, respectively. The only significant correlation was an inverse correlation between insulin and FT4. CONCLUSIONS: In profound hypothyroidism insulin concentrations correlate with FT4 only, but not with FT3 or TSH.

[Arterial stiffness in hypopituitary patients with life-long growth hormone deficiency]. / Sztywnosc tetnicza u chorych na niedoczynnosc przysadki z dlugoletnim niedoborem hormonu wzrostu.

INTRODUCTION: Patients with hypopituitarism have a shorter survival period from and premature mortality due to cardiovascular complications. OBJECTIVES: The aim of our study was to evaluate the arterial stiffness and hemodynamic parameters based on pulse wave analysis in 22 adult patients with long-life growth hormone (GH) and insulin-like factor I (IGF-I) deficiencies, lasting from 22 to 57 years. PATIENTS AND METHODS: In all patients, a combined pituitary hormone deficiency was diagnosed. All patients were on substitution therapy, receiving levothyroxine, sex hormones and hydrocortisone (when required), but none of the patients had ever received recombinant GH therapy. A control group consisted of 36 healthy subjects strictly matched to patients by age and body mass index. In the patients and control subjects pulse wave analysis was performed with the use of Sphigmocor MX reconstructing the aortic pulse wave in a real time. RESULTS: The peripheral and central augmentation indexes were significantly increased in the hypopituitary patients compared with the control subjects. The central pulse pressure was also elevated in the patients. These hemodynamic parameters pointed to an increased arterial stiffness. CONCLUSIONS: In patients with hypopituitarism, the life-long GH and IGF-I deficiencies lead to an increase in the arterial stiffness.

Circulating leptin levels are not influenced by thyroid status in hypothyroid and euthyroid women.

OBJECTIVES: Leptin regulates body weight by suppressing food intake and increasing energy expenditure. Alterations in thyroid hormone levels are also associated with changes in body weight but the effect of thyroid hormone deficiency on serum leptin in humans is unclear. DESIGN AND METHODS: The aim of this study was to measure leptin levels and to investigate their associations with thyroid hormones in 22 women with severe hypothyroidism after total thyroidectomy, and in a group of 22 healthy euthyroid control female subjects matched for age and body mass index (BMI). Their plasma leptin, free thyroxine, triiodothyronine and TSH were measured. RESULTS: Leptin levels in subjects and controls were (pg/mL) 18761.64+/-16973.96 and 18729.19+/-18014.05, respectively, p=0.9; leptin did not correlate with free thyroxine, triiodothyroinine and TSH: r=0.1039 and p=0.6453, r=0.0113 and p=0.9602, and r=-0.0525 and p=0.8165 for leptin and FT4, leptin and FT3, and leptin and TSH, respectively in subjects; r=-0.00056 and p=0.9980, r=0.248727 and p=0.2643, and r=-0.046919 and p=0.8357 for leptin and FT4, leptin and FT3, and leptin and TSH, respectively in controls. Leptin levels did not differ between subjects and controls and they did not correlate with thyroid hormones. CONCLUSIONS: Leptin levels are not influenced by hypothyroidism and do not correlate with thyroid hormones in euthyroid and hypothyroid women.

Abnormalities in bone mineral density distribution and bone scintigraphy in patients with childhood onset hypopituitarism.

The aim of our study was to evaluate the effects of long-life severe growth hormone deficiency on bone mineral density (BMD) and bone scintigraphy in adult patients with childhood onset (CO) hypopituitarism never treated with growth hormone. Our studies included 22 adult patients with CO hypopituitarism never treated with growth hormone (13 males and 9 females, aged 25-66 yr). The patients received replacement therapy with thyroxine, sex steroid hormones, and patients with secondary adrenocortical deficiency, hydrocortisone, but none of the patients had ever received GH treatment. In 22 patients, the total body with regional distribution of BMD, the lumbar spine L2-L4, and radial (33% site) BMD were determined by dual energy X-ray absorptiometry (DXA). In addition, 12 patients had the femoral neck BMD examined. In 10 cases, bone scintigraphy using 99-technetium labeled methylene diphosphonate was performed. Our studies revealed abnormalities, not yet described, in the regional distribution of BMD and bone scintigraphy in adults with CO hypopituitarism never treated with GH. In all patients, the results obtained from the total body showed definite disproportion in the regional distribution of BMD with a significantly advanced bone mineral deficit in the legs and a moderate deficit in the arms and total body. Local BMD measured at the radial (33% site) and lumbar spine L2-L4 revealed also a more pronounced bone mineral deficit in the cortical bone (33% distal radius) than in the trabecular bone (spine L2-L4). Bone scintigraphy showed a decrease in tracer accumulation in the shafts of the long bones but normal uptake in the spine, ribs, sternum, skull, and periarticular areas, indicating suppressed skeletal metabolism of cortical bone. Our studies indicate that long-life growth hormone deficiency leads to deficient and abnormal distribution of bone mineralization, a more pronounced deficit of BMD at the cortical bone, mainly expressed in the shafts of the long bones of the legs and arms, and moderately reduced BMD at the trabecular bone. Bone scans displaying low diphosphonates uptake in the shafts of the long bones point to greatly suppressed skeletal metabolism of the cortical bone in the patients with CO hypopituitarism never treated with GH.

Premature fusion and excessive calcification of coronal sutures in patients with Klinefelter syndrome.

OBJECTIVE: The purpose of this paper is to report on radiographic features of the cranial vault abnormalities frequently seen but not yet described in detail in patients with Klinefelter syndrome. SUBJECTS: Our studies comprised 72 patients with Klinefelter syndrome and 47,XXY karyotype. The majority of the patients were young between the ages of 16 to 28 years. METHODS: Plain skull radiographs were taken in the frontal and lateral projections. RESULTS: Several abnormalities were observed on skull radiographs of the Klinefelter patients. The most frequent was a premature fusion of the coronal sutures that occurred in 54 of 62 younger patients. In 42 cases extensive calcifications of these sutures were observed. The calcified sutures were dense and widened. In 24 patients the inner table in the anterior part or the parietal bone displayed a marked disruption with thinning of the calvaria at this place. In the posterior part of the parietal bone in 21 patients the inner table was thickened and excessively dense. On frontal radiographs, in 30 patients, there was a flattening of the squamous part of the temporal bones. CONCLUSIONS: Skull radiographs in Klinefelter patients frequently display abnormalities: premature fusion and excessive calcifications of the coronal sutures, irregularities of the inner table of the parietal bone, and flattening of the temporal bones. These radiographic features, when present, may draw attention to the XXY syndrome as the underlying cause of the abnormalities.