Ectopic Growth Hormone-Releasing Hormone Secretion by a Neuroendocrine Tumor Causing Acromegaly: Long-Term Follow-Up Results

Ectopic secretion of growth hormone-releasing-hormone (GHRH) is a rare cause of acromegaly—representing less than 1% of patients. A 25-year-old woman was admitted to the hospital with acromegaly and a 6 × 6 cm infrahepatic mass. Sellar magnetic resonance imaging indicated diffuse pituitary enlargement consistent with hyperplasia. The infrahepatic mass was resected, and the histopathological diagnosis was a well-differentiated invasive neuroendocrine carcinoma of the duodenum with metastases to local lymph nodes. The tumor cells contained cytoplasmic immunoreactivity for GHRH. Because increased IGF-1 concentrations persisted after the operation, the patient was treated with octreotide long-acting repeatable (LAR) injections of 20 mg/month. Growth hormone and IGF-1 levels normalized. After 6 years of surveillance, a left paraaortic mass was detected by uptake of indium¹¹¹ octreotide. Surgical exploration revealed metastatic neuroendocrine carcinoma in a 2.5-cm lymph node. Postoperatively, the IGF-1 concentration was mildly elevated. Octreotide LAR therapy is being continued at 10 mg/month. This case suggests that octreotide treatment may have a beneficial effect on disease course and can be maintained for as long as 7 years in a patient with acromegaly due to a GHRH-secreting neuroendocrine carcinoma.     

Expression of nuclear Ki-67 antigen in prostatic high grade intraepithelial neoplasia and prostatic carcinoma

BACKGROUND/AIM: Prostatic intraepithelial high grade neoplasia (PINHG) is accepted as preneoplastic lesion in prostatic carcinoma. One of the fundamental events in early oncogenesis is the disruption of proliferative activity. One of the numerous regulatory proteins is Ki-67 expressed in all proliferating cells. Index Ki-67 is considered to have prognostic significance. The aim of the study was to compare the level of proliferation in hyperplastic epithelium, prostatic carcinoma (Gleason score > 6) and PINHG. METHODS: Micromorphological examination was done in 85 patients. Pathohistological analysis was performed on standard histologic specimens with the estimation of Gleason score and the presence of PINHG in its surroundings. Nuclear proliferative activity was analyzed immunohistochemically in 19 cases, using a monoclonal anti-Ki-67 antibody. RESULTS: PINHG was found in prostatic carcinoma surrounding in 30% of the patients. In hyperplastic epithelia Ki-67 proliferative activity was 1,08, in PINHG 2,25 (p < 0,05), while in prostatic cancer, Ki-67 index was 17,64. Proliferative activity in prostatic carcinoma was significantly higher than in PINHG (p < 0,001) and hyperplasia (p < 0,001). CONCLUSION: This study confirmed that high grade PIN lesion predominately appears in the surrounding of poor or moderately differentiated prostate carcinoma, and that it represents progressive disorder of proliferation in preneoplastic and neoplastic prostatic epithelium.     

Metastatic Breast Cancer Survival according to HER2 and Topo2a Gene Status

The aim of this study was to determine the relationship between amplification of HER2 (Human epidermal growth factor receptor 2) and Topo2a (topoisomerase 2a) and their influence on prognosis in metastatic breast cancer (MBC) patients. Amplification of both HER2 and Topo2a genes was determined by chromogenic in situ hybridization (CISH) in primary tumor tissue of 71 MBC patients. Starting point for follow-up was the time of diagnosis of metastatic disease. Although there was significant correlation between HER2 amplification and Topo2a alterations, Topo2a amplification was not strictly related to HER2 amplification. Follow-up of patients showed that there was no difference in MBC survival between HER2-nonamplified and HER2-amplified patients for subgroup as whole, but there was significant difference in MBC survival between patients with and without Topo2a amplification. HER2 amplification showed prognostic value in subgroups of patients, as well as Topo2a. Combination of these two genes with different status (nonamplified, amplified, coamplified) indicated that they might have additive effect. Also, it has been shown that Topo2a-amplified cases have poorer survival than Topo2a-nonamplified, when treated with CMF therapy.Topo2a amplification seems to be more promising biomarker of MBC survival, than HER2, and potential marker of resistance to CMF therapy.     

Current approaches to the treatment of non-gonococcal urethritis in men

The study was made of 50 men suffering from non-gonococcal urethritis caused by mixed pathogenic and opportunistic urogenital infection. Clinical characteristics of urethritis in relation to infection pathogen are shown. The results of clinical and laboratory examinations were considered in choice of antibacterial therapy. Safocid, a combined antibacterial medicine, demonstrated its clinical and microbiological efficacy in the treatment of patients with non-gonococcal urethritis of mixed etiology.     

Using zidena in the treatment of erectile dysfunction associated with stress-induced arterial hypertension in workers of locomotive teams

Thirty train drivers with erectile dysfunction (ED) and arterial hypertension were examined : physical examination, blood count, urinalysis, penile laser Doppler flowmetry (LDF). ED severity was assessed by Loran-Segal questionnaire of male copulative function (MCF) and international index of erectile function (IIEF). Zidena was used in a dose 100 mg 30 min before coitus twice a weak. Examinations have detected mild and moderate ED, spastic disorders of penile microcirculation. MCF significant improvement (p < 0.05), rise of IIEF score were seen after 30 days of zidena treatment. A positive trend was observed after 15 days of treatment. LDF registered a significant (p < 0.05) improvement of microcirculation. Tissue hypoxia and ischemia lowered, blood inflow in the system of microcirculation increased. A passive mechanism of blood flow regulation, vasodilation almost corresponded to physiological standards. Administration of zidena in patients with stress-induced hypertension has improved libido, quality and duration of erection, penile microcirculation due to better tissue perfusion with blood, reduction of ischemia and blood congestion in the venules. Duration of coitus increased.     

Experience in vitaprost treatment of patients with chronic abacterial prostatitis and prostatic adenoma after prostatic arteries embolism

Pain and abnormal spermatogenesis are among symptoms deteriorating quality of life in patients with chronic prostatitis. Rectal suppositories vitaprost have no side effects, relieve pain, correct spermatogenesis. The effect of vitaprost treatment persists for 3 months and longer. Prostatic arteries embolization with vitaprost suppositories as preoperative preparation is a good alternative to surgical treatment in patients with prostatic adenoma.     

Divergent Squamous Differentiation in Upper Urothelial Carcinoma—Comparative Clinicopathological and Molecular Study

Upper urothelial carcinoma (UUC) has a plasticity to demonstrate divergent differentiation with squamous metaplastic elements. There was no previous study exploring profiling of molecular markers in metaplastic squamous upper urothelial carcinoma (SUUC) and conventional upper urothelial carcinoma (CUUC). The aims of this study was to compare expression of the phenotypic characteristics of tumors and molecular markers (p53, p16, cyclin D1, E-cadherin, HER-2, Ki-67, Bcl-2, Bax) in SUUC and CUUC. SUUC was detected in 20% of 44 patients. There was significant difference between SUUC and CUUC in the pathological stage, grade, growth and presence of lymphovasular invasion (p < 0.05; 0.05; 0.05; 0.01 respectively). The mean Ki-67 and p53 labeling index was significantly higher in SUUC than in CUUC (p < 0.05; 0.05). There was no significant difference in the expression of p16, cyclin D1, E-cadherin, HER-2, Bcl-2 and Bax between SUUC and CUUC. Univariant model showed that SUUC was significantly associated with lymphovascular invasion (p = 0.007), Ki-67 activity (p = 0.016) and growth (p = 0.026). Exploration of UUC with squamous divergent differentiation showed changes in phenotypic characteristics and Ki-67, as well as similar molecular profile with CUUC.     

Uncertainty analysis of in-situ gamma spectrometry measurements of air cleaning filter cartridges and 200 L drums by a HPGe detector

This work deals with most significant sources of uncertainty in determination of radionuclides massic activity in 200 L drums with radioactive waste (RAW) from decommissioning of nuclear power plant (NPP) A1 and operational air cleaning filters coming from different parts of NPP's ventilation system. It turned out that the most significant source of uncertainty is determination of photo peak detection efficiency, in particular measurement geometry. The detection efficiency of HPGe detector has been determined by calculation using ISOCS software (In Situ Object Counting System) and detector characteristics delivered by the manufacturer (LABSOCS). The detector efficiency is influenced by various factors like measurement geometry, deviation from standard geometry, environmental characteristics, sample properties (density, material composition), used collimator etc. Mentioned factors and their contributions to the uncertainty of detection efficiency and thus to the total uncertainty of massic activity determination have been individually evaluated in the paper. The main part of the work consists of evaluation of maximum uncertainty factor due to presence of hypothetical point source in measurement volume for both types of measurement geometry.     

VEGF protects brain against focal ischemia without increasing blood--brain permeability when administered intracerebroventricularly.

Delayed administration of vascular endothelial growth factor (VEGF) promotes functional recovery after focal cerebral ischemia. However, early intravenous injection of VEGF increases blood-brain barrier (BBB) leakage, hemorrhagic transformation and infarct volume whereas its application to cortical surface is neuroprotective. We have investigated whether or not early intracerebroventricular administration of VEGF could replicate the neuroprotective effect observed with topical application and the mechanism of action of this protection. Mice were subjected to 90 mins middle cerebral artery (MCA) occlusion and 24 h of reperfusion. Vascular endothelial growth factor (8 ng, intracerebroventricular) was administered 1 or 3 h after reperfusion. Compared with the vehicle-treated (intracerebroventricular) group, VEGF decreased the infarct volume along with BBB leakage in both treatment groups. Neurologic disability scores improved in parallel to the changes in infarct volume. Independently of the decrease in infarct size, VEGF also reduced the number of TUNEL-positive apoptotic neurons. Phospo-Akt levels were significantly higher in ischemic hemispheres of the VEGF-treated mice. Contrary to intracerebroventricular route, intravenous administration of VEGF (15 microg/kg) enhanced the infarct volume as previously reported for the rat. In conclusion, single intracerebroventricular injection of VEGF protects brain against ischemia without adversely affecting BBB permeability, and has a relatively long therapeutic time window. This early neuroprotective action, observed well before recovery-promoting actions such as angiogenesis, possibly involves activation of the PI-3-Akt pathway.     

Role of insulin-like growth factor-1 in colon cancerogenesis: a case-control study

BACKGROUND: Our aim was to establish whether individuals who developed colon cancer have elevated blood levels of insulin-like growth factor-1 (IGF-1). METHODS: This was a case/control study in which 52 patients with colon cancer and a corresponding control group were investigated. Data on age, weight, height, and sex of subjects were recorded and levels of IGF-1 and growth hormone, as well as insulin and C-peptide levels, were measured in the morning before eating, 90 min after breakfast and again 90 min after lunch. RESULTS: We found significantly higher levels of IGF-1 in blood of colon cancer patients compared to the control group. No differences in the levels of growth hormone, insulin and C-peptide in blood were found between colon cancer patients and the control group. It was found that the increase of IGF-1 level was followed by a 3.15-fold increased risk for developing colon cancer. There were no differences in the levels of IGF-1 in blood in all three measurements in the group of colon cancer patients, whereas differences were found in the control group. We found differences in the levels of insulin and C-peptide in blood in all three measurements in both groups of patients. No differences were found in the levels of growth hormone in blood in all three measurements in both groups of patients. CONCLUSIONS: The results of this study suggest a positive correlation between the increased levels of IGF-1 and colon cancer and are thus consistent with the hypothesis that the level of IGF-1 plays an important role in the development of colon cancer.