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.     

Preparation of novel apigenin‐enriched,liposomal and non‐liposomal,antiinflammatory topical formulations as substitutes for corticosteroid therapy

Two oil‐in‐water formulations, containing equal amounts of apigenin‐enriched chamomile flower extracts, for potential use as topical antiinflammatory agents, were prepared and their physicochemical properties evaluated. A pilot clinical study was then carried out to assess patient acceptability and efficacy. The creams were either non‐liposomal or liposomal. The liposomal formulations were more viscous, thus producing superior release characteristics in vitro. The clinical study also showed that the liposomal creams were, as antiinflammatory agents, slightly more effective in vivo than the non‐liposomal formulations. These results suggest that there is scope for the further development of even more effective and safer alternatives to corticosteroids. Copyright © 2010 John Wiley & Sons, Ltd.     

Nebulized Fluticasone Propionate vs. Budesonide as Adjunctive Treatment in Children with Asthma Exacerbation

Objectives: To compare the effects of nebulized fluticasone propionate (FP) and nebulized budesonide (BUD) in addition to inhaled salbutamol in children with mild asthma exacerbation. Methods: The study was a multicenter, randomized, single-blind, parallel group design. One hundred and sixty-eight children, aged 4-15 years, were randomly allocated to receive either nebulized FP (250 mcg) or nebulized BUD (500 mcg) twice daily for 10 days. On presentation, at the end of treatment, and after a 7-day follow-up, clinical assessment and pulmonary function measurements were performed. Daytime and nighttime asthma symptom scores, the use of rescue salbutamol, and morning/evening peak expiratory flow (PEF) values were recorded at home during the treatment period. Morning cortisol concentration (51 children) and overnight urinary cortisol excretion (30 children) were also measured in six centers at the start and at the end of the treatment. Results: Improvement of morning PEF was significantly higher in patients treated with FP (p = 0.032). The percentage of symptom-free nights was significantly higher in the BUD group (p = 0.006), but no difference was found in symptom-free days. No intergroup difference was detected in the percentage of days/nights free from rescue medication and in pulmonary function tests performed in outpatient settings. There was no evidence of hypothalamo-pituitary-adrenal axis suppression. Conclusions: A short course of nebulized FP has the same effects as a double dose of nebulized BUD, when either drug is added to bronchodilator therapy in children with mild asthma exacerbation.     

Hemosiderotic fibrohistiocytic lipomatous lesion: Early pleomorphic hyalinizing angiectatic tumor?

Hemosiderotic fibrohistiocytic lipomatous lesion (HFLL) and early pleomorphic hyalinizing angiectatic tumor (PHAT) are characterized histologically by an admixture of fat, moderately cellular fascicles of hemosiderin-laden spindle cells growing in a perivascular, periadipocytic and septal pattern, as well as the presence of macrophages and chronic inflammatory cells. In contrast to a suggested reactive nature of HFLL, PHAT is regarded as a non-metastasizing tumor of uncertain lineage in the recent World Health Organization classification of soft tissue tumors. Reported herein is the case of a 47-year-old woman with an unencapsulated and irregularly circumscribed recurring lesion in the ankle/foot region that developed following ankle distortion and that fulfills histological criteria for both HFLL and early PHAT. In summary, the present case suggests a reactive over-neoplastic nature of HFLL and confirms profound histological similarities with early PHAT. Until more data become available on the biological potential of HFLL/early PHAT, radical surgical excision and follow up of the patient remains the best treatment option.     

The role of the anterior temporal lobes in the comprehension of concrete and abstract words: rTMS evidence

Conceptual knowledge allows us to bring meaning to our world. Studies of semantic dementia (SD) patients and some functional neuroimaging studies indicate that the anterior temporal lobes, bilaterally, are a core neural substrate for the formation of conceptual representations. The majority of SD patients (who have circumscribed atrophy of the anterior temporal lobes) have better comprehension of concrete than abstract words. However, this finding remains controversial, as some individual SD patients have exhibited reverse imageability effects, i.e., relative preservation of abstract knowledge. This would imply that the anterior temporal lobes are particularly crucial for processing sensory aspects of semantic knowledge, which are an important part of concrete but not abstract concepts. To adjudicate on this debate, we used offline, low-frequency, repetitive transcranial magnetic stimulation to disrupt neural processing temporarily in the left or right temporal poles (TPs). We examined this effect using a synonym judgement task, comprising high, medium and low imageability items, which we have previously employed with a case-series of SD patients. The time required to make semantic decisions was slowed considerably, particularly for low imageability items, consistent with the pattern we observed in SD. These results confirm that both TPs make a critical contribution to semantic processing, even for abstract concepts that do not have strong sensory representations.     

Immunotherapy: A new standard in the treatment of metastatic clear cell renal cell carcinoma

Renal cell cancer (RCC) represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney (90%). In the mid-nineties of the last century, the standard of treatment for patients with metastatic RCC was cytokines. Sunititib and pazopanib were registered in 2007 and 2009, respectively, and have since been the standard first-line treatment for metastatic clear cell RCC (mccRCC). Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells (NK) and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy. With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved [immunotherapy and immunotherapy/tyrosine kinase inhibitors (TKI)] for the first-line treatment of mccRCC. Nivolumab/ipilimumab is approved for the treatment of patients with intermediate and poor prognoses. Several checkpoint inhibitors (pembrolizumab, nivolumab, avelumab) in combination with TKI (axitinib, lenvatinib, cabozantinib) are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression. There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.     

Osteoblastic bone metastases from renal cell carcinoma

Background

RCC accounts for only 2–3% of all cancers. Due to its’ non-specific symptoms disease is often diagnosed in advanced stage. Disseminated RCC frequently produces bone metastases that are almost always highly destructive, hyper vascularized and purely osteolytic.

Case report.

In this article we describe a case of a 71-year old male patient with disseminated osteoblastic bone metastases from renal cell carcinoma (RCC), and present a short review of published literature reporting cases of osteoblastic bone metastases from RCC. Our patient presented with thoracic pain aggravated by movement. He was diagnosed with predominantly osteoblastic bone metastases in the skeleton of thoracic and lumbar vertebra along with metastases in iliac bones, ribs, humerus and clavicles. Initially, origin of bone metastases was unknown, but later a small tumor in patient’s right kidney was identified. Microscopic evaluation of the open bone biopsy showed clear cell RCC with sarcomatoid differentiation.

Conclusions

Although, due to its’ rarity, RCC is not included in the primary differential diagnosis in patients with osteoblastic metastases, such rare cases suggest that RCC may be considered in the diagnosis when there no other primary tumor is found.     

Obesity Treatment Using a Bioenterics Intragastric Balloon (BIB)—Preliminary Croatian Results

Aim of Study  

This study aims to assess the effectiveness, tolerance, safety, and patient satisfaction of obesity treatments using the Bioenterics intragastric balloon (BIB).