Radioguided occult lesion localisation in combination with detection of the sentinel lymph node in non-palpable breast cancer tumours

PURPOSE OF THE INVESTIGATION: The aim of study was to determine the efficacy of radioguided occult lesion localisation (ROLL) for non-palpable invasive breast cancer combined with sentinel lymph node biopsy (SLNB) and to compare the amount of tissue excised by radioguided navigation versus the hook-wire technique. METHODS: We injected 45 MBq of radiolabelled technetium intratumourally and 15 MBq subdermally 18 hours before surgery in 21 women with bioptically verified non-palpable breast cancer. We identified by gamma probe non-palpable tumours, which were excised, followed by identification and excision of the sentinel lymph node. We compared our results with a group of 12 women with non-palpable lesions marked by hook-wire localisation. RESULTS: ROLL combined with SLNB was successful in 100%; volume of excised tissue was smaller in the hook-wire group but expressed higher variability in volume than in the ROLL group although the difference was not statistically significant. CONCLUSION: The method of ROLL combined with SLNB is technically possible and safe, resulting in minimisation of the surgical intervention and a decrease in postoperative morbidity. ROLL was more precise than the hook-wire procedure even though the amount of tissue excised was the same in both groups.     

Distribution of the Platinum Group Elements in Peat Deposit Near a Historic Lead and Silver Mining District

Concentrations of platinum group elements (PGE) and Ag were studied in a minerotrophic peat deposit near a historic Pb-Ag mining district (Príbram, Czech Republic). The PGE determinations were performed by quadrupole ICP-MS after NiS fire assay procedure. In the individual peat layers (dated by measurement of (210)Pb activity) the PGE concentrations were low and ranged from 0.015 ng g(-1) (Ir) to 11.8 ng g(-1) (Pt). The enrichment of PGE (especially Pt) compared to the Earth crust contents were observed during two periods. The peak in the second half of 19th century was explained by massive increase of ore mining and affinity of PGE to concentrate in molten lead during Pb processing. The recent PGE enrichment in peat layers might be explained by automobile (with catalytic converters) exhaust fumes or processing of computer electronic parts by the smelter.     

Mitomycin C in patients with gynecological malignancies

Mitomycin C (MMC) is an effective cytostatic agent used in the treatment of patients with gynecological malignancies and breast carcinoma. This review presents and discusses the current treatment options with MMC in patients with breast, cervical, and vulvar carcinomas, as well as rarer gynecological malignancies. New combinations and developments are also presented and their potential clinical relevance is examined. Consequently, also for the next years a MMC-containing chemotherapy continues to be a relevant part of an individualized therapy despite numerous innovative new drugs, especially for the salvage therapy of metastatic breast cancer and the simultaneous radiochemotherapy of other gynecological malignancies.     

Erythropoietin facilitates the return of spontaneous circulation and survival in victims of out-of-hospital cardiac arrest

Background

Erythropoietin activates potent protective mechanisms in non-hematopoietic tissues including the myocardium. In a rat model of ventricular fibrillation, erythropoietin preserved myocardial compliance enabling hemodynamically more effective CPR.

Objective

To investigate whether intravenous erythropoietin given within 2 min of physician-led CPR improves outcome from out-of-hospital cardiac arrest.

Methods

Erythropoietin (90,000 IU of beta-epoetin, n = 24) was compared prospectively with 0.9% NaCl (concurrent controls = 30) and retrospectively with a preceding group treated with similar protocol (matched controls = 48).

Results

Compared with concurrent controls, the erythropoietin group had higher rates of ICU admission (92% vs 50%, p = 0.004), return of spontaneous circulation (ROSC) (92% vs 53%, p = 0.006), 24-h survival (83% vs 47%, p = 0.008), and hospital survival (54% vs 20%, p = 0.011). However, after adjusting for pretreatment covariates only ICU admission and ROSC remained statistically significant. Compared with matched controls, the erythropoietin group had higher rates of ICU admission (92% vs 65%, p = 0.024) and 24-h survival (83% vs 52%, p = 0.014) with statistically insignificant higher ROSC (92% vs 71%, p = 0.060) and hospital survival (54% vs 31%, p = 0.063). However, after adjusting for pretreatment covariates all four outcomes were statistically significant. End-tidal PCO₂ (an estimate of blood flow during chest compression) was higher in the erythropoietin group.

Conclusions

Erythropoietin given during CPR facilitates ROSC, ICU admission, 24-h survival, and hospital survival. This effect was consistent with myocardial protection leading to hemodynamically more effective CPR (Trial registration: http://isrctn.org. Identifier: ISRCTN67856342).     

In vivo effects of recombinant human interleukin 2 on antitumor and antiviral natural immunity in induced or natural murine immunodeficiency states

We have examined the ability of in vivo treatment of mice with recombinant interleukin 2 (rIL-2) to affect natural immunity measured against tumor (YAC-1) or virally infected (herpes simplex type 1) target cells. rIL-2 treatment leads to significant increases in natural killer/lymphocyte-activated killer (NK/LAK) function and spleen cells recovered. This effect is dose dependent and strain related. The latter parameter correlated with the pretreatment NK activity level of the strain. The rIL-2 induced NK/LAK augmentation is also kinetically restricted as treatment must have occurred within 48-72 h of assay to be effective. The rIL-2 therapy effectively enhances both antitumor and antiviral NK/LAK activity and results in a noticeable increase in asialo-GM1-positive cells in the spleens of treated mice as well as a significant increase in IL-2 receptor expression as monitored by either cytometry or radioligand binding. In vivo treatment of mice with an antibody directed to the ASGM1 determinant effectively reduces the rIL-2 augmentation of both antitumor and antiviral activity even though this treatment does not affect the pretreatment level of antiviral activity. Various natural and induced immunodeficiency states (immunotherapy, irradiation, immunosuppressive drugs, cytoreductive drugs) have been examined for the ability of in vivo treatment with rIL-2 to enhance NK/LAK activity. In vivo rIL-2 administration is differentially effective in enhancing NK/LAK activity in these situations. Notably, in these induced immunodeficiency states, although NK/LAK activity is commonly enhanced, the number of spleen cells recovered often is only marginally affected. Thus, as expected, a limiting aspect in this use of a natural immunomodulator is the number of potentially responsive cells present in the immunodeficiency condition. In addition, correlations between rIL-2 effect, several of the immunodeficiency states, and vascular leak syndrome are briefly discussed.     

High-Dose Intracoronary Irradiation after De Novo Stent Implantation

PURPOSE: This randomized study was designed to compare the efficacy of high-dose coronary beta-radiation after intravascular ultrasound-(IVUS-)guided direct stenting with sham treatment in patients with de novo lesions. PATIENTS AND METHODS: 32 patients were enrolled in the study protocol. Following angioplasty procedure, intracoronary brachytherapy was performed with the Novoste Beta-Cath System. The prescribed dose was 24 Gy referred to the lamina elastica externa. Quantitative coronary angiography and IVUS were performed to analyze the treated coronary vessel. RESULTS: Angiographic results revealed a significantly smaller minimal lumen diameter compared with the pos-tprocedural minimal lumen diameter within the stented segment (p = 0.004) in the nonirradiated group. The same significant result was observed in the injured segment of the nonirradiated patients (p = 0.011). The IVUS data revealed a significant increase of the plaque volume after 8 months in the nonirradiated group compared to the post-procedural value (irradiated 5.41 +/- 8.83 mm(3) vs. nonirradiated 21.11 +/- 16.08 mm(3); p = 0.001). Late luminal loss was significantly greater in the nonirradiated group (p = 0.004). The primary clinical endpoint (death, myocardial infarction, repeat target lesion revascularization, percutaneous revascularization, coronary artery bypass surgery) was reached by seven irradiated (33.3%) and four (18.2%) nonirradiated patients (p = 0.623). Late stent thrombosis was observed in one irradiated patient. CONCLUSION: The EVEREST trial has demonstrated the feasibility of high-dose intracoronary brachytherapy in de novo coronary lesions. There is a significant reduction of neointimal proliferation within the stented segment. Nevertheless, this benefit is vitiated by an increase of restenotic lesions outside the stent segment.     

Multicatheter interstitial brachytherapy for breast cancer

Brachytherapy remains the best irradiation technique to deliver a high dose in a small volume. Breast brachytherapy is part of the arsenal of therapy in the management of breast cancer. In this article, we present the technical data related to multicatheter interstitial brachytherapy to the breast proceeding, from the implantation of the vectors to the treatment itself. The indications for brachytherapy in breast cancer are boost after whole breast irradiation, accelerated partial breast irradiation or selected patients with second ipsilateral breast tumor event. The results in terms of efficacy and toxicity are presented for each indication. Multicatheter interstitial breast brachytherapy remains a major technique for breast cancer treatment.     

Isoprenoids responsible for protein prenylation modulate the biological effects of statins on pancreatic cancer cells

Background

Statin treatment of hypercholesterolemia is accompanied also with depletion of the mevalonate intermediates, including farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) necessary for proper function of small GTPases. These include Ras proteins, prevalently mutated in pancreatic cancer. In our study, we evaluated the effect of three key intermediates of the mevalonate pathway on GFP-K-Ras protein localization and the gene expression profile in pancreatic cancer cells after exposure to individual statins.

Methods

These effects were tested on MiaPaCa-2 human pancreatic cancer cells carrying a K-Ras activating mutation (G12C) after exposure to individual statins (20 μM). The effect of statins (atorvastatin, lovastatin, simvastatin, fluvastatin, cerivastatin, rosuvastatin, and pitavastatin) and mevalonate intermediates on GFP-K-Ras protein translocation was analyzed using fluorescence microscopy. The changes in gene expression induced in MiaPaCa-2 cells treated with simvastatin, FPP, GGPP, and their combinations with simvastatin were examined by whole genome DNA microarray analysis.

Results

All tested statins efficiently inhibited K-Ras protein trafficking from cytoplasm to the cell membrane of the MiaPaCa-2 cells. The inhibitory effect of statins on GFP-K-Ras protein trafficking was partially prevented by addition of any of the mevalonate pathway’s intermediates tested. Expressions of genes involved in metabolic and signaling pathways modulated by simvastatin treatment was normalized by the concurrent addition of FPP or GGPP. K-Ras protein trafficking within the pancreatic cancer cells is effectively inhibited by the majority of statins; the inhibition is eliminated by isoprenoid intermediates of the mevalonate pathway.

Conclusions

Our data indicate that the anticancer effects of statins observed in numerous studies to a large extent are mediated through isoprenoid intermediates of the mevalonate pathway, as they influence expression of genes involved in multiple intracellular pathways.