抗肿瘤药外渗性皮肤损伤的防治进展

抗肿瘤药外渗是化疗过程中的常见并发症之一。药物渗漏到皮下组织,可引起局部红肿、疼痛,甚至造成皮肤组织坏死,给患者带来巨大的痛苦,应引起广泛重视。应以预防为主,一旦发生药物外渗,根据不同外渗药物,立即采取相应处理,减少炎症和组织坏死。近年来,随着大量研究和临床实践不断深入,抗肿瘤药外渗的防治有了一定提高。     

Prevention of cytotoxic drug induced skin ulcers with dimethyl sulfoxide (DMSO) and α-tocopherole

Accidental subcutaneous extravasation of several antineoplastic agents may provoke skin ulcerations for which there has been no simple and effective treatment. Since January 1983 we have treated all patients in our institution sustaining extravasation by a cytotoxic drug with a combination of DMSO and α-Tocopherole. During the first 48 hr after extravasation a mixture of 10% α-Tocopherole acetate and 90% DMSO was topically applied. The bandage was changed every 12 hr. So far eight patients with extravasation of an anthracycline or Mitomycin were treated on this protocol. No skin ulceration, functional or neurovascular impairment occured in any of these patients. The only toxic effect observed by this treatment was a minor skin irritation. The combination of DMSO and α-Tocopherole seems to prevent skin ulceration induced by anthracyclines and Mitomycin.     

Demonstration of cutaneous doxorubicin extravasation by rhodamine-filtered fluorescence microscopy

Accidental extravasation of the widely used antineoplastic anthracycline doxorubicin (adriamycin) is capable of causing serious and on-going skin and soft tissue necrosis leading to loss of limb function. The only effective cure has been the complete surgical excision of drug-contaminated tissue. Surgical excisions preparatory to skin grafting have often underestimated the extent of drug infiltration into tissue. Using an experimental technique utilizing the drug's natural property of red fluorescence, we were able to effect complete surgical excision by rhodamine fluorescence microscopy in frozen sections of resected skin.     

915 MHz microwave interstitial hyperthermia. Part I: Theoretical and experimental aspects with temperature control by multifrequency radiometry

Microwave interstitial hyperthermia now plays an increasing part in the various hyperthermia techniques used in cancer treatment. This paper will present the design, construction and theoretical as well as experimental study of miniature coaxial antennas designed to heat tumours of various volumes and sizes. Monitoring temperature using multifrequency radiometry during hyperthermia stems naturally from the very design of these antennas. Experiments on phantoms, animals and patients in phase I clinical assessment have demonstrated that microwave interstitial hyperthermia can be achieved with temperature control and monitoring by microwave radiometry.     

Etiology and treatment of chemotherapeutic agent extravasation injuries: a review

While extravasation from intravenous (IV) lines is common and usually benign, leakage of certain drugs can cause severe skin ulceration. These ulcerogenic drugs can be conveniently divided into two categories, depending on whether they bind to DNA. Chemotherapeutic agents such as doxorubicin, which bind to DNA, are especially prone to cause severe extravasation skin ulcers. These ulcers are often chronic and progressive. Neither clinical nor experimental studies have shown an antidote to doxorubicin extravasation, which is best prevented by careful technique. If extravasation is suspected, the infusion should be immediately stopped. In the event of extravasation, elevation and ice are the currently recommended treatment. While small ulcerations may on occasion heal, large ulcerations require surgical excision for relief of pain and salvage of underlying tissues.     

The influence of tissue layering on microwave thermographic measurements

Non-invasive thermal imaging and temperature measurement by microwave radiometry has been investigated for medical diagnostic applications and monitoring hyperthermia treatment of cancer, in the context of heterogeneous body structure. The temperature measured by a radiometer is a function of the emission and propagation of microwaves in tissue and the receiving characteristics of the radiometric probe. Propagation of microwaves in lossy media was analysed by a spectral diffraction approach. Extension of this technique via a cascade transmission line model provides an efficient algorithm for predicting the field patterns of aperture antennas contacting multi-layered tissue. A coherent radiative transfer analysis was used to relate the field pattern of a radiating antenna to its receiving characteristics when used as a radiometer probe, leading to a method for simulating radiometric data. Measurements and simulations were used to assess the effect of overlying fat layers upon radiometer response to temperature hot spots in muscle-type media. Results suggest that dielectric layering in tissue greatly influences measured temperatures and should be accounted for in the interpretation of radiometric data.     

The influence of tissue layering on microwave thermographic measurements

Non-invasive thermal imaging and temperature measurement by microwave radiometry has been investigated for medical diagnostic applications and monitoring hyperthermia treatment of cancer, in the context of heterogeneous body structure. The temperature measured by a radiometer is a function of the emission and propagation of microwaves in tissue and the receiving characteristics of the radiometric probe. Propagation of microwaves in lossy media was analysed by a spectral diffraction approach. Extension of this technique via a cascade transmission line model provides an efficient algorithm for predicting the field patterns of aperture antennas contacting multi-layered tissue. A coherent radiative transfer analysis was used to relate the field pattern of a radiating antenna to its receiving characteristics when used as a radiometer probe, leading to a method for simulating radiometric data. Measurements and simulations were used to assess the effect of overlying fat layers upon radiometer response to temperature hot spots in muscle-type media. Results suggest that dielectric layering in tissue greatly influences measured temperatures and should be accounted for in the interpretation of radiometric data.     

Overexpression of fatty acid synthase is an early and common event in the development of prostate cancer

The expression of fatty acid synthase (FAS), a key lipogenic enzyme and potential target for antineoplastic therapy, was analyzed in 87 frozen needle biopsies of prostate cancer using a highly sensitive immunohistochemical detection technique (Envision). In comparison to normal or benign, hyperplastic glandular structures, which were all negative for FAS staining, immunohistochemical signal was evident in 24/25 low grade prostatic epithelial neoplasia (PIN) lesions, in 26/26 high grade PIN lesions and in 82/87 invasive carcinomas. Staining intensity tended to increase from low grade to high grade PIN to invasive carcinoma. Cancers with a high FAS expression had an overall high proliferative index. No correlation was found between FAS expression and lipid accumulation. These findings indicate that increased FAS expression is one of the earliest and most common events in the development of prostate cancer, suggesting that FAS may be used as a general prostate cancer marker and that antineoplastic therapy based on FAS inhibition may be an option for chemoprevention or curative treatment for nearly all prostate cancers.     

Comparative analysis of radiometric and autoradiographic methods in the investigation of DNA synthetic activity of tumor cells in vitro

DNA synthesis in cell cultures of Ehrlich ascites carcinoma (EAC) was studied by means of autoradiography and liquid scintillation radiometry. The following parameters were compared for estimation of DNA synthesis: a) total radioactivity of incorporated [H-3]thymidine registered by a liquid scintillation counter, b) labeling index (LI) reflecting the relative number of cells which synthesize DNA, and c) mean grain count (MGC) indicating average intensity of DNA synthesis in the S-phase of the cell cycle. Kinetics of total radioactivity of incorporated [H-3]thymidine was determined to correlate better with LI. Changes in DNA synthesis in vitro were shown to be monitored with a higher level of significance by the radiometric technique, but autoradiography was more sensitive in some cases. Priority and informative value of the two methods were discussed. Autoradiography and liquid scintillation radiometry were concluded to be mutually complementary for investigation of DNA synthesis in tumor cells in vitro. Combination of the two methods was recommended for investigation of influence of cell proliferation inhibitors on DNA synthesis.     

Metabolic efficiency of the liver in patients with breast cancer as determined by pharmacokinetics of phenazone

Phenazone pharmacokinetics was determined in 24 healthy women and in 39 women with breast cancer; in the latter before and after antineoplastic treatment. The mean phenazone half-life time (t0.5) was significantly shorter in patients with breast cancer (8.880 +/- 2.5585 h) than in healthy persons (12.024 +/- 3.8486 h, P less than 0.001). Mean elimination rate constant (K, 0.063 +/- 0.0197 h-1) and mean metabolic clearance rate (MCR, 54.968 +/- 20.3476 ml/min) differed statistically (P less than 0.01) from the same parameters in control group, where K was 0.063 +/- 0.0197 h-1, MCR was 41.832 +/- 14.7153 ml/min. In patients receiving antineoplastic drugs, pharmacokinetic parameters of phenazone did not differ significantly in comparison with the initial values. Our results obtained with phenazone as a model substance suggest that in breast cancer elimination of other drugs metabolized by the pathway similar to phenazone also may be changed. This should be considered in selection of their dosage.     

Inductive heating of ferrimagnetic particles and magnetic fluids: Physical evaluation of their potential for hyperthermia

The potential of colloidal subdomain ferrite particle suspensions (SDP) (‘magnetic fluids’), exposed to an alternating magnetic field, is evaluated for hyperthermia. Power absorption measurements of different magnetic fluids are presented in comparison to multidomain ferrite particles (MDP). Variations with frequency as well as magnetic field strength have been investigated. The experimental results clearly indicate a definite superiority of even non-optimized magnetic fluids over MDP ferrites regarding their specific absorption rate (SAR). Based on the work of [Shliomis, Pshenichnikov, Morozov, Shurubor. Magnetic properties of ferrocolloids. J Magn Magn Mater 1990;85:40–46 and [Hanson The frequency dependence of the complex susceptibility of magnetic fluids. J Magn Magn Mater, 1991;96 (In press).], a solid-state physical model is applied to explain the specific properties of magnetic fluids with respect to a possible use in hyperthermia. The experimentally determined SAR data on magnetic fluids are used to estimate the heating capabilities of a magnetic induction heating technique assuming typical human dimensions and tissue parameters. It is considered that for a moderate concentration of 5 mg ferrite per gram tumour (i.e. 0.5% w/w) and clinically acceptable magnetic fields, intratumoral power absorption is comparable to RF heating with local applicators and superior to regional RF heating (by comparison with clinical SAR measurements from regional and local hyperthermia treatments). Owing to the high particle density per volume, inductive heating by magnetic fluids can improve temperature distributions in critical regions. Furthermore, localized application of magnetic fluids in a tumour might be easier and less traumatic than interstitial implantation techniques.     

Cardiotoxicity of Antineoplastic Agents: What Is the Present and Future Role for Imaging?

As antineoplastic treatment options expand at an increasing rate, both traditional and novel agents continue to be limited by their cardiotoxic effects. While functional decline becomes clinically apparent at late states of toxicity, little is known about early stages during which treatment or prevention may still be an option. Several imaging modalities, including echocardiography, multiple gated acquisition, and cardiac magnetic resonance imaging have the ability to identify cardiac effects before they produce clinical symptoms. Here we discuss the current and future role of cardiac imaging in the assessment of cardiotoxicity of antineoplastic agents.     

Hodgkin's disease in HIV

The outcome of patients with HIV-HD has improved with better, combined antineoplastic and antiretroviral approaches. New and effective antiretroviral drugs (ie, protease inhibitors), in conjunction with nucleoside analogs, improve the control of the underlying HIV infection when used during treatment of HD with chemotherapy. In fact, the possibility of reducing viral load to undetectable levels and increasing the CD4+ cell count reduces the risk of OIs during antineoplastic treatment. The inclusion of hematopoietic growth factors in the treatment of patients with HIV-HD may allow for the administration of higher dose-intensity chemotherapy and the prolonged use of antiretroviral drugs, with the aim of improving the survival. Finally, more effective antineoplastic regimens--such as high-dose chemotherapy with autologous stem cell transplantation (which is required in the case of HIV-HD, due to its aggressiveness)--should be considered to improve the response rate and disease-free survival of these patients.     

介入化疗治疗子宫颈癌49例分析

[目的]评价经子宫动脉介入灌注化疗对子宫颈癌的疗效及并发症.[方法]49例子宫颈癌采用Seldinger技术,经右侧股动脉穿刺并分别插管至左、右子宫动脉行灌注化疗.[结果]介入治疗后症状缓解率为100.0%,均行根治术.46例患者可观察到肿块体积明显缩小,总有效率为93.8%.[结论]经子宫动脉灌注化疗可作为根治术前常规的辅助方法.     

Recent advances in understanding the antineoplastic mechanisms of farnesyltransferase inhibitors

Farnesyltransferase (FTase) inhibitors (FTI) have broad antineoplastic actions targeting both cancer cells and mesenchymal cells involved in tumor angiogenesis. The small GTPases H-Ras, Rheb, and RhoB and the centromere proteins CENP-E and CENP-F are relevant targets of farnesylation inhibition; however, their relative importance in the antineoplastic effect of FTIs may vary in different cell types at different stages of the cell cycle and at different stages in oncogenesis. Three recent studies argue that Ras-independent and perhaps even FTase-independent properties are important to the antineoplastic action of this class of drugs. In mice, genetic ablation of FTase does not abolish the oncogenic activity of Ras, limiting the original conception of FTIs as an effective means to target Ras in cancer cells. FTase may not be the sole molecular target of these agents, and one study has suggested that FTIs act by targeting geranylgeranyl transferase II. Lastly, we have obtained evidence that induction of reactive oxygen species and reactive oxygen species-mediated DNA damage by FTIs may be critical for their antineoplastic action as a class. Together, these findings may alter thinking about how to apply FTIs in the clinic.     

Study of patients with intravenous contrast extravasation on CT studies, with radiology staff and ward staff cannulations

Introduction: Intravenous (IV) contrast extravasation is an adverse outcome of computed tomography (CT) studies. This study evaluates for any differences in rates of extravasation between radiology (radiographer) staff and ward medical staff cannulations, and secondarily by cannula size and study type. Method: A prospective study of 26 854 studies in adults between September 2004 and April 2008 accumulated 119 extravasations. Patients were divided into two groups, those cannulated by radiology staff and those cannulated by non‐radiology staff. Patients with extravasations were followed for treatment outcomes. Statistical analysis between our groups was undertaken. Results: The total extravasation rate was 0.44%. The extravasation rate for those patients cannulated by radiology staff was 0.34% (n = 11 470 cannulations) and those cannulated by non‐radiology staff was 0.52% (n = 15 384 cannulations). This was not statistically significantly different. The site where most extravasations occurred was at the elbow (71.4%). The injection rate where most extravasations occurred was in the 1–2 mL/s range (42%). No patient required surgical intervention or had any significant morbidity. Conclusion: Radiology radiographer staff can provide safe administration of IV contrast in CT scanning with low rates of extravasation. Extravasation may occur with high or low injection rates and when small or large size cannulas are used.     

Survival of intravenous chemotherapy infusion sites

Factors associated with the failure of intravenous infusions due to phlebitis and extravasation were studied with 218 infusions delivering cytotoxic drugs. The survival rate of these infusions was not significantly different from that of 56 non-cytotoxic infusions in oncology patients. Although survival analysis indicated that cisplatin was associated with longer survival, this was probably an artifact caused by this drug usually being preceded by 24 h prehydration. Multivariate analysis indicated that etoposide was the only drug associated with decreased infusion survival and that bleomycin, cyclophosphamide, doxorubicin, ifosphamide, methotrexate, treosulphan and 5-fluorouracil had no significant effects. Also age of patient, infusion site and flow rate had no effects but survival was shorter in women. Follow-up indicated that failure of an infusion tended to result in loss of the vein. It is suggested that irritancy of the large volumes of intravenous fluids given to hydrate these patients rather than the cytotoxic drugs was the main factor reducing the survival of these infusions.     

Antineoplastic effects and mechanism of action of IFN-alpha on brain tumors with use of fluorescent isothiocyanate-labelled IFN

The antineoplastic effects and mechanism of IFN-alpha with a newly designed fluorescent isothiocyanate-labelled IFN-alpha were studied on three established glioma-cell lines and cultured cells of clinical brain tumors. Viability, cell cycle and cells showing positive reaction with fluorescent isothiocyanate-labelled IFN were analyzed by flow cytometry. U373MG glioma cells in contact with 10(4) IU/ml of IFN for 24 hours had a dose dependency, decreased viability, S-phase block in the cell cycle and high rate of positive reaction with fluorescent isothiocyanate-labelled IFN. Two surgical cases, except for one case, showed similar results and other cell lines or meningiomas were not affected by IFN. As the antineoplastic effects of IFN-alpha correlated with the rate of occurrence of positive cells with fluorescent isothiocyanate-labelled IFN, sensitive tumor cells may have a respective specific receptor for IFN-alpha, and, therefore, fluorescent isothiocyanate-labelled IFN-alpha might be of clinical value with regard to the problem of the receptor as well as sensitivity test.     

The efficacy of saline washout technique in the management of exfoliant and vesicant chemotherapy extravasation: a historical case series report

This report presents the results from a historical case series of cytotoxic drug extravasations managed by saline washout; its purpose is to assess the efficacy of the procedure based on patient outcome. Eighty‐nine patients were identified as having experienced a vesicant or exfoliant extravasation from incident reports filed over a 10‐year period, from 1 April 2001 to 31 March 2011. Outcome was measured against the need for further surgical treatment being required. Of the 89 cases assessed for efficacy of saline washout one patient experienced a wound infection, which was treated effectively with oral antibiotics. There were no other complications reported and no patients required further treatment with surgical debridement. The majority of patients had no deferral of treatment as chemotherapy could be continued in their unaffected arm immediately following saline washout procedure. For patients where cannulation in their opposite arm for continuation of treatment was not advisable chemotherapy was delayed between 3 and 7 days. Hospitalisation as a result of the extravasation or subsequent treatment was not required in any of the 89 cases. Results indicate that saline washout technique is a safe and effective management strategy for the treatment of both vesicant and exfoliant chemotherapy extravasation.     

几丁糖、透明质酸酶治疗多西紫杉醇外渗性大鼠皮肤损伤

背景与目的:多西紫杉醇外渗至周围组织可导致严重皮肤损伤,目前还没有公认的治疗指南.本研究旨在探讨单用或联合局部外涂几丁糖、注射透明质酸酶对多西紫杉醇大鼠外渗性皮肤损伤的疗效.方法:在30只SD大鼠双后肢建立多西紫杉醇血管外渗模型.随机分为6组,分别给局部外涂几丁糖、局部注射透明质酸酶、局部注射透明质酸酶联合外涂几丁糖、局部外涂生理盐水、局部注射生理盐水和不进行任何处理(模型对照组).观察各组大鼠外渗性皮肤损伤发生率、损伤程度和损伤愈合时间.结果:透明质酸酶组和透明质酸酶联合几丁糖组的损伤发生率分别为30%和20%,显著低于几丁糖组、生理盐水外涂组、生理盐水注射组和模型对照组的损伤发生率(90%、100%、90%、100%)(P＜0.05).透明质酸酶组和透明质酸酶联合几丁糖组的损伤愈合时间为(12.00±3.00)天和(9.50±2.12)天,显著短于其它4组(P＜0.01).几丁糖组的损伤愈合时间为(18.33±2.00)天,显著短于生理盐水外涂组[(23.70±2.41)]天和模型对照组[(25.70±2.26)天](P＜0.01).结论:透明质酸酶单独局部注射或联合几丁糖外涂均可减少多西紫杉醇外渗性损伤的发生,缩短损伤愈合时间.单用几丁糖外涂不能防止损伤的发生,却可促进损伤愈合.