Percutaneous sclerotherapy of massive macrocystic lymphatic malformations of the face and neck using fibrin glue with OK-432 and bleomycin

Picibanil (OK-432) and bleomycin have been used as alternative sclerosing agents for lymphatic malformations. This study evaluated the clinical curative effect of sclerotherapy using fibrin glue combined with OK-432 and bleomycin for the treatment of macrocystic lymphatic malformations of the face and neck. Fifteen paediatric patients (6 males; 9 females, aged 13 months to 14 years) who had received percutaneous sclerotherapy for massive macrocystic lymphatic malformations of the face and neck were retrospectively reviewed. Affected regions included the neck, parotid region and parapharynx, mouth floor, face and cheek, and orbital regions. All patients showed preoperative symptoms of space-occupying lesions between 4 cm × 5 cm and 12 cm × 16 cm in size. Fibrin glue with OK-432 and bleomycin was injected under general anaesthesia. All patients received preoperative and follow-up CT scans. Outcomes were assessed by three surgeons. All patients exhibited mid-facial swelling for 3-4 weeks after surgery, but no major complications. Follow-up periods ranged from 8 to 16 months. Eight lesions were completely involuted, five were mostly involuted, and two were partially involuted. Percutaneous sclerotherapy using fibrin glue with OK-432 and bleomycin provided a simple, safe, and reliable alternative treatment for massive macrocystic lymphatic malformations of the face and neck.     

Fibroblast growth factor 2 decreases bleomycin‐induced pulmonary fibrosis and inhibits fibroblast collagen production and myofibroblast differentiation

Fibroblast growth factor (FGF) signaling has been implicated in the pathogenesis of pulmonary fibrosis. Mice lacking FGF2 have increased mortality and impaired epithelial recovery after bleomycin exposure, supporting a protective or reparative function following lung injury. To determine whether FGF2 overexpression reduces bleomycin‐induced injury, we developed an inducible genetic system to express FGF2 in type II pneumocytes. Double‐transgenic (DTG) mice with doxycycline‐inducible overexpression of human FGF2 (SPC‐rtTA;TRE‐hFGF2) or single‐transgenic controls were administered intratracheal bleomycin and fed doxycycline chow, starting at either day 0 or day 7. In addition, wild‐type mice received intratracheal or intravenous recombinant FGF2, starting at the time of bleomycin treatment. Compared to controls, doxycycline‐induced DTG mice had decreased pulmonary fibrosis 21 days after bleomycin, as assessed by gene expression and histology. This beneficial effect was seen when FGF2 overexpression was induced at day 0 or day 7 after bleomycin. FGF2 overexpression did not alter epithelial gene expression, bronchoalveolar lavage cellularity or total protein. In vitro studies using primary mouse and human lung fibroblasts showed that FGF2 strongly inhibited baseline and TGFβ1‐induced expression of alpha smooth muscle actin (αSMA), collagen, and connective tissue growth factor. While FGF2 did not suppress phosphorylation of Smad2 or Smad‐dependent gene expression, FGF2 inhibited TGFβ1‐induced stress fiber formation and serum response factor‐dependent gene expression. FGF2 inhibition of stress fiber formation and αSMA requires FGF receptor 1 (FGFR1) and downstream MEK/ERK, but not AKT signaling. In summary, overexpression of FGF2 protects against bleomycin‐induced pulmonary fibrosis in vivo and reverses TGFβ1‐induced collagen and αSMA expression and stress fiber formation in lung fibroblasts in vitro, without affecting either inflammation or epithelial gene expression. Our results suggest that in the lung, FGF2 is antifibrotic in part through decreased collagen expression and fibroblast to myofibroblast differentiation. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

平阳霉素碘油乳剂动脉内栓塞治疗原发性大肝癌初探

目的回顾性评价平阳霉素碘油乳剂（PLE）经肝动脉化疗栓塞治疗原发性大肝癌的安全性、技术成功率及临床疗效，以期提高患者生活质量及生存率。方法对20例原发性大肝癌患者实施超选择性肿瘤滋养动脉PLE栓塞治疗。随机抽取前期用丝裂霉素碘油乳剂（MLE）治疗的24例原发性大肝癌患者作为对照组，比较两组病例治疗后肿瘤大小、肿瘤血管的改变及生存率等变化。结果研究组较对照组术后肿瘤缩小更明显（X^2=7．51，P〈O．05），甲胎蛋白水平下降显著（X^2=8.290，P〈0．05）。研究组6、12、24、36个月生存率分别为95％（19／20）、70％（14／20）、30％（6／20）和20％（4／20），对照组6、12、24、36个月生存率分别为80％（19／24）、54％（13／24）、21％（5／24）和13％（3／24），两组生存率比较，差异有统计学意义。结论PLE超选择性肿瘤滋养动脉栓塞治疗原发性大肝癌安全，治疗效果明显，其疗效明显优于MLE栓塞治疗。     

Sonographically guided small-bore chest tubes and sonographic monitoring for rapid sclerotherapy of recurrent malignant pleural effusions.

OBJECTIVE: To evaluate the role of sonographically guided small-bore chest catheters and sonographically based monitoring of fluid evacuation in rapid sclerotherapy of malignant pleural effusions. METHODS: In 50 patients with recurrent malignant pleural effusions, a 9F catheter was inserted into the pleural space under sonographic guidance. When sonography documented complete fluid evacuation, bleomycin (0.75 mg/kg) was injected via the tube. Fluid drainage was monitored for 12 hours; if fluid output was less than 100 mL, the pleural catheter was removed; otherwise, a second dose of bleomycin was administered after 24 hours. If loculations or fluid reaccumulations due to tube malfunctioning were detected, they were evacuated by sonographically guided thoracentesis, and bleomycin (1.5 mg/100 mL of fluid) was injected through the thoracentesis needle. All patients were monitored for fluid recurrence with thoracic sonography. RESULTS: Twenty-nine patients received 1 dose of bleomycin, and 21 received 2 doses. In 11 patients with residual loculations, sonographically guided thoracentesis was performed, and bleomycin was injected into the loculations. In 29 patients, pleurodesis was completed within 24 hours; in 21, it was completed within 48 hours. The 30-day response was 84%; the long-term response was 60%. No complications or serious side effects were observed. CONCLUSIONS: Rapid pleurodesis can be accomplished within 24 to 48 hours, with good short- and long-term responses. Thoracic sonography plays a pivotal role. It guides placement of the pleural catheter and is valuable in the monitoring of fluid evacuation for determining the right time for sclerosing agent administration and in the detection and treatment of loculations or residual pleural fluid due to tube malfunctioning.     

Percutaneous treatment of orofacial vascular malformations

The aim of this study was to evaluate the efficacy of fluoroscopy-guided percutaneous injection of bleomycin as the primary treatment for low-flow vascular malformations. A total of 34 patients (mean (range) age 24 (8–51) years) with orofacial vascular lesions were treated in the Department of Interventional Radiology and Maxillofacial Surgery. There were 20 low-flow venous malformations, 11 lymphatic malformations, and three of mixed type. All patients were treated by fluoroscopy-guided percutaneous injection of a mixture of bleomycin (mean (range) 15 (5–15) mg) and a radio-opaque agent (Ultravist^® (iopromide), Bayer)/session. The number of sessions ranged from one to six. The clinical response was complete in 21 patients, obvious in nine, and of clinical benefit in four. Patients were reviewed within the first week, third week, and at three-month periods until 24 months. There were no serious complications such as pulmonary fibrosis. Fluoroscopy-guided intralesional injection of bleomycin should be considered as the first-line treatment for lymphatic malformations because it is effective and reliable with few complications.     

Role of electrochemotherapy in the treatment of metastatic melanoma and other metastatic and primary skin tumors

Electroporation is a novel therapeutic modality that uses pulsed electrical currents to enhance the uptake of drugs, vaccines and genes into cells, and has been used for over 20 years. Electroporation therapy using cytotoxic drugs is called electrochemotherapy. Electrochemotherapy has been studied in vitro, in vivo and in clinical trials. It is potentially useful for treating patients with metastatic tumors, such as melanoma, and even select primary tumors, such as head and neck squamous cell carcinomas and basal cell carcinoma. Various chemotherapeutic agents have been tested with electroporation therapy, but bleomycin and cisplatin are the two most widely used. The biological basis of electroporation therapy is outlined in this review and basic science studies and the limited clinical studies that have involved electrochemotherapy are reviewed. Particular focus is placed on trials involving melanoma, head and neck cancers and other primary and metastatic skin cancers.     

Comprehensive lipid profiling of bleomycin‐induced lung injury

Drug‐induced lung injury is an adverse effect of drug treatment that can result in respiratory failure. Because lipid profiling could provide cutting‐edge understanding of the pathophysiology of toxicological responses, we performed lipidomic analyses of drug‐induced lung injury. We used a mouse model of bleomycin‐induced lung injury and followed the physiological responses at the acute inflammatory (day 2), inflammatory‐to‐fibrosis (day 7) and fibrosis (day 21) phases. The overall lipid profiles of plasma, lung and bronchoalveolar lavage fluid (BALF) revealed that drastic changes in lipids occurred in the lung and BALF, but not in the plasma, after 7 and 21 days of bleomycin treatment. In the lung, the levels of ether‐type phosphatidylethanolamines decreased, while those of phosphatidylcholines, bismonophosphatidic acids and cholesterol esters increased on days 7 and 21. In BALF, the global lipid levels increased on days 7 and 21, but only those of some lipids, such as phosphatidylglycerols/bismonophosphatidic acids and phosphatidylinositols, increased from day 2. The lung levels of prostaglandins, such as prostaglandin D₂, were elevated on day 2, and those of 5‐ and 15‐lipoxygenase metabolites of docosahexaenoic acid were elevated on day 7. In BALF, the levels of 12‐lipoxygenase metabolites of polyunsaturated fatty acids were elevated on day 7. Our comprehensive lipidomics approach suggested anti‐inflammatory responses in the inflammatory phase, phospholipidosis and anti‐inflammatory responses in the inflammatory‐to‐fibrosis phase, and increased oxidative stress and/or cell phenotypic transitions in the fibrosis phase. Understanding these molecular changes and potential mechanisms will help develop novel drugs to prevent or treat drug‐induced lung injury.     

阿奇霉素脂质体对博来霉素致大鼠肺纤维化的影响

目的研究阿奇霉素脂质体对博来霉素诱导大鼠肺纤维化的保护作用。方法 SD大鼠72只,随机分为空白对照组(n=6)、模型组(n=18)、溶液组(n=24)和脂质体组(n=24),后3组一次性向大鼠气管内注入博来霉素5 mg.kg-1制成肺间质纤维化模型,分别每日尾静脉注射给予生理盐水、阿奇霉素溶液(2.50 g.L-1)和阿奇霉素脂质体(2.61 g.L-1),连续28 d,各组分别于d 7、d 14、d 28和停药后d 28(d 56)处死。各组动物处死后测量肺重系数,测定肺组织匀浆内丙二醛(MDA)、羟脯氨酸(HP)含量,提取肺组织进行HE、Masson染色并进行病理半定量分析。结果博来霉素诱导大鼠肺重系数增加,MDA和HP含量增高、肺泡炎和肺纤维化显著,与空白对照组相比有非常显著差异(P<0.01)。d 7、d 14、d 28溶液组和脂质体组与同时点模型组相比肺重系数、MDA和HP含量均显著降低(P<0.05),脂质体组肺泡炎程度于不同时点均减轻(P<0.05)。脂质体组d 56与d 28相比无明显反弹(P>0.05),而溶液组出现反弹(P<0.05)。结论阿奇霉素脂质体能够有效地治疗病变过程中的肺泡炎,对纤维化有明显的防治作用,停药后能持续有效地发挥作用。     

系统性硬化症动物模型

系统性硬化症是一种自身免疫病,以多系统纤维化、小血管病变、血清自身抗体阳性为主要特点。目前其病因尚未十分清楚,越来越多的证据显示可能有血管病变、炎性反应、纤维化、自身免疫四大机制参与并相互作用。在研究系统性硬化症的发病机制、探索新药治疗效果时需要用到动物模型来模拟病理生理过程,而每一种模型都有其特点却又不完美。本文将根据建模方法分类介绍一些经典的和创新的模型,以及它们各自的特点、应用价值,为研究者选择最合适的动物模型提供帮助。