The authors have no acknowledgements.

EBUS rehberliğinde sisplatin ile tedavi edilen tüm hastalarda ilgili veriler incelendi. Florida Üniversitesi&#39;nde kurumsal inceleme kurulu bu çalışmayı (# IRB201400823) onayladı. Tüm veriler prospektif olarak toplanmış ve geriye dönük olarak analiz edildi. Aşağıdaki kayıt ölçütleri kullanın. 1. Hasta Seçimi <ol><li> biyopsi ile doğrulanmış küçük hücreli olmayan akciğer kanseri (KHDAK) ya da küçük hücreli akciğer kanseri (KHAK) ve patolojik teyit nüks 18 ve 80 yaşları arasındaki seçin hastalar. 6 ay veya daha uzun süre hiler ve mediastinal yapılara radyasyon en az 50 gy almış hastaların kayıt yaptırmaktadır. EBUS ve uzak metastaz erişilebilir hiler, mediastinal sınırlı nüks hastaları ve peribronşiyal yapıları (lenf nodları, nodül ve kitleleri) içerir. </li><li> çok disiplinli bir göğüs onkoloji tümör kuruluna tüm bu hasta sunuldu ve in ile devam üzerinde fikir birliği elde etmekdiğer lokalize tedavi seçeneklerinin eksikliği nedeniyle tratumoral sisplatin. EBUS rehberliğinde ITC ile devam etme kararı kurumsal göğüs onkoloji tümör kurulu ortak öneri olmalıdır. </li></ol> 2. Endobronşiyal Ultrason (EBUS) Sisplatin, Enjeksiyon -Güdümlü <ol><li> ITC için hiler, mediastinal ve peribronşiyal yapıların esnek bronkoskop ultrason probu dahili ve sağlayan gerçek zamanlı görselleştirme sahip dışbükey bir prob EBUS kullanın. </li><li> Hastalar işlemden önce en az 6 saat süreyle ağızdan gıda ve sıvıların kaçınmaları emin olun. </li><li> Daha önce yayınlanmış literatürde 9, 10 göre, oturum başına 40 mg&#39;lık bir maksimum doz 1 mg / mL&#39;lik bir konsantrasyonda bir sulu çözelti sisplatin oluşturun. Kullanımdan hemen önce% 0.9 NaCI çözeltisi içinde liyofilize sisplatin tozu çözülür. </li><li> damardan başlar de deksametazon 10 mg ve ondansetronun 8 mgprosedürün ning bulantı önlemek için. </li><li> intravenöz midazolam ve fentanil ile bilinçli sedasyon ile yordamı gerçekleştirin (IV). prosedüründen önce% 4 lidokain nebülizasyon 5 mL şeklinde topik anestezi kullanın. </li><li> midazolam, 2 mg fentanil ve 50 ug IV enjeksiyonu ile başlayın. hastaya her 1-2 dakikada bir yeniden değerlendirmeye ve elde etmek ve bilinçli sedasyon devam etmek için ek 1 mg midazolam ve 25 ug fentanil bolus vermek (minimal depresif bilinç hasta sürekli ve bağımsız solunum yolunu korumak mümkün olduğu şekilde, koruyucu refleksleri korumak, ve sözlü komutlara ve fiziksel stimülasyon) duyarlı kalır. sırasıyla, fentanil ve midazolam, 200 ug ve 10 mg maksimum izin verilen doz aşmayın. </li><li> Bir kalp hızı izleme sürekli 3-kurşun elektrokardiyogram, sürekli pulse oksimetre ve solunum hızı ölçümleri dahil, standart izleme kullanın. Yerel ANEST sağlamaklerine ve gerektiği gibi tamamlayıcı O 2. </li><li> solunum yollarında ses tellerinin sayesinde kapsamını ilerlemek. Belirlemek ve hedef lezyon bulun. </li><li> EBUS işlemci açın ve serum fizyolojik 1-2 mL kullanarak kapsam ucundaki balonu şişirmek. Hava yolu duvarı boyunca kapsamını Flex ve lezyon bulun. Lezyonun yeri CT / PET bulguları bağlıdır, ancak ortak sitelerin bazıları subkarinal alanı, sağ ve sol paratrakeal alanları ve sağ ve sol hiler alanları bulunmaktadır. </li><li> kapsam çalışma kanalından bir kılıf içinde yer alır 22 G EBUS iğne dağıtmak ve konumda kilitleyin. NOT: Enjeksiyon sitesi için kesin bir cerrahi koordinatlar olmasına rağmen, yaygın olarak tedavi edilen bazı sitelerin sadece (medial sağ ve sol ana bronş kavşağında) subkarinal, yanal sağ ana bronş doğru paratrakeal (dahil sol paratrakeal) sağ üst lob deliği üzerindede ((sağ üst lob açıklığı altında yanal proksimal bronş intermedius de) sağ hiler ve sol hiler (distal trakea kavşak ve aort kemer ve sol pulmoner arter arasında sol ana at) sol üst lob birleşim ve sol alt lob bronşlar). </li><li> Gerçek zamanlı ultrasonografi eşliğinde, trakeobronşiyal duvar delinme ve hedef lezyon iğne yerleştirin. iğne içinde stile kaldırmak ve bir seferde lezyon 10 mL (1 mg / sisplatin mL) içine sisplatin enjekte. tabaka içinde iğne geri çekin. </li><li> boyunca ilaç enjeksiyonu kolaylaştırmak için farklı yerlerde seans başına dört delikler her lezyon davranın. ponksiyon başına sisplatin 10 mg enjekte edilir. </li><li> seans başına iki lezyonlara birini davranın. birden fazla lezyon oturum başına tedavi edilirse, 40 mg aşmayan oturum başına toplam doz, sisplatin 20 mg her site enjekte edilir. </li><li> worki iğne çıkarınkapsam ng kanalı. </li><li> Distal hava yollarına herhangi bir ek ilaç emme ve bronkoskop çıkarın. </li><li> Hastalar hastane protokolüne uygun olarak kurtarmak ve aynı gün bunları bitmesini sağlayın. </li><li> 4 haftalık toplam haftada bir kez (2.7-2.13 adımlar) sisplatin enjeksiyon tekrar (1. ve 8. günlerde, 15 ve 22). NOT: Bir kez işlendikten sonra, belirli bir lezyon sonraki karşılaşmalar üzerine ITC ile İşleme düşünülmemelidir. </li></ol> 3. Post-enjeksiyon <ol><li> bir takip toraks bilgisayarlı tomografi (BT) veya pozitron emisyon tomografisi (PET / BT) ile yanıtı değerlendirmek 8-12 haftalık son tedavi seansından sonra tarayın. Tedavinin yerinde nüks ve mediasten, hilusta nüks veya supraklaviküler fossa gibi bölgesel nüks olarak lokal nüks tanımlayın. </li></ol>

<ol>
	<li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> International Agency for Research on Cancer. , (2012).</li><li>Siegel, R., Ma, J., Zou, Z., Jemal, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cancer+statistics,+2014.">Cancer statistics, 2014.</a> CA Cancer J Clin. 64 (1), 9-29 (2014).</li><li>Jeremic, B., Videtic, G. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chest+reirradiation+with+external+beam+radiotherapy+for+locally+recurrent+non-small-cell+lung+cancer:+a+review.">Chest reirradiation with external beam radiotherapy for locally recurrent non-small-cell lung cancer: a review.</a> Int J Radiat Oncol Biol Phys. 80 (4), 969-977 (2011).</li><li>Perez, C. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impact+of+irradiation+technique+and+tumor+extent+in+tumor+control+and+survival+of+patients+with+unresectable+non-oat+cell+carcinoma+of+the+lung:+report+by+the+Radiation+Therapy+Oncology+Group.">Impact of irradiation technique and tumor extent in tumor control and survival of patients with unresectable non-oat cell carcinoma of the lung: report by the Radiation Therapy Oncology Group.</a> Cancer. 50 (6), 1091-1099 (1982).</li><li>Hainsworth, J. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Weekly+docetaxel+with+either+gemcitabine+or+vinorelbine+as+second-line+treatment+in+patients+with+advanced+nonsmall+cell+lung+carcinoma:+Phase+II+trials+of+the+Minnie+Pearl+Cancer+Research+Network.">Weekly docetaxel with either gemcitabine or vinorelbine as second-line treatment in patients with advanced nonsmall cell lung carcinoma: Phase II trials of the Minnie Pearl Cancer Research Network.</a> Cancer. 92 (9), 2391-2398 (2001).</li><li>Grossi, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Phase+II+study+of+irinotecan+and+docetaxel+in+patients+with+previously+treated+non-small+cell+lung+cancer:+an+Alpe-Adria+Thoracic+Oncology+Multidisciplinary+group+study+(ATOM+007).">Phase II study of irinotecan and docetaxel in patients with previously treated non-small cell lung cancer: an Alpe-Adria Thoracic Oncology Multidisciplinary group study (ATOM 007).</a> Lung Cancer. 52 (1), 89-92 (2006).</li><li>Celikoglu, F., Celikoglu, S. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intratumoural+chemotherapy+with+5-fluorouracil+for+palliation+of+bronchial+cancer+in+patients+with+severe+airway+obstruction.">Intratumoural chemotherapy with 5-fluorouracil for palliation of bronchial cancer in patients with severe airway obstruction.</a> J Pharm Pharmacol. 55 (10), 1441-1448 (2003).</li><li>Eisenhauer, E. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=New+response+evaluation+criteria+in+solid+tumours:+revised+RECIST+guideline+(version+1.1).">New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).</a> Eur J Cancer. 45 (2), 228-247 (2009).</li><li>Celikoglu, F., Celikoglu, S. I., York, A. M., Goldberg, E. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intratumoral+administration+of+cisplatin+through+a+bronchoscope+followed+by+irradiation+for+treatment+of+inoperable+non-small+cell+obstructive+lung+cancer.">Intratumoral administration of cisplatin through a bronchoscope followed by irradiation for treatment of inoperable non-small cell obstructive lung cancer.</a> Lung Cancer. 51 (2), 225-236 (2006).</li><li>Celikoglu, S. I., Celikoglu, F., Goldberg, E. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Endobronchial+intratumoral+chemotherapy+(EITC)+followed+by+surgery+in+early+non-small+cell+lung+cancer+with+polypoid+growth+causing+erroneous+impression+of+advanced+disease.">Endobronchial intratumoral chemotherapy (EITC) followed by surgery in early non-small cell lung cancer with polypoid growth causing erroneous impression of advanced disease.</a> Lung Cancer. 54 (3), 339-346 (2006).</li><li>Kilburn, J. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Management+of+mediastinal+relapse+after+treatment+with+stereotactic+body+radiotherapy+or+accelerated+hypofractionated+radiotherapy+for+stage+I/II+non-small-cell+lung+cancer.">Management of mediastinal relapse after treatment with stereotactic body radiotherapy or accelerated hypofractionated radiotherapy for stage I/II non-small-cell lung cancer.</a> J Thorac Oncol. 9 (4), 572-576 (2014).</li><li>Goldberg, E. P., Hadba, A. R., Almond, B. A., Marotta, J. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intratumoral+cancer+chemotherapy+and+immunotherapy:+opportunities+for+nonsystemic+preoperative+drug+delivery.">Intratumoral cancer chemotherapy and immunotherapy: opportunities for nonsystemic preoperative drug delivery.</a> J Pharm Pharmacol. 54 (2), 159-180 (2002).</li><li>Sandler, A. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Phase+III+trial+of+gemcitabine+plus+cisplatin+versus+cisplatin+alone+in+patients+with+locally+advanced+or+metastatic+non-small-cell+lung+cancer.">Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer.</a> J Clin Oncol. 18 (1), 122-130 (2000).</li><li>Ciotti, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prospective+evaluation+of+anthracycline-related+early+cardiac+damage:+how+do+we+monitor+it.">Prospective evaluation of anthracycline-related early cardiac damage: how do we monitor it.</a> J Clin Oncol. 19 (22), 4269-4270 (2001).</li><li>Burris, H. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intratumoral+cisplatin/epinephrine-injectable+gel+as+a+palliative+treatment+for+accessible+solid+tumors:+a+multicenter+pilot+study.">Intratumoral cisplatin/epinephrine-injectable gel as a palliative treatment for accessible solid tumors: a multicenter pilot study.</a> Otolaryngol Head Neck Surg. 118 (4), 496-503 (1998).</li><li>Vogl, T. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=CT-guided+intratumoural+administration+of+cisplatin/epinephrine+gel+for+treatment+of+malignant+liver+tumours.">CT-guided intratumoural administration of cisplatin/epinephrine gel for treatment of malignant liver tumours.</a> Br J Cancer. 86 (4), 524-529 (2002).</li><li>Monga, S. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Endoscopic+treatment+of+gastric+cancer+with+intratumoral+cisplatin/epinephrine+injectable+gel:+a+case+report.">Endoscopic treatment of gastric cancer with intratumoral cisplatin/epinephrine injectable gel: a case report.</a> Gastrointest Endosc. 48 (4), 415-417 (1998).</li><li>Monga, S. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intratumoral+therapy+of+cisplatin/epinephrine+injectable+gel+for+palliation+in+patients+with+obstructive+esophageal+cancer.">Intratumoral therapy of cisplatin/epinephrine injectable gel for palliation in patients with obstructive esophageal cancer.</a> Am J Clin Oncol. 23 (4), 386-392 (2000).</li><li>Shepherd, F. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prospective+randomized+trial+of+docetaxel+versus+best+supportive+care+in+patients+with+non-small-cell+lung+cancer+previously+treated+with+platinum-based+chemotherapy.">Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy.</a> J Clin Oncol. 18 (10), 2095-2103 (2000).</li><li>Hanna, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Randomized+phase+III+trial+of+pemetrexed+versus+docetaxel+in+patients+with+non-small-cell+lung+cancer+previously+treated+with+chemotherapy.">Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy.</a> J Clin Oncol. 22 (9), 1589-1597 (2004).</li></ol>

The authors have nothing to disclose.

<html> Bizim el yazması fazla radyasyon bir seçenek değildir hastalar için akciğer kanserinin izole mediastinal ve hiler nüks yönetimine odaklanmaktadır. IMHR insidansı yaklaşık% 9 11&#39;dir. Farklı tedavi seçenekleri palyatif kemoterapi, daha fazla harici ışın radyasyon tedavisi veya destekleyici bakım ve gözetim dahil olmak üzere, bu hastalarda denenmiştir. Kurumumuzda, biz bronkoskopi ile yönlendirilen intratümöral sisplatin ile bu hastaların tedavisinde. <p class="...

Akciğer kanseri tüm kanser bağlı ölümlerin 5 içinde 1 için hem erkek hem de kadın ve hesaplarına dünya çapında en yaygın kanser türüdür. Bu 0.87 1, 2 vaka ölüm oranı vardır. İlk tedaviden sonra nüks akciğer kanseri olan hastalarda en ölümlerin oluşturmaktadır. Tekrarlayan akciğer kanseri için tedavi seçenekleri sınırlıdır. Tekrarlayan akciğer kanseri daha da müdahaleler 3 kabul ve hoşgörü olasılığını azaltmak bütün bunlar, yaşam kalitesinin ve önemli bakıcı tükenmişlik önemli bozulma yol açar ve ek destekleyici bakım gerektirir. KHDAK hastalarının yaklaşık% 30&#39;u radyasyon 4 sonra lokal nüks var. Bu hastalar için tedavi seçenekleri sınırlıdır ve sadece% 10 5, 6 objektif yanıt oranı sistemik kemoterapi içerir.Tekrar göğüs radyasyon mümkün olmasına rağmen, bu palyatif amaçlarla ve belirtilerin giderilmesi için ağırlıklı olarak çalışılmış ve hastalık remisyon 3 için kullanılan olmamıştır. Kurumumuzda, bronkoskopi üzerinden erişilebilir izole mediastinal ve hiler nüks (IMHR) tüm hastalar sisplatin transbronşial tümör içi enjeksiyon (ITC) -Güdümlü endobronşiyal ultrason (EBUS) ile tedavi edildi. sistemik kemoterapi ve / veya eksternal radyoterapi (EBRT) ile eş zamanlı tedavi tedavi onkolog &#39;takdirine göre izin verildi. Bu el yazması güvenliği, etkinliği, fizibilite ve bizim kurumda kullanılan protokol ayrıntılı yöntemler vurgulamaktadır.

<table border="0" cellpadding="0" cellspacing="0" width="261">
	<tbody>
		<tr height="20">
			<td colspan="2" height="20" style="height:20px;width:261px;">Bronchoscope</td>
		</tr>
		<tr height="20">
			<td colspan="2" height="20" style="height:20px;">22 Guage olympus EBUS needle</td>
		</tr>
		<tr height="20">
			<td colspan="2" height="20" style="height:20px;">40 g of cisplatin in 40 mls of normal saline</td>
		</tr>
	</tbody>
</table>

endobronchial ultrasound-guided intratumoral injection of cisplatin for the treatment of isolated mediastinal recurrence of lung cancer

Akciğer kanserli hastalarda izole hiler ve eksternal radyoterapi (EBRT) aşağıdaki mediastinal nüks (IMHR) yaygındır. Bu hastalar birçok tedavi seçeneği yoktur ve genellikle palyatif kemoterapi ya da en iyi destekleyici bakım sunulmaktadır. Endobronşiyal ultrason (EBUS) sisplatin tümör içi enjeksiyon -Güdümlü (ITC) bu hastalar için yeni bir yaklaşımdır. prosedür bilinçli sedasyon altında yapılır. lezyon EBUS kullanarak bronkoskopi ile bulunur ve bir 22-gauge EBUS iğne kapsamında çalışma kanalından gelişmiş ve pozisyonda kilitlenir. ultrasonografi eşliğinde, trakeobronşiyal ağacın duvar delinir ve iğne hedef lezyonun taşınır. İğne stile daha sonra çıkarılır ve sisplatin (40 mg / 40 mi) bir lezyon içine enjekte edilir. Bir iki site seans başına tedavi edilir. prosedürün ayrıntıları kağıt protokolü bölümünde açıklanmıştır. Merkezimizde, 50 siteler 36 hastada tedavi edildi(19 erkek, 17 kadın). Bizim kohort yaş ortalaması 61.9 ± 8.5 yıl idi. Biz 35 hasta ve 41 sitelerinde son analizler gerçekleştirilmiştir. 11/35 (% 31) stabil veya progresif hastalığı (non-yanıt) sahipken 24/35 (% 69), tam ya da kısmi yanıt (yanıt) vardı. Genel olarak, bizim grupta sağkalım vermedi olanlardan çok daha iyi sağkalım sahip yanıtladı hastalarda 8 ay (6-11 ay% 95 CI), oldu.

yanıtı 8-12 hafta tedaviden sonra takip görüntülemesi ile ölçüldü. Yanıtı tam remisyon (CR), kısmi remisyon (PR), stabil hastalık (SD), progresif hastalığı (PH), ya da RECIST 1.1 kriter 8 dayalı yanıtı değerlendirmek mümkün olarak sınıflandırıldı. CR ve PR ile hastalar yanıt olarak kabul edildi, diğerleri olmayan yanıt olarak sınıflandırıldı. İkincil sonuçlar tümör histolojisi, nüks boyutu ve eşzamanlı sistemik tedavi daya...

Watch this Scientific Journal Video about Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer at JoVE.com

Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer

The management of isolated recurrent lung cancer in a previously-irradiated field is challenging. Here, we describe an endobronchial ultrasound (EBUS)-guided cisplatin injection for the management of patients with localized lung cancer recurrence in a previously-radiated field.

Endobronşiyal Akciğer Kanseri İzole Mediastinal Nüks Tedavisinde Sisplatin intratümöral Enjeksiyon Ultrason eşliğinde

Isolated hilar and mediastinal recurrence (IMHR) following external beam radiation therapy (EBRT) in patients with lung cancer is common. These patients ...

endobronchial-ultrasound-guided-intratumoral-injection-cisplatin-for

Research

JoVE Journal

Cancer Research

10.3K Görüntüleme.  University of Florida College of Medicine. The management of isolated recurrent lung cancer in a previously-irradiated field is challenging. Here, we describe an endobronchial ultrasound (EBUS)-guided cisplatin injection for the management of patients with localized lung cancer recurrence in a previously-radiated field. 

Video: Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer

Operating Procedures of the Electrochemotherapy for Treatment of Tumor in Dogs and Cats

Electrochemotherapy (ECT) is a local approach which is used for treating solid tumors of different histologies. Its mechanism is based on cell membrane permeabilization by means of &#34;electroporation&#34;. To achieve the &#34;electroporation&#34; of the cells, electric pulses are generated by a generator and delivered to the target tissue by the use of electrodes. Electroporation is a physical method which is used to introduce molecules, like cytostatic drugs, into the cells that could not pass the cell membrane on their own. In electrochemotherapy, currently, cisplatin and bleomycin are clinically used. Electrochemotherapy antitumor effectiveness is high, for example up to 100% complete response of canine mast cell tumors smaller than 2 cm3 was achieved. Additionally, electrochemotherapy can be used for the treatment of inoperable tumors. One of the important characteristics of electrochemotherapy is that it can be effective as a one-time treatment only. However, in the case of failure or partial tumor response it can be repeated several times with equal or improved effectiveness. Electrochemotherapy is already a standard treatment for cutaneous and subcutaneous tumors of various histologies in human and veterinary oncology. Furthermore, several clinical studies exploiting electrochemotherapy for deep-seated tumors are on-going.

Electrochemotherapy is the local treatment of solid tumors. The main mechanism is electroporation-mediated permeabilization of the tumor cells' membrane which enables increased internalization of cytostatics like bleomycin and cisplatin. Thus, antitumor effectiveness is potentiated at the site of the application of electric pulses to the tumors.

Köpek ve Kedilerde Tümör Tedavisinde Elektrokemoterapi İşletim Prosedürleri

Electrochemotherapy (ECT) is a local approach which is used for treating solid tumors of different histologies. Its mechanism is based on cell membrane ...

Kanser Araştırmaları

The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues

Metastasis is the major cause of cancer death. The role of circulating tumor cells (CTCs) in promoting cancer metastasis, in which lung colonization by CTCs critically contributes to early lung metastatic processes, has been vigorously investigated. As such, animal models are the only approach that captures the full systemic process of metastasis. Given that problems occur in previous experimental designs for examining the contributions of CTCs to blood vessel extravasation, we established an in vivo lung colonization assay in which a long-term-fluorescence cell-tracer, carboxyfluorescein succinimidyl ester (CFSE), was used to label suspended tumor cells and lung perfusion was performed to clear non-specifically trapped CTCs prior to lung removal, confocal imaging, and quantification. Polymeric fibronectin (polyFN) assembled on CTC surfaces has been found to mediate lung colonization in the final establishment of metastatic tumor tissues. Here, to specifically test the requirement of polyFN assembly on CTCs for lung colonization and extravasation, we performed short term lung colonization assays in which suspended Lewis lung carcinoma cells (LLCs) stably expressing FN-shRNA (shFN) or scramble-shRNA (shScr) and pre-labeled with 20 &#956;M of CFSE were intravenously inoculated into C57BL/6 mice. We successfully demonstrated that the abilities of shFN LLC cells to colonize the mouse lungs were significantly diminished in comparison to shScr LLC cells. Therefore, this short-term methodology may be widely applied to specifically demonstrate the ability of CTCs within the circulation to colonize the lungs.

An animal model is needed to decipher the role of circulating tumor cells (CTCs) in promoting lung colonization during cancer metastasis. Here, we established and successfully performed an in vivo assay to specifically test the requirement of polymeric fibronectin (polyFN) assembly on CTCs for lung colonization.

Tümör hücre görselleştirme akciğer dokusu içinde dolaşan bir akciğer kolonizasyon tahlil kurulması

Metastasis is the major cause of cancer death. The role of circulating tumor cells (CTCs) in promoting cancer metastasis, in which lung colonization by ...

Utilization of Ultrasound Guided Tissue-directed Cellular Implantation for the Establishment of Biologically Relevant Metastatic Tumor Xenografts

Preclinical testing of anticancer therapies relies on relevant xenograft models that mimic the innate tendencies of cancer. Advantages of standard subcutaneous flank models include procedural ease and the ability to monitor tumor progression and response without invasive imaging. Such models are often inconsistent in translational clinical trials and have limited biologically relevant characteristics with low proclivity to produce metastasis, as there is a lack of a native microenvironment. In comparison, orthotopic xenograft models at native tumor sites have been shown to mimic the tumor microenvironment and replicate important disease characteristics such as distant metastatic spread. These models often require tedious surgical procedures with prolonged anesthetic time and recovery periods. To address this, cancer researchers have recently utilized ultrasound-guided injection techniques to establish cancer xenograft models for preclinical experiments, which allows for rapid and reliable establishment of tissue-directed murine models. Ultrasound visualization also provides a noninvasive method for longitudinal assessment of tumor engraftment and growth. Here, we describe the method for ultrasound-guided injection of cancer cells, utilizing the adrenal gland for NB and renal sub capsule for ES. This minimally invasive approach overcomes tedious open surgery implantation of cancer cells in tissue-specific locations for growth and metastasis, and abates morbid recovery periods. We describe the utilization of both established cell lines and patient derived cell lines for orthotopic injection. Pre-made commercial kits are available for tumor dissociation and luciferase tagging of cells. Injection of cell suspension using image-guidance provides a minimally invasive and reproducible platform for the creation of preclinical models. This method is utilized to create reliable preclinical models for other cancers such as bladder, liver and pancreas exemplifying its untapped potential for numerous cancer models.

Here, we present a protocol to utilize ultrasound-guided injection of neuroblastoma (NB) and Ewing's sarcoma (ES) cells (established cell lines and patient-derived tumor cells) at biologically relevant sites to create reliable preclinical models for cancer research.

Ultrason kullanımı doku Yönetmen: hücresel implantasyon biyolojik ilgili metastatik tümör Xenografts kurulması için güdümlü

Preclinical testing of anticancer therapies relies on relevant xenograft models that mimic the innate tendencies of cancer. Advantages of standard ...

Evaluation of the Feasibility, Safety, and Accuracy of an Intraoperative High-intensity Focused Ultrasound Device for Treating Liver Metastases

Today, the only potentially curative option in patients with colorectal liver metastases is surgery. However, liver resection is feasible in less than 20% of patients. Surgery has been widely used in association with radiofrequency, cryotherapy, or microwaves to expand the number of treatments performed with a curative intent. Nevertheless, several limitations have been documented when using these techniques (i.e., a traumatic puncture of the parenchyma, a limited size of lesions, and an inability to monitor the treatment in real-time).High-intensity focused ultrasound (HIFU) technology can achieve precise ablations of biological tissues without incisions or radiation. Current HIFU devices are based on an extracorporeal approach with limited access to the liver. We have developed a HIFU device designed for intraoperative use. The use of a toroidal transducer enables an ablation rate (10 cm3&#183;min-1) higher than any other treatment and is independent of perfusion.
The feasibility, safety, and accuracy of intraoperative HIFU ablation were evaluated during an ablate-and-resect prospective study. This clinical phase I and IIa study was performed in patients undergoing hepatectomy for liver metastases. The HIFU treatment was performed on healthy tissue scheduled for resection.Liver metastases measuring less than 20 mm will be targeted during phase IIb (currently ongoing). This set-up allows the real-time evaluation of HIFU ablation while protecting participating patients from any adverse effects related to this new technique.
Fifteen patients were included in phase I&#8211;IIa and 30 HIFU ablations were safely created within 40 s and with a precision of 1&#8211;2 mm. The average dimensions of the HIFU ablations were 27.5 x 21.0 mm2, corresponding to a volume of approximately 7.5 cm3. The aim of the ongoing phase IIb is to ablate metastases of less than 20 mm in diameter with a 5 mm margin.

Here, we present an ablate-and-resect prospective study to evaluate the feasibility, safety, and accuracy of intraoperative high-intensity focused ultrasound ablation in patients undergoing hepatectomy for liver metastases.

Fizibilite, Emanet ve intraoperatif bir yoğun doğruluğunu karaciğer metastaz tedavisi için ultrason cihazı odaklı

Today, the only potentially curative option in patients with colorectal liver metastases is surgery. However, liver resection is feasible in less than 20% ...

Elastic Staining on Paraffin-embedded Slides of pT3N0M0 Gastric Cancer Tissue

The elastic lamina, which is usually located in the sub-mesothelial layer, adjacent to the peritoneum mesothelial cells, is amphiphilic on hematoxylin and eosin (H&amp;E) staining but can be visualized through elastic staining. One of the important benefits of elastic staining is that it makes it easy to determine whether tumor cells have invaded beyond the elastic lamina. This helps in examining the extent of peritoneal surface invasion, thereby distinguishing the pT3 and pT4 stages in gastrointestinal cancer. In this study, we present a protocol to identify elastic fibers in the formalin-fixed, paraffin-embedded pT3N0M0 gastric cancer tissue sections. We prepare 5-&#181;m paraffin sections fixed on slides, and then all the slides are deparaffinated and rehydrated during the staining procedure. Subsequently, all the sections are oxidized by potassium permanganate, bleached by oxalic acid, stained by elastic staining, and counterstained by Van Gieson's. Finally, we examine the effect of staining; elastic lamina is stained blue-black and collagen fibers are stained red, while the cancer cells are stained in varying shades of yellow. We also describe in detail the methods used for determining the positional relationship between cancer cells and elastic lamina. This method is simple, low-cost, and widely applicable in the identification of peritoneal surface invasion in gastrointestinal cancer because of its outstanding selectivity for elastic fibers and authentic results.

Here, we present a protocol of elastic staining to identify elastic fibers in pT3N0M0 gastric cancer tissues on formalin-fixed, paraffin-embedded sections. Subsequently, we describe a method to determine whether tumor cells invade beyond the elastic lamina.

Parafin üzerinde elastik boyama-pT3N0M0 gastrik kanser dokusu gömülü slaytlar

The elastic lamina, which is usually located in the sub-mesothelial layer, adjacent to the peritoneum mesothelial cells, is amphiphilic on hematoxylin and ...

Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma

The recent success of immune checkpoint blockade in melanoma and lung adenocarcinoma has galvanized the field of immuno-oncology as well as revealed the limitations of current treatments, as the majority of patients do not respond to immunotherapy. Development of accurate preclinical models to quickly identify novel and effective therapeutic combinations are critical to address this unmet clinical need. Pancreatic ductal adenocarcinoma (PDA) is a canonical example of an immune checkpoint blockade resistant tumor with only 2% of patients responding to immunotherapy. The genetically engineered KrasG12D+/-;Trp53R172H+/-;Pdx-1 Cre (KPC) mouse model of PDA recapitulates human disease and is a valuable tool for assessing therapies for immunotherapy resistant in the preclinical setting, but time to tumor onset is highly variable. Surgical orthotopic tumor implantation models of PDA maintain the immunobiological hallmarks of the KPC tissue-specific tumor microenvironment (TME) but require a time-intensive procedure and introduce aberrant inflammation. Here, we use an ultrasound-guided orthotopic tumor implantation model (UG-OTIM) to non-invasively inject KPC-derived PDA cell lines directly into the mouse pancreas. UG-OTIM tumors grow in the endogenous tissue site, faithfully recapitulate histological features of the PDA TME, and reach enrollment-sized tumors for preclinical studies by four weeks after injection with minimal seeding on the peritoneal wall. The UG-OTIM system described here is a rapid and reproducible tumor model that may allow for high throughput analysis of novel therapeutic combinations in the murine PDA TME.

We describe a protocol for the ultrasound guided implantation of murine-derived pancreatic ductal adenocarcinoma cell lines directly into the native tumor site. This approach resulted in pancreatic tumors detectable by ultrasound scanning within 2-4 weeks of injection, and significantly reduced the proportion tumor cell seeding on the peritoneal wall as compared to surgical orthotopic implantation.

Murine Pankreatik Duktal Adenokarsinomun Ultrason Eşliğinde Ortotopik İmplantasyonu

The recent success of immune checkpoint blockade in melanoma and lung adenocarcinoma has galvanized the field of immuno-oncology as well as revealed the ...

Perfusion and Inflation of the Mouse Lung for Tumor Histology

The ability to evaluate lung histology is critical for the fields of lung cancer research and cancer metastasis. It is equally important to perform necropsies rapidly and efficiently from studies without sacrificing the quality of the tissues procured. The goal of this protocol is to present a method to rapidly perfuse, inflate, and fix mouse lungs for downstream histological analysis. This method does not standardize lung inflation; thus, it does not require any special procedures or equipment and instead simply instills fixative directly through the trachea following perfusion through the heart. This allows for sufficient estimation of tumor size, histology, and scoring. This also allows for the collection of frozen tissue prior to lung tissue fixation. This method is limited in that it does not allow for later morphometric quantification of the lung; however, it is more than sufficient for lung tumor analysis from genetically engineered mouse models (GEMMs), syngeneic models, as well as xenograft tumor and metastasis studies.

The purpose of this method is to present a simple and efficient method for the perfusion, inflation, and fixation of mouse lungs for the examination of lung tumor pathology and evaluation of metastases to the lung.

Tümör Histolojisi için Fare Akciğerinin Perfüzyonu ve Enflasyonu

The ability to evaluate lung histology is critical for the fields of lung cancer research and cancer metastasis. It is equally important to perform ...

Pathological Analysis of Lung Metastasis Following Lateral Tail-Vein Injection of Tumor Cells

Metastasis, the primary cause of morbidity and mortality for most cancer patients, can be challenging to model preclinically in mice. Few spontaneous metastasis models are available. Thus, the experimental metastasis model involving tail-vein injection of suitable cell lines is a mainstay of metastasis research. When cancer cells are injected into the lateral tail-vein, the lung is their preferred site of colonization. A potential limitation of this technique is the accurate quantification of the metastatic lung tumor burden. While some investigators count macrometastases of a pre-defined size and/or include micrometastases following sectioning of tissue, others determine the area of metastatic lesions relative to normal tissue area. Both of these quantification methods can be exceedingly difficult when the metastatic burden is high. Herein, we demonstrate an intravenous injection model of lung metastasis followed by an advanced method for quantifying metastatic tumor burden using image analysis software. This process allows for investigation of multiple end-point parameters, including average metastasis size, total number of metastases, and total metastasis area, to provide a comprehensive analysis. Furthermore, this method has been reviewed by a veterinary pathologist board-certified by the American College of Veterinary Pathologists (SEK) to ensure accuracy.

Intravenous injection of cancer cells is often used in metastasis research, but the metastatic tumor burden can be difficult to analyze. Herein, we demonstrate a tail-vein injection model of metastasis and include a novel approach to analyze the resulting metastatic lung tumor burden.

Tümör Hücrelerinin Lateral Kuyruk-Damar Enjeksiyonu Sonrasında Akciğer Metastazının Patolojik Analizi

Metastasis, the primary cause of morbidity and mortality for most cancer patients, can be challenging to model preclinically in mice. Few spontaneous ...

Modeling Brain Metastases Through Intracranial Injection and Magnetic Resonance Imaging

Metastatic spread of cancer is an unfortunate consequence of disease progression, aggressive cancer subtypes, and/or late diagnosis. Brain metastases are particularly devastating, difficult to treat, and confer a poor prognosis. While the precise incidence of brain metastases in the United States remains hard to estimate, it is likely to increase as extracranial therapies continue to become more efficacious in treating cancer. Thus, it is necessary to identify and develop novel therapeutic approaches to treat metastasis at this site. To this end, intracranial injection of cancer cells has become a well-established method in which to model brain metastasis. Previously, the inability to directly measure tumor growth has been a technical hindrance to this model; however, increasing availability and quality of small animal imaging modalities, such as magnetic resonance imaging (MRI), are vastly improving the ability to monitor tumor growth over time and infer changes within the brain during the experimental period. Herein, intracranial injection of murine mammary tumor cells into immunocompetent mice followed by MRI is demonstrated. The presented injection approach utilizes isoflurane anesthesia and a stereotactic setup with a digitally controlled, automated drill and needle injection to enhance precision, and reduce technical error. MRI is measured over time using a 9.4 Tesla instrument in The Ohio State University James Comprehensive Cancer Center Small Animal Imaging Shared Resource. Tumor volume measurements are demonstrated at each time point through use of ImageJ. Overall, this intracranial injection approach allows for precise injection, day-to-day monitoring, and accurate tumor volume measurements, which combined greatly enhance the utility of this model system to test novel hypotheses on the drivers of brain metastases.

Intracranial brain metastasis modeling is complicated by an inability to monitor tumor size and response to treatment with precise and timely methods. The presented methodology couples intracranial tumor injection with magnetic resonance imaging analysis, which when combined, cultivates precise and consistent injections, enhanced animal monitoring, and accurate tumor volume measurements.

İntrakraniyal Enjeksiyon ve Manyetik Rezonans Görüntüleme Ile Beyin Metastazlarının Modellenmesi

Metastatic spread of cancer is an unfortunate consequence of disease progression, aggressive cancer subtypes, and/or late diagnosis. Brain metastases are ...

Modeling Brain Metastasis Via Tail-Vein Injection of Inflammatory Breast Cancer Cells

Metastatic spread to the brain is a common and devastating manifestation of many types of cancer. In the United States alone, about 200,000 patients are diagnosed with brain metastases each year. Significant progress has been made in improving survival outcomes for patients with primary breast cancer and systemic malignancies; however, the dismal prognosis for patients with clinical brain metastases highlights the urgent need to develop novel therapeutic agents and strategies against this deadly disease. The lack of suitable experimental models has been one of the major hurdles impeding advancement of our understanding of brain metastasis biology and treatment. Herein, we describe a xenograft mouse model of brain metastasis generated via tail-vein injection of an endogenously HER2-amplified cell line derived from inflammatory breast cancer (IBC), a rare and aggressive form of breast cancer. Cells were labeled with firefly luciferase and green fluorescence protein to monitor brain metastasis, and quantified metastatic burden by bioluminescence imaging, fluorescent stereomicroscopy, and histologic evaluation. Mice robustly and consistently develop brain metastases, allowing investigation of key mediators in the metastatic process and the development of preclinical testing of new treatment strategies.

We describe a xenograft mouse model of breast cancer brain metastasis generated via tail-vein injection of an endogenously HER2-amplified inflammatory breast cancer cell line.

İnflamatuar Meme Kanseri Hücrelerinin Kuyruk-Ven Enjeksiyonu ile Beyin Metastazının Modellenmesi

Metastatic spread to the brain is a common and devastating manifestation of many types of cancer. In the United States alone, about 200,000 patients are ...