<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="other" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Bone and soft tissue sarcomas, tumors of the skin</journal-id><journal-title-group><journal-title xml:lang="en">Bone and soft tissue sarcomas, tumors of the skin</journal-title><trans-title-group xml:lang="ru"><trans-title>Саркомы костей, мягких тканей и опухоли кожи</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2219-4614</issn><issn publication-format="electronic">2782-3687</issn><publisher><publisher-name xml:lang="en">Publishing House ABV Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">186</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>TUMORS OF THE SKIN</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ОПУХОЛИ КОЖИ</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">Isolated regional chemotherapeutic perfusion oflimbs</article-title><trans-title-group xml:lang="ru"><trans-title>Опыт использования методики изолированной регионарной химиотерапевтической перфузии конечностей</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Aliev</surname><given-names>M. D.</given-names></name><name xml:lang="ru"><surname>Алиев</surname><given-names>М. Д.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Dolgushin</surname><given-names>B. I.</given-names></name><name xml:lang="ru"><surname>Долгушин</surname><given-names>Б. И.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Demidov</surname><given-names>L. V.</given-names></name><name xml:lang="ru"><surname>Демидов</surname><given-names>Л. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Charatishvili</surname><given-names>T. K.</given-names></name><name xml:lang="ru"><surname>Харатишвили</surname><given-names>Т. К.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Buydenok</surname><given-names>Y. V.</given-names></name><name xml:lang="ru"><surname>Буйденок</surname><given-names>Ю. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Narkevitch</surname><given-names>B. Y.</given-names></name><name xml:lang="ru"><surname>Наркевич</surname><given-names>Б. Я.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Martynkov</surname><given-names>D. V.</given-names></name><name xml:lang="ru"><surname>Мартынков</surname><given-names>Д. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>generaloncology@rambler.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Fedenko</surname><given-names>A. A.</given-names></name><name xml:lang="ru"><surname>Феденко</surname><given-names>А. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Bokhyan</surname><given-names>B. Y.</given-names></name><name xml:lang="ru"><surname>Бохян</surname><given-names>Б. Ю.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences</institution></aff><aff><institution xml:lang="ru">Российский онкологический научный центр имени Н.Н. Блохина РАМН</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2010-11-11" publication-format="electronic"><day>11</day><month>11</month><year>2010</year></pub-date><volume>2</volume><issue>4</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>46</fpage><lpage>54</lpage><history><date date-type="received" iso-8601-date="2022-01-11"><day>11</day><month>01</month><year>2022</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2010, Aliev M.D., Dolgushin B.I., Demidov L.V., Charatishvili T.K., Buydenok Y.V., Narkevitch B.Y., Martynkov D.V., Fedenko A.A., Bokhyan B.Y.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2010, Алиев М.Д., Долгушин Б.И., Демидов Л.В., Харатишвили Т.К., Буйденок Ю.В., Наркевич Б.Я., Мартынков Д.В., Феденко А.А., Бохян Б.Ю.</copyright-statement><copyright-year>2010</copyright-year><copyright-holder xml:lang="en">Aliev M.D., Dolgushin B.I., Demidov L.V., Charatishvili T.K., Buydenok Y.V., Narkevitch B.Y., Martynkov D.V., Fedenko A.A., Bokhyan B.Y.</copyright-holder><copyright-holder xml:lang="ru">Алиев М.Д., Долгушин Б.И., Демидов Л.В., Харатишвили Т.К., Буйденок Ю.В., Наркевич Б.Я., Мартынков Д.В., Феденко А.А., Бохян Б.Ю.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://sarbon.abvpress.ru/jour/article/view/186">https://sarbon.abvpress.ru/jour/article/view/186</self-uri><abstract xml:lang="en"><p>Among patients suffering from diseases such as skin melanoma, skin cancer and soft tissue sarcoma, there is a group with locally advanced forms. Standard treatment options may not be effective. For some patients, limbsparing approach is often not possible. Amputation decrease quality of life. Isolated regional perfusion - the method of temporary isolation of the affected limb with the implementation of cardiopulmonary bypass and chemotherapy agents loaded in it. The method of ILP was developed to be able to achieve regional concentrations of chemotherapeutic agents that are 15 to 25 times higher than can be reached with systemic administration, but without the systemic sideeffects. Melphalanbased ILP is associated with complete response rates of 40-50%, and overall response rates of 75-80%. When Tumor Necrosis Factor-alfa was introduced in the isolated limb perfusion model by Lejeune and Lienard in 1988, complete response rates of 80-90% were reported. Multicenter trials confirmed that TNFbased ILP was a highly effective new method of induction biochemotherapy for extremity soft tissue sarcomas with a 20-30% complete remission rate, a 50% partial remission rate and a limb salvage percentage of 80%. We treated 2 patients in RCRC N.N. Blokhin RAMS with isolated limb perfusion with melfalan and mild hyperthermia. Progression not observed for 9 months.</p></abstract><trans-abstract xml:lang="ru"><p>Среди пациентов, страдающих такими заболеваниями, как меланома кожи, рак кожи и саркомы мягких тканей, выделяют группу с местно-распространенными формами опухолевого процесса. Стандартные методы лечения, включающие хирургическое лечение, химио- и лучевую терапию, не всегда оказываются эффективными. Особенности течения болезни иногда не позволяют использовать сохранные оперативные вмешательства, а калечащие операции снижают качество жизни пациентов. Использование методики изолированной регионарной химиотерапевтической перфузии позволяет в этих случаях локально воздействовать на пораженную опухолью область. Изолированная регионарная перфузия - метод временной изоляции пораженной конечности с осуществлением искусственного кровообращения и проведением химиотерапии в ее пределах. Изолированная перфузия конечности позволяет использовать местную концентрацию химиопрепаратов в конечности с опухолью, в 15-25 раз превышающую таковую при системном введении, без системных побочных эффектов. При использовании в качестве химиотерапевтического агента мелфалана полный ответ на лечение при транзиторных метастазах меланомы наблюдается примерно в 40-50% случаев. А общий ответ на лечение составляет 75-80%. Использованный в перфузионном контуре в 1988 гг. исследователями Lejeune и Lienard фактор некроза опухоли-α позволил увеличить частоту полных ответов до 80-90%, а общих ответов - до 95-100%. Мультицентровые исследования подтвердили, что методика изолированной регионарной перфузии с фактором некроза опухоли-α - новый высокоэффективный метод индукционной биохимиотерапии для сарком мягких тканей, локализованных на конечностях, с 20-30% полных ремиссий, 50% частичных ремиссий и процентом сохранения конечности, достигающим 80%. В РОНЦ нами была выполнена изолированная регионарная химиотерапевтическая перфузия в гипертермическом варианте с мелфаланом у двух специально отобранных больных. Прогрессирования не отмечено в течение 9 мес.</p></trans-abstract><kwd-group xml:lang="en"><kwd>isolated regional perfusion</kwd><kwd>melanoma</kwd><kwd>sarcoma</kwd><kwd>melfalan</kwd><kwd>tumor necrosis factor-α</kwd><kwd>hyperthermia</kwd><kwd>cardiopulmonary bypass</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>изолированная регионарная перфузия</kwd><kwd>меланома</kwd><kwd>саркома</kwd><kwd>мелфалан</kwd><kwd>фактор некроза опухоли-α</kwd><kwd>искусственное кровообращение</kwd><kwd>гипертермия</kwd></kwd-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Benckhuijsen С., Kroon В.В., van Geel A.N. et al. Regional perfusion treatment with melphalan for melanoma in a limb: an evaluation of drug kinetics. Eur. J. Surg. Oncol. 1988, v. 14, p. 157-163.</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Omlor G., Gross G., Ecker K.W. et al. Optimization of isolated hyperthermic limb perfusion. World J. Surg. 1993, v. 16, p. 1117-1119.</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Cavaliere R., Ciocatto R.C., Giovanella B.C. et al. Selective heat sensitivity of cancer cells: biochemical and clinical studies. Cancer. 1967, v. 20, p. 1351-1381.</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Clark J., Grabs A.J., Parsons P.G. et al. Melphalan uptake, hyperthermic synergism and drug resistance in a human cell culture model for the isolated limb perfusions of melanoma. Melanoma Res. 1994, v. 4, p. 365-370.</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Rosin R.D., Westbury G. Isolated limb perfusion for malignant melanoma. Practitioner. 1980, v. 224, p. 1031-1036.</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Lejeune F.J., Deloof T., Ewalenko P. Objective regression of unexcised melanoma intransit metastases after hyperthermic isolation perfusion of the limbs with melphalan. Recent. Results Cancer. Res. 1983, v. 86, p. 268-276.</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Minor D.R., Allen R.E., Alberts D. et al. A clinical and pharmokinetic study of isolated limb perfusion with heat and melphalan for melanoma. Cancer. 1985, v. 55, p. 2638-2644.</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Skene A.I., Bulman A.S., Williams T.R. et al. Hyperthermic isolated perfusion with melphalan in the treatment of advanced malignant melanoma of the lower limb. Br. J. Surg. 1990, v. 77, p. 765-767.</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Kettelhack Ch., Kraus Th., Hupp Th. et al. Hyperthermic limb perfusion for malignant melanoma and soft tissue sarcoma. Eur. J. Surg. Oncol. 1990, v. 16, p. 370-375.</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Lienard D., Eggermont A.M.M., Schraffordt Koops H. et al. Isolated limb perfusion with tumour necrosis factor-alpha and melphalan with or without interferon-gamma forthe treatment of in-transit melanoma metastases: a multicentre randomized phase II study. Melanoma Res. 1999, v. 9, p. 491-502.</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Klaase J.M., Kroon B.B.R., Eggermont A.M.M. et al. A retrospective comparative study evaluating the results of «mild» hyperthermic versus «controlled» normothermic perfusion for recurrent melanoma of the extremities. Eur. J. Cancer. 1995, v.31,p. 73-81.</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Vaglini M., Andreola S., Attili A. et al. Hyperthermic antiblastic perfusion in the treatment of cancer of the extremities. Tumori. 1985, v. 71, p. 355-359.</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Bryant P.J., Balderson G.A., Mead P., Egerton W.S. Hyperthermic isolated limb perfusion for malignant melanoma: response and survival. World J. Surg. 1995, v. 19, p. 363-368.</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Cavaliere R., Calabro A., Di Filippo F. et al. Prognosic parameters in limb recurrent melanoma treated with hyperthermic antiblastic perfusion. Proceedings of the International Conference on Regional Cancer. Treatment. Ulm. 1987, G7, p. 163.</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Di Filippo F., Calabro A., Giannarelli D. et al. Prognostic variables in recurrent limb melanoma treated with hyperthermic antiblasticperfusion. Cancer. 1989, v. 63, p. 2551-2561.</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Kroon B.B.R., Klaase J.M., Van Geel A.N., Eggermont A.M.M. Application of hyperthermia in regional isolated perfusion for melanoma of the limbs. Reg. Cancer. Treat. 1992, v. 4, p. 223-226.</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>McBride C.M., Sugarbaker E.V., Hickey R.C. Prophylactic isolation perfusion as the primary therapy for invasive malignant melanoma of the limbs. Ann. Surg. 1975, v. 182, p. 316-324.</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Schraffordt-Koops H., Vaglini M., Suciu S. et al. Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. J. Clin. Oncol. 1999, v. 16, p. 2906-2912.</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Hafstrom L., Rudenstam C.M., Blomquist E. et al. Regional hyperthermic perfusion with melphalan after surgery for recurrent malignant melanoma of the extremities. J. Clin. Oncol. 1991, v. 9, p. 2091-2094.</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Krementz E.T., Carter R.D., Sutherland C.M., Hutton I. Chemotherapy of sarcomas of the limbs by regional perfusion. Ann. Surg. 1977, v. 185, p. 555-564.</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Muchmore J.H., Carter R.D., Krementz E.T. Regional perfusion for malignant melanoma and soft tissue sarcoma: a review. Cancer. Invest. 1985, v. 3, p. 129-143.</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Pommier R.F., Moseley H.S., Cohen J. et al. Pharmacokinetics, toxicity, and short-term results of cisplatin hyperthermic isolated limb perfusion for soft tissue sarcoma and melanoma of the extremities. Am. J. Surg. 1988, v. 155, p. 667-671.</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Klaase J.M., Kroon B.B.R., Benckhuysen C. et al. Results of regional isolation perfusion with cytostatics in patients with soft tissue tumors of the extremities. Cancer. 1989, v. 64, p. 616-621.</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Eggermont A.M.M., Schraffordt Koops H., Klausner J.M. et al. Limb salvage by isolation limb perfusion with tumor necrosis factor alpha and melphalan for locally advanced extremity soft tissue sarcomas: results of 270 perfusions in 246 patients. Proc. Am. Soc. Clin. Oncol. 1999, v. 11, p. 497 (Abstr).</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Eggermont A.M.M., Lienard D., Schraffordt Koops H. et al. Treatment of irresectable soft tissue sarcomas of the limbs by isolation perfusion with high dose TNF-α in combination with gamma-interferon and melphalan. In: Fiers W., Buurman W.A. (Eds). Tumor necrosis factor: molecular and cellular biology and clinical relevance. Basel, Karger. 1993, p. 239-243.</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Eggermont A.M.M., Schraffordt Koops H., Lienard D. et al. Isolated limb perfusion with high-dose tumor necrosis factoralpha in combination with interferon-gamma and melphalan for nonresectable extremity soft tissue sarcomas: a multicenter trial. J. Clin. Oncol. 1996, v. 14, p. 2653-2665.</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Santinami M., Deraco M., Azzarelli A. et al. Treatment of recurrent sarcoma of the extremities by isolated perfusion using tumor necrosis factor alpha and melphalan. Tumori. 1996, v. 82, p. 579-584.</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Eggermont A.M.M., Schraffordt Koops H., Klausner J.M. et al. Isolated limb perfusion with tumor necrosis factor and melphalan for limb salvage in 186 patients with locally advanced soft tissue extremity sarcomas: the cumulative multicenter European experience. Ann. Surg. 1996, v. 224, p. 756-764.</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Gutman M., Inbar M., Lev-Shlush D. et al. High dose tumor necrosis factor-а and melphalan administered via isolated limb perfusion for advanced limb soft tissue sarcoma results in a &gt;90% response rate and limb preservation. Cancer. 1997, v.79,p. 1129-1137.</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Eggermont A.M.M., Schraffordt Koops H., Klausner J.M. et al. Limb salvage by isolation limb perfusion with tumor necrosis factor alpha and melphalan for locally advanced extremity soft tissue sarcomas: results of 270 perfusions in 246 patients. Proc. Am. Soc. Clin. Oncol. 1999, v. 11, p. 497 (Abstr).</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Rossi C.R., Foletto M., Di Filippo F. et al. Soft tissue limb sarcomas: Italian clinical trials with hyperthermic antiblastic perfusion. Cancer. 1999, v. 86, p. 1742-1749.</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Lejeune F.J., Pujol N., Lienard D. et al. Limb salvage by neoadjuvant isolated perfusion with TNFalpha and melphalan for non-resectable soft tissue sarcoma of the extremities. Eur. J. Surg. Oncol. 2000, v. 26, p. 669-678.</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Lans T.E., de Wilt J.H.W., van Geel A.N., Eggermont A.M.M. Isolated limb perfusion with tumor necrosis factor and melphalan for nonresectable Stewart-Treves lymphangiosarcoma. Ann. Surg. Oncol. 2002, v. 9, p. 1004-1009.</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Etten van B., van Geel A.N., de Wilt J.H.W., Eggermont A.M.M. Fifty tumor necrosis factor based isolated limb perfusions for limb salvage in patients older than 75 years with limb-threatening soft tissue sarcomas and other extremity tumors. Ann. Surg. Oncol. 2003, v. 10, p. 32.</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Hill S., Fawcett W.J., Sheldon J. et al. Low dose tumor necrosis factor alpha and melphalan in hyperthermic isolated limb perfusion. Br. J. Surg. 1993, v. 80, p. 995-997.</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>DeWilt J.H.W., Manusama E.R., van Tiel S.T. et al. Prerequisites for effective isolated limb perfusion using tumour necrosis factor-alpha and melphalan in rats. Br. J. Cancer. 1999, v. 80, p. 161-166.</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Manusama E.R., de Wilt J.H.W. ten Hagen T.L.M. et al. Toxicity and antitumor activity of interferon-gamma alone and in combinations with TNF and melphalan in isolated limb perfusion in the BN175 sarcoma tumor model in rats. Oncol. Rep. 1999, v. 6, p. 173-177.</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Lienard D., Eggermont A.M.M., Schraffordt Koops H. et al. Isolated limb perfusion with tumour necrosis factor-alpha and melphalan with or without interferon-gamma for the treatment of in-transit melanoma metastases: a multicentre randomized phase II study. Melanoma Res. 1999, v. 9, p. 491-502.</mixed-citation></ref></ref-list></back></article>
