Медицинская литература. Новинки

 

 

 

 

 

 

Трансартериальная химиоэмболизация микросферами с доксорубицином в лечении неоперабельных больных гепатоцеллюлярным раком (отдаленные результаты)

Вы можете загрузить полный текст статьи в формате pdf

Цель. Оценить эффективность артериальной химиоэмболизации микросферами с доксорубицином у неоперабельных больных гепатоцеллюлярным раком. Материал и методы. В качестве основного лечения артериальная химиоэмболизация выполнена 77 неоперабельным пациентам с гепатоцеллюлярным раком. Применялись методы суперселективной катетеризации долевых (18,2%) либо сегментарных печеночных артерий (81,8%). При этом у 60 (77,9%) больных для катетеризации использовали микрокатетер. Всего 77 больным было выполнено 145 артериальных химиоэмболизаций (в среднем 1,9). Результаты. Тотальный или частичный некроз опухоли по данным КТ и МРТ был достигнут у всех больных. Во время внутриартериального лечения наблюдали существенное уменьшение или стабилизацию уровня αфетопротеина более чем в 90% наблюдений. У 5 (8,5%) пациентов отмечено внепеченочное прогрессирование после 1 курса химиоэмболизации. Один год прожили 78,5% больных, 2 года – 45,8%, 3 года – 30%, 4 года – 17% и 5 лет – 3,4% неоперабельных больных гепатоцеллюлярным раком. Медиана выживаемости составила 23 мес. Живы 30 больных, которые находятся под наблюдением 5–64 мес. Тяжелых осложнений и летальных исходов после эндоваскулярного лечения не было. Заключение. Артериальная химиоэмболизация микросферами с доксорубицином является безопасной и эффективной технологией и может быть рекомендована в качестве метода выбора при лечении больных промежуточной стадии гепатоцеллюлярного рака.

Ключевые слова:
гепатоцеллюлярный рак, артериальная химиоэмболизация, микросферы с доксорубицином.

Литература:
1. Ferlay J., Shin H.R., Bray F., Forman D., Mathers C., Parkin D.M.
Estimates of worldwide burden of cancer in 2008: GLOBOCAN
2008. Int. J. Cancer. 2010; 127 (12): 2893–2917.
2. Kudo M. The 2008 Okuda lecture: Management of hepatocellular carcinoma: from surveillance to molecular targeted therapy.
J. Gastroenterol. Hepatol. 2010; 25 (3): 439–452.
3. Parkin D.M., Bray F., Ferlay G., Pisany P. Global cancer statistics, 2002. CA Cancer J. Clin. 2005; 55 (2): 74–108.
4. Farrell G. AsiaPacific working party on prevention of hepatocellular carcinoma. Prevention of hepatocellular carcinoma in the
AsiaPacific region: consensus statements. J. Gastroenterol.
Hepatol. 2010; 25 (4): 657–663.
5. Llovet J.M., Bruix J. Novel advancements in the management of
hepatocellular carcinoma in 2008. J. Hepatol. 2008; 48 (Suppl. 1):
520–537.
6. Sandhu D.S., Tharayii V.S., Lai J.6P., Roberts L.R. Treatment
options for hepatocellular carcinoma. Expert. Rev. Gastro
enterol. Hepatol. 2008; 2 (1): 81–92.
7. Faber W., Sharafi S., Stockmann M., Sinn B., Puhl G., Bahra M.,
Malinowski M.B., Neuhaus P., Seehofer D. Longterm results of
liver resection for hepatocellular carcinoma in noncirrhotic liver.
Surgery. 2013; 153 (4): 510–517.
8. Yan T., Zhao J.J., Bi X.Y., Zhao H., Huang Z., Li Z.Y., Zhou J.G.,
Li Y., Li C., Cai J.Q., Zhao P. Prognosis of hepatocellular carcinoma: a study of 832 cases. Zhonghua Zhong Liu Za Zhi. 2013;
35 (1): 54–58.
9. Mazzaferro V., Bhoori S., Sposito C., Bongini M., Langer M.,
Miceli R., Mariani L. Milan criteria in liver transplantation for
hepatocellular carcinoma: an evidencebased analysis of 15 years
of experience. Liver Transpl. 2011; 17 (suppl. 2): S44–S57.
10. Bruix J., Llovet J.M. Major achievements in hepatocellular car
cinoma. Lancet. 2009; 373 (9664): 614–616.
11. Palmer D.H., Hussain S.A., Johnson P.J. Systemic therapies for
hepatocellular carcinoma. Expert Opin. Investig. Drugs. 2004;
13 (12): 1555–1568.
12. Gorbunova V.A. Conservative treatment of primary and metastatic liver cancer. Moscow: Medical Information Agency, 2013.
287 p.
13. Bazin I.S. Hepatocellular carcinoma  the current state of problem. Practical Oncology. 2008; 9 (4): 216–228.
14. Ikeda M., Okusaka T., Ueno H., Takezako Y., Morizane C.
A phase II trial of continuous infusion of 5fluorouracil, mitoxantrone, and cisplatin for metastatic hepatocellular carcinoma.
Cancer. 2005; 103 (4): 756–762.
15. Yeo W., Mok T.S., Zee B., Leung T.W., Lai P.B., Lau W.Y.,
Koh J., Mo F.K., Yu S.C., Chan A.T., Hui P., Ma B., Lam K.C.,
Ho W.M., Wong H.T., Tang A., Johnson P.J. A randomized phase
III study of doxorubicin versus cisplatin/interferon alpha
2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma. J. Natl. Cancer
Inst. 2005; 97 (20): 1532–1538.
16. Louafi S., Boige V., Ducreux M., Bonyhay L., Mansourbakht T.,
de Baere T., Asnacios A., Hannoun L., Poynard T., Taieb J.
Gemcitabine plus oxaliplatin (GEMOX) in patients with
advanced hepatocellular carcinoma (HCC): results of a phase II
study. Cancer. 2007; 109 (7): 1384–1390.
17. Llovet J.M., Hilgard P., Gane E., Blanc J.F., de Oliveira A.C.,
Santoro A., Raoul J.L., Forner A., Schwartz M., Porta C.,
Zeuzem S., Bolondi L., Greten T.F., Galle P.R., Seitz J.F.,
Borbath I., Haussinger D., Giannaris T., Shan M., Moscovici M.,
Voliotis D., Bruix J. SHARP (Sorafenib HCC Assessment
Randomized Protocol Trial). N. Engl. J. Med. 2008; 359 (4):
378–390.
18. Wang J.6H., Changchien C.S., Hu T.H., Lee C.M., Kee K.M.,
Lin C.Y., Chen C.L., Chen T.Y., Huang Y.J., Lu S.N. The efficacy of treatment schedules according to Barcelona Clinic Liver
Cancer staging for hepatocellular carcinoma – Survival analysis
of 3892 patients. EJC. 2008; 44 (7): 1000–1006.
19. Cormier J.N., Thomas K.T., Chari R.S., Pinson C.W. Manage
ment of hepatocellular carcinoma. J. Gastrointestinal Surgery.
2006; 10 (5): 761–780.
20. Llovet J.M., Fuster J., Bruix J. The Barcelona approach: diagnosis, staging, and treatment of hepatocellular carcinoma. Liver
Transplantation. 2004; 10 (2 suppl. 1): 115–120.
21. Bruix J., Sala M., Llovet J. Chemoembolization for hepatocellular carcinoma. Gastroenterology. 2004; 127 (5): 179–188.
22. Lencioni R. Management of hepatocellular carcinoma with
transarterial chemoembolization in the era of systemic targeted
therapy. Crit. Rev. Oncol. Hematol. 2012; 83 (2): 216–224.
23. Llovet J.M., Real M.I., Montana X., Planas R., Coll S., Aponte J.,
Ayuso C., Sala M., Muchart J., Solà R., Rodés J., Bruix J. Arterial
embolisation or chemoembolisation versus symptomatic treat
ment in patients with unresectable hepatocellular carcinoma: a
randomised controlled trial. Lancet. 2002; 359 (9319):
1734–1739.
24. Lo C.M., Ngan H., Tso W.K., Liu C.L., Lam C.M., Poon R.T.,
Fan S.T., Wong J. Randomized controlled trial of transarterial
lipiodol chemoembolization for unresectable hepatocellular car
cinoma. Hepatology. 2002; 35 (5): 1164–1171.
25. Hiraoka A., Kumagi T., Hirooka M., Uehara T., Kurose K.,
Iuchi H., Hiasa Y., Matsuura B., Michitaka K., Kumano S.,
Tanaka H., Yamashita Y., Horiike N., Mochizuki T., Onji M.
Prognosis following transcatheter arterial embolization for 121
patients with unresectable hepatocellular carcinoma with or
without a history of treatment. World J. Gastroenterol. 2006; 12
(13): 2075–2079.
26. Kettenbach J., Stadler A., Katzler I.V., Schernthaner R., Blum M.,
Lammer J., Rand T. Drugloaded microspheres for the treatment
of liver cancer: review of current results. Cardiovasc. Intervent.
Radiol. 2008; 31 (3): 468–476.
27. Malagari K., Pomoni M., Moschouris H., Bouma E., Koskinas J.,
Stefaniotou A., Marinis A., Kelekis A., Alexopoulou E., Chatziio6
annou A., Chatzimichael K., Dourakis S., Kelekis N., Rizos S.,
Kelekis D. Chemoembolization with doxorubicineluting beads
for unresectable hepatocellular carcinoma: Fiveyear survival
analysis. Cardiovasc. Intervent. Radiol. 2012; 35 (5): 1119–1128.
28. Poon R. Treatment of Asian Patients with Hepatocellular Carcinoma (HCC) using doxorubicin Eluting Bead Embolization
(PRECISION ASIA STUDY). Presentation at CIRSE 2004.
29. Lewis A.L., Gonzalez M.V., Lloyd A.W., Hall B., Tang Y.,
Willis S.L., Leppard S.W., Wolfenden L.C., Palmer R.R., Strat6
ford P.W. DC bead: in vitro characterization of a drugdelivery
device for transarterial chemoembolization. J. Vasc. Interv.
Radiol. 2006; 17 (2 Pt 1): 335–342.
30. van Malenstein H., Maleux G., Vandecaveye V., Heye S.,
Laleman W., van Pelt J., Vaninbroukx J., Nevens F., Verslype C.
A randomized phase II study of drugeluting beads versus
transarterial chemoembolization for unresectable hepatocellular
carcinoma. Onkologie. 2011; 34 (7): 368–376.
31. Poon R.T., Fan S.T., Lo C.M., Liu C.L., Wong J. Difference in
tumor invasiveness in cirrhotic patients with hepatocellular carcinoma fulfilling the Milan criteria treated by resection and
transplantation: impact on longterm survival. Ann. Surg. 2007;
245 (1): 51–58.
32. Malagari K., Pomoni M., Kelekis A., Pomoni A., Dourakis S.,
Spyridopoulos T., Moschouris H., Emmanouil E., Rizos S.,
Kelekis D. Prospective randomized comparison of chemoem
bolization with doxorubicineluting beads and bland embolization with BeadBlock for hepatocellular carcinoma. Cardiovasc.
Intervent. Radiol. 2010; 33 (3): 541–551.

Transcatheter Arterial Chemoembolization with DoxorubicinLoaded Microspheres in Management of Nonresectable Hepatocellular Carcinoma (Longterm results)

Aim. To evaluate the efficacy of transcatheter arterial chemoembolization (TACE) with Doxorubicinloaded microshperes in management of nonresectable hepatocellular carcinoma (HCC). Materials and Methods. TACE was performed in 77 patients with unoperable HCC as major therapeutic procedure. Superselective approach with embolizations of lobar (18.2%) or segmental (81.8%) hepatic arteries was used. In 60 (77.9%) patients microcatheter was used for the TACE procedure. Totally 145 TACE procedures were performed in 77 patients (average 1.9 per patient). Results. Based on CT or MRI findings complete or partial tumor necrosis was achieved in all patients. During the course of TACE procedures significant decreases or stabilization in the levels of αfetal protein were achieved in more than 90% of cases. In 5 (8.5%) patients extrahepatic progression was documented after one course of TACE. Oneyear survival was documented in 78.5% patients, 2 years – in 45.8%, 3 years – in 30%, 4 years – in 17%, and 5 years – in 3.4% with nonresectable HCC. The survival mediana was 23 months. 30 patients are still alive so far, with FU duration between 5–64 Mo. There were no TACEassociated severe complications of lethal outcomes. Conclusion. TACE procedure with Doxorubicinloaded microspheres is safe and effective modality which can be recommended as a method of choice in management of intermediate HCC stage.

Keywords:
hepatocellular carcinoma, arterial chemoembolization, microspheres with Doxorubicin