The role of transarterial chemoembolization in the treatment of hepatocellular carcinoma in the stage b of BCLC Текст научной статьи по специальности «Клиническая медицина»

II. ХИРУРГИЯ

THE ROLE OF TRANSARTERIAL CHEMOEMBOLIZATION IN THE TREATMENT OF HEPATOCELLULAR CARCINOMA IN THE STAGE B OF BCLC

Tajibayev T.K., Medeubekov U.Sh., Chormanov A.T., Kaniev Sh.A., Issamatov B.K., MD, Baimakhanov B.B.

JSC "National scientific center of surgery named after A.N.Syzganov", Almaty, Kazakhstan

Abstract

Hepatocellular carcinoma is the most common primary tumor pathology of the liver (> 85%), an aggressive course with an unfavorable prognosis. Objective: To analyze the results of transarterial chemoembolization in the intermediate stage of hepatocellular carcinoma. Materials and methods: The study was conducted on the basis of the JSC "National Scientific Center of Surgery" named after A.N. Syzganov in the period 2013-2018. Statistical calculations were performed using Excel, SPSS Statistics by estimating the survival rate using the Kaplan-Meier method. Results: The study included 58 patients with HCC in the B stage of BCLC. The average age of the patients was 60.4 years. The follow-up period was 6-64 months. In 42 patients, the test results for viral hepatitis were positive. 58 patients underwent 103 TACE interventions. After chemoembolization, 8 patients subsequently underwent surgery (liver resection). The one-year survival after TACE in the total cohort was 42%, 2-year - 15% and 3-year - 5%, respectively. In patients older than 60 and 70 years, the 3-year and 5-year survival rates were 0%, the one-year survival rate of the subjects studied in the group over 70 years old was 14.3%. The survival rate among patients in stage B on the Chile-Pugh scale was significantly lower to patients in stage A (82% versus 56% for 6 months and 50% versus 31% for the year, respectively). Statistically significant differences were found in the group with a substantial increase in AFP (> 1000IU/ ml), the Kaplan-Meier survival curve showed a survival rate of 0% after 18 months since the first TACE. Six months after TACE contrast enhanced CT was performed on 36 patients, of which 15 patients showed positive dynamics, in the form of a reduction in size or transformation of the formation, in 6 patients a negative dynamics in the form of an increase in the size of the formation. Conclusion: Despite the small number of patients studied, TACE showed good results in the intermediate stage of HCC. Elderly and senile age, a high degree of liver dysfunction, as well as high AFP values are additional factors that dramatically reduce the life expectancy of patients after TA CE with HCC in stage B-BCLC.

B-BCLC сатысындагы гепатоцеллюлярлы карциноманьщ емдеушде трансартериалды химиоэмболизацияныц рeлi

Таджибаев Т.К., Медеубеков У.Ш., Чорманов А.Т., Каниев Ш.А., Исаматов Б.К., Баймаханов Б.Б.

«А.Н. Сь^анов атындаш Улттык гылыми хирургия орталь™» АК, Алматы, Казахстан

кцддапа

Гепатоцеллюлярлык карцинома - бул бауырдыц ец нег1зг1 таралган патологиясы (> 85%), колайсыз болжамды агрессивт курс. Мацсаты: гепатоцеллюлярлык карциноманыц аралык сатысында трансартериалды химиоэмболиясыныц нэтижелерн талдау. Материалдар мен эдСтер: Зерттеу 2013-2018 жылдардагы А.Н. Сызганов атындагы «Улттык гылыми хирургия орталыгы» базасында етюзшд. Статистикалык есептеулер Excel, SPSS статистикасы бойынша KaplanMeier эд1с1н колданып вм1р суружылдамдыгын багалау аркылы орындалды. Нэтижелер!: Зерттеуде ГЦК бар 58 наукас BCLC аралык сатысында болды. Пациенттердц орташа жасы 60,4 жасты курады. Бакылау кезец 6-64 ай болды. 58 наукаска 103 ТАХЭ жасалынды. Химмиэмболизациядан кей1н 8 наукас кей1н ашык хирургиялык ота (бауырдыц резек-циясы) жасалынды. ТАХЭ ден кейн б\р жылдык ем1р суру керсеткш 42%, 2 жыл - 15% жэне 3 жыл - 5% боллды. 60 жастан 70 жаска дейЫ жастагы наукастарда 3 жылдык жэне 5 жылдык ом1р суру керсеткш 0% болды, 70 жастан аскан топтагы б\р жылдык ем1р сурудецгей 14,3% курады. Чайлд-Пью шкаласы бойынша В кезецщеп пациенттердц ем1р суру децгей А кезецщег! наукастардан айтарлыктай темен болан (82%га карсы 56 % 6 ай 1ш1нде, 50%га карсы 31% б\р жыл 1ш1нде). АФП (> 1000 IU / ml) децгейщег! айкын байкалган топта статистикалык ^ргыдан айтарлыктай айырмашылыктар байкалды, б1р1нш1 ТАХЭ-ден бастап 18 айдан кей1н Каплан-Меерд1ц графиг керсеткш 0% керсетт.i. ТАХЭ ден кей1н КТ алты ай еткен соц 36 наукаска зерттеу журпзшд!, оныц шнде 15 пациент формацияныц мелшер1н азайту немесе турленд1ру турнде оц динамикасын керсетт.i, 6 наукаста тер1с динамика болды. Цорытынды: Зерт-телген наукастардыц аздыгына карамастан, ТАХЭ ГЦК-д.ц аралык сатысында жаксы нэтижелер керсетт.i. %арт жасы, бауыр дисфункциясыныц жогары дэрежесi, сондай-ак жогары АФП керсеткш ГЦК-ныц B-BCLC сатысында ем.р суру узактыгын айтарлыктай темендететн косымша факторлар болып саналады.

ID:2019(59)216 D0l:10.35805/kazsurgeryvhk 2019(59)216 МРНТИ 76.29.49

ABOUT THE АUTHORS

Tajibayev Talgat Kydyraliyevich - MD,

Department of Hepatopancreatobiliary surgery and liver transplantation, JSC «NSCS named after A.N. Syzganov»

Baimakhanov Bolatbek Bimendievich

- Doct. of Med. Sciences, Professor, Chairman of the Board JSC «NSCS named after A.N. Syzganov»

Medeubekov Ulugbek Shalkarovich -

Doct. of Med. Sciences, Professor, Deputy Chairman of the Board of JSC «NSCS named after A.N. Syzganov».

Kaniev Shokan Ahmedbekovich

- Surgeon, Department of Hepatopancreatobiliary surgery and liver transplantation, JSC «NSCS named after A.N. Syzganov»

Issamatov Bekzhan Kalibayevich

- researcher of the JSC «NSCS named after A.N. Syzganov»; doctorant of the Department «Visual diagnostics», JSC "National Medical University"

Keywords

Chemoembolization, Hepatocellular carcinoma, TACE

АВТОРЛАР ТУРАЛЫ

Таджибаев Талгат Кыдыралиулы

- «A.H.CbtfFaHOB атындаш Улттык FbrnbiMH хирургия орталы^ы» FbrnbiMtt кызметкер^ хирург.

Баймаханов Болатбек Бимендеулы -

м.ьд. профессор, А.Н.СызЕанов атындаш Улттык рыылыми хирургия орталы^ы» баскармасынын тераЕасы. Медеубеков Улыцбек Шалхарулы -м.ед. профессор, А.Н.СызЕанов атындаш Улттык рыылыми хирургия орталы^ы» баскарма тераЕасынын орынбасары. Чорманов Алмат Турсыжанулы - м^.к., АМСы^анов атындаш Улттык Fылыми хирургия орталы^ы» бас дэр1гер1 Каниев Шоцан Ахмедбекулы -«А.Н.СызFанов атындаш Улттык Fылыми хирургия орталы^ы» Гепатобилиарлы хирургия жэне бауыр трансплантациясы бол!мшн хирург-дэргерi. Исаматов Бекжан Калибайулы-«А.Н.СызFанов атындаш Улттык шлыми хирургия орталы^ы» Fылыми кызметкерi, «Улттык медицина университетi» «Визуалды диагностика» кафедрасынын докторанты.

ТуЙ1И сездер

Химиоэмболизация, Гепатоцеллюлярлы карцинома, ТАХЭ.

ОБ АВТОРАХ

Таджибаев Талгат Кыдыралиевич -

хирург, научный сотрудник, АО«ННЦХ

им.А.Н.Сызганова».

Баймаханов Болатбек Бимендеевич -

д.м.н, профессор, председатель правления АО «ННЦХим.А.Н.Сызганова».

Медеубеков Улугбек Шалхарович -

д.м.н., профессор, зам. председателя правления по научно-клинической работе АО «ННЦХим.А.Н.Сызганова».

Чорманов Алмат Турсынжанович -

к.м.н., главный врач АО «ННЦХ

им.А.Н.Сызганова».

Каниев Шокан Ахметбекович - хирург отдела гепатобилиарной хирургии и трансплантации печени АО «ННЦХ

им.А.Н.Сызганова».

Исаматов Бауржан Калибаевич -

научный сотрудник, АО «ННЦХ

им.А.Н.Сызганова».

Ключевые слова

Химиоэмболизация, Гепатоцел-люлярная карцинома, ТАХЭ.

Роль трансартериальной химиоэмболизации при лечении гепатоцеллюлярной карциономы в стадии B-BCLC

Таджибаев Т.К., Медеубеков У.Ш., Чорманов А.Т., Каниев Ш.А., Исаматов Б.К., Баймаханов Б.Б.

АО «Национальный научный центр хирургии им. А.Н.Сызганова, Алматы, Казахстан

Аннотация

Гепатоцеллюлярная карцинома - самая частая первичная опухолевая патология печени (>85%), агрессивного течения с неблагоприятным прогнозом. Цель: Проанализировать результаты трансартериальной химиоэмболизации в промежуточной стадии гепатоцеллюлярной карциномы. Материалы и методы: Исследование проводилось на базе АО «Национальный научный центр хирургии»им А.Н.Сызганова в периоде 2013-2018 годы. Статистические расчеты проводились с применением программы Excel, SPSS Statistics путем оценки выживаемости методом Каплана-Майера. Результаты: В исследование были включены 58 пациентов с ГЦК в промежуточной стадии по BCLC. Средний возраст пациентов было 60,4 лет. Период наблюдения пациентов составил 6-64 месяца. У 42 пациентов результаты тестов на вирусные гепатиты были положительными. 58 пациентам выполнено 103 вмешательства ТАХЭ. После химиоэмболизации 8 пациентов в последующем перенесли открытые оперативные вмешательства (резекция печени). Годичная выживаемость после ТАХЭ в общей когорте оставил 42%, 2х-годичная - 15 % и Зх-годичная - 5% соответственно. У пациентов старше 60 и 70 лет 3х летняя и 5 летняя выживаемость составила 0%, годичная выживаемость исследуемых в группе старше 70 лет составила 14,3 %. Процент выживаемости среди пациентов в стадии В по шкале Чайл-Пью значительно уступали пациентам в стадии А (82% против 56% в течение 6 месяцев и 50% против 31% в течение года соответственно). Статистически значимые различия выявлены у группы с выраженным повышением АФП (>1000 IU/ml), кривая выживаемости Каплана-Майера показала выживаемость 0% спустя 18 месяцев с момента первого ТАХЭ. Через 6 месяцев после ТАХЭ КТисследование с контрастным усилением было проведено 36 пациентам, из них у 15 пациентов отмечалась положительная динамика, в виде уменьшения размеров или трансформации образования, у 6 пациентов отрицательная динамика - в виде увеличения размеров образования. Заключение: Несмотря на небольшое количество исследуемых пациентов, ТАХЭ показал хорошие результаты в промежуточной стадии ГЦК. Пожилой и старческий возраст, высокая степень нарушения функции печени, а так же высокие значения АФП являются дополнительными факторами, резко снижающими продолжительность жизни пациентов после ТАХЭ с ГЦК в стадии B-BCLC.

Introduction

Hepatocellular carcinoma (HCC) is the most common primary tumor pathology of the liver (> 85%), an aggressive course with an unfavorable prognosis - 5 years of survival does not exceed 15% [1]. Among the causes of cancer mortality in the world, HCR ranks 2nd - about 746,000 patients died in 2012 [2], [3].

According to various sources, in patients with hepatocellular cancer, the diagnosis of concomitant cirrhosis varies from 30 to 80% [4]. In the etiology of HCC, the leading theory is the theory of viral carcinogenesis, which is a complex and multi-step process. The risk groups for HCC are patients with cirrhosis of any etiology, chronic viral hepatitis, alcoholic and nonalcoholic steatohepatitis, hemochromatosis [5].

Currently, the generally accepted and widespread classification of HCC is the Barcelona Clinical Liver Classification (BCLC, Barcelona Clinic Liver Cancer), which takes into account the prevalence of the tumor process, the functional state of the liver, the objective state of the patient and the intended effectiveness of the treatment. People with hepatocellular carcinoma in the intermediate (B by BCLC) stage have large, multiple cancer nod-

ules, without severe liver failure and macrovascular invasion [6].

Transcatheter arterial chemoembolization (TACE) is the widely used treatment for unresectable HCC. In early stages it is not recommended as first line therapy because of a effectiveness lower than surgery and percutaneous ablation (7); so it represents the treatment of choice in the intermediate HCC and selected cases of advanced HCC. The main goal of this approach is to a obtain tumor necrosis, local neoplastic control, with preserving as much as possible remainder functional liver.

In the presence of all possible types of surgical intervention (transplantation, liver resection), correct interpretation of the results of local (TACE, ablation) and systemic effects is extremely important. Timely rejection of locoregional exposure with a predicted low efficacy of repeated TACE and timely initiation of systemic therapy increases the life expectancy of patients with HCC BCLC B (8).

For untreated HCC in stage B (the expected median of the agent is 16 months [9], [10] or 49% by 2 years [9]. According to a meta-analysis of clinical studies, chemoembolization increases survival in this group of patients up to 19-210 months [9]. However, here, in the intermediate stage, there is

Gender

Degree of liver damage

HBV and HCV HBV, hepatitis B virus;

Male

Female

Child-Pugh A

Child-Pugh B

HBV +

HCV +

Both positive

HCV,

Both negative hepatitis C virus.

n=58

34

24

38

20

21

18

16

%

58,6

41,4

65,5

34,5

36,2

31

5,1

27,6

Age(n=50) Survival (%)

less than 1 year 1-year 3-years 5-years

30-39 y (n=2) 50 50 50 0

40-49 y (n=2) 50 50 0 0

50-59 y (n=29) 65,5 37,9 34,4 3,4

60-69 y (n=10) 100 100 0 0

70-79 y (n=7) 85,7 14,3 0 0

a significant heterogeneity of the median of overall survival - from 36-45 months [11], [12] with a good immediate effect of TACE, up to 11 months with no further treatment (placebo group from the study SHARP for BCLC B patients [13].

This article analyzes the results of TACE and its value at the intermediate stage of HCC.

Purpose

To analyze the results of transarterial chemo-embolization in the intermediate stage of hepato-cellular carcinoma.

Material and methods

The study was conducted on the basis of the JSC «National Scientific Center of Surgery» named after A.N. Syzganov in the period 2013-2018. All subjects underwent blood sampling for routine laboratory tests; alpha-fetoprotein (AFP) level; the presence of hepatitis B, C; ultrasound examination of the liver and CT. When analyzing survival, patients were divided into the following categories: gender, age, degree of liver function damage according to Child-Pugh, the presence of viral hepatitis B and C, and the level of AFP. It is worth noting that the study did not analyze the survival of patients depending on the number and size of HCC nodes, invasion of tumor in the hepatic or portal vein, as well as the number and combination of chemotherapeutic agents during TACE. Statistical calculations were performed using Excel, SPSS Statistics by estimating the survival rate using the Kaplan-Meier method.

Results

The study included 58 patients with HCC in the intermediate stage of BCLC. The average age of the

Table 1.

Features of patients.

Table 2.

Distribution by age of patients.

patients was 60.4 years. The follow-up period was 6-64 months. The average duration of stay in the hospital was 7.2 days.

According to statistics, the study prevailed men over women, 34 to 24, respectively. The patients were also distributed according to the degree of liver damage and the results of viral hepatitis in the blood (Table 1).

The procedure of transarterial chemoemboliza-tion was carried out with the use of Doxorubicin in dosages of 50 mg in combination with Lipiodol or embolizing microspheres of different diameters. In many cases, TACE was conducted with an intercourse interval of 1.5-2 months. Thus, only 58 patients underwent 103 TACE interventions in isolation, of which 18 patients underwent 2 courses of TACE, 10 patients - 3 courses, 5 patients - 4 courses, 3 patients - 5 courses and in 1 case 6 courses, respectively.

The study period of survival was 6-64 months, the overall survival of the entire cohort of patients correlated with world literature data (Figure 1).

One-year survival after TACE in the total cohort left 42%, 2-years- 15% and 3-years - 5%, respectively. It is worth noting that the patient's comorbid background, as well as complications such as portal vein thrombosis, were not considered here.

The study revealed the following statistically significant differences: the influence of old age (> 60 years old) is directly proportional to the decrease in survival, so in patients over 60 and 70 years old, 3 years and 5 years survival rate was 0%, moreover, the 1-year survival rate of the studied people in the group over 70 years old amounted to 14.3% (Table 2). After chemoembolization, 8 patients subsequently underwent open surgery (liver resection).

3

Fig 1.

Overall survival in total cohort (n=58).

12 18 24 30 36 42 48 Survival time (months)

54

60

66

Fig 2.

Distribution by degree of liver function damag e.

Child-Pugh A (n=38) ■Child-Pugh B (n=20)

18 24 30 36 42 48 54 Survival time (months)

In the distribution of groups according to the degree of liver tissue damage, we used the Chi I d-Pugh stendardscale (Fie|ure2).

Tekisg ate accounr tSe hsrdaired livee fuecdieei e c^m^r^i^i^ti^dcineiy:^iti or gjcCietef gurnival sIcwsT me foilowrnuchevges: there wvre ^det^^u^^iehesidr ulficant FiWdteeees of 6 moa-r and vnayearsur-vival, eo iSv (je^r^^i^^^c^^ vS earvlcai among patients instage l -)h fheChileueggrscale wags)gnificant,y (ow infteti^e^ with FtggcA(82% vhi 56% wiiein a megihsand 5d% ve. 31%0uring tteoeeauar.re-spectiveia)iMoreover, one patient from the group with a violation of the liver function of stage A according to Child-Pugh l Fed upto5 years.

The average AFP value was 399 lU/ml (12.760500 lU/ml), while the median rate was 63.8 lU/ml (Figure 3.). 34 patients were tested to determine the level of AFP in the blood, according to these data, the subjects were divided into 3 groups: group 1 -

patients with normal values or with a slight increase of AFP (0-99 IU/ ml), group 2d - 100-999 lU/ml and 3thgroup withamarked increase>1000IU/ml.

In this category, patients with statistically significant differences were found in the group with a pronounced increase in AFP (> 1000 IU / ml), the Kaplan-Meier survival curve shows a survival rate of 0% after 18 months since the first TACE. Thus, it can be assumed that the level of AFP, in particular, a pronounced increase in its value correlates with a lowsurvivalrate.

Six months after the TACE contrast enhanced CT was conducted in 36 patients (Figure 4), of which changes were observed in 21 patients. In 15 patients, there was a positive trend, in the form of a reduction in size or transformation of the formation, in 6 patients, a negative trend was observed in the form of an increase in the size of the formation.

6

Fig 3.

Distribution by degree of alpha-fetoprotein (lU/ml).

W. '•[.

f- - IbSR^u

kwfei f.'-'y^m L'J^fll if&Li

Fig 4.

62 y.o. patient (female). Multinodular form of HCC in SVIII of liver, intensively, unevenly accumulating a contrast agent in the arterial phase.

We would like to note that in this study, the number and size of nodes, the presence of concomitant pathology and the cause of death of the patient were not taken into account, which requires additional observation.

Conclusion

Summarizing the above results, we concluded that, despite the small number of patients studied, TACE showed good results in the intermediate stage of HCC.

Elderly and senile age, a high degree of liver dysfunction, as well as high AFP values are additional factors that dramatically reduce the life expectancy of patients after TACE with HCC in stage B-BCLC.

Active discussions continue between surgeons, interventionists, therapists regarding the priority treatment options for intermediate stage HCC. Undoubtedly, only as a result of constant productive dialogue within a multidisciplinary group can the effectiveness of medical care be increased.

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