Potential and outcomes of surgical treatment of patients with retroperitoneal non-organ liposarcoma invading great vessels

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INTRODUCTION

The majority of patients with retroperitoneal non-organ liposarcomas with invasions to major vessels are considered inoperable in Russi and many other countries. In the literature we were able to find only several reports on resection of major arteries and veins in such patients. In most cases, interventions are performed in the inferior vena cava (IVC) and iliac veins [1-3]. Resections of the aorta, celiac trunk and iliac arteries are performed very seldom [4-7]. At the same time, M.H.M. Schwarzbach et al. (2006) [7] consider that resection of vessels affected by the tumor is required for 18% of patients with retroperitoneal sarcoma, 64% of them need resections of veins, 16% need resections of arteries and 20% require simultaneous resections of arteries and vein. It was demonstrated that large liposarcomas compress or partially infiltrate the inferior vena cava and neighboring veins. Direct invasion of the wall of the vessel is found in histological tests in less than 8% of patients [2, 8]. Depending on the length of infiltration of the vessel wall, parietal or circular resection of the vessel is performed. Patients with less than 50% involvement of the vein circumference undergo parietal resection with direct suturing or closure of the defect with a patch [1]. After circular resection and removal of the affected segment, prosthetic repair or ligation of the vein is performed. The type of repair is directly dependent on the intensity of collateral outflow [1, 9-11]. After circular resection the IVC ligation is performed, as a rule, only in patients with a well-developed venation. F.C.M. Cananzi (2021) and N.A. Devaud et al. (2023) [12, 13] reported possibility of circular resection and ligation of the left renal vein only in the presence of outflow in the adrenal, diaphragm, lumbar and gonadal veins that required to be preserved during the surgery.

After the circular resection of the major arteries, M.M. Bertrand et al. (2016) [14] formed a direct anastomosis or performed re-implantation or prosthetic repair. The only exceptions were allowed for the internal iliac arteries. In the event of involvement of the peritoneal section of the aorta, prosthetics were used, while the visceral branches were preserved. In the literature, there are individual reports of clinical cases of resection with re-implantation and prosthetic repair of the celiac trunk and the superior mesenteric artery in the operation for the resection of the retroperitoneal tumor. All of them were attended with severe complications [5, 7].

There are few reports on the simultaneous resection of iliac arteries and veins as well [6, 14]. A. Lv et al. (2022) [6] found invasion of iliac vessels in 9% of patients with retroperitoneal sarcomas; in 70.8% of them, combined artery and vein resection was performed, in 25.0%, only the vein was resected, and in 4.2%, only the artery.

Multi-organ resections are performed in 50–80% of patients with retroperitoneal sarcomas with invasion of major vessels [9, 15-19]. A.Yu. Volkov et al. (2024) [15] performed multi-organ resections in 53% of patients with G1 retroperitoneal non-organ liposarcomas and in 72% of patients with G2-G3 tumors.

Thus, it follows from literature that radical surgical treatment of retroperitoneal non-organ liposarcoma with invasion of major vessels depends on the active surgical tactic in the volume of tumor resection en bloc with invaded vessels and organs and an adequate approach towards subsequent reconstruction of arteries and veins. This allows for local control and improves remote outcomes of treatment [15, 16] with an acceptable level of complications and mortality [9, 16, 17, 19, 20].

AIM

To demonstrate the feasibility, safety, and efficacy of resection of major arteries (aorta, right/left iliac artery) and veins (inferior vena cava, right/left iliac vein) in patients with retroperitoneal non-organ liposarcomas with major vessel invasion.

MATERIAL AND METHODS

The retrospective study included patients with retroperitoneal non-organ liposarcomas with major vessel invasion who underwent surgical treatment at the N.N. Blokhin National Medical Research Center of Oncology from 2001 to 2023. This included liposarcoma removal with multi-organ resection and resection of major arteries (aorta, right/left iliac artery) and veins (inferior vena cava, right/left iliac vein). Gore-Tex synthetic grafts were used for vascular reconstruction, and neoadjuvant chemotherapy used doxorubicin and ifosfamide. Complications of surgical treatment were assessed using the Clavien-Dindo scale (1992) [21]. Statistical analysis of the study material was performed using Statistica for Windows v.10 and SPSS v21. Differences in the obtained results were considered statistically significant at a p level of ≤0.05 (≥95% accuracy). Survival was calculated using the Kaplan-Meier method, and the significance of differences was assessed using the log-rank test.

RESULTS

Among the 28 patients with retroperitoneal non-organ liposarcomas with invasion of the great vessels there were 9 (32.1%) men and 19 (67.9%) women aged from 22 to 73 years (median age 49.5 [42.5; 55.0] years). Eleven patients (39.3%) had a primary tumor, and 17 (60.7%) had a recurrent tumor. In 13 patients (46.4%), liposarcoma corresponded to stage Ib according to the TNM classification, in 6 (21.4%), stage IIIa, and in 9 (32.1%), stage IIIb. The median size of the tumor was 15.0 [10.0; 28.5] cm (from 6 to 50 cm), and no patients had remote or regionary metastases. In 13 patients (46.4%), the tumor had a high degree of differentiation (G1), in 7 (25%), moderate grade (G2), and in 8 (28.6%), low grade (G3). Multinodular liposarcoma was diagnosed in 12 cases (42.9%). Neoadjuvant chemotherapy (doxorubicin + ifosfamide) was received by 6 patients (21.4%) with a stabilizing effect on the RECIST scale. Along with liposarcoma removal, resection of the main arteries (aorta, right/left iliac artery) was performed in 9 (32.1%) cases, resection of the main veins (inferior cava, right/left iliac veins) in 13 (46.5%) cases, and resection of arteries and veins in 6 (21.4%) cases. The extent of surgery on the major vessels is shown in Table 1. Gore-Tex synthetic grafts were used for vascular reconstruction. In the event a satisfactory collateral outflow was present, in all cases circular resection of the inferior vena cava with ligation was performed.

 

Extent of surgical intervention on the main vessels	Total (n=28)
	Abs.	%
Longitudinal resection
Right/left iliac artery	4	14,3
Inferior vena cava	3	10,7
Left iliac vein	1	3,6
Circular resection
Aortic bifurcation with prosthetic	1	3,6
Left iliac artery with end-to-end repair	1	3,6
Right/left iliac artery with end-to-end repair + circular resection of the right/left iliac vein with ligation	2	7,1
Left iliac artery with prosthetic	3	10,7
Left iliac artery with prosthetic + circular resection of the left iliac vein with ligation	4	14,3
Inferior vena cava with ligation	6	21,4
Inferior vena cava with prosthetic	1	3,6
Right/left iliac vein with ligation	2	7,1

Table 1. The extent of surgical intervention on the main vessels in 28 patients with retroperitoneal non-organ liposarcomas with invasion of the main vessels

Таблица 1. Объем оперативного вмешательства на магистральных сосудах у 28 больных забрюшинными неорганными липосаркомами с инвазией магистральных сосудов

 

Multiorgan resections of 1-5 organs were performed in 21 (75%) patients. In 11 (39.3%) patients, a kidney was removed, in 10 (35.7%) the colon was resected, in 8 (28.6%), the diaphragm, in 4 (14.3%), the adrenal gland was removed, in 2 (7.1%), the liver/duodenum/small intestine/rectum were resected, and in 1 (3.6%) patient, the pancreas.

All 28 patients underwent radical surgery. The median duration of the surgical intervention was 290 [245; 315] min. (170-540 min.). The blood loss varied from 300 to 9000 mL (median 750 [550; 1400] mL). Complications (from 1 to 7) of the surgical treatment developed in 19 (67.9%) patients. In six cases, their severity corresponded to ≥ Class III on the Clavien-Dindo scale. The prevailing complications were the thrombosis of the deep veins of the lower limbs (n=18; 64.3%), followed by pleuritis (n=15; 53.6%), pneumonia (n=8; 28.6%), thrombosis of the inferior vena cava (n=2; 7.1%), renal failure (n=2; 7.1%). In individual cases (3.6% each) there developed type A pancreatic fistula, pancreatic necrosis, hemorrhage from the acute gastrointestinal tract ulcer, multiorgan failure, sepsis and acute cardiovascular failure. Due to complications, 2 (7.1%) patients underwent urgent repeat laparotomy surgeries to stop the bleeding from the duodenum ulcer and to amputate the lower limb against the background of vein thrombosis. The postoperative mortality was 3.6% (n=1).

The duration of the follow-up period for the 28 patients varied from 2.3 to 189.8 months (median 62.5 [14.8; 84.6] months). Within that period, disease progression occurred in 20 (71.4%) patients, in 12 (42.9%), local recurrence, in 7 7 (25%), remote metastases and in 1 (3.6%), both the local recurrence and the remote metastases. Eight (28.6%) of patients dies from progression of the liposarcoma. The overall 1- and 3-year survival was the same: 96.4 ± 3.5%; 5-year survival: 84.4 ± 8.5%; 10-year survival: 39.8 ± 14.6% (median 88.8 [72.3; -] months). Survival without liposarcoma progression, respectively, was 84.8 ± 7.0%, 48.9 ± 11.2%, 21.7 ± 9.5%, 5.4 ± 5.3% and 21.7 [12.2; 52.5] months.

Multivariate Cox regression analysis showed that the overall survival of 28 patients with retroperitoneal non-organ liposarcoma with invasion of great vessels was negatively affected by 3 independent factors. The first factor is the low degree of tumor differentiation: 5-year overall survival of patients with a G3 tumor is reliably lower as compared to G1 and G2 (43.7 ± 31.5% vs. 100% in G1, р=0.045 and 43.7 ± 31.5% vs. 66.7 ± 27.2% in G2, р=0.049). The median of overall survival inpatients with a G3 tumor was 50.7 [24.2;72.2] months, and in the G1 and G2 groups the median was not reached. The second factor is the presence of multinodular tumor. The median of overall survival of patients with a multinodular liposarcoma is credibly lower as compared with a single-nodular tumor (65 [38.2; 79.1] months vs. median not reached, р=0.049), in 5-year outcomes, respectively, 68.8 ± 20.7% and 91.7 ± 8.0%. The third factor is the presence of tumor invasion of organs located near the retroperitoneal non-organ liposarcoma, for which multiorgan resection was performed. The overall survival median of patients who underwent multiorgan resection is credibly (р=0.036) lower at 79.0 [62.3; 94.1] months with the 5-year value of 77.9 ± 11.7% as compared to patients without multiorgan resection who did not reach an overall survival median, the 5-year value being 100%.

Progression-free survival in retroperitoneal non-organ liposarcoma with great vessel invasion was statistically significantly negatively impacted by two independent factors. The first factor was the low tumor differentiation. The median survival of patients with G1 liposarcoma was statistically higher (36.8 [5.0; 42.9] months) as compared to G2 (14.7 [12.4; 19.3] months, р=0.015) and G3 (17.5 [6.3; 59.3] months, р=0.049) at 5-year survival, respectively, of 33.3 ± 23.2%, median not reached, and 26.0 ± 12.8%. The second factor was the presence of tumor recurrence. The median survival of patients with recurrent liposarcoma was credibly (р=0.008) lower at only 16.3 [9.9; 39.5] months with 5-year survival of 11.8 ± 7.8% vs. 96 [37; -] months and 5-year survival in 66.7 ± 27.2% in patients with primary tumors.

DISCUSSION

The results of our study align with literature data. We were able to perform radical surgeries on all patients with a 21.4% (n=6) incidence of complications of ≥ Class III according to the Clavien-Dindo scale and postoperative mortality of 3.6% (n=1). In the work of M.M. Bertrand et al. (2016) [14], the prevalence of R0-resections was 87%, the incidence of severe postoperative complications was 19.3% with no mortalities in the postoperative period. It follows from the literature that the incidence rate of Class III–V on the Clavien–Dindo scale after the resection of retroperitoneal sarcomas with vascular reconstruction varies from 16 to 54% [7, 9, 22-27]. In the large study of the TARPSWG group, such complications arose in 16.4% patients, the postoperative mortality being 1.8% [25]. M. Ferraris et al. (2019) [22] report the level of severe complications at 22.4% with no data on mortality being available.

We stated progression of the liposarcoma, following the treatment, in 71.4% (n=20) patients, the 5-year overall survival rate was 84.4%, and progression-free survival was 21.7%. Multivariate Cox regression analysis showed that the independent factors negatively affecting the overall survival were the low degree of tumor differentiation, the presence of multinodular tumor and the presence of tumor invasion of nearby organs. Progression-free survival in was negatively impacted the low tumor differentiation and the presence of tumor recurrence. According to the transatlantic register, recurrence of the disease is the cause of death for 75% of patients with retroperitoneal sarcomas [28]. In the study of G. Spolverato et al. (2021) [27], in patients with highly malignant tumors with vascular invasion, the incidence rate of local recurrences over 5 years was 45%; in the study of A. Gronchi et al. (2016) [4], the similar metric for 10 years was 59.3%. The generalized literature data shows that 5-year recurrence-free survival rate is 20–35% with the 5-year overall survival being 50-60% [29].

Despite the high technical complexity, radical surgical treatment of patients with retroperitoneal non-organ liposarcomas with invasion of the main vessels is feasible and relatively safe. The patients’ survival largely depends on the degree of tumor malignity and its invasion of the surrounding tissue. We were able to reach an 84.4% of overall 5-year survival. To that end, in 75% of the patients we performed multi-organ resections to ensure that the surgical treatment was radical. Based on many years of personal experience, in performing resections and reconstructions of the main arteries and veins in patients with retroperitoneal liposarcomas with invasion of the main vessels, we recommend, in the presence of a well-developed collateral outflow, resign from the inferior vena cava repair to reduce the risk of thrombosis and infection of the prosthetic, and to relieve the patient from life-long intake of anticoagulants.

CONCLUSION

The results of our study demonstrated that radical surgical treatment of patients with retroperitoneal non-organ liposarcoma with great vessel invasion, including the aorta, is feasible in a specialized clinic. This treatment is associated with an acceptable complication rate and ensures a high overall 5-year survival rate of 84.4 ± 8.5%.

 

ADDITIONAL INFORMATION	ДОПОЛНИТЕЛЬНАЯ ИНФОРМАЦИЯ
Ethical Approval Statement. The article was performed as part of the dissertation “Angioplasty operations in abdominal oncology” for the degree of Doctor of Medical Sciences. The thesis topic was approved by the Scientific Council of the Scientific Research Institute of Clinical Oncology n.a. Academician of the Russian Academy of Sciences and the Russian Academy of Medical Sciences N.N. Trapeznikov, Blokhin National Research Medical Center of Oncology.	Этическая экспертиза. Статья выполнена в рамках диссертации «Ангиопластические операции в абдоминальной онкологии» на соискание ученой степени доктора медицинских наук. Тема диссертации утверждена на ученом совете НИИ Клинической онкологии имени академика РАН и РАМН Н.Н. Трапезникова ФГБУ НМИЦ онкологии имени Н.Н. Блохина Минздрава России.
Study funding. The study was the authors’ initiative without external funding.	Источник финансирования. Работа выполнена по инициативе авторов без привлечения финансирования.
Conflict of interest. The authors declare that there are no obvious or potential conflicts of interest associated with the content of this article.	Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи.
Contribution of individual authors. Abgaryan M.G., Kovalenko E.I., Titova T.A., Nikulin M.P.: concept and design of the work, collection, analysis and interpretation of data, preparation of the text of the article. Artamonova E.V., Berdnikov S.N., Stilidi I.S.: editing of the text of the article. The authors gave their final approval of the manuscript for submission, and agreed to be accountable for all aspects of the work, implying proper study and resolution of issues related to the accuracy or integrity of any part of the work.	Участие авторов. Абгарян М.Г., Коваленко Е.И., Титова ТА., Никулин М.П.: концепция и дизайн работы, сбор, анализ и интерпретация данных, подготовка текста статьи. Артамонова Е.В., Бердников С.Н., Стилиди И.С.: редактирование текста статьи. Все авторы одобрили финальную версию статьи перед публикацией, выразили согласие нести ответственность за все аспекты работы, подразумевающую надлежащее изучение и решение вопросов, связанных с точностью или добросовестностью любой части работы.
Statement of originality. No previously published material (text, images, or data) was used in this work.	Оригинальность. При создании настоящей работы авторы не использовали ранее опубликованные сведения (текст, иллюстрации, данные).
Data availability statement. The editorial policy regarding data sharing does not apply to this work.	Доступ к данным. Редакционная политика в отношении совместного использования данных к настоящей работе не применима.
Generative AI. No generative artificial intelligence technologies were used to prepare this article.	Генеративный искусственный интеллект. При создании настоящей статьи технологии генеративного искусственного интеллекта не использовали.
Provenance and peer review. This paper was submitted unsolicited and reviewed following the standard procedure. The peer review process involved 2 external reviewers.	Рассмотрение и рецензирование. Настоящая работа подана в журнал в инициативном порядке и рассмотрена по обычной процедуре. В рецензировании участвовали 2 внешних рецензента.

 

About the authors

Mikael G. Abgaryan

N.N. Blokhin National Medical Research Center of Oncology

Author for correspondence.
Email: abgaryan.mikael@gmail.com
ORCID iD: 0000-0001-8893-1894

MD, Cand. Sci. (Medicine), Senior researcher, Oncologist of the Department of Abdominal Oncology No. 1 of the N.N. Trapeznikov Research Institute of Clinical Oncology.

Russian Federation, Moscow

Elena V. Artamonova

N.N. Blokhin National Medical Research Center of Oncology

Email: artamonovae@mail.ru
ORCID iD: 0000-0001-7728-9533

MD, Dr. Sci. (Medicine), Professor, Head of the Department of Antitumor Drug Therapy No. 1 of the N.N. Trapeznikov Research Institute of Clinical Oncology.

Russian Federation, Moscow

Elena I. Kovalenko

N.N. Blokhin National Medical Research Center of Oncology

Email: e.i.kovalenko@mail.ru
ORCID iD: 0000-0003-4763-7992

MD, Cand. Sci. (Medicine), Senior researcher of the Department of Antitumor Drug Therapy No. 1 of the N.N. Trapeznikov Research Institute of Clinical Oncology.

Russian Federation, Moscow

Tatyana A. Titova

N.N. Blokhin National Medical Research Center of Oncology

Email: tatiana.titovadoc@gmail.com
ORCID iD: 0000-0002-5039-6360

MD, Cand. Sci. (Medicine), research fellow of the Department of Antitumor Drug Therapy No. 1 of the N.N. Trapeznikov Research Institute of Clinical Oncology.

Russian Federation, Moscow

Maksim P. Nikulin

N.N. Blokhin National Medical Research Center of Oncology

Email: maximpetrovich@mail.ru
ORCID iD: 0000-0002-9608-4696

MD, Cand. Sci. (Medicine), Senior researcher of the Department of Abdominal Oncology No. 1 of the N.N. Trapeznikov Research Institute of Clinical Oncology.

Russian Federation, Moscow

Sergei N. Berdnikov

N.N. Blokhin National Medical Research Center of Oncology

Email: berdnikov_sn@mail.ru
ORCID iD: 0000-0003-2586-8562

MD, Cand. Sci. (Medicine), Leading researcher, Head of the ultrasound diagnostics department of the consultative and diagnostic center.

Russian Federation, N.N. Blokhin National Medical Research Center of Oncology

Ivan S. Stilidi

N.N. Blokhin National Medical Research Center of Oncology

Email: biochimia@yandex.ru
ORCID iD: 0000-0002-0493-1166

MD, Academician of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences, Director.

Russian Federation, Moscow

References

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