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\begin{document}

\title{Complete resection of a cavoatrial metastatic dedifferentiated
liposarcoma under hypothermic circulatory arrest}



\author[1]{Ryumon Matsumoto}%
\author[1]{Koki Maekawa}%
\author[2]{Toshiki Fujiyoshi}%
\author[3]{Kentaro Kamiya}%
\author[1]{Jun Matsubayashi}%
\author[1]{Shoji Fukuda}%
\author[4]{Toshiya Nishibe}%
\author[3]{Hitoshi Ogino}%
\affil[1]{Affiliation not available}%
\affil[2]{Pediatric Cardiovascular Surgery}%
\affil[3]{Tokyo Medical University}%
\affil[4]{Tokyo Medical University Hospital}%


\vspace{-1em}



  
  \date{May 02, 2024}


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\selectlanguage{english}
\begin{abstract}
A patient had undergone surgical resection twice for primary and
metastatic dedifferentiated liposarcomas. Follow-up computed tomography
revealed a new tumor mass located at the cavoatrial junction. Prompt
surgical resection of the tumor with thrombectomy was successfully
performed using cardiopulmonary bypass with hypothermic circulatory
arrest. We report a rare case of a patient surviving for 8 years after
the first tumor resection despite the poor prognosis of metastatic or
recurrent liposarcoma.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Although liposarcoma is a common soft tissue sarcoma, pleural
liposarcoma has rarely been reported and its prognosis is poor due to
higher incidences of metastasis and recurrence\textsuperscript{1}. We
report the case of a patient who underwent successful complete resection
of a cavoatrial metastatic tumor originating from primary pleural
liposarcoma using cardiopulmonary bypass (CPB) and hypothermic
circulatory arrest (HCA). The patient is surviving without any
metastasis or recurrence.

A 68-year-old man was referred to our department for resection of a
tumor located at the cavoatrial junction between the inferior vena cava
(IVC) and the right atrium (RA). At the age of 62, he was diagnosed with
lung cancer and underwent a left lower lobectomy. However, the final
diagnosis of the resected tumor was pleural dedifferentiated liposarcoma
as the pathological analysis was positive for murine double minute 2
(MDM2), adipophilin, and perilipin. In one year, surgical adrenalectomy
was performed for the right adrenal tumor and was repeated one year
later for the left-side tumor. The pathological examination of the
bilateral adrenal tumors also showed dedifferentiated liposarcoma
metastasizing from the primary pleural liposarcoma. Follow-up computed
tomography scans after surgery revealed a new mass in the IVC. Direct
oral anticoagulant was administered with the diagnosis of venous
thromboembolism. Repeated computed tomography revealed enlargement of
the mass, which was suspected to be a metastatic liposarcoma
(\textbf{Fig. 1} ).

The patient was asymptomatic. Blood examinations revealed no significant
abnormality. All tumor markers were negative. Transthoracic
echocardiography revealed a 60-mm, very mobile, right atrial mass
extending into the right ventricle through the tricuspid valve
(\textbf{Fig. 2} ).

Materials and Methods

Resection of the cavoatrial tumor with thrombectomy was performed. CPB
was established with ascending aortic cannulation and venous drainage
from the right femoral vein with a 21-Fr long cannula and the superior
vena cava. The tip of the femoral vein cannula was carefully adjusted in
the proximal part of the IVC with a transesophageal echo guide to avoid
contact with the tumor or thrombus. After CPB was established
successfully, cardiac arrest with ascending aortic cross-clamping was
induced by antegrade cardioplegia. The superior vena cava was snugged,
and a right atriotomy was made. A yellowish granular tumor mass was
observed in the RA extending distally into the IVC beyond the hepatic
vein junction. It was difficult to remove the tumor completely in the
bloody surgical field. Hence, with the IVC gently snugged, core cooling
was initiated along with simultaneous surface head cooling with ice bags
until targeted tympanic temperature of 25\selectlanguage{ngerman}°C was achieved. HCA was then
induced and the tumor was removed smoothly. Endoscopy was used to ensure
complete resection of the tumor. The duration of HCA was 3 min. The
patient was smoothly weaned from CPB using a low dose of catecholamine.
The time of aortic cross-clamp, CPB, and surgery was 84, 172, and 304
min, respectively.

Results

The resected tumor comprised pleomorphic tumor cells containing
lipoblastic cells with vacuolated cytoplasms. Immunohistochemical
analysis showed diffuse positivity for MDM2 in tumor cells.
Histopathological diagnosis of the tumors was dedifferentiated
liposarcoma (Fig. 3). On postoperative day 14, the patient was
discharged and followed up without adjuvant chemotherapy or
radiotherapy. He has survived for 8 years since the initial surgery and
2 years since the second surgery.

Conclusions

Liposarcomas commonly occur in the extremities, however, primary pleural
liposarcoma is extremely rare with very few reported
cases\textsuperscript{1}. We could only find 34 reported cases of
pleural liposarcomas\textsuperscript{1-4}.

The World Health Organization classifies liposarcoma into five types:
atypical, well-differentiated, dedifferentiated, myxoid, and
pleomorphic\textsuperscript{1}. Of these, the dedifferentiated
liposarcomas have a significantly poor prognosis with rates of local
recurrence and metastasis of 41\% and 17\%, respectively, and 5-year
survival rate of only 28\%. Conversely, the 5-year survival rate for
well-differentiated liposarcomas is 80\% \textsuperscript{5}. The
curative treatment for liposarcoma is surgical resection, with
chemotherapy and/or radiotherapy. Adjuvant chemotherapy is selectively
applied because the subtypes differ in chemosensitivity; it is not
indicated in the resistant subtypes of dedifferentiated liposarcomas.
Radiation therapy reportedly reduces the risk of local recurrence,
especially in cases with myxoid liposarcoma\textsuperscript{3}.

Regarding surgical resection of the tumor at the cavoatrial junction,
Neves and Zincke classified venous tumor thrombus into four categories:
level I--renal vein thrombus, level II-- infrahepatic IVC thrombus,
level III--retrohepatic IVC thrombus, and level IV--intraatrial IVC
thrombus. In the presented case, the cavoatrial tumor thrombus can be
classified as level IV. The standard surgical technique for level IV
tumor thrombus is resection with CPB. However, the use of CPB in
patients suffering from malignant diseases is controversial because CPB
decreases the immunity of patients and potentially causes the spread of
malignant cells to the whole body. Furthermore, CPB is associated with
the release of inflammatory mediators, coagulopathy, platelet
dysfunction, and increased bleeding. There have been contradictory
reports on the use of CPB in cancer patients\textsuperscript{6, 7}.
Among 74 patients with metastatic cancer undergoing open-heart surgery
with and without CPB, no significant difference was reportedly observed
in cancer-specific mortality (patients with and without CPB: 26.7\% and
24.1\%, respectively, p=0.8)\textsuperscript{6}. Conversely, another
report demonstrated among 43,347 patients undergoing isolated CABG
surgery, the adjusted relative risk of cancer-specific mortality caused
by CPB was 1.16 (95\% CI: 0.92--1.46, p=0.20)\textsuperscript{7}. The
lack of significant association between CPB and the progression of
malignant diseases allowed us to perform aggressive surgical resection
with CPB.

Similarly, there are no reports on HCA in cases with cavoatrial tumors,
particularly liposarcoma. It was reported that CPB with HCA to treat
level III or IV renal or adrenal tumors enabling complete tumor
resection did not increase operative risks and was relatively
safe\textsuperscript{8}. The HCA proved useful in removing the
cavoatrial tumor completely and in viewing the inside of the IVC clearly
with endoscopy.

In conclusion, prompt complete resection of the cavoatrial metastatic
dedifferentiated liposarcoma associated with poor prognosis was
successfully performed using CPB with HCA, which resulted in
satisfactory mid-term survival without recurrence.

\textbf{Acknowledgements:} I acknowledge Jun Matsubayashi, a professor
at Tokyo Medical University, Department of Pathology, for assisting with
the pathological analysis of this case.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Matsukuma S, Oshika Y, Utsumi
  Y,\emph{Obara}K,~\emph{Tanimoto}T,~\emph{Katsurada}Y,~\emph{Takeo}H.
  Pleural dedifferentiated liposarcoma: A case report. Mol Clin Oncol
  2019;10:132-136.
\item
  Lin CJ, Chou SH, Yang SF, Kao CN, Chang PC, Liu YW. Rapidly growing
  pleural liposarcoma masquerading as extrapleural hematoma. Thorac
  Cancer 2019;10:365-368.
\item
  Prabhakar N, Vaiphei K, Vishwajeet V, Ramamoorthy E,~Gorsi U,~Dhooria
  S,~Kapoor R,~Sandhu MS. Primary pleural liposarcoma: A rare entity.
  Lung India 2019;36:438-440.
\item
  Kang LH, Hwang CS, Yoon SH. Primary pleural liposarcoma combined
  spindle cell lipoma of the lung. Thorac Cancer 2020;11:2059-2062.
\item
  Henricks WH, Chu YC, Goldblum JR, Weiss SW. Dedifferentiated LPS: A
  clinicopathological analysis of 155 cases with a proposal for an
  expanded definition of dedifferentiation. Am J Surg Pathol
  1997;21:271-281.
\item
  Suzuki S, Usui A, Yoshida K, Matsuura A, Ichihara T, Ueda Y. Effects
  of cardiopulmonary bypass on cancer prognosis. Asian Cardiovasc Thorac
  Am 2010;18:536-540.
\item
  Pinto CA, Marcella S, August DA, Holland B, Kostis JB, Demissie K.
  Cardiopulmonary bypass has a modest association with cancer
  progression: A retrospective cohort study. BMC Cancer 2013;13:519.
\item
  Zhu P, Du S, Chen
  S,\emph{Zheng}S,~\emph{Hu}Y,~\emph{Liu}L,~\emph{Zheng}S\emph{.} The
  role of deep hypothermic circulatory arrest in surgery for renal or
  adrenal tumor with vena cava thrombus: A single-institution
  experience. J Cardiothorac Surg 2018;13:85.
\end{enumerate}

\textbf{Figure legends}

Fig.1

Preoperative contrast-enhanced computed tomography scans showing a tumor
located at the cavoatrial junction

Fig.2

Preoperative echocardiogram showing a large tumor in the right atrium
prolapsing through the tricuspid valve into the right ventricle

RA-Right Atrium

RV-Right Ventricle

Fig.3

Macroscopic and microscopic appearance of the extirpated tumor

a: Macroscopic appearance of the extirpated tumor. b: Microscopic
examination of the lesion demonstrated tumor cells containing
lipoblastic cells with vacuolated cytoplasms characteristic to
liposarcoma (HE: High power field).

c: Immunohistochemically, the tumor cells showing diffuse positivity for
MDM2 (HE: High power field)\selectlanguage{english}
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