|Year : 2022 | Volume
| Issue : 2 | Page : 58-61
Rare case reports of hepatocellular carcinoma with inferior vena cava and right atrium tumor thrombus and extension into left renal vein
Parimita Barua1, K Narayanasamy2, Santhi Selvi2, Prem Kumar2
1 Department of Medicine, Dr. RML Hospital and Atal Bihari Vajpayee Institute of Medical Sciences, New Delhi, India
2 Department of Hepatology, Madras Medical College, Chennai, Tamil Nadu, India
|Date of Submission||01-Nov-2021|
|Date of Decision||10-Feb-2022|
|Date of Acceptance||15-Feb-2022|
|Date of Web Publication||23-Mar-2022|
Department of Medicine, Dr. RML Hospital and Atal Bihari Vajpayee Institute of Medical Sciences, New Delhi - 110 001
Source of Support: None, Conflict of Interest: None
Hepatocellular carcinoma with tumor thrombus extending to hepatic vein, inferior vena cava (IVC), and right atrium is rare and considered to be fairly advanced with a poor prognosis. We report two such cases from a single tertiary care center in South India. Treatment options in such patients are limited as the disease is extensive. We conducted a literature search for such case reports on PubMed. Compared with published literature, one of our cases had hepatic vein, IVC, left renal vein with tumor thrombus in the right atrium which has not been reported so far. Both the patients were started on systemic chemotherapy but succumbed to illness 4 and 7 weeks after initiation of chemotherapy.
Keywords: Hepatocellular carcinoma, inferior vena cava thrombus, right atrial tumor thrombus
|How to cite this article:|
Barua P, Narayanasamy K, Selvi S, Kumar P. Rare case reports of hepatocellular carcinoma with inferior vena cava and right atrium tumor thrombus and extension into left renal vein. Gastroenterol Hepatol Endosc Pract 2022;2:58-61
|How to cite this URL:|
Barua P, Narayanasamy K, Selvi S, Kumar P. Rare case reports of hepatocellular carcinoma with inferior vena cava and right atrium tumor thrombus and extension into left renal vein. Gastroenterol Hepatol Endosc Pract [serial online] 2022 [cited 2022 May 24];2:58-61. Available from: http://www.ghepjournal.com/text.asp?2022/2/2/58/340391
| Introduction|| |
Hepatocellular carcinoma (HCC) is the most common primary liver tumor. The common risk factors for HCC include chronic hepatitis B, chronic hepatitis C, alcohol-related liver cirrhosis, and nonalcoholic steatohepatitis. Patients who present at an advanced stage and with metastasis have a poor prognosis. HCC is commonly associated with intravascular invasion and tumor thrombus formation. HCC with tumor thrombus into inferior vena cava (IVC) and right atrium are rare with dismal prognosis, and the median survival duration of untreated patients is 2–5 months., Patients who present with tumor thrombus have bad outcomes with very limited treatment options. There is currently no consensus on the treatment modalities regarding the management of HCC with IVC and right atrium extension. These patients are classified as Barcelona Clinic Liver Cancer (BCLC) staging-C due to vascular invasion, and the standard of treatment in this staging system is sorafenib. The treatment options in such patients are surgery, ablation, transarterial chemoembolization, radiotherapy, chemotherapy or chemoradiotherapy, targeted therapy or antiangiogenic drugs, and combination therapy. The choice of treatment can markedly affect patient outcomes.
We report two such cases from a single tertiary care center in India.
| Case Reports|| |
A 60-year-old female with a history of diabetes for 6 years and hypertension for the past 40 years presented with abdominal distension, pedal edema, and exertional breathlessness for 10 days. She also complained of easy fatiguability. She had no history of alcohol use disorder or any addiction. She had no significant family history. On examination, pulse rate was 84/min, blood pressure – 140/80 mmHg, and saturation – 99% at room air. Physical examination revealed pedal edema and systemic examination revealed ascites and dilated veins on the abdominal wall anteriorly and posteriorly with no organomegaly. Other systemic examination was within the normal limits. Routine biochemical investigations revealed hemoglobin – 12.2 g/dl, total leukocyte count (TLC) – 7800/mm3, platelet count – 2.18 lakh, random blood sugar – 240 mg/dl, blood urea – 22, serum creatinine – 0.8 mg/dl, liver function test total bilirubin – 0.6 mg/dl, direct bilirubin – 0.3 mg/dl, aspartate aminotransferase (AST) – 30 IU/L, alanine aminotransferase (ALT) – 23 IU/L, alkaline phosphatase (ALP) – 110 IU/L, total protein – 6.8 g/dl, and serum albumin – 3 g/dl. HbSAg and anti-HCV were negative. Serum alpha-fetoprotein (AFP) was 2.6 ng/ml. Ascitic fluid cytology showed a cell count of 135 cells/mm3 and transudative ascites, endoscopy showed small esophageal varices. On urine routine microscopy there was mild albuminuria with no red blood cells or pus cells, ultrasound abdomen with portal vein, hepatic vein and IVC Doppler study revealed multiple hyperechoic lesions in left and right lobe of liver with Iso echoic mass lesion with minimal intralesional vascularity in caudate lobe (possibly HCC), portal vein showed hepat-petal flow, velocity 20 cm/s, middle hepatic vein and left hepatic vein show evidence of thrombus, right hepatic vein–normal, thrombus was noted in IVC in suprahepatic and intrahepatic part. Contrast-enhanced computed tomography (CECT) abdomen with CT-angiography showed multiple ill-defined heterogeneous lesions in both lobes of the liver with ill-defined mass in caudate lobe (4.8 cm × 5.5 cm) with arterial enhancement and washout in the portal-venous phase with tumor thrombus in middle and left hepatic vein, IVC and extension into the right atrium (3.4 cm × 2.7 cm attached to interatrial septum), with thrombus extension into intrahepatic and extrahepatic (suprahepatic and infrahepatic) portion of IVC and left renal vein for the length of 2.9 cm from the IVC [Figure 1]. CT chest confirmed the presence of tumor thrombus in IVC extending into the right atrium [Figure 2]. 2D echocardiography showed echogenic 3.3 cm × 2.9 cm right atrial mass with no regional wall motion abnormality and ejection fraction (EF) – 60% [Figure 3]. The patient was started on diuretics furosemide 40 mg and spironolactone 100 mg and sorafenib 400 mg. The patient could not be taken for interventional procedure due to poor performance status (PS-3). The patient succumbed to illness after 4 weeks of initiation of chemotherapy.
|Figure 1: Triple phase computed tomography abdomen – 4.8 cm × 5.5 cm mass lesion in caudate lobe with minimal extension in segment 8 with arterial enhancement and wash out in portal venous phase with filling defect in IVC which extends into the right atrium (3.4 × 2.7) cm and is attached to interatrial septum. Thrombosis is also seen extending to middle and left hepatic vein and left renal vein|
Click here to view
|Figure 2: Soft-tissue density lesion measuring 3.3 cm × 2.9 cm in right atrium attached to interatrial septum with thrombosis of inferior vena cava suprarenal portion with tumor thrombus exceeding to right atrium|
Click here to view
|Figure 3: Echogenic thrombus in right atrium, concentric left ventricular hypertrophy, ejection fraction = 60% with no regional wall motion abnormality|
Click here to view
A 59-year-old male, alcohol use disorder presented with breathlessness on exertion for 1 month, pain abdomen and pedal edema for 10 days. He had no significant past history. The patient had consumed alcohol for the past 15 years with an intake of country liquor 30 g/day and no history of smoking. His family history was not significant. Physical examination revealed pedal edema. Systemic examination revealed hepatomegaly with liver span – 15 cm, no ascites, and no other organomegaly. Other systems were within the normal limits. Routine biochemical investigations revealed hemoglobin – 13.9 g/dl, TLC – 10,600/mm3, platelet count – 3.37 lakh, random blood sugar – 125 mg/dl, blood urea – 36, serum creatinine – 0.9 mg/dl, liver function test total bilirubin – 1.2 mg/dl, D. bilirubin – 0.8 mg/dl, AST – 71, ALT – 52, ALP – 143, total protein – 7.0 g/dl, and serum albumin – 2.8 g/dl. HbS Ag and Anti-HCV were negative. Serum AFP was 6577 ng/ml. CECT shows multifocal HCC (largest-10.9 cm × 7.6 cm in right lobe) with extension in middle and left hepatic veins, IVC, and right atrium (3.2 cm × 2.5 cm) [Figure 4].
|Figure 4: Contrast-enhanced computed tomography shows multifocal hepatocellular carcinoma (largest-10.9 cm × 7.6 cm in right lobe) with extension in middle and left hepatic veins, inferior vena cava, and right atrium (3.2 cm × 2.5cm)|
Click here to view
2D echocardiography showed IVC mass with extension into the right atrium 32 mm × 25 mm, no wall motion abnormality, and EF – 60%. Performance status score of the patient was 3 and hence could not be taken for interventional procedures. The patient was started on sorafenib 400 mg but he succumbed to illness after 7 weeks from initiation of chemotherapy.
The presentation of HCC with hepatic vein and IVC extension has been described in the literature. However, the extension to the right atrium in both the cases is a rare presentation and into left renal vein in case 1 is even more rare.
| Discussion|| |
HCC is the most common primary neoplasm of liver. It is the fifth most frequently diagnosed cancer in men. Vascular invasion and tumor thrombus formation are common in advanced-stage HCC. Incidence of vascular invasion increases with a large tumor diameter >5 cm and elevated AFP >1000 μg/L and is reported in >82% of patients. The most frequent type of tumor thrombosis in HCC is portal vein thrombosis (20%–65%), followed by systemic thromboembolism (6%)., The incidence of hepatic vein thrombosis in HCC is 1.4%–4.9%. Tumor thrombus from HCC invading the hepatic veins and extension into IVC and right atrium is reported in 0.67%–3% of the cases. In this article, the first patient presented with a multifocal HCC with tumor diameter of 4.8 cm × 5.5 cm in caudate lobe and normal serum AFP with a massive tumor thrombus extension into IVC and right atrium. The multifocal HCC explains the middle and left hepatic vein thrombosis in the first case. The caudate lobe drains directly into IVC and hence thrombus extension into IVC contiguous with HCC in caudate lobe is seen. The tumor thrombus in the first case is seen involving intrahepatic and extrahepatic (suprahepatic and infrahepatic) IVC and left renal vein for the length of 2.9 cm from the IVC. The left renal vein drains into the IVC which explains the tumor thrombus extension into the left renal vein. In the second reported case, the patient has multifocal HCC with the largest tumor diameter in the right lobe with tumor thrombus in middle and left hepatic vein and IVC and right atrium thrombosis. As the HCC is multifocal, it explains the middle and left hepatic vein tumor thrombus with contiguous extension into IVC and right atrium. IVC thrombosis is often asymptomatic but symptoms related to portal hypertension may develop such as upper gastrointestinal bleeding, ascites, and abdominal pain. Patients reported in this study were symptomatic and presented with abdominal distension, abdominal pain, pedal edema, and breathlessness on exertion. Exertional breathlessness is not a common symptom reported previously with HCC and tumor thrombus extension to the right atrium; however, in this article, it is one of the chief complaints of both the patients. While tumor thrombus in the right atrium was seen in CECT abdomen, patients underwent 2D echocardiography to rule out other cardiac causes for breathlessness and to confirm the CT findings. Both the patients were symptomatic and had HCC in a noncirrhotic background.
Treatment options are limited in such patients. Treatment with a single modality of therapy is difficult to obtain and hence a combination of therapies is followed such as surgery, ablation, chemotherapy, or transarterial chemoembolization. Treatment option is based on the general condition of the patient, performance status, the location, number and size of intrahepatic tumors and extrahepatic metastases, classification of tumor thrombus, and treatment facility available.
The European Association of Study of Liver (EASL) recommends patients with preserved liver function and minimally affected performance status (PS 0–2), stage C according to the BCLC to undergo treatment with systemic chemotherapy. Sorafenib as a multi-kinase inhibitor was introduced in EASL guidelines in 2008. Sorafenib showed a survival benefit documenting prolonged median survival and nearly 3-month time to radiologic progression. The patients were advised sorafenib based on the existing guidelines at the time of presentation of the patients to the hospital.
As per EASL position article on systemic treatment for HCC, the decision to start a systemic therapy should be based on tumor stage and suitability for local liver-directed therapies. Patients with extrahepatic disease, vascular invasion, or bulky liver involvement are the main candidates. The combination of atezolizumab and bevacizumab is the preferred option for naïve patients if they meet the criteria established in the pivotal clinical trial.
For patients in whom atezolizumab and bevacizumab combination are contraindicated, sorafenib or lenvatinib are alternate first line options.
The combination of atezolizumab and bevacizumab is beneficial or not in such patients with advanced HCC with tumor thrombus extension into the right atrium needs consideration and enrolment of such patients into trials.
In a study retrospectively conducted in 50 patients with advanced HCC with RA involvement, the median survival was only 2 months with supportive care and improved marginally up to 4 months with aggressive therapy.
Invasive treatment approaches such as resection of tumor thrombus and liver tumor, external beam radiotherapy, and transarterial chemoembolization are also reported. The postoperative survival of patients with HCC and tumor thrombus in IVC and right atrium varied from 18 to 56 days with a mean survival of 20 months. In patients with HCC and IVC and RA, tumor thrombus extension treated with hepatectomy + thrombectomy and TACE, the median survival was 19 and 4.5 months, respectively. These data indicate that removal of thrombus surgically combined with hepatectomy or only tumor thrombus extraction might result in improvement of survival in selected patients with other nonsurgical procedures.
In the present study, both the patients were started on sorafenib with BCLC-C stage. Interventional procedures such as RFA and TACE were not options due to advanced age of the patients and poor performance status. Both the patients succumbed to illness after 4 and 7 weeks of initiation of chemotherapy.
| Conclusion|| |
HCC with tumor thrombus extension into IVC, right atrium, and hepatic veins and renal vein indicate advanced stage of the disease with limited treatment options and dismal prognosis. With interventional techniques in appropriate patients, survival may be prolonged. At present, there is no treatment consensus for such patients. Here, we report two such cases from a single tertiary care center in southern India.
Declaration of patient consent
The authors declare that they have obtained consent from patients. Patients have given their consent for their images and other clinical information to be reported in the journal. Patients understand that their names will not be published and due efforts will be made to conceal their identity but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Fujiwara N, Friedman SL, Goossens N, Hoshida Y. Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine. J Hepatol 2018;68:526-49.
Bouattour M, Mehta N, He AR, Cohen EI, Nault JC. Systemic treatment for advanced hepatocellular carcinoma. Liver Cancer 2019;8:341-58.
Quencer KB, Friedman T, Sheth R, Oklu R. Tumor thrombus: Incidence, imaging, prognosis and treatment. Cardiovasc Diagn Ther 2017;7:165-77.
Chun YH, Ahn SH, Park JY, Kim DY, Han KH, Chon CY, et al
. Clinical characteristics and treatment outcomes of hepatocellular carcinoma with inferior vena cava/heart invasion. Anticancer Res 2011;31:4641-6.
Wang Y, Yuan L, Ge RL, Sun Y, Wei G. Survival benefit of surgical treatment for hepatocellular carcinoma with inferior vena cava/right atrium tumor thrombus: Results of a retrospective cohort study. Ann Surg Oncol 2013;20:914-22.
Le Treut YP, Hardwigsen J, Ananian P, Saïsse J, Grégoire E, Richa H, et al.
Resection of hepatocellular carcinoma with tumor thrombus in the major vasculature. A European case-control series. J Gastrointest Surg 2006;10:855-62.
Sonsuz A. Barcelona Clinic Liver Cancer (BCLC) staging: Does it cover all our expectation. J Gastrointest Cancer 2017;48:260-1.
Sakamoto K, Nagano H. Outcomes of surgery for hepatocellular carcinoma with tumor thrombus in the inferior vena cava or right atrium. Surg Today 2018;48:819-24.
Sakata J, Shirai Y, Wakai T, Kaneko K, Nagahashi M, Hatakeyama K. Preoperative predictors of vascular invasion in hepatocellular carcinoma. Eur J Surg Oncol 2008;34:900-5.
Connolly GC, Chen R, Hyrien O, Mantry P, Bozorgzadeh A, Abt P, et al.
Incidence, risk factors and consequences of portal vein and systemic thromboses in hepatocellular carcinoma. Thromb Res 2008;122:299-306.
Panduranga P, Al-Mukhaini M, Ratnam L, Al-Harthy S. Mobile right atrial thrombus with pulmonary thromboembolism in a patient with advanced hepatocellular carcinoma and disseminated tumor thrombosis. Heart Views 2011;12:173-77.
] [Full text]
Zhang YF, Wei W, Guo ZX, Wang JH, Shi M, Guo RP. Hepatic resection versus transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with hepatic vein tumor thrombus. Jpn J Clin Oncol 2015;45:837-43.
Masci G, Magagnoli M, Grimaldi A, Covini G, Carnaghi C, Rimassa L, et al.
Metastasis of hepatocellular carcinoma to the heart: A case report and review of the literature. Tumori 2004;90:345-7.
Gomez-Puerto D, Mirallas O, Vidal-González J, Vargas V. Hepatocellular carcinoma with tumor thrombus extends to the right atrium and portal vein: A case report. World J Hepatol 2020;12:1128-35.
Xia Y, Zhang J, Ni X. Diagnosis, treatment and prognosis of hepatocellular carcinoma with inferior vena cava/right atrium tumor thrombus. Oncol Lett 2020;20:101.
European Association for the Study of the Liver. EASL clinical practice guidelines: Management of hepatocellular carcinoma. J Hepatol 2018;69:182-236.
Bruix J, Chan SL, Galle PR, Rimassa L, Sangro B. Systemic treatment of hepatocellular carcinoma: An EASL position paper. J Hepatol 2021;75:960-74.
Miyazawa M, Torii T, Asano H, Yamada M, Toshimitsu Y, Shinozuka N, et al.
Does a surgery for hepatocellular carcinoma with tumor thrombus highly occupying in the right atrium have significance? A case report and review of the literature. Hepatogastroenterology 2005;52:212-6.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]