Acute Budd–Chiari syndrome caused by tumor thrombus of the inferior vena cava secondary to non-small cell lung cancer

1. Introduction 

Budd–Chiari syndrome is caused by occlusion of the hepatic vein or inferior vena cava and typically presents with the classical triad of abdominal pain, ascites, and hepatomegaly. Direct compression or invasion of vascular structures and the hypercoagulable state associated with malignancy can result in venous thrombosis and obstruction. This syndrome can be fulminant, acute, chronic, or asymptomatic, and is idiopathic in half of patients. Only 10% of cases appear to result from compression of the hepatic vein by an outside body like a tumor1; bronchogenic carcinoma was cited as the cause of Budd–Chiari syndrome in only a few cases.2, 3, 4

Here, we describe a rare case of acute Budd–Chiari syndrome caused by tumor thrombus of the inferior vena cava secondary to lung cancer. In addition, we review previous cases reported in the past 3 decades and discuss the possibility of treatment with stent placement therapy.

2. Case report 

An 83-year-old woman presented with an abnormality on a chest radiograph. At the time of admission, physical examination was normal. Laboratory evaluation confirmed a normal blood count and normal levels of liver enzymes, glucose, creatinine, and plasma sodium and potassium. The patient had a history of chronic hepatitis C, for which she received no medication, and a 30 pack-year history of smoking. Child-Pugh score on admission was class A. Performance status (PS) of the patient was 1 on the Eastern Cooperative Oncology Group (ECOG) scale.

An enhanced chest computed tomography (CT) scan in February 2008 showed a mass (3×3cm) in the right upper lobe, swelling in multiple mediastinal lymph nodes, and a left adrenal metastasis (Fig. 1A). Specimens obtained by bronchoscope revealed poorly differentiated non-small cell lung cancer (NSCLC). Gemcitabine was administered as single-agent chemotherapy, due to the patient's age and the presence of chronic hepatitis. She underwent 2 cycles of chemotherapy, after which her cancer was classified as stable disease.

View Large Image Download to PowerPoint

Fig. 1 A) Chest CT scan shows a primary lung cancer of the right upper lobe in October 2008. (B, C) Enhanced abdominal CT scan shows a low-attenuation mass (arrows) in the liver that has occupied and distended the vena cava (arrow). There is evidence of enhanced tumor vascularity (arrowheads) within the tumor. (D, E) A coronal section of the upper abdomen and lower chest shows a tumor occupying the vena cava (arrows) and invading the right atrium (arrowheads).

In October 2008, she was presented for treatment again, this time with dyspnea, general fatigue, low-grade fever, and abdominal discomfort. On admission, physical examination revealed mild edema of the lower extremities. Her PS was 2 on the ECOG scale. Laboratory data revealed slight elevation in lactate dehydrogenase (LDH) at 298IU/L and C-reactive protein (CRP) at 0.7mg/dl. An enhanced chest CT scan showed progression of the mass (3.5×4cm) in the right upper lobe. An enhanced abdominal CT scan revealed mild splenomegaly, progressive adrenal gland metastasis, and a tumor in the right atrium, inferior vena cava, and hepatic vein, which suggests that a recurrence of NSCLC was responsible for the onset of Budd–Chiari syndrome (Fig. 1, B-E). Palliative care was provided to relieve pain and other distressing symptoms. Beginning on the 10th day of admission, appetite loss, abdominal swelling, and progression of edema in the lower extremities was observed. On the 14th day, laboratory data showed that the aspartate aminotransferase (AST) level was 102IU/L (normal, <40), the alanine aminotransferase (ALT) level was 54IU/L (normal, <40), LDH level was 498IU/L, total bilirubin (T-Bil) level was 0.7mg/dl, CRP level was 2.0mg/dl, and prothrombin activity was 80% of control. On the 16th day, a sudden decline in the level of consciousness and a worsening of respiratory status were observed. Emergency laboratory data showed that AST level was 863IU/L (normal, <40), ALT level was 267IU/L (normal, <40), LDH level was 1258IU/L, T-Bil level was 4.0mg/dl, CRP level was 8.4mg/dl, prothrombin activity was 25% of control, and serum ammonia level was 280ug/dl. These data indicated the presence of acute liver failure due to tumor thrombus of the inferior vena cava, i.e., Budd–Chiari syndrome. She suffered respiratory failure and hypotension on the 17th day, and died on the 18th day.

3. Discussion 

The cause of Budd–Chiari syndrome cannot be determined in half of patients. The most common known cause is coagulation abnormality due to the concomitant presence of polycythemia rubra vera and myeloproliferative disorders.3 Malignancies are responsible for only approximately 10% of Budd–Chiari syndrome cases.1 Malignancies known to cause tumor thrombus are those of the liver and kidney3, 5; cancers of the lung, pancreas, and stomach are only rarely implicated.1 Once rare, there has been a recent increase in the number of the cases due to leiomyosarcoma.6, 7, 8

In our case, it appears that Budd–Chiari syndrome was caused by direct invasion of the inferior vena cava by a metastasis to the adrenal gland and a metastasis to the hepatic portal region. This is indicated by the fact that a metastasis to the adrenal gland was observed at the time of first diagnosis and had progressed at the time of the second evaluation. CT findings provide additional support for this diagnosis.

We conducted a MEDLINE search to identify cases of Budd–Chiari syndrome secondary to lung cancer that were reported in the past 3 decades; the characteristics of these, and our case, are summarized in Table 1. There were 3 men and 2 women; all but our case were diagnosed in their seventh decade. Histologically, 4 cases occurred in patients with NSCLC, and 3 in patients with confirmed squamous cell carcinoma. The primary tumors were located in the right lung in all cases. Except for 1 case with small cell lung cancer (SCLC), all patients received best supportive care only and their outcomes were very poor. In our case, salvage chemotherapy was not administered because of her poor PS and her refusal to grant consent for therapy.

Table 1. Budd–Chiari syndrome secondary to lung cancer (MEDLINE search).

	Reference	Yeara	Age	Sexb	Histology	Location of primary cancer	Treatment	Survival timec
	Ough, et al.2	1981	60	M	Squamous cell	Right upper lobe	None	2 Weeks
	Ough, et al.2	1981	66	M	Squamous cell	Right lower lobe	None	4 Days
	Muretto, et al.3	1992	66	F	Squamous cell	Right lower lobe	None	6 Weeks
	Demura, et al.4	1998	68	M	Small cell	Right mediastinum	Chemotherapy	6 Months
	Present case	2008	83	F	Non-small cell	Right upper lobe	None	4 Weeks

a Year: year in press. b Sex: M=male, and F=female. c Survival time: survival from the time of diagnosis.

In general, patients with Budd–Chiari syndrome have already suffered serious liver damage at the time of diagnosis. Although chemotherapy is not usually indicated for NSCLC, it is an option in the treatment of SCLC.4 Palliative radiotherapy may be beneficial for some patients, but requires considerable time to be effective in patients with NSCLC. Recently, stent placement therapy has received increasing attention. It was first described by Charnsangavej et al. in 19869 and since then, many patients have received this treatment. It has been reported to be effective in a short period of time; however, the only reports describing its effectiveness have been small-scale retrospective studies.10, 11 At this writing, there is insufficient evidence of its safety and efficacy.

In conclusion, we described a rare case of Budd–Chiari syndrome secondary to lung cancer and the clinical features of past cases. Consideration of past cases suggests that there are certain common features that are related to this syndrome. Although Budd–Chiari syndrome secondary to lung cancer has a grim prognosis, recent reports suggest that stent placement therapy might be effective as a palliative therapy for this rare condition.

Conflict of interest statement 

The authors have no conflicts of interest to declare.