CASE REPORT

Acute portal vein thrombosis due to chronic relapsingpancreatitis: a fistula between a pancreatic pseudocystand the splenic vein

Masahiro Kikuchi • Yasuhiro Nishizaki • Kota Tsuruya •

Ikuko Hamada • Toru Higashi • Keiko Sakuma • Hirokazu Shiozawa •

Jun Aoki • Rena Nagashima • Jun Koizumi • Yoshitaka Arase •

Koichi Shiraishi • Masashi Matsushima • Tetsuya Mine

Received: 19 March 2013 / Accepted: 4 November 2013 / Published online: 12 December 2013

� Springer Japan 2013

Abstract Portal vein thrombosis (PVT) is a relatively

common complication in patients with liver cirrhosis, but

several other causes might play an important role in PVT

pathogenesis. We present a case of alcoholic chronic

pancreatitis complicated by acute extensive PVT. The

patient was managed conservatively with danaparoid

sodium at first, but the thrombosis gradually extended. We

then tried radiological intervention using the direct tran-

shepatic and transjugular intrahepatic postsystemic shunt

approaches. Although we were able to successfully cathe-

terize the percutaneous transhepatic portal vein (PTP), we

could not achieve recanalization of the portal vein.

Therefore, PTP catheterization and systemic intravenous

infusion of urokinase and heparin was performed to prevent

further progression of the thrombosis and cavernous

transformation was finally achieved. Computed tomogra-

phy (CT) and magnetic resonance cholangiopancreatogra-

phy revealed a pancreatic stone which had possibly

induced dilatation of the tail duct and formation of a

pancreatic pseudocyst and caused intractable pancreatitis.

We performed endoscopic retrograde cholangiopancrea-

tography and placed a stent in the pancreatic duct, which

completely cured the pancreatitis. Retrospectively, the

previous CT with curved multi-planar reconstruction was

reviewed and a fistula was detected between the pancreatic

pseudocyst and splenic vein. We concluded that the etiol-

ogy of the PVT was not only inflammatory extension from

pancreatitis but also a fistula between the pancreatic duct

and the splenic vein.

Keywords Portal vein thrombosis � Splenic vein

thrombosis � Pancreatic stent

Introduction

For activated portal vein thrombosis (PVT) an adequate

choice of treatment is required. There are two main

approaches to reduce PVT-associated morbidity and mor-

tality—(1) to reverse or prevent the progression of

thrombosis within the portal venous system, and (2) to treat

the complications of established PVT, specifically gastro-

intestinal varices or biliary complications. Recent studies

demonstrate the efficacy of thrombolytic therapy in acute

thrombosis, and the apparent safety and benefit of antico-

agulation in patients with chronic PVT.

Pancreatitis has been identified as the cause of PVT, and

the incidence of splenic vein thrombosis in patients with

chronic pancreatitis is 20-40 % [1–3]. In chronic pan-

creatitis, splenic vein thrombosis is considered to be

M. Kikuchi � K. Tsuruya � I. Hamada � T. Higashi �K. Sakuma � H. Shiozawa � J. Aoki � M. Matsushima

Department of Gastroenterology, Tokai University Tokyo

Hospital, Tokyo, Japan

e-mail: kikuchim490611@yahoo.co.jp

Y. Nishizaki (&)

Life Care Center, Tokai University Tokyo Hospital, 1-2-5,

Yoyogi, Shibuya-ku, Tokyo 153-0065, Japan

e-mail: y-nishizaki@tok.u-tokai.ac.jp

R. Nagashima

Department of Radiology, Tokai University Tokyo Hospital,

Tokyo, Japan

J. Koizumi

Department of Diagnostic Radiology, Tokai University School

of Medicine, Isehara, Kanagawa, Japan

Y. Arase � K. Shiraishi � T. Mine

Department of Gastroenterology, Tokai University School of

Medicine, Isehara, Kanagawa, Japan

123

Clin J Gastroenterol (2014) 7:52–57

DOI 10.1007/s12328-013-0442-6

multifactorial in origin, namely due to local, pro-throm-

botic, inflammatory changes in the vascular endothelium,

extrinsic splenic vein compression by pseudocysts, rela-

tively low perfusion, and later in the course of the disease,

pancreatic fibrosis. This suggests that management of

pancreatitis is also required to prevent the progression of

thrombosis.

Case presentation

A 63-year-old male presented to our outpatient clinic with a

history of alcoholic chronic pancreatitis. He complained of

dull pain in his upper abdomen for 5 days without fever or

other symptoms in the digestive organs. He had been con-

suming alcohol (140 g/day) for the last 40 years (last drink

5 days before admission). Laboratory tests revealed white

blood cells (10,800/ll; normal \8,200), C-reactive protein

(6.1 mg/dl; normal \0.6), D-dimer (1,000–2,000 ng/ml;

normal \200), total bilirubin (0.9 mg/dl; normal \1.2),

aspartate amino transferase (34 IU/l; normal \40), alanine

amino transferase (39 IU/l; normal \35), alkaline phos-

phatase (302 IU/l; normal\338), c-glutamyl transpeptidase

(86 IU/l; normal \79), amylase (404 IU/l; normal \134),

lipase (1,023 U/l; normal\57), and elastase-1 (4,704 ng/dl;

normal\300). The prothrombotic work-up, including anti-

phospholipid antibody, protein C and S, and antithrombin III

was negative. By ultrasonography and CT, the patient was

diagnosed with extensive PVT from the superior mesenteric

vein to the portal and splenic veins caused by chronic active

pancreatitis (Figs. 1, 2). Initially, the patient was managed

conservatively with danaparoid sodium for thrombosis, and

gabexate mesilate and antibiotics for pancreatitis, but his

abdominal pain developed with fever spikes. CT examina-

tion showed the thrombosis had gradually extended and

limited activity of pancreatitis at the head was detected. We

diagnosed thrombophlebitis, not pancreatitis activity,

because the level of pancreatic enzymes was not high. The

clinical course is shown in Fig. 3.

Ten days after admission, we twice attempted radio-

logical intervention using the transjugular intrahepatic

postsystemic shunt (TIPS) approach, but we could not

achieve recanalization of the portal vein. However, we

were able to successfully catheterize the percutaneous

transhepatic portal vein (PTP) (Fig. 4). Therefore, PTP

catheterization and systemic intravenous infusion of anti-

biotics, urokinase and heparin was performed to prevent

further progression of the thrombosis. The range of

thrombosis did not decrease but the patient’s abdominal

pain and high fever gradually disappeared. CT showed

cavernous transformation was finally achieved (Fig. 5).

Although the thrombophlebitis was stable, the patient

noticed low-grade fever and epigastric pain after starting a

diet. CT revealed a pancreatic stone which may have

induced dilatation of the tail duct and formation of a

pancreatic pseudocyst and caused intractable pancreatitis

(Fig. 6a). Therefore, we performed endoscopic retrograde

cholangiopancreatography (ERCP) and placed a stent in

Fig. 1 Ultrasonography shows

a thrombosis at the main branch

of the portal vein (arrow),

b right PVT (arrow), and c left

PVT (arrow)

Clin J Gastroenterol (2014) 7:52–57 53

123

the pancreatic duct after dilation with a balloon, which

completely cured the pancreatitis (Fig. 6b).

Retrospectively, we reviewed the previous CT (day 1)

image using curved multi-planar reconstruction (MPR).

We detected a fine low-density structure between the

pancreatic pseudocyst and the splenic vein, surrounded by

edematous and necrotic tissue. We diagnosed this as a

fistula which had developed in necrotic tissue bridged over

the pancreatic pseudocyst to the splenic vein. This might

have had an influence on the formation and extension of the

PVT in this patient (Fig. 7).

The patient has been progressing well since discharge

with the pancreatic stent being exchanged every 3 months.

When he underwent ERCP after discharge, we tried to

detect the existence of a fistula but could not find one. At the

same time, we performed upper gastrointestinal endoscopy

every 3 months. We detected a mild esophageal varix [F1,

Li, Cb, Rc(-), Lg(-)], but it has not changed or enlarged.

Fig. 2 Enhanced CT (portal phase) shows a pancreas head swelling

and new appearance of a pancreatic stone at the body (arrow),

b expansion of inflammation from the pancreas head to the portal vein

(arrow), c left PVT (arrow), d right PVT (arrow), and e expansion of

splenic vein thrombosis to the splenic hilum (arrow)

Fig. 3 Clinical time course

54 Clin J Gastroenterol (2014) 7:52–57

123

Discussion

The presentation of PVT has been divided into two cate-

gories—acute PVT or chronic PVT. No definitive time-

frame distinguishes acute from chronic PVT, but studies of

the former have considered patients who developed

symptoms \60 days prior to hospital assessment [4]. The

typical presentation of acute PVT is with abdominal pain,

nausea and fever. In a patient with proven PVT, the

absence of clinical, endoscopic or radiological evidence of

portal hypertension may also suggest that thrombosis is of

recent onset. In the present case, we diagnosed acute PVT

because of the recent development of thrombosis without

the establishment of cavernous transformation.

In a retrospective study of 172 adult patients with

established PVT, the overall 10-year survival rate was

54 %, but this figure increased to 81 % in those without

cirrhosis, cancer or mesenteric vein thrombosis [5]. In non-

cirrhotic and non-neoplastic patients, PVT generally has a

good outcome [6, 7]. In addition, acute PVT, when rec-

ognized and treated before the occurrence of intestinal

infarction, has a good prognosis [8–10].

The treatment of portal vein thrombosis remains some-

what controversial and has ranged from conservative

strategies such as watchful waiting for spontaneous

recanalization, bowel rest and anticoagulation to more

active approaches such as stenting, thrombolytics, and

surgery.

The effectiveness of anticoagulation in patients with

evidence of acute PVT has been reported in a small number

of studies and case reports [9, 11].

In one study, anticoagulation achieved recanalization in

approximately 40 % of patients and recanalization (com-

plete or partial) was observed in [60 % of patients in

whom anticoagulation was initiated within the first week

but in \20 % of patients who started later [12]. Another

study, clearly showed that in acute PVT onset, the sooner

the treatment is given the better the outcome will be; the

rate of recanalization is approximately 69 % if anticoagu-

lation is instituted within the first week after diagnosis,

Fig. 6 CT shows a the pancreatic stone which possibly induced

dilatation of the tail duct and formation of the pancreatic pseudocyst

and caused an intractable pancreatitis, b pseudocyst reduction and

calming of pancreatitis after stenting the pancreatic duct

Fig. 4 Portography with percutaneous transhepatic portal vein cath-

eterization (PTP) shows an obstinate PVT. Infusion of antibiotics and

urokinase with PTP catheterization was performed to prevent further

progression of the thrombosis

Fig. 5 CT shows the constitution of cavernous transformation and

mass reduction of the PVT

Clin J Gastroenterol (2014) 7:52–57 55

123

while it falls to 25 % when instituted in the second week

[4, 12, 13]. Thus, early anticoagulation is recommended for

the prevention of thrombosis extension.

In the present case, we started administering danaparoid

sodium instead of heparin as soon as possible. Danaparoid

sodium is a drug for deep venous thrombosis and pul-

monary embolism in Western countries and does not need

monitoring unlike heparin and warfarin. The drug is

expected to be useful for treating PVT because it is

effective for the treatment of thrombosis and has a low risk

of bleeding tendency [14]. In the present case, unfortu-

nately the thrombosis appeared to gradually extend and the

patient developed abdominal pain with fever spikes.

Thrombolytic therapy, given either into the systemic

venous circulation, the superior artery, or the portal vein

via the transjugular or transhepatic route, is also effective

for achieving recanalization in acute PVT [15–19]. Despite

the high incidence of adverse effects, thrombolysis should

be considered when initial anticoagulation therapy has

failed, even if there is no consistent evidence concerning

the conditions in which anticoagulation therapy is prefer-

able [15]. PTP catheterization might also be effective in

cases with recent thrombosis, but vascular traumas are

frequent and may stimulate rethrombosis [16], so we

decided to attempt thrombolytic therapy via the transju-

gular route after TIPS placement. However, a technical

problem with a sharp angle in the TIPS route prevented us

from placing the TIPS. We achieved alternative thrombo-

lytic therapy with PTP catheterization which enabled us to

inject highly concentrated thrombolytic agents directly into

the portal vein. PTP catheterization and systemic intrave-

nous infusion of antibiotics, urokinase and heparin was

performed to prevent further progression of the thrombosis

and finally the thrombophlebitis was calmed.

The mechanism of pancreatitis associated with thrombus

formation within the splenic vein seems to involve both

extrinsic and intrinsic factors. This means that a direct

mass affects the venous wall or there is cellular infiltration

into the venous wall and that there is an inflammatory

process involving the vein. The anatomic location of the

splenic vein might greatly contribute to these mechanisms

[20].

In addition, fibrotic extension involving the splenic vein

is important in this phenomenon. Long-standing compres-

sion of the wall of the splenic vein by fibrosis induces a

mild mechanical trauma [21] of the vein, which might

injure the endothelial cells and finally lead to venous

involvement, such as phlebosclerosis and thrombus for-

mation [22]. In the present case, long-standing inflamma-

tion of pancreatic parenchyma due to chronic alcoholic

pancreatitis which led to formation of a pseudocyst was

related to the formation of PVT. Moreover, an abnormal

communication between the pseudocyst and the splenic

vein was detected.

Development of a fistula between a pseudocyst and

portal or splenic vein has been only rarely reported [23–

25]. Pseudocyst rupture into surrounding structures is a

result of pancreatic enzymes, without the inhibitory cas-

cades of the normally functioning pancreas, and inflam-

matory cells within the pseudocyst weakening the

surrounding tissues and vessel walls [26]. Sometimes such

a rupture is responsible for disseminated subcutaneous fat

necrosis and recurrent bacteremia, and surgical treatment is

needed. Most patients with a pancreaticoportal fistula have

Fig. 7 CT (day 1) with curved

MPR shows that a fistula existed

between the pancreatic

pseudocyst and splenic vein

(white large arrow)

56 Clin J Gastroenterol (2014) 7:52–57

123

thrombosis of the portal venous system which suggests that

pancreatic enzymes and inflammatory cells within the

pseudocyst directly worsen endothelial inflammation of the

vein.

In the present case, the patient had a high fever and

remarkably elevated inflammatory observation (CRP was

nearly 30 mg/dl) on days 7-10, and a blood culture test

revealed bacteremia (Corynebacterium). Considered ret-

rospectively, direct infusion of antibiotics through the PTP

route might have contributed to the treatment of bacteremia

which was thought to have been caused by a fistula.

Finally, treatment for the pancreatic stone which had

induced intractable pancreatitis and formation of the

pseudocyst led to the remission of pancreatitis.

We consider that the optimum therapy would have been

to eliminate the pancreatic stone by extracorporeal shock

wave lithotripsy or basket catheterization with ERCP, but

these methods have a high risk under anticoagulation

therapy, so we chose stenting for the pancreatic duct and

then exchanged the stent every 3 months with gradual

dilatation.

Acknowledgment Authors express deep appreciation to Professor T

Tajiri (Department of pathology, Tokai University Hachioji hospital)

for his valuable comments and advices in discussion part of this

paper.

Disclosures Conflict of Interest: M Kikuchi, Y Nishizaki, K

Tsuruya, I Hamada, T Higashi, K Sakuma, H Shiozawa, J Aoki, R

Nagashima, J Koizumi, Y Arase, K Shiraishi, M Matsushima and T

Mine declare that they have no conflict of interest.Human/AnimalRights: All procedures followed were in accordance with the ethical

standards of the responsible committee on human experimentation

(institutional and national) and with the Helsinki Declaration of 1975,

as revised in 2008(5).Informed Consent: Informed consent was

obtained from all patients for being included in the study.

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