Clin J Gastroenterol (2014) 7:52–57 DOI 10.1007/s12328-013-0442-6
CASE REPORT
Acute portal vein thrombosis due to chronic relapsing pancreatitis: a fistula between a pancreatic pseudocyst and 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 Ó 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 transhepatic and transjugular intrahepatic postsystemic shunt approaches. Although we were able to successfully catheterize 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 tomography (CT) and magnetic resonance cholangiopancreatography 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 cholangiopancreatography 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 etiology 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
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: [email protected] Y. Nishizaki (&) Life Care Center, Tokai University Tokyo Hospital, 1-2-5, Yoyogi, Shibuya-ku, Tokyo 153-0065, Japan e-mail: [email protected] 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
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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 mortality—(1) to reverse or prevent the progression of thrombosis within the portal venous system, and (2) to treat the complications of established PVT, specifically gastrointestinal varices or biliary complications. Recent studies demonstrate the efficacy of thrombolytic therapy in acute thrombosis, and the apparent safety and benefit of anticoagulation 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 pancreatitis, splenic vein thrombosis is considered to be
Clin J Gastroenterol (2014) 7:52–57
multifactorial in origin, namely due to local, pro-thrombotic, inflammatory changes in the vascular endothelium, extrinsic splenic vein compression by pseudocysts, relatively 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 consuming 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 phosphatase (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 antiphospholipid 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
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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 examination 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 radiological 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 antibiotics, 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)
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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
Clin J Gastroenterol (2014) 7:52–57
(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
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
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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.
Clin J Gastroenterol (2014) 7:52–57
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Fig. 4 Portography with percutaneous transhepatic portal vein catheterization (PTP) shows an obstinate PVT. Infusion of antibiotics and urokinase with PTP catheterization was performed to prevent further progression of the thrombosis
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. 5 CT shows the constitution of cavernous transformation and mass reduction of the PVT
Discussion The presentation of PVT has been divided into two categories—acute PVT or chronic PVT. No definitive timeframe 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 noncirrhotic and non-neoplastic patients, PVT generally has a good outcome [6, 7]. In addition, acute PVT, when recognized and treated before the occurrence of intestinal infarction, has a good prognosis [8–10]. The treatment of portal vein thrombosis remains somewhat 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 (complete 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 anticoagulation is instituted within the first week after diagnosis,
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Clin J Gastroenterol (2014) 7:52–57
Fig. 7 CT (day 1) with curved MPR shows that a fistula existed between the pancreatic pseudocyst and splenic vein (white large arrow)
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 pulmonary 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, unfortunately 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 preferable [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 transjugular 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 thrombolytic therapy with PTP catheterization which enabled us to inject highly concentrated thrombolytic agents directly into the portal vein. PTP catheterization and systemic intravenous infusion of antibiotics, urokinase and heparin was
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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 compression 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 formation [22]. In the present case, long-standing inflammation 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 cascades of the normally functioning pancreas, and inflammatory 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
Clin J Gastroenterol (2014) 7:52–57
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 retrospectively, 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/Animal Rights: 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.
References 1. Weber SM, Rikkers LF. Splenic vein thrombosis and gastrointestinal bleeding in chronic pancreatitis. World J Surg. 2003;27:1271–4. 2. Heider RT, Azeem S, Galanko JA, et al. The natural history of pancreatitis-induced splenic vein thrombosis. Ann Surg. 2004;239:876–80. 3. Sakorafos GH, Sarr MG, Farley DR, et al. The significance of sinistral portal hypertension complicating chronic pancreatitis. Am J Surg. 2000;179:129–33. 4. Malkowski P, Pawlak J, Michalowicz B, et al. Thrombolytic treatment of portal thrombosis. Hepatogastroenterology. 2003; 50:2098–100. 5. Janssen HL, Wijnhoud A, Haagsma EB, et al. Extrahepatic portal vein thrombosis: etiology and determinants of survival. Gut. 2001;49:720–4.
57 6. Plessier A, Murad SD, Hernandez-Guerra M, et al. A prospective multicentric follow-up study on 105 patients with acute portal vein thrombosis (PVT): results from the European network for vascular disorders of the liver. Hepatology. 2007;46:310a-a. 7. Amitrano L, Guardascione MA, Scaglione M, et al. Prognostic factors in non-cirrhotic patients with splanchnic vein thromboses. Am J Gastroenterol. 2007;102:2464–70. 8. Kumar S, Sarr MG, Kamath PS, et al. Mesenteric venous thrombosis. N Engl J Med. 2001;345(23):1683–8. 9. Sheen CL, Lamparelli H, Milne A, et al. Clinical features, diagnosis and outcome of acute portal vein thrombosis. QJM. 2000;93(8):531–4. 10. Lagasse JP, Bahallah ML, Salem N, et al. Acute thrombosis of the portal system. Treatment with alteplase and heparin or with heparin alone in 10 patients. Gastroenterol Clin Biol. 1997;21:919–23. 11. Baril N, Wren S, Radin R, et al. The role of anticoagulation in pylephlebitis. Am J Surg. 1996;172:449–52. 12. Turnes J, Garcı´a-Paga´n JC, Gonza´lez M, et al. Portal hypertension-related complications. After acute portal vein thrombosis: impact of early anticoagulation. Clin Gastroenterol Hepatol. 2008;6(12):1412–7. 13. Hoekstra J, Janssen HL, et al. Vascular liver disorders (II): portal vein thrombosis. Neth J Med. 2009;67(2):46–53. 14. Uchiyama T, Hirokazu T, Hosono K, et al. Portal vein thrombosis treated using danaparoid sodium and antithrombin III. Hepatogastroenterology. 2010;57(97):52–3. 15. Schafer C, Zundler J, Bode JC, et al. Thrombolytic therapy in patients with portal vein thrombosis: case report and review of the literature. Eur J Gastroenterol Hepatol. 2000;12:1141–5. 16. Henao EA, Bohannon WT, Silva MB Jr, et al. Treatment of portal venous thrombosis with selective superior mesenteric artery infusion of recombinant tissue plasminogen activator. J Vasc Surg. 2003;38:1411–5. 17. Tateishi A, Mitsui H, Oki T, et al. Extensive mesenteric vein and portal vein thrombosis successfully treated by thrombolysis and anticoagulation. J Gastroenterol Hepatol. 2001;16:1429–33. 18. Aytekin C, Boyvat F, Kurt A, et al. Catheter-directed thrombolysis with transjugular access in portal vein thrombosis secondary to pancreatitis. Eur J Radiol. 2001;39:80–2. 19. Lopera JE, Correa G, Brazzini A, et al. Percutaneous transhepatic treatment of symptomatic mesenteric venous thrombosis. J Vasc Surg. 2002;36:1058–61. 20. Moosa AR, Gadd MA. Isolated splenic vein thrombosis. World J Surg. 1985;9:384–90. 21. Hoff HF. Ultrastructural changes of large rabbit blood vessels following mild mechanical trauma. Virchows Arch Abt A Pathol Anat. 1968;345:93–106. 22. Takase M, Suda K, Suzuki F, et al. A histopathologic study of localized portal hypertension as a consequence of chronic pancreatitis. Arch Pathol Lab Med. 1997;121:612–4. 23. Demetrick DJ, Kelly JK. Variceal hemorrhage as a consequence of spontaneous rupture of a pancreatic pseudocyst into the splenic vein. Am J Gastroenterol. 1989;84:1103–5. 24. Procacci C, Mansueto GC, Graziani R, et al. Spontaneous rupture of a pancreatic pseudocyst into the portal vein. Cardiovasc Intervent Radiol. 1995;18:399–402. 25. Van Steenbergen W, Ponette E. Pancreaticoportal fistula: a rare complication of chronic pancreatitis. Gastrointes Radiol. 1990;15:299–300. 26. Willis SM, Brewer TG. Pancreatic duct-portal vein fistula. Gastroenterology. 1989;97:1025–7.
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CASE REPORT
Acute portal vein thrombosis due to chronic relapsing pancreatitis: a fistula between a pancreatic pseudocyst and 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 Ó 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 transhepatic and transjugular intrahepatic postsystemic shunt approaches. Although we were able to successfully catheterize 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 tomography (CT) and magnetic resonance cholangiopancreatography 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 cholangiopancreatography 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 etiology 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
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: [email protected] Y. Nishizaki (&) Life Care Center, Tokai University Tokyo Hospital, 1-2-5, Yoyogi, Shibuya-ku, Tokyo 153-0065, Japan e-mail: [email protected] 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
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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 mortality—(1) to reverse or prevent the progression of thrombosis within the portal venous system, and (2) to treat the complications of established PVT, specifically gastrointestinal varices or biliary complications. Recent studies demonstrate the efficacy of thrombolytic therapy in acute thrombosis, and the apparent safety and benefit of anticoagulation 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 pancreatitis, splenic vein thrombosis is considered to be
Clin J Gastroenterol (2014) 7:52–57
multifactorial in origin, namely due to local, pro-thrombotic, inflammatory changes in the vascular endothelium, extrinsic splenic vein compression by pseudocysts, relatively 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 consuming 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 phosphatase (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 antiphospholipid 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
53
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 examination 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 radiological 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 antibiotics, 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)
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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
Clin J Gastroenterol (2014) 7:52–57
(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
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
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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.
Clin J Gastroenterol (2014) 7:52–57
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Fig. 4 Portography with percutaneous transhepatic portal vein catheterization (PTP) shows an obstinate PVT. Infusion of antibiotics and urokinase with PTP catheterization was performed to prevent further progression of the thrombosis
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. 5 CT shows the constitution of cavernous transformation and mass reduction of the PVT
Discussion The presentation of PVT has been divided into two categories—acute PVT or chronic PVT. No definitive timeframe 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 noncirrhotic and non-neoplastic patients, PVT generally has a good outcome [6, 7]. In addition, acute PVT, when recognized and treated before the occurrence of intestinal infarction, has a good prognosis [8–10]. The treatment of portal vein thrombosis remains somewhat 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 (complete 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 anticoagulation is instituted within the first week after diagnosis,
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Clin J Gastroenterol (2014) 7:52–57
Fig. 7 CT (day 1) with curved MPR shows that a fistula existed between the pancreatic pseudocyst and splenic vein (white large arrow)
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 pulmonary 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, unfortunately 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 preferable [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 transjugular 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 thrombolytic therapy with PTP catheterization which enabled us to inject highly concentrated thrombolytic agents directly into the portal vein. PTP catheterization and systemic intravenous infusion of antibiotics, urokinase and heparin was
123
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 compression 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 formation [22]. In the present case, long-standing inflammation 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 cascades of the normally functioning pancreas, and inflammatory 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
Clin J Gastroenterol (2014) 7:52–57
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 retrospectively, 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/Animal Rights: 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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