Kaohsiung J Med Sci May 2007 • Vol 23 • No 5 254
Portal venous thrombosis (PVT) may be primary or secondary in origin [1–4]. Secondary PVT can be caused by various acquired disorders such as antithrombin III deficiency, sepsis, disseminated intravascular coagula-tion, intra-abdominal infectious or inflammatory condi-tions, liver cirrhosis, surgical intervention, or abdominal malignancies such as pancreatic or hepatocellular
carcinoma (HCC). Symptom development in PVT is often insidious and related to the progression of por-tal hypertension which can lead to hemorrhage from esophageal or cardiac varices. Moreover, malignant PVT can cause wide dissemination of cancer cells. Man-agement of PVT should be based on its etiology and the condition of the patient, e.g. anticoagulation ther-apy for benign PVT, and treatment of underlying cancer for malignant PVT. However, the side effects of treat-ment cannot be tolerated by some of these patients. In this case report, a cirrhotic patient with HCC suffered from acute pancreatitis complicated with transient PVT in the main trunk. Our experience may provide useful information for the management of such patients. Received: October 23, 2006 Accepted: December 11, 2006
Address correspondence and reprint requests to: Dr Zu-Yau Lin, Division of Hepatobiliary Medicine, Department of Internal Medicine, Kaohsiung Medical University, 100 Tzyou 1stRoad, Kaohsiung 807, Taiwan.
E-mail: [email protected]
A
CUTE
P
ANCREATITIS
C
OMPLICATED WITH
T
RANSIENT
P
ORTAL
V
ENOUS
T
HROMBOSIS IN
O
NE
P
ATIENT WITH
H
EPATOCELLULAR
C
ARCINOMA AND
C
IRRHOSIS
Hugo You-Hsien Lin,1Zu-Yau Lin,1,3Paul Ming-Chen Shih,2and Wan-Long Chuang1,3
1Division of Hepatobiliary Medicine, Department of Internal Medicine, and 2Department of Radiology,
Kaohsiung Medical University Hospital, and 3Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Portal venous thrombosis (PVT) is a condition associated with high morbidity. The etiologies of PVT include intra-abdominal inflammation or infection, surgical intervention, abdominal malig-nancies such as hepatocellular carcinoma (HCC) and pancreatic carcinoma, or abnormality in coagulation caused by various reasons such as liver cirrhosis. Management of PVT should be based on its etiology and the condition of the patient. We describe a cirrhotic patient with HCC who suffered from acute pancreatitis. PVT in the main trunk was detected at admission due to the episode of acute pancreatitis. The etiology of thrombosis was considered to be inflammation around the main portal trunk caused by pancreatitis rather than cirrhosis or HCC. We did not instigate any management for the thrombosis. Acute pancreatitis was relieved after conservative treatment. Follow-up imaging study performed 46 days after detection of thrombosis showed spontaneous complete resolution of the thrombus. Our experience may provide useful information for the management of such patients.
Key Words:hepatocellular carcinoma, liver cirrhosis, pancreatitis, portal venous thrombosis
PVT in pancreatitis
C
ASEP
RESENTATIONThe patient was a 33-year-old man with HCC and liver cirrhosis caused by chronic hepatitis B virus infec-tion. Multiple nodular type HCC was diagnosed based on high serum α-fetoprotein (AFP) level (3,296ng/mL; normal< 20 ng/mL) [5] and imaging studies [6] in December 2004. He received three sessions of trans-catheter arterial chemoembolization and one session of percutaneous pure ethanol injection for the man-agement of HCC. The functional reserve of liver cirrhosis was maintained in Child–Pugh class A. Serum AFP level returned to within normal range after this treatment, but it rebounded to 165.9 ng/mL on March 22, 2006.
Serial imaging studies including whole body bone scan, chest X-ray, abdominal ultrasonography, magnetic resonance imaging and angiography were performed to detect the possibility of recurrent HCC. However, no definite viable HCC was found. The serum AFP level increased to 422 ng/mL on June 7, 2006. The condition of the patient was quite satis-factory until June 25, 2006 when he suffered severe abdominal pain and was sent to our emergency de-partment. The characteristics of the pain were dull, radiating to the back, aggravated by food intake and relieved by bed rest. The location of the pain was around the epigastric area. Physical examination showed diffuse abdominal tenderness, diminished bowel sounds but no rebounding pain or fever. Labo-ratory data showed serum C-reactive protein 15.32μg/ mL (normal< 5 μg/mL), amylase 308 U/L (normal < 123U/L), lipase 284IU/L (normal<58IU/L), aspar-tate aminotransferase 51 U/L (normal< 35 U/L), ala-nine aminotransferase 66 U/L (normal<92U/L), total bilirubin 2.13 mg/dL (normal<1.11mg/dL), and con-jugated bilirubin 1.17 mg/dL (normal< 0.4 mg/dL). The coagulation profile was: prothrombin time, 11.6 seconds/10.7 seconds (control); international normal-ized ratio, 1.05; partial prothrombin time, 33.4 seconds/ 30.1 seconds (control).
Under the impression of acute pancreatitis, contrast-enhanced computed tomography (CT) was performed. Peripancreatic fluid collection around the pancreatic head was found, which supported the diagnosis of pancreatitis. Moreover, CT also showed deposition of lipiodol caused by previous transcatheter arterial chemoembolization in segments 3 and 6 by Couinaud Segmental Classification [7], suspected dysplastic
nodules in segments 5 and 6 [7], liver cirrhosis with splenomegaly, gallbladder stones, main portal trunk thrombosis, and ascites (Figure 1).
He was admitted to our institution for the treat-ment of acute pancreatitis. The general condition of the patient improved rapidly after conservative man-agement and he was discharged 9 days later. Reserve liver function did not deteriorate during admission. The main portal trunk thrombosis was not treated because thrombosis was considered to be caused by local inflammation during the episode of pancreatitis and observation was advised.
Unfortunately, he suffered from another similar episode of severe abdominal pain on August 10, 2006. The characteristics of the pain were dull, radiating to the back, aggravated by food intake and relieved by bed rest. The location of the pain was around the epi-gastric area. Physical examination showed diffuse ab-dominal tenderness, decreased bowel sounds but no rebounding pain or fever. Laboratory data showed an elevated serum lipase level (215 IU/L). Under the impression of acute pancreatitis, contrast-enhanced CT was again performed. Compared to the previous study, the amount of ascites had slightly increased. The sizes of the hepatic nodules remained unchanged and the main portal trunk was free of thrombosis Figure 1.Contrast-enhanced computed tomography in this slice showed peripancreatic fluid collection (arrow) around the pancre-atic head and thrombosis of the main portal trunk (arrowhead) that was not detected by magnetic resonance imaging performed 1 month previously. This slice also showed deposition of lipiodol in segments 3 and 6, a suspected dysplastic nodule in segment 6, liver cirrhosis with splenomegaly and collateral circulation at the splenic hilum and perigastric region.
(Figure 2). He was admitted to our institution for conservative treatment of acute pancreatitis and dis-charged 7 days later.
D
ISCUSSIONLiver cirrhosis plays an important role in adult patients with PVT. Splenomegaly, wide main portal trunk, high portal venous pressure and the terminal stage of liver function are reported to be risk factors for the development of PVT in patients with cirrhosis [8,9]. However, the actual mechanism for the development of PVT in patients with cirrhosis still needs to be clarified [10]. It has been reported that a decrease in portal blood flow and the presence of peripheral lym-phangitis and fibrosis may be associated with the devel-opment of PVT [11]. Reduced liver synthetic activity made the coagulation and anticoagulation factors abnormal in patients with liver cirrhosis [12]. Abnor-mality in coagulation can be a precipitating factor for the development of PVT.
Neoplasm is another important cause of the devel-opment of PVT. Among malignancies causing PVT, HCC and pancreatic carcinoma are the two most fre-quent causes [13]. The mechanisms for the develop-ment of PVT in malignancy can be due to the invasion of cancer cells to the portal lumen, compression of the portal vein by tumor burden, or by neoplasm-related prothrombotic changes [14].
Management of PVT should be based on its etiology and the condition of the patient. Spontaneous resolu-tion of PVT caused by benign etiology is possible but uncommon [13]. Anticoagulation therapy is remended for the treatment of acute benign PVT as com-plete or partial resolution can be achieved in up to 80% of patients [15]. Heparin and tissue-type plasminogen activator (t-PA) are used in most studies [15–17]. Anti-coagulation may not increase the risk of bleeding but reduces that of mesenteric infarction, which is possi-bly life-threatening. However, systemic anticoagula-tion therapy may be unsuitable for cirrhotic patients with severe abnormality in coagulation. Thrombolysis through a transhepatic route is another choice for the treatment of acute benign PVT to avoid the adverse effects of systemic anticoagulant therapy [17–19]. This is an invasive management and carries the risk of intra-abdominal hemorrhage or hemobilia. The management of PVT caused by malignancy is quite different from that used for the management of benign PVT. The res-olution of malignant PVT can be achieved only when the involved cancer cells can be well treated. Systemic chemotherapy, local irradiation therapy, or transcath-eter arterial chemoembolization are choices for the management of malignant PVT. However, each of the above carries its own side effects and cannot be applied to all patients with malignant PVT.
The case presented above had HCC and cirrhosis, both of which could possibly develop to PVT. Progres-sive increase in serum AFP levels during the follow-up period strongly suggested recurrence of HCC. Therefore, new-onset PVT detected by CT was rea-sonably considered to be malignant in origin. However, the location of PVT was in the main trunk. There was no detectable hepatofugal portal flow in imaging stud-ies and the other parts of the portal system were com-pletely free of thrombosis. The locations of all treated HCC nodules and the suspected dysplastic nodules were far away from the main trunk thrombus. There was also no detectable tumor burden around the main portal trunk. PVT in this case was not considered to be caused by HCC. On the other hand, the possibility of PVT caused by cirrhosis could not be completely excluded. However, this case did not have past history of abnormality in coagulation. Sudden onset of throm-bosis located only in part of the main trunk was not easily explained by the reason of abnormality in coag-ulation. Pancreatitis is a possible etiology of PVT. The mechanism is suggested to be either portal venous Figure 2.Compared to the previous contrast-enhanced computed
tomography, the amount of peripancreatic fluid collection (arrow) around the pancreatic head had decreased, but ascites had slightly increased. The main portal trunk was free of thrombosis (arrowhead).
PVT in pancreatitis compression caused by pseudocyst or abscess, or an
imbalance between blood coagulation and fibrinolysis [19]. Portal phlebitis caused by leakage of pancreatic juice around the portal vein may also be a factor in the development of PVT in pancreatitis. The location of thrombus in this case was surrounded by the fluid induced by the episode of pancreatitis. Formation of thrombus caused by local phlebitis was the most rea-sonable explanation in this case. PVT can elevate the portal pressure which had the potential to cause rup-ture of esophageal or cardiac varices. In this case, we did not examine the change in portal pressure or varices during admission, because there was no evidence of gastrointestinal hemorrhage to support the necessity of performing further examination. We did not treat the PVT and chose close observation instead. Disap-pearance of thrombus soon after recovery from acute pancreatitis confirmed that PVT was caused by the inflammatory process. The second episode of acute pancreatitis did not show evidence of PVT. This could be explained by fluid collection around the main trunk in the second episode being much less than that in the first episode. Two episodes of acute pancreatitis could be successfully treated by a conservative approach. No obvious cause of pancreatitis could be identified by imaging studies, patient drug abuse history, or labo-ratory data. Although the imaging studies did not show any evidence of biliary stones, according to the clini-cal course of this patient, pancreatitis caused by pas-sage of common bile stones combined with or without cholangitis was the most likely etiology.
In conclusion, PVT can be caused by pancreatitis. Control of the underlying disease may be the first choice for treatment of this kind of PVT. Development of PVT in a patient with HCC and cirrhosis necessarily originates from one of these two possible etiologies and the other possibilities should also be considered.
R
EFERENCES1. Belli L, Romani F, Riolo F, et al. Thrombosis of portal vein in absence of hepatic disease. Surg Gynecol Obstet 1989;169:46–9.
2. Cohen J, Edelman RR, Chopra S. Portal vein thrombo-sis: a review. Am J Med 1992;92:173–82.
3. Brown K, Kaplan M, Donowitz M. Extrahepatic portal venous thrombosis: frequent recognition of associated diseases. J Clin Gastroenterol 1985;7:153–9.
4. Walker AP. Portal vein thrombosis: what is the role of genetics? Eur J Gastroenterol Hepatol 2005;17:705–7. 5. Wiwanitkit V. Alpha fetoprotein for screening for
hepa-tocellular cancer in populations with viral hepatitis B: an appraisal of Thai reports. Asian Pac J Cancer Prev 2005;6:535–6.
6. Kamel IR, Liapi E, Fishman EK. Multidetector CT of hepatocellular carcinoma. Best Pract Res Clin Gastroenterol 2005;19:63–89.
7. Rieker O, Klos G, Beckmann P, et al. Automatic classifi-cation of liver segments according to Couinaud: devel-opment of a new algorithm and evaluation spiral CT data. Rofo 2003;175:1655–9.
8. Jiang X, Liu Y. Clinical analysis of portal vein thrombosis in patients with liver cirrhosis. Chin J Digestion 2004; 24:329–31.
9. Okuda K, Ohnishi K, Kimura K, et al. Incidence of portal vein thrombosis in liver cirrhosis. An angiography study in 708 patients. Gastroenterology 1985;89:279–86. 10. Ögren M, Bergqvist D, Björck M, et al. Portal vein
thrombosis: prevalence, patient characteristics and life-time risk: a population study based on 23796 consecu-tive autopsies. World J Gastroenterol 2006;12:2115–9. 11. Kimura K, Okuda K, Takara K, et al. Membranous
obstruction of the portal vein. A case report.
Gastroen-terology 1985;88:571–5.
12. Amitrano L, Guardascione MA, Brancaccio V, et al. Coagulation disorders in liver disease. Semin Liver Dis 2002;22:83–96.
13. Wang JT, Zhao HY, Liu YL. Portal vein thrombosis.
Hepatobiliary Pancreat Dis Int 2005;4:515–7.
14. Bick R. Coagulation abnormalities in malignancy: a review. Semin Thromb Hemost 1992;18:353–72.
15. Joh JH, Kim DI. Mesenteric and portal vein thrombo-sis: treated with early initiation of anticoagulation. Eur
J Vasc Endovasc Surg 2005;29:204–8.
16. Schafer C, Zundler J, Bode J. Thrombolytic therapy in patients with portal vein thrombosis: case report and review of the literature. Eur J Gastroenterol Hepatol 2000; 12:1141–5.
17. Webster GJM, Burroughs AK, Riordan SM. Review arti-cle: portal vein thrombosis—new insights into aetiology and management. Aliment Pharmacol Ther 2005;21:1–9. 18. Ozkan U, Oguzkurt L, Tercan F, et al. Percutaneous
transhepatic thrombolysis in the treatment of acute portal venous thrombosis. Diagn Interv Radiol 2006;12: 105–7.
19. Hollingshead M, Burke C, Mauro M, et al. Transcatheter thrombolytic therapy for acute mesenteric and portal vein thrombosis. J Vasc Interv Radiol 2005;16:651–61.
!"VR==NM==OP= !"VR==NO==NN= !"#$%&' !"!#$ %&'()* UMT !"#$NMM
