Journal of Gastroenterology and Hepatologv (1990) 5, 708-713
CASE REPORT Portal vein obstruction complicating intra-arterial chemo-infusion for hepatic metastases KENICHI TAKAYASU,* MASATOSHI MAKUUCHI' AND YOSHIHIRO MORIYA' Departments of *Diagnostic Radiology and 'Surgery, National Cancer Center Hospital, Tokyo
Abstract In three patients with colon cancer and liver metastases who had received inua-arterial chemoinfusion of fluorouracil (5FU) and mitomycin C and/or cis-diamminedichloroplatinum (CDDP), intrahepatic portal vein thrombosis (PVT) was incidentally demonstrated by computerized tomography (CT) 6, 1 and 7 months respectively after the cessation of administration of anti-cancer agents. One patient developed complete PVT in the whole liver as shown by follow-up CT 6 months after a diagnosis of pre-existing sclerosing cholangitis, and died from rupture of oesophageal varices. In the remaining two patients, PVT was found incidentally by follow-up CT in the right portal vein (Case 2) and the right anterior portal vein (Case 3) respectively; it spontaneously recanalized in Case 2 and was still present in Case 3 2 months later. PVT seems to be one of the complications of hepatic arterial chemo-infusion and its possibility must be borne in mind in such patients, even though the exact interval between the arterial chemo-infusion and occurrence of PVT could not be determined.
Key words: chemo-infusion, hepatic metastases, portal vein obstruction
INTRODUCTION Intermittent and/or continuous hepatic chemoinfusion therapy using a surgically implanted pump is a palliative therapy for liver metastases from colorectal cancer.1*2However, several complications such as sclerosing cholangitis, gastritis and gastroduodenal ulcers have .been reported.3-' We recently encountered portal vein thrombosis (PVT) following hepatic arterial chemo-infusion in three patients. PVT as a complication of hepatic arterial chemo-infusion has not been reported previously.
CASE REPORTS Case 1 A 34 year old male was referred to our hospital because of tarry stool. On admission, laboratory
data were normal except for elevation of carcinoembryonic antigen (CEA) to 92 ng/mL (normal c4.9). Barium enema study revealed an advanced cancer measuring 6 x 5 cm in the sigmoid colon. Computerized tomography (CT) also revealed two metastatic lesions in the right lobe of the liver. On 18 March 1987, sigmoidectomy was carried out, followed by hepatic enucleation for metastases. Staging for colon cancer showed this to be Dukes C, and well differentiated adenocarcinorna was histopathologically diagnosed. T h e gastroduodenal artery was catheterized operatively, using an Infuse-A-Port system (Shiley Infusaid, Inc. MA, USA). Infusion of 6 m g of mitomycin C and 500 mg of fluorouracil (5FU) was given once a week for approximately 5 months. In October, after a total dose of 70 mg of mitomycin C and 7750mg of SFU, jaundice developed abruptly. Remarkable elevations of
Correspondence: Kenichi Takayasu, MD, Department of Diagnostic Radiology, 5-1-1, Tsukiji, Chuo-ku Tokyo 104 Japan.
Accepted for publication 13 May 1990.
PVT in chew-infusion for hepatic metastases total bilirubin (32.4 mg/dL) and alkaline phosphatase (1190 iu/L, normal, 54-230) were noted. Ultrasonography (US) and C T (Fig. la) revealed moderate dilatation of intrahepatic bile ducts, and percutaneous transbiliary drainage was carried out subsequently; there was a complete obstruction of the common hepatic duct. Sclerosing cholangitis secondary to intraarterial administration of anticancer drugs was the diagnosis. Chemo-infusion was discontinued and prednisolone was commenced. Hepatic arteriography revealed stenotic changes of the right hepatic artery and its peripheral arteries, and postarterial portography revealed stenosis of the beginning of the posterior portal branch and non-opacification of its peripheral branches (Fig. lb). During followup at the outpatient department, recanalization of the common hepatic duct was confirmed by cholangiography and the bilirubin level became normal and so the PTC drainage tube was removed. However, the level of alkaline phosphatase, which was 721 iu/L in February, gradually increased to 2186 iu/L, even though the levels of total bilirubin and other liver enzymes were normal. Enhanced CT (Figs lc and d) performed 6 months after the cessation of intra-arterial administration of anticancer drugs, showed complete obstruction of the intrahepatic portal vein system and dilatation of the bile ducts; these were also confirmed by US. The patient eventually died 2 months later from rupture of oesophageal varices complicated by ascites. Autopsy was not carried out. Case 2
A 66 year old female complained of abdominal discomfort in summer 1987. Nine months later she underwent barium enema examination which disclosed an advanced cancer in the transverse colon. Five metastatic lesions were also found by US in both lobes of the liver. Patency of the intrahepatic portal vein was confirmed by US and by C T (Fig. 2a). Laboratory data were almost normal. On April 12 right hemicolectomy, followed by placement of an Infuse-A-Port in the gastroduodenal artery without hepatectomy, were carried out. The colon cancer was at stage Dukes C and the histological diagnosis was poorly differentiated adenocarcinoma. A total of 9750 mg of 5FU and 72 mg of mitomycin C were administered via the hepatic artery. In December this was
709 discontinued because of anaemia. Follow-up C T performed 1 month later incidentally demonstrated almost complete obstruction of the right portal vein with an inhomogeneous density in the ipsilateral lobe (Fig. 2b), even though the metastatic lesions were reduced in size and number. No dilatation of bile ducts was seen. Bilirubin and alkaline phosphatase were normal during these 3 months. Repeat C T performed two months later showed spontaneous recanalization of the right portal vein. The patient is well and is being followed up. Case 3
A 52 year old male underwent resection of the rectum for cancer in July 1986. Histopathological study revealed moderately differentiated tubular adenocarcinoma. Eight months later, the serum CEA level gradually increased to 99 ng/mL and subsequent US and C T showed multiple metastases in the whole liver. After confirming liver metastases on laparotomy, an Infuse-A-Port was placed in the gastroduodenal artery. Follow-up CT, performed four months after the arterial administration of 10 mg of mitomycin C via the hepatic artery every week and 500mg of 5FU every 2 months, showed complete response which lasted for 1 year. A total of 146 mg of mitomycin C and 3.5 g of 5FU were administered during 14 months. However, the serum CEA level increased again and repeat US and C T showed multiple small recurrent foci measuring less than 1.5 cm in the liver. Neither portal vein obstruction nor biliary dilatation was seen on either image (Fig. 3a). Intraarterial administration of 1000 mg of 5FU per day was begun again in May 1988; this was continued for 5 days, then discontinued for 1 month. Altogether three courses were given. However, follow-up US revealed progression of the metastatic lesions, and hepatic arterial administration of 125 mg of cis-diamminedichloro platinum (CDDP) every month was started. After four courses, the catheter became obstructed and arterial administration was changed to systemic chemotherapy with 125mg of CDDP. In July 1989, follow-up CT, performed 7 months after the cessation of intraarterial administration of anticancer drugs, showed a segmental attenuation difference with portal vein obstruction in the right anterior segment of the liver as well as metastatic lesions (Fig. 3b). When the patient’s
K. Takayasu et al.
710
Figure 1 In case 1, (a) Enhanced CT shows moderate dilatation of intrahepatic bile ducts. Right portal veins are well visualized except for posterior portal vein, which usually runs medial to the accompanying bile duct. Arrow shows operatively placed catheter in gastroduodenal artery. (b) Postarterial portography shows non-opacification of posterior portal vein branch and stenosis of its beginning (right arrow). Biliary drainage tube is visible (left arrow). (c) Follow-up CT shows non-opacification of portal veins which ordinarily run lateral to bile ducts in anterior in right lobe (arrows show slightly dilated bile ducts). Hepatic infarction is shown in posterior of liver. Spleen is much larger than in (a), which may be due to portal hypertension secondary to portal vein obstruction. (d) Slice 2 cm caudal to (c) shows thrombosis of posterior portal vein, which is much thicker than calibre of dilated bile ducts in (c).
medical records were reviewed during this year, there was no complaint, symptom or abnormal value of liver enzyme and bilirubin was recognized. Repeat CT performed 2 months later showed PVT to be still present.
DISCUSSION Direct infusion of chemotherapeutic agents into the liver with an implantable infusion pump or a reservoir in the treatment of hepatic metastases
PVT in chemo-infusion for hepatic metastases
71 1
Figure 2 In case 2, (a) Enhanced C T in hepatic hilum shows good opacification of portal veins. (b) Follow-up C T shows almost complete obstruction of right portal veins and low density area with non-homogeneous lower area in ipsilateral lobe of liver. Slight opacification of thin anterior portal vein (lower arrow) is shown. Upper arrow indicates an implanted pump.
Figure 3 In case 3, (a) Dbnamic C T shows good opacification of portal veins in right lobe of liver. Arrows indicate portal veins in anterior segment of right lobe. Intrahepatic metastases are not shown in this slice. (b) Follow-up C T shows segmental attenuation difference in anterior segmental area (black arrows) consistent with obstruction of anterior portal vein (white arrows) in right lobe.
from colorectal cancer gives good response rates, ranging from 29% to 88y0,6 which are much superior to those obtained with systemic chemothe rap^.^ With frequent uses of this therapeutic system, several complications, such as sclerosing cholangitis have been e n c o ~ n t e r e d . ~ However, -~ to our knowledge, portal vein obstruction following intraarterial chemo-infusion has not yet been reported. The three patients who received intraarterial administration of SFU, mitomycin C and/or CDDP developed PVT after various intervals following cessation of intraarterial administration. It was found incidentally without specific
symptoms, in Cases 2 and 3. However, the process leading to and the outcome of PVT were different between the three cases. In Case 1, partial PVT of the posterior portal vein (Fig. lb) was observed by postarterial portography at the time of diagnosis of arterial vasculitis, which perhaps resulted in sclerosing cholangitis, and subsequently all major portal branches (Figs l c and d) were obstructed approximately 6 months after the cessation of administration of 5FU and mitomycin C. At that time, sclerosing cholangitis, which had developed prior to PVT, was improved. However, while the level of alkaline phosphatase, not bilirubin, was increasing with
K. Takayasu et al.
712
no other changes, the patient developed acute abdominal pain. Splenomegaly and oesophageal varices suggested portal hypertension due to PVT. Unfortunately, autopsy was not performed. In contrast, in the asymptomatic patients, Cases 2 and 3, partial PVT in the right portal vein and segmental PVT in the right anterior portal vein were found incidentally by follow-up C T 1 month and 7 months respectively after the cessation of anti-cancer drugs. There was no indication of biliary obstruction in these patients. This PVT was recanalized spontaneously in Case 2 but not in Case 3, as confirmed by repeat C T 2 months later. Enhanced CT, especially dynamic CT, is one of the reliable imaging modalities for demonstrating PVT, as is ultrason~graphy;~ it is recognized from the characteristic findings such as lobar or segmental attenuation differences shown in Figs 2b and 3b and an enlarged intraluminal low density area (Fig. 3b).9-10 Ring enhancement around PVT due to opacification of the vasa vasorum was not recognized in our cases." Unfortunately, these PVTs were not confirmed by angiography after the confirmation of PVT on CT. Intrahepatic PVT is usually insidious and asymptomatic and therefore it is very difficult to recognize fresh PVT by imaging. In all our cases, PVT was detected incidentally by routine followup C T and the exact interval between the beginning of the arterial chemotherapy and the occurrence of PVT could not be determined. In all, the portal vein trunk was well opacified and no known causes for PVT such as pancreatitis, thrombocytaemia or oestrogen therapy were found during the clinical c0urse.l' Portal tumour thrombus from the metastasized tumour was very unlikely, because metastatic lesions were not very large.13 The combined use of mitomycin C and 5FU in the hepatic artery through an implantable infusion pump is common in Japan for liver metastases from colorectal cancer. Even though complicating sclerosing cholangitis is encountered infrequently, PVT following arterial chemo-infusion has been very uncommon. In our cases, the cause of portal vein obstruction is unclear. However, the following are speculated: direct portal toxicity onto the portal vein followed by vasculitis as a result of inflow of anticancer agents via arterial-portal shunt (transvasal and/or transplexal) under special conditions such as
stenotic changes or obstruction of accompanying arteries due to long-standing chemoinfusion;14-16 or involvement of the portal vein in scar formation in the porta hepatis, which is frequently observed in sclerosing cholangiti~.~ PVT was irreversible in Cases 1 and 3 but reversible in Case 2. A similar outcome has been described in patients with sclerosing ch~langitis.~ During follow-up of patients receiving intrahepatic arterial chemo-infusion, possible complications involving the portal vein and biliary tract should be kept in mind.
ACKNOWLEDGEMENTS We thank Emeritus Professor Kunio Okuda, of the Chiba University School of Medicine, for his review. This study is supported by Grants-in-Aid for Cancer Research from the Ministry of Health and Welfare.
REFERENCES 1. DALY J. M., KEMENY N., ODERMAN P.& BOTETJ.
Long-term hepatic arterial infusion chemotherapy. Anatomic considerations, operative technique, and treatment morbidity.Arch. Surg. 1984, 119: 936-41. 2. STAGG R. J., LEWISB. J., FRIEDMAN M. A,, IGNOFFOR. J. & HOHND. C. Hepatic arterial chemotherapy for colorectal cancer metastatic to the liver. Ann. Intern. Med. 1984; 100: 736-43. 3. PIENE. H., ZEMANR. K., BENJAMIN S. B. et al. Iatrogenic sclerosing cholangitis following hepatic arterial chemotherapy infusion. Radiology 1985; 156: 329-30. 4. BOTETJ . F., WATSONR. C., KEMENY N. K., DALY J. M. & YEH S . Cholangitis complicating intra-
arterial chemotherapy in liver metastasis. Radiology 1985; 156: 335-7. 5. SHEAW. J., DEMAS B. E., GOLDBERG H. I., Horn D. C., FERREL L. D. & KERLANR. K. Sclerosing
cholangitis associated with hepatic arterial FUDR chemotherapy: Radiographic-histologic correlation. Amer. 3. Roentgenol. 1986; 146: 717-21. F. J., RAMIREZ G., DAVISH. L. et al. 6. ANSFIELD Further clinical studies with intrahepatic arterial infusion with 5-fluorouracil. Cancer 1975; 36: 2413-7. 7. FORTNERJ. G., MULCARER. J., SOLIS A., WATSONR. C. & GOLBEYR. B. Treatment of
primary and secondary liver cancer by hepatic artery ligation and infusion chemotherapy. Ann. Surg. 1973; 178: 162-72.
P V T in chemo-infusion for hepatic metastases 8. SCHWERK W. B. Portal vein thrombosis: Real-time sonographic demonstration and follow-up. Gastrointest. Radiol. 1986; 11: 312-8. 9. ITAIY., Moss A. A. & GOLDBERG H. I. Transient hepatic attenuation difference of lobar or segmental distribution detected by dynamic computed tomography. Radiology 1982; 144: 835-9. 10. TAKAYASU K., MORIYAMA N., MURAMATSU Y. & TAJIRI H. Transient perihilar attenuation difference in the liver on dynamic C T secondary to portal thrombosis: Report of two cases. Gastroenterol.3pn
713
13.
4.
5.
1989; 24: 205-8.
D., VASILEN. & GRENIER P. Portal 11. MATHIEU thrombosis: Dynamic C T features and course. Radiology 1985; 154: 737-41. M., GANSBEKE D. V., MATOSC., ENGEL12. ZALCMAN HOLM L. & STRUWEN J. Sonographic demonstration of portal venous system thromboses secondary
16.
to inflammatory diseases of the pancreas. Gastroinrest. Radiol. 1987; 12: 114-6. HEASTON D. K., CHUANC V. P., WALLACE S. & SANTOSL. A. Metastatic hepatic neoplasms: Angiographic features of portal vein involvement. Amer. 3. Roentgenol. 1981; 136: 897-900. BOOKSTEIN J. J., CHOK. J., DAVISG. B. & DAIL D. Arterioportal communications: Observations and hypotheses concerning transsinusoidal and transvasal types. Radiology 1982; 142: 581-90. CHO K. J. & LUNDERQUIST A. The peribiliary vascular plexus: The microvascular architecture of the bile duct in the rabbit and in clinical cases. Radiology 1983; 147: 357-64. NAKAMURA H., HASHIMOTO T., Or H. & SAWADA S. Iodized oil in the portal vein after arterial embolization. Radiology 1988; 167: 415-7.
CASE REPORT Portal vein obstruction complicating intra-arterial chemo-infusion for hepatic metastases KENICHI TAKAYASU,* MASATOSHI MAKUUCHI' AND YOSHIHIRO MORIYA' Departments of *Diagnostic Radiology and 'Surgery, National Cancer Center Hospital, Tokyo
Abstract In three patients with colon cancer and liver metastases who had received inua-arterial chemoinfusion of fluorouracil (5FU) and mitomycin C and/or cis-diamminedichloroplatinum (CDDP), intrahepatic portal vein thrombosis (PVT) was incidentally demonstrated by computerized tomography (CT) 6, 1 and 7 months respectively after the cessation of administration of anti-cancer agents. One patient developed complete PVT in the whole liver as shown by follow-up CT 6 months after a diagnosis of pre-existing sclerosing cholangitis, and died from rupture of oesophageal varices. In the remaining two patients, PVT was found incidentally by follow-up CT in the right portal vein (Case 2) and the right anterior portal vein (Case 3) respectively; it spontaneously recanalized in Case 2 and was still present in Case 3 2 months later. PVT seems to be one of the complications of hepatic arterial chemo-infusion and its possibility must be borne in mind in such patients, even though the exact interval between the arterial chemo-infusion and occurrence of PVT could not be determined.
Key words: chemo-infusion, hepatic metastases, portal vein obstruction
INTRODUCTION Intermittent and/or continuous hepatic chemoinfusion therapy using a surgically implanted pump is a palliative therapy for liver metastases from colorectal cancer.1*2However, several complications such as sclerosing cholangitis, gastritis and gastroduodenal ulcers have .been reported.3-' We recently encountered portal vein thrombosis (PVT) following hepatic arterial chemo-infusion in three patients. PVT as a complication of hepatic arterial chemo-infusion has not been reported previously.
CASE REPORTS Case 1 A 34 year old male was referred to our hospital because of tarry stool. On admission, laboratory
data were normal except for elevation of carcinoembryonic antigen (CEA) to 92 ng/mL (normal c4.9). Barium enema study revealed an advanced cancer measuring 6 x 5 cm in the sigmoid colon. Computerized tomography (CT) also revealed two metastatic lesions in the right lobe of the liver. On 18 March 1987, sigmoidectomy was carried out, followed by hepatic enucleation for metastases. Staging for colon cancer showed this to be Dukes C, and well differentiated adenocarcinorna was histopathologically diagnosed. T h e gastroduodenal artery was catheterized operatively, using an Infuse-A-Port system (Shiley Infusaid, Inc. MA, USA). Infusion of 6 m g of mitomycin C and 500 mg of fluorouracil (5FU) was given once a week for approximately 5 months. In October, after a total dose of 70 mg of mitomycin C and 7750mg of SFU, jaundice developed abruptly. Remarkable elevations of
Correspondence: Kenichi Takayasu, MD, Department of Diagnostic Radiology, 5-1-1, Tsukiji, Chuo-ku Tokyo 104 Japan.
Accepted for publication 13 May 1990.
PVT in chew-infusion for hepatic metastases total bilirubin (32.4 mg/dL) and alkaline phosphatase (1190 iu/L, normal, 54-230) were noted. Ultrasonography (US) and C T (Fig. la) revealed moderate dilatation of intrahepatic bile ducts, and percutaneous transbiliary drainage was carried out subsequently; there was a complete obstruction of the common hepatic duct. Sclerosing cholangitis secondary to intraarterial administration of anticancer drugs was the diagnosis. Chemo-infusion was discontinued and prednisolone was commenced. Hepatic arteriography revealed stenotic changes of the right hepatic artery and its peripheral arteries, and postarterial portography revealed stenosis of the beginning of the posterior portal branch and non-opacification of its peripheral branches (Fig. lb). During followup at the outpatient department, recanalization of the common hepatic duct was confirmed by cholangiography and the bilirubin level became normal and so the PTC drainage tube was removed. However, the level of alkaline phosphatase, which was 721 iu/L in February, gradually increased to 2186 iu/L, even though the levels of total bilirubin and other liver enzymes were normal. Enhanced CT (Figs lc and d) performed 6 months after the cessation of intra-arterial administration of anticancer drugs, showed complete obstruction of the intrahepatic portal vein system and dilatation of the bile ducts; these were also confirmed by US. The patient eventually died 2 months later from rupture of oesophageal varices complicated by ascites. Autopsy was not carried out. Case 2
A 66 year old female complained of abdominal discomfort in summer 1987. Nine months later she underwent barium enema examination which disclosed an advanced cancer in the transverse colon. Five metastatic lesions were also found by US in both lobes of the liver. Patency of the intrahepatic portal vein was confirmed by US and by C T (Fig. 2a). Laboratory data were almost normal. On April 12 right hemicolectomy, followed by placement of an Infuse-A-Port in the gastroduodenal artery without hepatectomy, were carried out. The colon cancer was at stage Dukes C and the histological diagnosis was poorly differentiated adenocarcinoma. A total of 9750 mg of 5FU and 72 mg of mitomycin C were administered via the hepatic artery. In December this was
709 discontinued because of anaemia. Follow-up C T performed 1 month later incidentally demonstrated almost complete obstruction of the right portal vein with an inhomogeneous density in the ipsilateral lobe (Fig. 2b), even though the metastatic lesions were reduced in size and number. No dilatation of bile ducts was seen. Bilirubin and alkaline phosphatase were normal during these 3 months. Repeat C T performed two months later showed spontaneous recanalization of the right portal vein. The patient is well and is being followed up. Case 3
A 52 year old male underwent resection of the rectum for cancer in July 1986. Histopathological study revealed moderately differentiated tubular adenocarcinoma. Eight months later, the serum CEA level gradually increased to 99 ng/mL and subsequent US and C T showed multiple metastases in the whole liver. After confirming liver metastases on laparotomy, an Infuse-A-Port was placed in the gastroduodenal artery. Follow-up CT, performed four months after the arterial administration of 10 mg of mitomycin C via the hepatic artery every week and 500mg of 5FU every 2 months, showed complete response which lasted for 1 year. A total of 146 mg of mitomycin C and 3.5 g of 5FU were administered during 14 months. However, the serum CEA level increased again and repeat US and C T showed multiple small recurrent foci measuring less than 1.5 cm in the liver. Neither portal vein obstruction nor biliary dilatation was seen on either image (Fig. 3a). Intraarterial administration of 1000 mg of 5FU per day was begun again in May 1988; this was continued for 5 days, then discontinued for 1 month. Altogether three courses were given. However, follow-up US revealed progression of the metastatic lesions, and hepatic arterial administration of 125 mg of cis-diamminedichloro platinum (CDDP) every month was started. After four courses, the catheter became obstructed and arterial administration was changed to systemic chemotherapy with 125mg of CDDP. In July 1989, follow-up CT, performed 7 months after the cessation of intraarterial administration of anticancer drugs, showed a segmental attenuation difference with portal vein obstruction in the right anterior segment of the liver as well as metastatic lesions (Fig. 3b). When the patient’s
K. Takayasu et al.
710
Figure 1 In case 1, (a) Enhanced CT shows moderate dilatation of intrahepatic bile ducts. Right portal veins are well visualized except for posterior portal vein, which usually runs medial to the accompanying bile duct. Arrow shows operatively placed catheter in gastroduodenal artery. (b) Postarterial portography shows non-opacification of posterior portal vein branch and stenosis of its beginning (right arrow). Biliary drainage tube is visible (left arrow). (c) Follow-up CT shows non-opacification of portal veins which ordinarily run lateral to bile ducts in anterior in right lobe (arrows show slightly dilated bile ducts). Hepatic infarction is shown in posterior of liver. Spleen is much larger than in (a), which may be due to portal hypertension secondary to portal vein obstruction. (d) Slice 2 cm caudal to (c) shows thrombosis of posterior portal vein, which is much thicker than calibre of dilated bile ducts in (c).
medical records were reviewed during this year, there was no complaint, symptom or abnormal value of liver enzyme and bilirubin was recognized. Repeat CT performed 2 months later showed PVT to be still present.
DISCUSSION Direct infusion of chemotherapeutic agents into the liver with an implantable infusion pump or a reservoir in the treatment of hepatic metastases
PVT in chemo-infusion for hepatic metastases
71 1
Figure 2 In case 2, (a) Enhanced C T in hepatic hilum shows good opacification of portal veins. (b) Follow-up C T shows almost complete obstruction of right portal veins and low density area with non-homogeneous lower area in ipsilateral lobe of liver. Slight opacification of thin anterior portal vein (lower arrow) is shown. Upper arrow indicates an implanted pump.
Figure 3 In case 3, (a) Dbnamic C T shows good opacification of portal veins in right lobe of liver. Arrows indicate portal veins in anterior segment of right lobe. Intrahepatic metastases are not shown in this slice. (b) Follow-up C T shows segmental attenuation difference in anterior segmental area (black arrows) consistent with obstruction of anterior portal vein (white arrows) in right lobe.
from colorectal cancer gives good response rates, ranging from 29% to 88y0,6 which are much superior to those obtained with systemic chemothe rap^.^ With frequent uses of this therapeutic system, several complications, such as sclerosing cholangitis have been e n c o ~ n t e r e d . ~ However, -~ to our knowledge, portal vein obstruction following intraarterial chemo-infusion has not yet been reported. The three patients who received intraarterial administration of SFU, mitomycin C and/or CDDP developed PVT after various intervals following cessation of intraarterial administration. It was found incidentally without specific
symptoms, in Cases 2 and 3. However, the process leading to and the outcome of PVT were different between the three cases. In Case 1, partial PVT of the posterior portal vein (Fig. lb) was observed by postarterial portography at the time of diagnosis of arterial vasculitis, which perhaps resulted in sclerosing cholangitis, and subsequently all major portal branches (Figs l c and d) were obstructed approximately 6 months after the cessation of administration of 5FU and mitomycin C. At that time, sclerosing cholangitis, which had developed prior to PVT, was improved. However, while the level of alkaline phosphatase, not bilirubin, was increasing with
K. Takayasu et al.
712
no other changes, the patient developed acute abdominal pain. Splenomegaly and oesophageal varices suggested portal hypertension due to PVT. Unfortunately, autopsy was not performed. In contrast, in the asymptomatic patients, Cases 2 and 3, partial PVT in the right portal vein and segmental PVT in the right anterior portal vein were found incidentally by follow-up C T 1 month and 7 months respectively after the cessation of anti-cancer drugs. There was no indication of biliary obstruction in these patients. This PVT was recanalized spontaneously in Case 2 but not in Case 3, as confirmed by repeat C T 2 months later. Enhanced CT, especially dynamic CT, is one of the reliable imaging modalities for demonstrating PVT, as is ultrason~graphy;~ it is recognized from the characteristic findings such as lobar or segmental attenuation differences shown in Figs 2b and 3b and an enlarged intraluminal low density area (Fig. 3b).9-10 Ring enhancement around PVT due to opacification of the vasa vasorum was not recognized in our cases." Unfortunately, these PVTs were not confirmed by angiography after the confirmation of PVT on CT. Intrahepatic PVT is usually insidious and asymptomatic and therefore it is very difficult to recognize fresh PVT by imaging. In all our cases, PVT was detected incidentally by routine followup C T and the exact interval between the beginning of the arterial chemotherapy and the occurrence of PVT could not be determined. In all, the portal vein trunk was well opacified and no known causes for PVT such as pancreatitis, thrombocytaemia or oestrogen therapy were found during the clinical c0urse.l' Portal tumour thrombus from the metastasized tumour was very unlikely, because metastatic lesions were not very large.13 The combined use of mitomycin C and 5FU in the hepatic artery through an implantable infusion pump is common in Japan for liver metastases from colorectal cancer. Even though complicating sclerosing cholangitis is encountered infrequently, PVT following arterial chemo-infusion has been very uncommon. In our cases, the cause of portal vein obstruction is unclear. However, the following are speculated: direct portal toxicity onto the portal vein followed by vasculitis as a result of inflow of anticancer agents via arterial-portal shunt (transvasal and/or transplexal) under special conditions such as
stenotic changes or obstruction of accompanying arteries due to long-standing chemoinfusion;14-16 or involvement of the portal vein in scar formation in the porta hepatis, which is frequently observed in sclerosing cholangiti~.~ PVT was irreversible in Cases 1 and 3 but reversible in Case 2. A similar outcome has been described in patients with sclerosing ch~langitis.~ During follow-up of patients receiving intrahepatic arterial chemo-infusion, possible complications involving the portal vein and biliary tract should be kept in mind.
ACKNOWLEDGEMENTS We thank Emeritus Professor Kunio Okuda, of the Chiba University School of Medicine, for his review. This study is supported by Grants-in-Aid for Cancer Research from the Ministry of Health and Welfare.
REFERENCES 1. DALY J. M., KEMENY N., ODERMAN P.& BOTETJ.
Long-term hepatic arterial infusion chemotherapy. Anatomic considerations, operative technique, and treatment morbidity.Arch. Surg. 1984, 119: 936-41. 2. STAGG R. J., LEWISB. J., FRIEDMAN M. A,, IGNOFFOR. J. & HOHND. C. Hepatic arterial chemotherapy for colorectal cancer metastatic to the liver. Ann. Intern. Med. 1984; 100: 736-43. 3. PIENE. H., ZEMANR. K., BENJAMIN S. B. et al. Iatrogenic sclerosing cholangitis following hepatic arterial chemotherapy infusion. Radiology 1985; 156: 329-30. 4. BOTETJ . F., WATSONR. C., KEMENY N. K., DALY J. M. & YEH S . Cholangitis complicating intra-
arterial chemotherapy in liver metastasis. Radiology 1985; 156: 335-7. 5. SHEAW. J., DEMAS B. E., GOLDBERG H. I., Horn D. C., FERREL L. D. & KERLANR. K. Sclerosing
cholangitis associated with hepatic arterial FUDR chemotherapy: Radiographic-histologic correlation. Amer. 3. Roentgenol. 1986; 146: 717-21. F. J., RAMIREZ G., DAVISH. L. et al. 6. ANSFIELD Further clinical studies with intrahepatic arterial infusion with 5-fluorouracil. Cancer 1975; 36: 2413-7. 7. FORTNERJ. G., MULCARER. J., SOLIS A., WATSONR. C. & GOLBEYR. B. Treatment of
primary and secondary liver cancer by hepatic artery ligation and infusion chemotherapy. Ann. Surg. 1973; 178: 162-72.
P V T in chemo-infusion for hepatic metastases 8. SCHWERK W. B. Portal vein thrombosis: Real-time sonographic demonstration and follow-up. Gastrointest. Radiol. 1986; 11: 312-8. 9. ITAIY., Moss A. A. & GOLDBERG H. I. Transient hepatic attenuation difference of lobar or segmental distribution detected by dynamic computed tomography. Radiology 1982; 144: 835-9. 10. TAKAYASU K., MORIYAMA N., MURAMATSU Y. & TAJIRI H. Transient perihilar attenuation difference in the liver on dynamic C T secondary to portal thrombosis: Report of two cases. Gastroenterol.3pn
713
13.
4.
5.
1989; 24: 205-8.
D., VASILEN. & GRENIER P. Portal 11. MATHIEU thrombosis: Dynamic C T features and course. Radiology 1985; 154: 737-41. M., GANSBEKE D. V., MATOSC., ENGEL12. ZALCMAN HOLM L. & STRUWEN J. Sonographic demonstration of portal venous system thromboses secondary
16.
to inflammatory diseases of the pancreas. Gastroinrest. Radiol. 1987; 12: 114-6. HEASTON D. K., CHUANC V. P., WALLACE S. & SANTOSL. A. Metastatic hepatic neoplasms: Angiographic features of portal vein involvement. Amer. 3. Roentgenol. 1981; 136: 897-900. BOOKSTEIN J. J., CHOK. J., DAVISG. B. & DAIL D. Arterioportal communications: Observations and hypotheses concerning transsinusoidal and transvasal types. Radiology 1982; 142: 581-90. CHO K. J. & LUNDERQUIST A. The peribiliary vascular plexus: The microvascular architecture of the bile duct in the rabbit and in clinical cases. Radiology 1983; 147: 357-64. NAKAMURA H., HASHIMOTO T., Or H. & SAWADA S. Iodized oil in the portal vein after arterial embolization. Radiology 1988; 167: 415-7.
