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Portal embolization relieves persistent jaundice after complete biliary drainage
Portal embolization relieves persistent jaundice after complete biliary drainage Masayoshi Ijichi, MD, Masatoshi Makuuchi, MD, PhD, Hiroshi Imamura, MD, PhD, and Tadatoshi Takayama, MD, PhD, Tokyo, Japan
From the Division of Hepato-Biliary-Pancreatic and Transplantation Surgery, Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan
BILIARY TRACT MALIGNANCIES are often accompanied by obstructive jaundice. Long-term cholestasis causes fibrous changes in the liver and a deterioration in liver function. Biliary drainage before a major operation, such as extended hepatectomy, is recommended to improve liver function and reduce morbidity and mortality.1 However, some patients have a poor recovery of liver function after biliary drainage, suggesting the presence of severe liver injury. In such cases, further surgical interventions are generally abandoned because of the strong possibility of liver failure. We herein report a case of hilar cholangiocarcinoma with worsening jaundice despite complete biliary drainage. Portal embolization (PE) was performed, and the jaundice was successfully relieved. A radical operation was then performed 10 weeks after the PE. CASE REPORT An 81-year-old man was admitted in December 1996 for obstructive jaundice. His serum bilirubin level was 8.2 mg/dL. Biliary drainage was performed by using 3 catheters: to the right paramedian and lateral branches and to the left hepatic duct. A cholangiography (Fig 1) and abdominal computed tomography indicated the presence of a hilar bile duct carcinoma with predominant left duct involvement. Radical treatment involving an extended left hepatectomy was deemed mandatory. Drained bile from each catheter was collected and administered orally. Despite complete biliary decompression on the ultrasound image and no signs of cholangitis, the serum biliruAccepted for publication February 17, 2001. Reprint requests: Masatoshi Makuuchi, MD, PhD, Division of Hepato-Biliary-Pancreatic and Transplantation Surgery, Department of Surgery, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Surgery 2001;130:116-8.
bin level continued to increase for more than 1 week (to 13.8 mg/dL) and the bile output remained low (20-40 mL/d). The patient appeared to have severe liver injury as a result of long-standing cholestasis. It was noteworthy, however, that the right lateral sector showed a particularly high bilirubin concentration of 21.7 mg/dL in the bile compared with 9.4 mg/dL in the right paramedian sector and 1.5 mg/dL in the left hemiliver. Correspondingly, bilirubin clearance (CLbil) in the right lateral sector (72 mL/d) was much higher than in the other 2 areas (25 mL/d in the right paramedian sector, and 3 mL/d in the left hemiliver). The functional ratio of the right lateral sector as evaluated by CLbil accounted for 72% of the total liver, while its volumetric ratio calculated from computed tomography images was 36%. Thus, we hypothesized that the inducement of hypertrophy in the right lateral sector might increase the functional capacity of the liver and relieve the worsening jaundice in the patient. PE of the left hemiliver and the right paramedian sector was conducted by using a transileocolic approach 8 days after biliary drainage. The embolization material consisted of a mixture of 2.0 g absorbable gelatin sponge powder, 40 mL diatrizoate sodium meglumine, 200 mg amikacin sulfate, and 10,000 U thrombin. The serum bilirubin value began to decrease in parallel with an increase in CLbil in the right lateral sector 10 days after the PE. After 2 months, the serum bilirubin value had decreased to 1.7 mg/dL (Fig 2). The right lateral sector showed a 23% increase (474 mL to 582 mL) in volume, and its CLbil rose by 84 times (6050 mL/d). CLbil in the right paramedian sector also increased, probably as a result of portal recanalization and the ensuing increase in volume (19%), while the left hemiliver atrophied (–24%). A left hepatectomy concomitant with the caudate lobe and extrahepatic bile duct was performed 10 weeks after the PE. A histopathologic examination showed a left-dominant hilar cholangiocarcinoma only 10 mm in size; all biliary stumps were cancer free. The postoperative course was uneventful, and there has been no evidence of recurrence for the past 31⁄2 years.
DISCUSSION
Copyright © 2001 by Mosby, Inc. 0039-6060/2001/$35.00 + 0 11/57/115358 doi:10.1067/msy.2001.115358
116 SURGERY
PE is a radiologic technique causing atrophy in the embolized region and compensatory hypertro-
Surgery Volume 130, Number 1
Fig 1. Cholangiography showing the disruption in right and left bile duct communication at hepatic confluence. The right paramedian and lateral branches are also separated from each other.
phy in the contralateral region of the liver.2 The technique is widely performed before hepatectomy to induce hypertrophy in the future remnant liver and increase the safety of an extensive hepatectomy.2 In the current case, this technique was applied to improve liver function. PE was performed to induce functional enhancement in the selected liver sector and relieve worsening jaundice. Pathologic and functional reversibility after biliary drainage depends on the duration of the obstructive jaundice. Zimmermann et al3 stated that the biliary fibrosis resulting from 3 weeks of biliary obstruction was reversible in a rat model. On the other hand, Koyama et al4 showed insufficient recovery of ketogenesis and pathologic change in dogs with a 12-week obstruction. Although the duration of the obstruction was unknown in the current case, a continuous increase in bilirubin levels occurred despite complete biliary drainage; it suggested severe liver injury and poor recovery of mitochondrial function.4 Biliary infection can be another factor in prolonged bilirubinemia, resulting in the inhibition of hepatocyte bilirubin-transport activity; however, our patient did not show any signs of cholangitis. Despite the unfavorable outlook, the right lateral sector of the liver appeared to have a higher level of function than the other regions. The functional ratio of this sector as evaluated by CLbil accounted for 72% of the total liver. The functional disparity among the liver sectors probably resulted from the
Ijichi et al 117
slowly growing primary cancer lesion that first obstructed the left hepatic duct and after a long interval began to involve the right paramedian or lateral branch. We noticed this disparity and performed a PE to redirect all of the portal flow into the right lateral sector. As expected, the function of this sector was enhanced and the jaundice was relieved. Additionally, total liver blood flow and perfusion and liver volume are reduced with aging.5 A decline in blood flow may account for various age-related alterations in the liver; the maximum functional capacity of the liver is also reduced in the elderly.6 The increase in portal flow and perfusion to the selected sector, therefore, might in itself have provided considerable benefit to our elderly patient. The right paramedian sector also showed an increase in volume and a functional gain after the right lateral sector. Portal recanalization sometimes occurs after PE with an absorbable gelatin sponge. We use this powder routinely as an embolizing material because it induces apoptosis in hepatocytes without a necrotic or inflammatory reaction and the functional burden on the liver is thought to be minimal.2 Despite the possibility of recanalization, this absorbable material appears to be more suitable than other agents such as cyanoacrylate or absolute ethanol, particularly in patients with chronic injured liver. In the current case, we did not perform a second embolization because the serum bilirubin level continued to decrease even after the recanalization and because this sector would be preserved in the remnant liver after the scheduled radical operation. In the end, 2 sectors recovered as a result of cholestatic change, contributing to the functional recovery of the entire liver. There have been numerous controlled studies that demonstrated no advantage of preoperative biliary drainage.7,8 These studies, however, included patients with various benign and malignant diseases and with very few hepatic resections. Despite advances in surgical technique, hepatic resection in patients with jaundice is still associated with high morbidity and mortality.1,9 Recently, Cherqui et al10 compared outcomes of major hepatic resection in jaundiced patients with and without preoperative biliary drainage; the overall morbidity and transfusion rates were significantly higher than those in patients without jaundice. Obstructive jaundice causes deterioration of liver function, including mitochondrial respiratory function, ketogenesis, various kinds of metabolism and reticuloendothelial system. To restore liver function, we routinely perform preoperative biliary drainage in patients with obstructive jaundice when major hepatectomy is intended for curative resection. In addition, meticu-
118 Ijichi et al
Surgery July 2001
Fig 2. Changes in serum bilirubin value and bilirubin clearance before and after portal embolization. Bilirubin clearance (CLbil) = VBBil/Sbil.V = daily bile volume (mL); BBil = bilirubin concentration in bile (mg/dL); SBil = bilirubin concentration in serum (mg/dL).
lous care is essential for preventing drainage-related complications during and after this intervention. The interval between PE and the radical operation in this case was 10 weeks. Imamura et al2 noted 3 factors retarding hypertrophy after PE: diabetes mellitus, male sex, and hyperbilirubinemia. Cholestatic livers may need a longer time to achieve sufficient hypertrophy after PE than healthy livers. On the other hand, internal biliary drainage has many advantages over external drainage with respect to liver regeneration.11 We perform, in principle, internal biliary drainage or external drainage with oral intake of drained bile. When the drainage is temporary and the ensuing curative operation is intended, we often choose the latter, as we did in the current case. CONCLUSION Recovery of liver function may be possible in some patients with persistent jaundice after biliary drainage. If the patient has a functional disparity among liver sectors, jaundice can be relieved by a PE that induces functional enhancement of a selected sector(s). Moreover, patients may subsequently be capable of undergoing radical operation. PE should be considered as an option in patients who have persistent or worsening jaundice after biliary drainage. REFERENCES 1. Belghiti J, Hiramatsu K, Benoist S, Massault PP, Sauvanet A, Farges O. Seven hundred forty-seven hepatectomies in the
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
1990s: an update to evaluate the actual risk of liver resection. J Am Coll Surg 2000;191:38-46. Imamura H, Shimada R, Kubota M, Matsuyama Y, Nakayama A, Miyagawa S, et al. Preoperative portal vein embolization: an audit of 84 patients. Hepatology 1999;29: 1099-105. Zimmermann H, Reichen J, Zimmermann A, Sagesser H, Thenisch B, Hoflin F. Reversibility of secondary biliary fibrosis by biliodigestive anastomosis in the rat. Gastroenterology 1992;103:579-89. Koyama K, Takagi Y, Ito K, Sato T. Experimental and clinical studies on the effect of biliary drainage in obstructive jaundice. Am J Surg 1981;142:293-9. Wynne HA, Cope LH, Mutch E, Rawlins MD, Woodhouse KW, James OFW. The effect of age upon liver volume and apparent liver blood flow in healthy man. Hepatology 1989;9:297-301. Marchesini G, Bua V, Brunori A, Bianchi G, Pisi P, Fabbri A, et al. Galactose elimination capacity and liver volume in aging man. Hepatology 1988;8:1079-83. Hatfield ARW, Terblanche J, Fataar S, Kernoff L, Tobias R, Girdwood AH, et al. Preoperative external biliary drainage in obstructive jaundice: a prospective controlled clinical trial. Lancet 1982;2:896-9. McPherson GAD, Benjamin IS, Hodgson HJF, Bowley NB, Allison DJ, Blumgart LH. Pre-operative percutaneous transhepatic biliary drainage: the results of a controlled trial. Br J Surg 1984;71:371-5. Su CH, Tsay SH, Wu CC, Shyr YM, King KL, Lee CH, et al. Factors influencing postoperative morbidity, mortality, and survival after resection for hilar cholangiocarcinoma. Ann Surg 1996;223:384-94. Cherqui D, Benoist S, Malassagne B, Humeres R, Rodriguez V, Fagniez PL. Major liver resection for carcinoma in jaundiced patients without preoperative biliary drainage. Arch Surg 2000;135:302-8. Suzuki H, Iyomasa S, Nimura Y, Yoshida S. Internal biliary drainage, unlike external drainage, does not suppress the regeneration of cholestatic rat liver after partial hepatectomy. Hepatology 1994;20:1318-22.
From the Division of Hepato-Biliary-Pancreatic and Transplantation Surgery, Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan
BILIARY TRACT MALIGNANCIES are often accompanied by obstructive jaundice. Long-term cholestasis causes fibrous changes in the liver and a deterioration in liver function. Biliary drainage before a major operation, such as extended hepatectomy, is recommended to improve liver function and reduce morbidity and mortality.1 However, some patients have a poor recovery of liver function after biliary drainage, suggesting the presence of severe liver injury. In such cases, further surgical interventions are generally abandoned because of the strong possibility of liver failure. We herein report a case of hilar cholangiocarcinoma with worsening jaundice despite complete biliary drainage. Portal embolization (PE) was performed, and the jaundice was successfully relieved. A radical operation was then performed 10 weeks after the PE. CASE REPORT An 81-year-old man was admitted in December 1996 for obstructive jaundice. His serum bilirubin level was 8.2 mg/dL. Biliary drainage was performed by using 3 catheters: to the right paramedian and lateral branches and to the left hepatic duct. A cholangiography (Fig 1) and abdominal computed tomography indicated the presence of a hilar bile duct carcinoma with predominant left duct involvement. Radical treatment involving an extended left hepatectomy was deemed mandatory. Drained bile from each catheter was collected and administered orally. Despite complete biliary decompression on the ultrasound image and no signs of cholangitis, the serum biliruAccepted for publication February 17, 2001. Reprint requests: Masatoshi Makuuchi, MD, PhD, Division of Hepato-Biliary-Pancreatic and Transplantation Surgery, Department of Surgery, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Surgery 2001;130:116-8.
bin level continued to increase for more than 1 week (to 13.8 mg/dL) and the bile output remained low (20-40 mL/d). The patient appeared to have severe liver injury as a result of long-standing cholestasis. It was noteworthy, however, that the right lateral sector showed a particularly high bilirubin concentration of 21.7 mg/dL in the bile compared with 9.4 mg/dL in the right paramedian sector and 1.5 mg/dL in the left hemiliver. Correspondingly, bilirubin clearance (CLbil) in the right lateral sector (72 mL/d) was much higher than in the other 2 areas (25 mL/d in the right paramedian sector, and 3 mL/d in the left hemiliver). The functional ratio of the right lateral sector as evaluated by CLbil accounted for 72% of the total liver, while its volumetric ratio calculated from computed tomography images was 36%. Thus, we hypothesized that the inducement of hypertrophy in the right lateral sector might increase the functional capacity of the liver and relieve the worsening jaundice in the patient. PE of the left hemiliver and the right paramedian sector was conducted by using a transileocolic approach 8 days after biliary drainage. The embolization material consisted of a mixture of 2.0 g absorbable gelatin sponge powder, 40 mL diatrizoate sodium meglumine, 200 mg amikacin sulfate, and 10,000 U thrombin. The serum bilirubin value began to decrease in parallel with an increase in CLbil in the right lateral sector 10 days after the PE. After 2 months, the serum bilirubin value had decreased to 1.7 mg/dL (Fig 2). The right lateral sector showed a 23% increase (474 mL to 582 mL) in volume, and its CLbil rose by 84 times (6050 mL/d). CLbil in the right paramedian sector also increased, probably as a result of portal recanalization and the ensuing increase in volume (19%), while the left hemiliver atrophied (–24%). A left hepatectomy concomitant with the caudate lobe and extrahepatic bile duct was performed 10 weeks after the PE. A histopathologic examination showed a left-dominant hilar cholangiocarcinoma only 10 mm in size; all biliary stumps were cancer free. The postoperative course was uneventful, and there has been no evidence of recurrence for the past 31⁄2 years.
DISCUSSION
Copyright © 2001 by Mosby, Inc. 0039-6060/2001/$35.00 + 0 11/57/115358 doi:10.1067/msy.2001.115358
116 SURGERY
PE is a radiologic technique causing atrophy in the embolized region and compensatory hypertro-
Surgery Volume 130, Number 1
Fig 1. Cholangiography showing the disruption in right and left bile duct communication at hepatic confluence. The right paramedian and lateral branches are also separated from each other.
phy in the contralateral region of the liver.2 The technique is widely performed before hepatectomy to induce hypertrophy in the future remnant liver and increase the safety of an extensive hepatectomy.2 In the current case, this technique was applied to improve liver function. PE was performed to induce functional enhancement in the selected liver sector and relieve worsening jaundice. Pathologic and functional reversibility after biliary drainage depends on the duration of the obstructive jaundice. Zimmermann et al3 stated that the biliary fibrosis resulting from 3 weeks of biliary obstruction was reversible in a rat model. On the other hand, Koyama et al4 showed insufficient recovery of ketogenesis and pathologic change in dogs with a 12-week obstruction. Although the duration of the obstruction was unknown in the current case, a continuous increase in bilirubin levels occurred despite complete biliary drainage; it suggested severe liver injury and poor recovery of mitochondrial function.4 Biliary infection can be another factor in prolonged bilirubinemia, resulting in the inhibition of hepatocyte bilirubin-transport activity; however, our patient did not show any signs of cholangitis. Despite the unfavorable outlook, the right lateral sector of the liver appeared to have a higher level of function than the other regions. The functional ratio of this sector as evaluated by CLbil accounted for 72% of the total liver. The functional disparity among the liver sectors probably resulted from the
Ijichi et al 117
slowly growing primary cancer lesion that first obstructed the left hepatic duct and after a long interval began to involve the right paramedian or lateral branch. We noticed this disparity and performed a PE to redirect all of the portal flow into the right lateral sector. As expected, the function of this sector was enhanced and the jaundice was relieved. Additionally, total liver blood flow and perfusion and liver volume are reduced with aging.5 A decline in blood flow may account for various age-related alterations in the liver; the maximum functional capacity of the liver is also reduced in the elderly.6 The increase in portal flow and perfusion to the selected sector, therefore, might in itself have provided considerable benefit to our elderly patient. The right paramedian sector also showed an increase in volume and a functional gain after the right lateral sector. Portal recanalization sometimes occurs after PE with an absorbable gelatin sponge. We use this powder routinely as an embolizing material because it induces apoptosis in hepatocytes without a necrotic or inflammatory reaction and the functional burden on the liver is thought to be minimal.2 Despite the possibility of recanalization, this absorbable material appears to be more suitable than other agents such as cyanoacrylate or absolute ethanol, particularly in patients with chronic injured liver. In the current case, we did not perform a second embolization because the serum bilirubin level continued to decrease even after the recanalization and because this sector would be preserved in the remnant liver after the scheduled radical operation. In the end, 2 sectors recovered as a result of cholestatic change, contributing to the functional recovery of the entire liver. There have been numerous controlled studies that demonstrated no advantage of preoperative biliary drainage.7,8 These studies, however, included patients with various benign and malignant diseases and with very few hepatic resections. Despite advances in surgical technique, hepatic resection in patients with jaundice is still associated with high morbidity and mortality.1,9 Recently, Cherqui et al10 compared outcomes of major hepatic resection in jaundiced patients with and without preoperative biliary drainage; the overall morbidity and transfusion rates were significantly higher than those in patients without jaundice. Obstructive jaundice causes deterioration of liver function, including mitochondrial respiratory function, ketogenesis, various kinds of metabolism and reticuloendothelial system. To restore liver function, we routinely perform preoperative biliary drainage in patients with obstructive jaundice when major hepatectomy is intended for curative resection. In addition, meticu-
118 Ijichi et al
Surgery July 2001
Fig 2. Changes in serum bilirubin value and bilirubin clearance before and after portal embolization. Bilirubin clearance (CLbil) = VBBil/Sbil.V = daily bile volume (mL); BBil = bilirubin concentration in bile (mg/dL); SBil = bilirubin concentration in serum (mg/dL).
lous care is essential for preventing drainage-related complications during and after this intervention. The interval between PE and the radical operation in this case was 10 weeks. Imamura et al2 noted 3 factors retarding hypertrophy after PE: diabetes mellitus, male sex, and hyperbilirubinemia. Cholestatic livers may need a longer time to achieve sufficient hypertrophy after PE than healthy livers. On the other hand, internal biliary drainage has many advantages over external drainage with respect to liver regeneration.11 We perform, in principle, internal biliary drainage or external drainage with oral intake of drained bile. When the drainage is temporary and the ensuing curative operation is intended, we often choose the latter, as we did in the current case. CONCLUSION Recovery of liver function may be possible in some patients with persistent jaundice after biliary drainage. If the patient has a functional disparity among liver sectors, jaundice can be relieved by a PE that induces functional enhancement of a selected sector(s). Moreover, patients may subsequently be capable of undergoing radical operation. PE should be considered as an option in patients who have persistent or worsening jaundice after biliary drainage. REFERENCES 1. Belghiti J, Hiramatsu K, Benoist S, Massault PP, Sauvanet A, Farges O. Seven hundred forty-seven hepatectomies in the
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
1990s: an update to evaluate the actual risk of liver resection. J Am Coll Surg 2000;191:38-46. Imamura H, Shimada R, Kubota M, Matsuyama Y, Nakayama A, Miyagawa S, et al. Preoperative portal vein embolization: an audit of 84 patients. Hepatology 1999;29: 1099-105. Zimmermann H, Reichen J, Zimmermann A, Sagesser H, Thenisch B, Hoflin F. Reversibility of secondary biliary fibrosis by biliodigestive anastomosis in the rat. Gastroenterology 1992;103:579-89. Koyama K, Takagi Y, Ito K, Sato T. Experimental and clinical studies on the effect of biliary drainage in obstructive jaundice. Am J Surg 1981;142:293-9. Wynne HA, Cope LH, Mutch E, Rawlins MD, Woodhouse KW, James OFW. The effect of age upon liver volume and apparent liver blood flow in healthy man. Hepatology 1989;9:297-301. Marchesini G, Bua V, Brunori A, Bianchi G, Pisi P, Fabbri A, et al. Galactose elimination capacity and liver volume in aging man. Hepatology 1988;8:1079-83. Hatfield ARW, Terblanche J, Fataar S, Kernoff L, Tobias R, Girdwood AH, et al. Preoperative external biliary drainage in obstructive jaundice: a prospective controlled clinical trial. Lancet 1982;2:896-9. McPherson GAD, Benjamin IS, Hodgson HJF, Bowley NB, Allison DJ, Blumgart LH. Pre-operative percutaneous transhepatic biliary drainage: the results of a controlled trial. Br J Surg 1984;71:371-5. Su CH, Tsay SH, Wu CC, Shyr YM, King KL, Lee CH, et al. Factors influencing postoperative morbidity, mortality, and survival after resection for hilar cholangiocarcinoma. Ann Surg 1996;223:384-94. Cherqui D, Benoist S, Malassagne B, Humeres R, Rodriguez V, Fagniez PL. Major liver resection for carcinoma in jaundiced patients without preoperative biliary drainage. Arch Surg 2000;135:302-8. Suzuki H, Iyomasa S, Nimura Y, Yoshida S. Internal biliary drainage, unlike external drainage, does not suppress the regeneration of cholestatic rat liver after partial hepatectomy. Hepatology 1994;20:1318-22.