J Hepatobiliary Pancreat Sci (2015) 22:310–315 DOI: 10.1002/jhbp.200
ORIGINAL ARTICLE
Assessment of percutaneous transhepatic portal vein embolization with portal vein stenting for perihilar cholangiocarcinoma with severe portal vein stenosis Ryota Hyodo · Kojiro Suzuki · Tomoki Ebata · Tomohiro Komada · Yoshine Mori · Yukihiro Yokoyama · Tsuyoshi Igami · Gen Sugawara · Shinji Naganawa · Masato Nagino
Published online: 25 December 2014 © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery
Abstract Background The aim of the present study was to assess the clinical efficiency of portal vein (PV) stenting when performed with preoperative percutaneous transhepatic portal vein embolization (PTPVE) in patients with severe PV stenosis due to tumor invasion. Methods Between 2007 and 2013, four consecutive patients (one male, three females; mean age, 52 years; age range, 25–73 years) with perihilar cholangiocarcinoma and PV stenosis underwent PTPVE and PV stenting. Patients were analyzed with regard to the procedure, hypertrophy of the future remnant liver (FRL), and plasma clearance rate of indocyanine green by the FRL (ICGK-F). Further, the %FRL volume increase in PTPVE was compared between the stenting group and the usual PTPVE group who have perihilar cholangiocarcinomas without PV stenosis. Results Preoperative PTPVE with PV stenting was successfully performed and portal flow to the FRL improved after stenting in all four patients. The %FRL volume increase was 18–60% (mean, 34%) in the stenting group and was 12–51% (mean, 21%) in the usual PTPVE group. The ICGK-F value after PTPVE exceeded 0.05 in all four patients. All patients achieved R0 resection. Conclusions Preoperative PTPVE with PV stenting appears to be feasible in cases of severe PV tumor invasion
R. Hyodo (*) · K. Suzuki · T. Komada · Y. Mori · S. Naganawa Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan e-mail: [email protected] T. Ebata · Y. Yokoyama · T. Igami · G. Sugawara · M. Nagino Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
and stenosis. This procedure may allow a broader indication for surgery. Keywords Percutaneous transhepatic portal vein embolization · Perihilar cholangiocarcinoma · Portal vein stenosis · Stent Introduction Perihilar cholangiocarcinoma is a serious disease that requires management via surgical resection in order to achieve long-term survival [1, 2]. However, early diagnosis is often difficult, meaning that most cases are diagnosed at an advanced stage in the disease. If not resected, the 3-year survival rate is only 2.1% [3]. Extended hepatectomy combined with portal vein (PV) and/or hepatic artery resection with reconstruction is often needed for complete resection, and these surgical approaches are associated with a 3-year survival of 40.6% and a 5-year survival of 26.8% [3]. However, the smaller the future remnant liver (FRL), the higher the risk of postoperative liver dysfunction [4]. An increase in the FRL volume is required to minimize postoperative liver dysfunction. Therefore, preoperative percutaneous transhepatic portal vein embolization (PTPVE) is performed before an extended hepatectomy [2, 5, 6]. Advanced perihilar cholangiocarcinoma often invades into the main PV, resulting in main PV stenosis and a decrease in hepatopetal portal flow. In this situation, sufficient hypertrophy of the FRL cannot be expected after PTPVE. In such cases, we have attempted to improve portal flow via stent placement at the site of main PV stenosis combined with simultaneous PV embolization. The report describes four consecutive cases in which preoperative PTPVE with PV stenting was used for the
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management of advanced perihilar cholangiocarcinoma with severe PV stenosis secondary to tumor invasion. We evaluate the clinical utility of this procedure when compared with the usual PTPVE procedure in patients without PV stenosis. Methods Patients Our institutional review board approved the retrospective collection of data and analysis for this study, and the need for informed consent from the patients was waived. Between July 2007 and April 2013, four consecutive patients (one male, three females; mean age, 52 years; age range, 25–73 years) with advanced perihilar cholangiocarcinoma (Bismuth IV, three patients; recurrence of extrahepatic bile duct cancer, one patient) with PV stenosis secondary to tumor invasion underwent PTPVE with PV stenting before surgery. Volumetric computed tomography (CT) examination was performed 9 to 24 days (mean, 18 days) after PTPVE. These patients subsequently underwent left hepatic trisectionectomy and caudate lobectomy combined with resection and reconstruction of the main PV and the right hepatic artery. Two patients (cases 1, 2) also underwent combined pancreatoduodenectomy at the same time. The PV stent was removed together with the invaded PV at the time of surgery. None of the patients had underlying chronic liver disease (e.g. hepatitis B or C virus, alcoholic liver disease). Between November 2009 and April 2011, 20 consecutive patients (11 males, nine females; mean age, 67 years; age range, 46–80 years), who had undergone usual PTPVE for advanced perihilar cholangiocarcinoma without PV stenosis (Bismuth IV, n = 19; Bismuth IIIb, n = 1) and were scheduled to undergo left hepatic trisectionectomy and caudate lobectomy, were selected as a control group. Sex and age was not matched to the PTPVE with PV stenting group. The exclusion criteria for the control group included a history of chronic liver disease (e.g. hepatitis B or C virus infection or alcoholic liver disease) and severe cholangitis after PTPVE. Patients who underwent volumetric CT examination within 9 days after PTPVE were also excluded.
branch of the right anterior hepatic segment under local anesthesia. The Seldinger technique was used to place a 5-Fr (for patients undergoing usual PTPVE) or 6-Fr (for patients undergoing PTPVE with PV stenting) vascular sheath into the main PV. To identify individual branches and anatomic variations, portography was performed using a 4-Fr or 5-Fr modified shepherd hook catheter (Selecon; Terumo Clinical Supply, Kakamigahara, Japan). Then, the catheter was inserted into the left and the right anterior PV. Absolute ethanol was first injected to occlude the smaller distal portal branches. To occlude the left PV and anterior branches, 0.035-inch coils (MReye; William Cook Europe, Bjaeverskov, Denmark) were used. The diameter of the coils ranged from 3 to 10 mm. In some cases, 2.2- to 2.4-Fr microcatheter and micro-coils (Tornade; Cook Medical, Bloomington, IN, USA) were also used. Embolization was performed until stasis or near-stasis was achieved. The access tract was finally embolized with 3- to 4-mm coils. In cases 1 (Fig. 1) and 2 in the PV-stenting group, we first embolized the left PV. Then, a 12 × 40 mm self-expandable stent (E-Luminexx; Bard, Tempe, AZ, USA) was deployed from the main PV to the right PV across the orifice of the left PV. Postdilatation was performed with a 10-mm balloon catheter (Fox Cross; Abbott, Green Oaks, IL, USA). The portal branch of the caudate lobe was also embolized after PV stenting in case 1. Finally, the anterior portal branches were embolized. In case 3, the left PV was already occluded secondary to tumor invasion. First, we dilated the PV stenosis with a 6-mm balloon catheter. Then, we embolized the anterior PV branches. Finally, a 10 × 37 mm balloon-expandable stent (Express LD; Boston Scientific, Natick, MA, USA) was deployed from the main PV to the right anterior PV. In case 4 (Fig. 2), the orifice of the left PV was occluded secondary tumor invasion, but the flow to the left portal system was preserved via a collateral venous channel of the gastric vein. Therefore, we performed PTPVE in a twostage procedure. In the first procedure, a 12 × 42 mm selfexpandable stent (Epic Vascular Stent; Boston Scientific) was deployed from the main PV to the right PV. Postdilatation was performed with a 9-mm balloon catheter. Then, the anterior portal branches were embolized. Thirteen days later, the left portal venous system was embolized via ultrasonographic-guided puncture of the left PV.
PTPVE and PV stenting procedure Assessments Preoperative PTPVE procedure with and without PV stenting was performed as follows. In all patients, the portal venous system was accessed by an ultrasound-guided percutaneous transhepatic approach (ipsilateral approach) [7]. An 18-gauge Cliny ultrasound puncture needle (Create Medic, Yokohama, Japan) was placed into a peripheral PV
Using CT image data, FRL volume and embolized liver (EL) volume were calculated before and after PTPVE. The difference in FRL volume before and after embolization in relation to the FRL volume before embolization (%FRL volume increase) and the difference in EL volume before
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(a)
(c)
(b)
Fig. 1 Case 1: (a) Contrast-enhanced computed tomography (CT) shows the recurrence of extrahepatic bile duct cancer (arrow) invading into the porta hepatis, main portal vein (PV) and common hepatic artery. There is a metallic stent in the common bile duct (arrowhead). (b) Portography shows PV stenosis (arrow) and reflux in the left gastric vein. (c) Portography after stent placement and left PV embolization shows resolution of PV stenosis and decompression of the associated hepatofugal collateral vein. PV embolization of the caudate lobe and the right anterior segment was subsequently performed. Fig. 2 Case 4: (a) Contrastenhanced computed tomography (CT) shows perihilar cholangiocarcinoma (arrow) invading into the main portal vein (PV) and right hepatic artery (not shown). There is severe PV stenosis. (b) Portography shows the main PV stenosis and occlusion of the orifice of the left PV (arrow). Cavernous transformation and reflux in the left gastric vein are also recognized. (c) Portography after PV stent placement and embolization of the right anterior segment shows resolution of the PV stenosis, decompression of cavernous transformation, and an increase in portal flow to the right posterior segment. (d) Contrast-enhanced CT after preoperative percutaneous transhepatic portal vein embolization (PTPVE) with PV stenting shows nearly full-expansion of the stent and a resolution of PV stenosis.
(a)
(b)
(c)
and after embolization in relation to the EL volume before embolization (%EL atrophy) were calculated according to the following formula described by Lienden et al. [8]:
%FRL volume increase = [%FRL ( post-PTPVE ) − %FRL ( pre-PTPVE )] %FRL ( pre-PTPVE ) ×100%
(d)
%EL atrophy = [(%EL ( post-PTPVE ) − %EL ( pre-PTPVE )] %EL ( pre-PTPVE ) ×100% In this study, the caudate lobe’s volume was included in the embolized liver’s volume even when the portal branch of the caudate lobe was not embolized. This is because all
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J Hepatobiliary Pancreat Sci (2015) 22:310–315 Table 1 Results of the stenting group Case
1 2 3 4
Age/ Sex 25/F 73/F 60/F 51/M
Stent
SS SS BS SS
Stent diameterlength
PV diameter Pre
Post
12–40 mm 12–40 mm 10–37 mm 12–42 mm
5 mm 4 mm 2 mm 2 mm
12 mm 12 mm 7 mm 12 mm
Technical success Yes Yes Yes Yes
FRL volume
%FRL increase
Pre (proportion)
Post
594 ml (44%) 250 ml (27%) 338 ml (32%) 288 ml (18%)
662 ml 308 ml 348 ml 485 ml
18% 25% 30% 60%
%EL atrophy −15% −9% −14% −13%
ICGK-F
Clinical efficacy
Pre
Post
0.094 0.041 0.045 0.032
0.106 0.052 0.064 0.064
Yes Yes Yes Yes
BS balloon-expandable stent, EL embolized liver, FRL future remnant liver, ICGK-F indocyanine green clearance rate for future remnant liver, Post post PTPVE with PV stenting, Pre pre PTPVE with PV stenting, PV portal vein, SS self-expandable stent.
patients were planned to undergo surgical resection of the caudate lobe. The increase in %FRL volume and the %EL atrophy of the PTPVE with PV stenting group was compared with those of the usual PTPVE group. In addition, the diameter of the PV stenosis site was measured using volumetric CT images before and after PTPVE. Technical successes and clinical efficacy in the stenting group were also assessed. Technical success was defined as: (i) successful dilation of the main PV stenosis; (ii) improvement in portal flow secondary to stent placement; and (iii) successful completion of PV embolization without complication. Clinical efficacy was defined as a %FRL volume increase that was equal to or greater than the minimum level of %FRL volume increase in the control group. Plasma clearance rate of indocyanine green (ICGK) was assessed before and after PTPVE in all cases. ICGK of the FRL (ICGK-F) was calculated according to the formula: ICGK × proportion of the FRL [9]. ICGK-F before and after PTPVE was also evaluated, and patient outcomes after surgery were reviewed from medical records. Results The results of the stenting group are summarized in Table 1. In all patients undergoing PTPVE with stenting, the stent was successfully deployed. In addition, portal flow improved visually on portography just after stenting and on ultrasound performed after several days. Further, PTPVE was successfully performed. There were no complications associated with the procedure in any patient. Therefore, technical success was achieved in all four patients (100%). The %FRL volume increase was 18–60% (mean, 33%) in the stenting group and 12–51% (mean, 21%) in the usual PTPVE group. Of these, the left PV occlusion by tumor invasion was found in one patient (case 3) of the stenting group and three patients of the usual PTPVE group. The %FRL volume increase in the patients with the left PV occlusion was 30% in the stenting group and 15–22% (mean, 19%) in the usual PTPVE group. On the other hand, the %FRL volume increase in the patients without the left
PV occlusion was 18%, 25%, and 60% in the stenting group and 12–51% (mean, 22%) in the usual PTPVE group. All four patients who underwent PTPVE with stenting exceeded an increase in %FRL volume of 12%, which was the minimum increase in %FRL volume seen in the usual PTPVE group. The %EL atrophy was −15 to −9% (mean, −13%) in the stenting group and −24 to −6% (mean, −12%) in the usual PTPVE group. Therefore, clinical efficacy was achieved in all four patients (100%). In addition, the ICGK-F values after PTPVE were more than 0.05 in all four cases. Portography before stenting showed the left gastric vein as a hepatofugal collateral vessel in cases 1 and 4, cavernous transformation of the PV in cases 3 and 4. After stenting, the hepatofugal collateral flow of case 1 disappeared, and that of case 4 decreased. The hepatopetal collateral flow of cases 3 and 4 also decreased. The volumetric CT after PTPVE showed the extension of PV diameter at stenosis site in all cases. In the PTPVE with stenting group, the days from PTPVE to operation was 13 to 50 days (mean, 30 days). All patients underwent planned hepatic resection and achieved R0 resection. The PV was resected between the main PV and the right posterior PV, including the PV stent. We did not resect the PV stent itself or remove the stent from the PV during the operation. An end-to-end anastomosis was performed in one patient (case 2) and a right external iliac vein interposition grafting was performed in the other three patients (cases 1, 2 and 4). Pathologically, an epithelial hyperplasia was not seen in the PV epithelium, which a stent was contacted with in all four patients. Three of the patients did not develop postoperative liver dysfunction and were discharged. However, one patient (case 4) developed sepsis from the next day of the operation. Antibiotic therapy was performed, but the infection was not controlled. Subsequently, the patient developed refractory ascites, renal failure and liver dysfunction. And the patient died of multiorgan failure caused by sepsis at 47 days after surgery. During the follow-up period, case 2 died of tumor recurrence at 38 months after surgery. Cases 1 and 3 are alive at 56 months and 16 months after surgery, respectively. In the
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usual PTPVE group, 16 patients underwent planned hepatic resection, and none of the patients developed postoperative liver dysfunction. The other four patients did not undergo subsequent hepatectomy because of peritoneal seeding (n = 2), periaortic node metastasis (n = 1) or locally advanced disease (n = 1; extensive nerve plexus invasion). Discussion Preoperative PTPVE with PV stenting was conducted in four patients with perihilar cholangiocarcinoma and severe main PV stenosis due to tumor invasion. The PV stenosis improved after PV stenting, and the %FRL volume increase after PTPVE was comparable to that seen in patients undergoing the usual PTPVE procedure without PV stenting. In addition, ICGK-F values after PTPVE were more than 0.05 in all cases. These data demonstrate that PTPVE with PV stenting could broaden the indications for surgery in patients with advanced perihilar cholangiocarcinoma. In the case of PTPVE, the increase in portal flow and hepatocyte growth factor in the FRL after PTPVE plays an important role for an increase in the FRL volume [10, 11]. Further, the increase in FRL volume correlates with the increasing in FRL function [12]. However, major portal hypertension with portosystemic shunting can result in insufficient FRL hypertrophy after PTPVE [13]. In the present cases, stenting resulted in an increase in portal flow to the FRL and a decrease in portosystemic shunting, thereby leading to an increase in FRL volume and function after PTPVE. The ICGK-F value is an indicator of the function of the FRL. Yokoyama et al. reported that a ICGK-F value less than 0.05 was associated with an increase in the risk of postoperative liver dysfunction in the case of extended hepatectomy, such as left hepatic trisegmentectomy for biliary cancer [9]. An ICGK-F value more than 0.05 is associated with a 3.5% rate of postoperative liver dysfunction, while a ICGK-F value less than 0.05 is associated with a 22% rate of postoperative liver dysfunction [9]. In the four patients described in the present study, the ICGK-F values after PTPVE were more than 0.05, suggesting that the FRL function was adequate for surgery. In principal, PTPVE is usually indicated when the FRL volume is less than 40% of whole liver [1, 14]. The FRL volume of cases 2, 3 and 4 were less than 40%; however, the FRL volume of case 1 was 44%. This is because a recurrent tumor of case 1 was very aggressive and surgeons required increasing liver function before surgery. In this study, we used a self-expandable stent in three patients (cases 1, 2 and 4) and a balloon-expandable stent in one patient (case 3). In past reports, a self-expandable stent was usually used for management of PV stenosis [15–18]. However a balloon-expandable stent has also been used
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when the lesion being treated necessitated precise placement of the stent [18]. In case 3 in the present study, a balloon-expandable stent was selected because the excision margin of the PV was close to the stenosis site; therefore, the stent had to be deployed more precisely. The stents were deployed at the exact planning position in all cases. In addition, they did not disturb the surgical procedure in any of the cases. According to previous reports, the indications for PV stenting include the treatment of the PV hypertension associated with PV stenosis, such as varices of portal collateral vessels, refractory ascites, pancytopenia and liver dysfunction due to advanced or recurrent pancreaticobiliary tumor [15, 16, 18]. In addition, PV stenting is indicated for PV stenosis after liver transplantation [17]. To the best of our knowledge, there is only one case report about PTPVE with PV stenting. Kaneoka et al. reported PTPVE with PV stenting for a patient of advanced gallbladder carcinoma with PV stenosis [19]. They reported only the change of FRL volume before and after the procedure. Therefore, our study is the first report which evaluates hypertrophy rate and liver function of FRL. Further, we also compare the stenting group with the usual PTPVE group in relation to the procedure and %FRL volume increase. This study has several limitations. First, the number of patients was small. This is because few patients with perihilar cholangiocarcinoma have PV stenosis without metastasis and are still candidates for surgery. Therefore, the accumulation of further cases is necessary to assess the utility of PTPVE with PV stenting. Second, PV pressure and velocity were not measured. PV flow was evaluated only by portography and ultrasound visually. Third, %FRL volume increase and ICGK-F value that would otherwise have resulted if PTPVE were performed without stenting in these four cases are unknown. In conclusion, preoperative PTPVE with portal vein stenting for patients with advanced perihilar cholangiocarcinoma and PV severe stenosis secondary to tumor invasion appears to be feasible and may broaden the indications for surgical resection. Conflict of interest
None declared.
Author contributions Study design: Ryota Hyodo and Kojiro Suzuki. Acquisition of data: Ryota Hyodo, Tomoki Ebata, Yukihiro Yokoyama, Tsuyoshi Igami, and Gen Sugawara. Analysis and interpretation: Ryota Hyodo, Kojiro Suzuki, and Tomohiro Komada. Manuscript drafted by: Ryota Hyodo, Kojiro Suzuki, and Yoshine Mori. Revision: Shinji Naganawa and Masato Nagino.
References 1. Nagino M. Perihilar cholangiocarcinoma: a surgeon’s viewpoint on current topics. J Gastroenterol. 2012;47:1165–76.
J Hepatobiliary Pancreat Sci (2015) 22:310–315 2. Lee SG, Song GW, Hwang S, Ha TY, Moon DB, Jung DH, et al. Surgical treatment of hilar cholangiocarcinoma in the new era: the Asan experience. J Hepatobiliary Pancreat Sci. 2010;17:476– 89. 3. Nagino M, Ebata T, Yokoyama Y, Igami T, Sugawara G, Takahashi Y, et al. Evolution of surgical treatment for perihilar cholangiocarcinoma: a single-center 34-year review of 574 consecutive resections. Ann Surg. 2013;258:129–40. 4. Anaya DA, Blazer DG, Abdalla EK. Strategies for resection using portal vein embolization: hepatocellular carcinoma and hilar cholangiocarcinoma. Semin Interv Radiol. 2008;25:110–22. 5. Yokoyama Y, Nagino M, Nishio H, Ebata T, Igami T, Nimura Y. Recent advances in the treatment of hilar cholangiocarcinoma: portal vein embolization. J Hepatobiliary Pancreat Surg. 2007; 14:447–54. 6. Ebata T, Yokoyama Y, Igami T, Sugawara G, Takahashi Y, Nagino M. Portal vein embolization before extended hepatectomy for biliary cancer: current technique and review of 494 consecutive embolizations. Dig Surg. 2012;29:23–9. 7. Nagino M, Nimura Y, Kamiya J, Kondo S, Kanai M. Selective percutaneous transhepatic embolization of the portal vein in preparation for extensive liver resection: the ipsilateral approach. Radiology. 1996;200:559–63. 8. van Lienden KP, van den Esschert JW, de Graaf W, Bipat S, Lameris JS, van Gulik TM, et al. Portal vein embolization before liver resection: a systematic review. Cardiovasc Intervent Radiol. 2013;36:25–34. 9. Yokoyama Y, Nishio H, Ebata T, Igami T, Sugawara G, Nagino M. Value of indocyanine green clearance of the future liver remnant in predicting outcome after resection for biliary cancer. Br J Surg. 2010;97:1260–8.
315 10. Abdalla EK, Hicks ME, Vauthey JN. Portal vein embolization: rationale, technique and future prospects. Br J Surg. 2001;88:165– 75. 11. Michalopoulos GK, DeFrances MC. Liver regeneration. Science. 1997;276:60–6. 12. Uesaka K, Nimura Y, Nagino M. Changes in hepatic lobar function after right portal vein embolization. An appraisal by biliary indocyanine green excretion. Ann Surg. 1996;223:77–83. 13. Farges O, Belghiti J, Kianmanesh R, Regimbeau JM, Santoro R, Vilgrain V, et al. Portal vein embolization before right hepatectomy: prospective clinical trial. Ann Surg. 2003;237:208–17. 14. Higuchi R, Yamamoto M. Indications for portal vein embolization in perihilar cholangiocarcinoma. J Hepatobiliary Pancreat Sci. 2014;21:542–9. 15. Novellas S, Denys A, Bize P, Brunner P, Motamedi JP, Gugenheim J, et al. Palliative portal vein stent placement in malignant and symptomatic extrinsic portal vein stenosis or occlusion. Cardiovasc Intervent Radiol. 2009;32:462–70. 16. Yamakado K, Nakatsuka A, Tanaka N, Fujii A, Terada N, Takeda K. Malignant portal venous obstructions treated by stent placement: significant factors affecting patency. J Vasc Interv Radiol. 2001;12:1407–15. 17. Wei BJ, Zhai RY, Wang JF, Dai DK, Yu P. Percutaneous portal venoplasty and stenting for anastomotic stenosis after liver transplantation. World J Gastroenterol. 2009;15:1880–5. 18. Woodrum DA, Bjarnason H, Andrews JC. Portal vein venoplasty and stent placement in the nontransplant population. J Vasc Interv Radiol. 2009;20:593–9. 19. Kaneoka Y, Yamaguchi A, Isogai M, Hori A. Intraportal stent placement combined with right portal vein embolization against advanced gallbladder carcinoma. Surg Today. 1998;28:862–5.
ORIGINAL ARTICLE
Assessment of percutaneous transhepatic portal vein embolization with portal vein stenting for perihilar cholangiocarcinoma with severe portal vein stenosis Ryota Hyodo · Kojiro Suzuki · Tomoki Ebata · Tomohiro Komada · Yoshine Mori · Yukihiro Yokoyama · Tsuyoshi Igami · Gen Sugawara · Shinji Naganawa · Masato Nagino
Published online: 25 December 2014 © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery
Abstract Background The aim of the present study was to assess the clinical efficiency of portal vein (PV) stenting when performed with preoperative percutaneous transhepatic portal vein embolization (PTPVE) in patients with severe PV stenosis due to tumor invasion. Methods Between 2007 and 2013, four consecutive patients (one male, three females; mean age, 52 years; age range, 25–73 years) with perihilar cholangiocarcinoma and PV stenosis underwent PTPVE and PV stenting. Patients were analyzed with regard to the procedure, hypertrophy of the future remnant liver (FRL), and plasma clearance rate of indocyanine green by the FRL (ICGK-F). Further, the %FRL volume increase in PTPVE was compared between the stenting group and the usual PTPVE group who have perihilar cholangiocarcinomas without PV stenosis. Results Preoperative PTPVE with PV stenting was successfully performed and portal flow to the FRL improved after stenting in all four patients. The %FRL volume increase was 18–60% (mean, 34%) in the stenting group and was 12–51% (mean, 21%) in the usual PTPVE group. The ICGK-F value after PTPVE exceeded 0.05 in all four patients. All patients achieved R0 resection. Conclusions Preoperative PTPVE with PV stenting appears to be feasible in cases of severe PV tumor invasion
R. Hyodo (*) · K. Suzuki · T. Komada · Y. Mori · S. Naganawa Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan e-mail: [email protected] T. Ebata · Y. Yokoyama · T. Igami · G. Sugawara · M. Nagino Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
and stenosis. This procedure may allow a broader indication for surgery. Keywords Percutaneous transhepatic portal vein embolization · Perihilar cholangiocarcinoma · Portal vein stenosis · Stent Introduction Perihilar cholangiocarcinoma is a serious disease that requires management via surgical resection in order to achieve long-term survival [1, 2]. However, early diagnosis is often difficult, meaning that most cases are diagnosed at an advanced stage in the disease. If not resected, the 3-year survival rate is only 2.1% [3]. Extended hepatectomy combined with portal vein (PV) and/or hepatic artery resection with reconstruction is often needed for complete resection, and these surgical approaches are associated with a 3-year survival of 40.6% and a 5-year survival of 26.8% [3]. However, the smaller the future remnant liver (FRL), the higher the risk of postoperative liver dysfunction [4]. An increase in the FRL volume is required to minimize postoperative liver dysfunction. Therefore, preoperative percutaneous transhepatic portal vein embolization (PTPVE) is performed before an extended hepatectomy [2, 5, 6]. Advanced perihilar cholangiocarcinoma often invades into the main PV, resulting in main PV stenosis and a decrease in hepatopetal portal flow. In this situation, sufficient hypertrophy of the FRL cannot be expected after PTPVE. In such cases, we have attempted to improve portal flow via stent placement at the site of main PV stenosis combined with simultaneous PV embolization. The report describes four consecutive cases in which preoperative PTPVE with PV stenting was used for the
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management of advanced perihilar cholangiocarcinoma with severe PV stenosis secondary to tumor invasion. We evaluate the clinical utility of this procedure when compared with the usual PTPVE procedure in patients without PV stenosis. Methods Patients Our institutional review board approved the retrospective collection of data and analysis for this study, and the need for informed consent from the patients was waived. Between July 2007 and April 2013, four consecutive patients (one male, three females; mean age, 52 years; age range, 25–73 years) with advanced perihilar cholangiocarcinoma (Bismuth IV, three patients; recurrence of extrahepatic bile duct cancer, one patient) with PV stenosis secondary to tumor invasion underwent PTPVE with PV stenting before surgery. Volumetric computed tomography (CT) examination was performed 9 to 24 days (mean, 18 days) after PTPVE. These patients subsequently underwent left hepatic trisectionectomy and caudate lobectomy combined with resection and reconstruction of the main PV and the right hepatic artery. Two patients (cases 1, 2) also underwent combined pancreatoduodenectomy at the same time. The PV stent was removed together with the invaded PV at the time of surgery. None of the patients had underlying chronic liver disease (e.g. hepatitis B or C virus, alcoholic liver disease). Between November 2009 and April 2011, 20 consecutive patients (11 males, nine females; mean age, 67 years; age range, 46–80 years), who had undergone usual PTPVE for advanced perihilar cholangiocarcinoma without PV stenosis (Bismuth IV, n = 19; Bismuth IIIb, n = 1) and were scheduled to undergo left hepatic trisectionectomy and caudate lobectomy, were selected as a control group. Sex and age was not matched to the PTPVE with PV stenting group. The exclusion criteria for the control group included a history of chronic liver disease (e.g. hepatitis B or C virus infection or alcoholic liver disease) and severe cholangitis after PTPVE. Patients who underwent volumetric CT examination within 9 days after PTPVE were also excluded.
branch of the right anterior hepatic segment under local anesthesia. The Seldinger technique was used to place a 5-Fr (for patients undergoing usual PTPVE) or 6-Fr (for patients undergoing PTPVE with PV stenting) vascular sheath into the main PV. To identify individual branches and anatomic variations, portography was performed using a 4-Fr or 5-Fr modified shepherd hook catheter (Selecon; Terumo Clinical Supply, Kakamigahara, Japan). Then, the catheter was inserted into the left and the right anterior PV. Absolute ethanol was first injected to occlude the smaller distal portal branches. To occlude the left PV and anterior branches, 0.035-inch coils (MReye; William Cook Europe, Bjaeverskov, Denmark) were used. The diameter of the coils ranged from 3 to 10 mm. In some cases, 2.2- to 2.4-Fr microcatheter and micro-coils (Tornade; Cook Medical, Bloomington, IN, USA) were also used. Embolization was performed until stasis or near-stasis was achieved. The access tract was finally embolized with 3- to 4-mm coils. In cases 1 (Fig. 1) and 2 in the PV-stenting group, we first embolized the left PV. Then, a 12 × 40 mm self-expandable stent (E-Luminexx; Bard, Tempe, AZ, USA) was deployed from the main PV to the right PV across the orifice of the left PV. Postdilatation was performed with a 10-mm balloon catheter (Fox Cross; Abbott, Green Oaks, IL, USA). The portal branch of the caudate lobe was also embolized after PV stenting in case 1. Finally, the anterior portal branches were embolized. In case 3, the left PV was already occluded secondary to tumor invasion. First, we dilated the PV stenosis with a 6-mm balloon catheter. Then, we embolized the anterior PV branches. Finally, a 10 × 37 mm balloon-expandable stent (Express LD; Boston Scientific, Natick, MA, USA) was deployed from the main PV to the right anterior PV. In case 4 (Fig. 2), the orifice of the left PV was occluded secondary tumor invasion, but the flow to the left portal system was preserved via a collateral venous channel of the gastric vein. Therefore, we performed PTPVE in a twostage procedure. In the first procedure, a 12 × 42 mm selfexpandable stent (Epic Vascular Stent; Boston Scientific) was deployed from the main PV to the right PV. Postdilatation was performed with a 9-mm balloon catheter. Then, the anterior portal branches were embolized. Thirteen days later, the left portal venous system was embolized via ultrasonographic-guided puncture of the left PV.
PTPVE and PV stenting procedure Assessments Preoperative PTPVE procedure with and without PV stenting was performed as follows. In all patients, the portal venous system was accessed by an ultrasound-guided percutaneous transhepatic approach (ipsilateral approach) [7]. An 18-gauge Cliny ultrasound puncture needle (Create Medic, Yokohama, Japan) was placed into a peripheral PV
Using CT image data, FRL volume and embolized liver (EL) volume were calculated before and after PTPVE. The difference in FRL volume before and after embolization in relation to the FRL volume before embolization (%FRL volume increase) and the difference in EL volume before
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(a)
(c)
(b)
Fig. 1 Case 1: (a) Contrast-enhanced computed tomography (CT) shows the recurrence of extrahepatic bile duct cancer (arrow) invading into the porta hepatis, main portal vein (PV) and common hepatic artery. There is a metallic stent in the common bile duct (arrowhead). (b) Portography shows PV stenosis (arrow) and reflux in the left gastric vein. (c) Portography after stent placement and left PV embolization shows resolution of PV stenosis and decompression of the associated hepatofugal collateral vein. PV embolization of the caudate lobe and the right anterior segment was subsequently performed. Fig. 2 Case 4: (a) Contrastenhanced computed tomography (CT) shows perihilar cholangiocarcinoma (arrow) invading into the main portal vein (PV) and right hepatic artery (not shown). There is severe PV stenosis. (b) Portography shows the main PV stenosis and occlusion of the orifice of the left PV (arrow). Cavernous transformation and reflux in the left gastric vein are also recognized. (c) Portography after PV stent placement and embolization of the right anterior segment shows resolution of the PV stenosis, decompression of cavernous transformation, and an increase in portal flow to the right posterior segment. (d) Contrast-enhanced CT after preoperative percutaneous transhepatic portal vein embolization (PTPVE) with PV stenting shows nearly full-expansion of the stent and a resolution of PV stenosis.
(a)
(b)
(c)
and after embolization in relation to the EL volume before embolization (%EL atrophy) were calculated according to the following formula described by Lienden et al. [8]:
%FRL volume increase = [%FRL ( post-PTPVE ) − %FRL ( pre-PTPVE )] %FRL ( pre-PTPVE ) ×100%
(d)
%EL atrophy = [(%EL ( post-PTPVE ) − %EL ( pre-PTPVE )] %EL ( pre-PTPVE ) ×100% In this study, the caudate lobe’s volume was included in the embolized liver’s volume even when the portal branch of the caudate lobe was not embolized. This is because all
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J Hepatobiliary Pancreat Sci (2015) 22:310–315 Table 1 Results of the stenting group Case
1 2 3 4
Age/ Sex 25/F 73/F 60/F 51/M
Stent
SS SS BS SS
Stent diameterlength
PV diameter Pre
Post
12–40 mm 12–40 mm 10–37 mm 12–42 mm
5 mm 4 mm 2 mm 2 mm
12 mm 12 mm 7 mm 12 mm
Technical success Yes Yes Yes Yes
FRL volume
%FRL increase
Pre (proportion)
Post
594 ml (44%) 250 ml (27%) 338 ml (32%) 288 ml (18%)
662 ml 308 ml 348 ml 485 ml
18% 25% 30% 60%
%EL atrophy −15% −9% −14% −13%
ICGK-F
Clinical efficacy
Pre
Post
0.094 0.041 0.045 0.032
0.106 0.052 0.064 0.064
Yes Yes Yes Yes
BS balloon-expandable stent, EL embolized liver, FRL future remnant liver, ICGK-F indocyanine green clearance rate for future remnant liver, Post post PTPVE with PV stenting, Pre pre PTPVE with PV stenting, PV portal vein, SS self-expandable stent.
patients were planned to undergo surgical resection of the caudate lobe. The increase in %FRL volume and the %EL atrophy of the PTPVE with PV stenting group was compared with those of the usual PTPVE group. In addition, the diameter of the PV stenosis site was measured using volumetric CT images before and after PTPVE. Technical successes and clinical efficacy in the stenting group were also assessed. Technical success was defined as: (i) successful dilation of the main PV stenosis; (ii) improvement in portal flow secondary to stent placement; and (iii) successful completion of PV embolization without complication. Clinical efficacy was defined as a %FRL volume increase that was equal to or greater than the minimum level of %FRL volume increase in the control group. Plasma clearance rate of indocyanine green (ICGK) was assessed before and after PTPVE in all cases. ICGK of the FRL (ICGK-F) was calculated according to the formula: ICGK × proportion of the FRL [9]. ICGK-F before and after PTPVE was also evaluated, and patient outcomes after surgery were reviewed from medical records. Results The results of the stenting group are summarized in Table 1. In all patients undergoing PTPVE with stenting, the stent was successfully deployed. In addition, portal flow improved visually on portography just after stenting and on ultrasound performed after several days. Further, PTPVE was successfully performed. There were no complications associated with the procedure in any patient. Therefore, technical success was achieved in all four patients (100%). The %FRL volume increase was 18–60% (mean, 33%) in the stenting group and 12–51% (mean, 21%) in the usual PTPVE group. Of these, the left PV occlusion by tumor invasion was found in one patient (case 3) of the stenting group and three patients of the usual PTPVE group. The %FRL volume increase in the patients with the left PV occlusion was 30% in the stenting group and 15–22% (mean, 19%) in the usual PTPVE group. On the other hand, the %FRL volume increase in the patients without the left
PV occlusion was 18%, 25%, and 60% in the stenting group and 12–51% (mean, 22%) in the usual PTPVE group. All four patients who underwent PTPVE with stenting exceeded an increase in %FRL volume of 12%, which was the minimum increase in %FRL volume seen in the usual PTPVE group. The %EL atrophy was −15 to −9% (mean, −13%) in the stenting group and −24 to −6% (mean, −12%) in the usual PTPVE group. Therefore, clinical efficacy was achieved in all four patients (100%). In addition, the ICGK-F values after PTPVE were more than 0.05 in all four cases. Portography before stenting showed the left gastric vein as a hepatofugal collateral vessel in cases 1 and 4, cavernous transformation of the PV in cases 3 and 4. After stenting, the hepatofugal collateral flow of case 1 disappeared, and that of case 4 decreased. The hepatopetal collateral flow of cases 3 and 4 also decreased. The volumetric CT after PTPVE showed the extension of PV diameter at stenosis site in all cases. In the PTPVE with stenting group, the days from PTPVE to operation was 13 to 50 days (mean, 30 days). All patients underwent planned hepatic resection and achieved R0 resection. The PV was resected between the main PV and the right posterior PV, including the PV stent. We did not resect the PV stent itself or remove the stent from the PV during the operation. An end-to-end anastomosis was performed in one patient (case 2) and a right external iliac vein interposition grafting was performed in the other three patients (cases 1, 2 and 4). Pathologically, an epithelial hyperplasia was not seen in the PV epithelium, which a stent was contacted with in all four patients. Three of the patients did not develop postoperative liver dysfunction and were discharged. However, one patient (case 4) developed sepsis from the next day of the operation. Antibiotic therapy was performed, but the infection was not controlled. Subsequently, the patient developed refractory ascites, renal failure and liver dysfunction. And the patient died of multiorgan failure caused by sepsis at 47 days after surgery. During the follow-up period, case 2 died of tumor recurrence at 38 months after surgery. Cases 1 and 3 are alive at 56 months and 16 months after surgery, respectively. In the
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usual PTPVE group, 16 patients underwent planned hepatic resection, and none of the patients developed postoperative liver dysfunction. The other four patients did not undergo subsequent hepatectomy because of peritoneal seeding (n = 2), periaortic node metastasis (n = 1) or locally advanced disease (n = 1; extensive nerve plexus invasion). Discussion Preoperative PTPVE with PV stenting was conducted in four patients with perihilar cholangiocarcinoma and severe main PV stenosis due to tumor invasion. The PV stenosis improved after PV stenting, and the %FRL volume increase after PTPVE was comparable to that seen in patients undergoing the usual PTPVE procedure without PV stenting. In addition, ICGK-F values after PTPVE were more than 0.05 in all cases. These data demonstrate that PTPVE with PV stenting could broaden the indications for surgery in patients with advanced perihilar cholangiocarcinoma. In the case of PTPVE, the increase in portal flow and hepatocyte growth factor in the FRL after PTPVE plays an important role for an increase in the FRL volume [10, 11]. Further, the increase in FRL volume correlates with the increasing in FRL function [12]. However, major portal hypertension with portosystemic shunting can result in insufficient FRL hypertrophy after PTPVE [13]. In the present cases, stenting resulted in an increase in portal flow to the FRL and a decrease in portosystemic shunting, thereby leading to an increase in FRL volume and function after PTPVE. The ICGK-F value is an indicator of the function of the FRL. Yokoyama et al. reported that a ICGK-F value less than 0.05 was associated with an increase in the risk of postoperative liver dysfunction in the case of extended hepatectomy, such as left hepatic trisegmentectomy for biliary cancer [9]. An ICGK-F value more than 0.05 is associated with a 3.5% rate of postoperative liver dysfunction, while a ICGK-F value less than 0.05 is associated with a 22% rate of postoperative liver dysfunction [9]. In the four patients described in the present study, the ICGK-F values after PTPVE were more than 0.05, suggesting that the FRL function was adequate for surgery. In principal, PTPVE is usually indicated when the FRL volume is less than 40% of whole liver [1, 14]. The FRL volume of cases 2, 3 and 4 were less than 40%; however, the FRL volume of case 1 was 44%. This is because a recurrent tumor of case 1 was very aggressive and surgeons required increasing liver function before surgery. In this study, we used a self-expandable stent in three patients (cases 1, 2 and 4) and a balloon-expandable stent in one patient (case 3). In past reports, a self-expandable stent was usually used for management of PV stenosis [15–18]. However a balloon-expandable stent has also been used
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when the lesion being treated necessitated precise placement of the stent [18]. In case 3 in the present study, a balloon-expandable stent was selected because the excision margin of the PV was close to the stenosis site; therefore, the stent had to be deployed more precisely. The stents were deployed at the exact planning position in all cases. In addition, they did not disturb the surgical procedure in any of the cases. According to previous reports, the indications for PV stenting include the treatment of the PV hypertension associated with PV stenosis, such as varices of portal collateral vessels, refractory ascites, pancytopenia and liver dysfunction due to advanced or recurrent pancreaticobiliary tumor [15, 16, 18]. In addition, PV stenting is indicated for PV stenosis after liver transplantation [17]. To the best of our knowledge, there is only one case report about PTPVE with PV stenting. Kaneoka et al. reported PTPVE with PV stenting for a patient of advanced gallbladder carcinoma with PV stenosis [19]. They reported only the change of FRL volume before and after the procedure. Therefore, our study is the first report which evaluates hypertrophy rate and liver function of FRL. Further, we also compare the stenting group with the usual PTPVE group in relation to the procedure and %FRL volume increase. This study has several limitations. First, the number of patients was small. This is because few patients with perihilar cholangiocarcinoma have PV stenosis without metastasis and are still candidates for surgery. Therefore, the accumulation of further cases is necessary to assess the utility of PTPVE with PV stenting. Second, PV pressure and velocity were not measured. PV flow was evaluated only by portography and ultrasound visually. Third, %FRL volume increase and ICGK-F value that would otherwise have resulted if PTPVE were performed without stenting in these four cases are unknown. In conclusion, preoperative PTPVE with portal vein stenting for patients with advanced perihilar cholangiocarcinoma and PV severe stenosis secondary to tumor invasion appears to be feasible and may broaden the indications for surgical resection. Conflict of interest
None declared.
Author contributions Study design: Ryota Hyodo and Kojiro Suzuki. Acquisition of data: Ryota Hyodo, Tomoki Ebata, Yukihiro Yokoyama, Tsuyoshi Igami, and Gen Sugawara. Analysis and interpretation: Ryota Hyodo, Kojiro Suzuki, and Tomohiro Komada. Manuscript drafted by: Ryota Hyodo, Kojiro Suzuki, and Yoshine Mori. Revision: Shinji Naganawa and Masato Nagino.
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