Abstract
Objective:
Major liver resection is an effective treatment option for patients with liver malignancy. The future liver remnant (FLR) volume and complications after portal vein embolization (PVE) were compared between the ipsilateral right portal vein (PTPE) and transileocolic (TIPE) approaches.
Methods:
A total of 42 patients (TIPE, n = 22; PTPE, n = 20) underwent right lobectomy after PVE. CT and hepatobiliary scintigraphy were repeated before and after PVE. The blood examination findings and the FLR values (FLRCT: calculated from CT, %FLRCT: FLRCT ratio, %FLRSPECT: FLR ratio using single photon emission CT, FLRCT/BS: FLRCT to body surface ratio) were compared between two approach sites. The complications and mortality were also analyzed after PVE and major right hepatectomy.
Results:
There were no significant differences in the patient characteristics, blood examination findings or FLR values between two groups. Adequate liver regeneration was observed without significant differences between PTPE and TIPE (increased ratio of FLRCT: 8.7% vs 19.2%, p = 0.15 [25–75 percentile: 17.1–60.4], %FLRCT: 11.2% vs 8.3%, p = 0.25 [6.3–13.3], %FLRSPECT: 15.4% vs 19.2%, p = 0.09 [16.0–22.4], FLRCT/BS: 33.6% vs 47.1%, p = 0.19 [17.2–60.4], respectively), but TIPE required a significantly longer procedure time than PTPE [181.4 min vs 108.7 min, p < 0.01 (103.3–193.5)]. However, one patient was converted to TIPE due to bleeding during PTPE. After right lobectomy, portal vein stenosis or thrombosis was noted in three patients [two with TIPE (9.1%) and one with PTPE (5%)] and three TIPE patients died within 90 days (13.6%) after right hepatectomy.
Conclusion:
FLR volume significantly increased after PVE, regardless of the approach sites; however, PTPE is a useful technique with a shorter procedure time.
Advances in knowledge
Portal venous embolization (PVE) improved the pre-operative future liver remnant, regardless of approach site. The ipsilateral percutaneous transhepatic approach is a reliable method for PVE with a shorter procedure time, fewer complications after major hepatectomy and a shorter hospital stay.
Introduction
Liver resection remains a viable therapeutic option that allows for the long-term survival of patients with primary or secondary malignant tumors of the liver. 1 Complete resection of the tumor load is directly linked to overall survival, but some patients are unsuited for major hepatectomy because of an insufficient future liver remnant (FLR) volume. Postoperative liver failure, the incidence of which is up to 30%, remains the major cause of death after major hepatectomy. 1 Several studies have shown that the FLR volume is a key element in postoperative liver failure. 2–4 Pre-operative portal vein embolization (PVE) is an option for improving the FLR volume in patients with an insufficient FLR and may lead to the prevention of liver insufficiency after major hepatectomy. PVE is performed by several techniques, including the use of intraoperative portal vein ligation, 5–7 transileocecal PVE (TIPE), 8–10 and percutaneous transhepatic ipsilateral PVE (PTPE) 11,12 or percutaneous transhepatic contralateral PVE. 13,14 An enlarged FLR after PVE is correlated with an increased residual liver function and can minimize liver dysfunction after hepatectomy. 15
TIPE requires general anesthesia due to laparotomy guidance and leads to long occupancy time of operating room. Technique of TIPE itself is simple after placement of introducer into an ileocecal vein, because of antegrade embolization of target portal branches. However, ipsilateral PTPE requires a procedure time equivalent to an expert catheter technique, including a portal vein puncture and retrograde manner in embolization of target vessels. The present study compared the changes in the FLR values and liver function after PVE, PVE-related complications, procedure time during PVE, the hospital stay, and complications and 90-day mortality after right lobectomy between the TIPE and PTPE groups.
Methods and materials
57 patients with primary or metastatic liver malignancies without additional distant metastasis underwent right PVE in Yamaguchi University Hospital (Ube, Japan) between June 2007 and January 2016. All patients had a low FLR ratio (<40%), which was calculated with a combination of CT volumetry and hepatobiliary scintigraphy (HBS). 10 of the 57 patients who underwent left portal embolization and left hepatectomy were excluded from this study. 5 of the remaining 47 patients dropped out due to disease progression within a short period after PVE and avoided right hepatectomy. Finally, a total of 42 patients (PTPE, n = 20; mean age, 64.4 years old ; TIPE, n = 22; mean age, 64.5 years old) were included in this study (Figure 1) and underwent right hepatectomy after PVE.
Figure 1.
Flow diagram of PVE. 57 patients underwent PVE between June 2007 and January 2016. 10 patients were excluded from this analysis due to left portal embolization and another 5 patients dropped out due to tumor regression after PVE. PTPE, percutaneous transhepatic ipsilateral; PVE, portal vein embolization; TIPE, transileocecal PVE.
The liver malignancies included hepatocellular carcinoma (HCC; n = 9), cholangiocarcinoma (n = 4), metastatic tumors from colorectal carcinoma (Mets; n = 12), gallbladder carcinoma (GBC; n = 7), and bile duct cancer (BDC; n = 10) (Table 1). The blood examination findings, quantitative FLR values, and rates of complications and 90-day mortality were compared between the TIPE and PTPE groups. Dynamic contrast-enhanced CT and HBS using 99mTc galactosyl human serum albumin (GSA) were performed before and after PVE.
Table 1.
Future liver remnant values before and after porta embolization based on diseases
| Diseases | PTPE | TIPE | Before PVE | After PVE | growth ratio | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| %FLRCT
(%) |
%FLRSPECT
(%) |
FLRCT/BS (ml/m2) |
%FLRCT
(%) |
%FLRSPECT
(%) |
FLRCT/BS (ml/m2) |
Δ%FLRCT
(%) |
Δ%FLRSPECT
(%) |
ΔFLRCT/BS (%) |
|||
| Hepatocellular carcinoma | 4 (20.0%) | 5 (22.7%) | 37.9 | 35.5 | 337.9 | 43.9 | 51.7 | 414.8 | 6.1 | 16.2 | 27.3 |
| Metastatic tumor (colon carcinoma) | 8 (40.0%) | 4 (18.2%) | 32.2 | 30.1 | 253.0 | 47.4 | 49.3 | 358.6 | 15.2 | 19.8 | 45.7 |
| Biliary tumor | 8 (40.0%) | 13 (59.1%) | 30.6 | 29.4 | 245.5 | 42.2 | 44.8 | 335.0 | 11.6 | 16.4 | 42.6 |
| Cholangiocarcinoma | 3 (15.0%) | 1 (4.5%) | |||||||||
| Gallbladder carcinoma | 4 (20.0%) | 3 (13.6%) | |||||||||
| Bile duct cancer | 1 (5.0%) | 9 (40.9%) | |||||||||
| p value | 0.29 | 0.09 | 0.18 | 0.15 | 0.38 | 0.14 | 0.49 | 0.04 | 0.26 | 0.09 | |
%FLRCT, the ratio of future liver remnant volume (FLR) volume calculated using CT (%); FLRCT/BS, FLR volume calculated using CT/body surface (ml/m2); %FLRSPECT, the ratio of FLR volume calculated using SPECT; PTPE, percutaneous transhepatic portal embolization; PVE, portal vein embolization; TIPE, trans-ileocecal portal embolization; Δ = 100;Δ%FLRCT, %FLRCT (after PVE) - %FLRCT (before PVE); ΔFLRCTBS, 100×(FLRCT/BS[after PVE] - FLRCT/BS [before PVE])/ FLRCT/BS (before PVE); Δ%FLRSPECT, %FLRSPECT (after PVE) - %FLRSPECT (before PVE).
PVE
PTPE was performed under local anesthesia via an ipsilateral percutaneous transhepatic approach (through the tumor-bearing liver) in an interventional X-ray room. The portal venous system was accessed under sonographic and fluoroscopic guidance and a 5-Fr introducer was inserted to facilitate subsequent catheter exchanges. The right anterior and posterior portal veins were selected and completely embolized using coils or gelatin sponge after absolute ethanol injection under flow guidance using a 5-Fr balloon catheter (Figure 2).
Figure 2.
A 62-year-old male with hilar bile duct cancer. Portography via the ipsilateral percutaneous transhepatic approach shows normal intrahepatic portal branches (A). The right anterior and posterior branches were embolized with the mixture of absolute ethanol and lipiodol and metallic coils (B). Contrast-enhanced CT shows the accumulation of lipiodol and an increased arterial flow in the right hepatic lobe (C).
TIPE was carried out under general anesthesia via the ileocolic vein in an operating theater. A 5-Fr introducer was placed into a branch of the ileocolic vein under fluoroscopic guidance after right lower quadrant incision. The right anterior and posterior portal branches were embolized using the same embolic materials under flow control using a 5-Fr balloon catheter (Figure 3).
Figure 3.
A 66-year-old male with gallbladder carcinoma. Direct portography via the transileocecal vein approach was carried out under laparotomy (A). The right portal branch was occluded with a mixture of absolute ethanol and lipiodol and metallic coils (B). CT after PVE shows the diffuse accumulation of embolic material in the right hepatic lobe (C). PVE, portal vein embolization.
Liver volumetry
Contrast-enhanced CT was repeated with a 64-slice single or dual source CT system (SOMATOM Sensation 64 or Definition; Siemens Medical Solutions, Erlangen, Germany) before and after PVE. The CT parameters were as follows: tube voltage, 120 kVp with 250–450 effective mAs. All images were reconstructed using a slice thickness and interval of 5.0 mm. A non-ionic contrast material (almost 600 mgI/kg) was injected over 30 s using a power injector at the rate of 3–5 ml s−1. The arterial phase scan started when the region of interest placed in the abdominal aorta exceeded an attenuation of 100 HU. The portal venous and delayed phase images were obtained at 70 and 180 s after the start of the injection of the contrast material, respectively.
After fasting overnight, all patients underwent HBS using single photon emission computed tomography (SPECT) with a Symbia EvoExcel collimator (Canon Medical System Co., Otawara, Japan) after the intravenous injection of 99mTc-GSA (Nihon Medi-Physics Co., Ltd, Tokyo, Japan) (185 MBq/3 mg). SPECT data (90 steps of 20 s/step, 360°, 128 × 128 matrix) were obtained in the step-and-shoot mode with 64 projections at 8° intervals.
Reconstructed SPECT and CT images were converted into the DICOM format and transferred to a workstation (GMS-5500A/PI: Canon Medical System Co. Otawara, Japan) to combine both images. For image registration, a container (inner diameter, 4 mm; length, 10 mm) containing an aqueous solution of 99mTc-GSA and contrast medium was used as an external fiducial marker. The SPECT and CT images were manually fused by registration of the external fiducial markers of the two images. Along the middle hepatic vein, the residual liver area was decided and the FLR was automatically calculated using three-dimensional (3D) fused images. 16 The FLR volume calculated from CT (FLRCT) reflected the anatomical residual liver volume, the %FLRCT reflected the volumetric change of FLR using CT, and the %FLRSPECT reflected both the anatomical and functional results of the residual liver in combination with CT and HBS with SPECT. For standardization, FLRCT value was divided by each patient’s body surface (FLRCT/BS: ml/m2).
Blood examinations
A hemogram, laboratory tests [albumin, total bilirubin, prothrombin time, prothrombin activity, and an indocyanine green test (ICG15)], and the Child-Pugh score were evaluated before and after PVE and after right lobectomy.
Statistical analyses
Variables are summarized as the mean and standard deviation. All statistical analyses were performed using the Statistical Package for Social Science (SPSS) software program (Windows v.20.0 J; Chicago, IL).
Categorical variables were compared using the χ2 test, and the Mann–Whitney U test was used for the evaluation of FLR values between TIPE and PTPE groups and before and after PVE. p values of <0.05 were considered to indicate statistical significance.
Wilcoxon’s signed-rank test was performed for matched pairs of the residual liver function and the results of the blood examinations before and after PVE in the TIPE and PTPE groups.
Results
There were no significant differences in tumor characteristics, including HCC, metastatic carcinoma, and biliary tumor, between the TIPE and PTPE groups (p = 0.28) (Table 1). There were also no significant differences in quantitative FLR values of %FLRCT, %FLRSPECT and FLRCT/BS among these tumors (p-value ranging from 0.09 to 0.49). The increased FLR ratio was smaller in the HCC group than in the groups of metastatic and biliary tumor (Table 1). Volumetric value of %FLRCT was smallest in patients with HCC (6.1% p < 0.04). However, there were no significant differences in the increase ratio of %FLRSPECT or FLRCT/BS among the three tumor groups using the Kruskal–Wallis test (Table 1).
There were no significant differences between the TIPE and PTPE groups with regard to gender, age, body weight, ICG15, prothrombin activity, Child-Pugh score, FLRCT, %FLRCT, %FLRSPECT, or FLRCT/BW before PVE (Table 2). The serum albumin level before PVE was significantly lower in the TIPE group than in the PTPE group (p < 0.01) (Table 2). However, the serum albumin level significantly decreased, but was within normal range after PVE in both groups (Table 3). In both TIPE and PTPE groups, the quantitative FLR values significantly increased after PVE with high z value (in the TIPE group, FLRCT: from 413.6 ± 104.4 ml to 518.5 ± 100.9 ml, %FLRCT: 33.8±9.1to 45.7%±9.2%, %FLRSPECT: 32.8±9.4 to 46.4%±8.5%, FLRCT/BS: 267.4 ± 67.0 ml/m2 to 340.5 ± 74.4 ml/m2; p < 0.01, in the PTPE group, FLRCT: from 431.9 ± 210.4 ml to 600.2 ± 228.4 ml, %FLRCT: 31.4±8.2 to 42.6%±8.9%, %FLRSPECT: 28.8±9.5 to 47.9%±9.1%, FLRCT/BS: 263.1 ± 110.3 ml/m2 to 368.7 ± 113.9 ml/m2, p < 0.01) (Table 3). PVE led to the successful enlargement of the remnant liver volume (%FLRCT and %FLRSPECT>40%) irrespective of the approach site, but there were no significant differences in the increases in the FLRCT or %FLRSPECT values after PVE (Table 2).
Table 2.
The patient characteristics, liver remnant and complication after PVE and right lobectomy
| TIPE (n = 22) | PTPE (n = 20) | p value | 25–75 percentile | ||
|---|---|---|---|---|---|
| Mean (SD) | Mean (SD) | ||||
| Before PVE | Gender | 76.50% | 47.60% | 0.07a | |
| Age | 64.5 (9.2) | 64.4 (12.0) | 0.97 b | 59.5–72.0 | |
| Body weight (Kg) | 56.2 (12.9) | 57.7 (12.9) | 0.72 b | 46.3–68.6 | |
| Child-Pugh score | 5.86 (1.04) | 5.30 (0.47) | 0.08 b | 5.0–6.0 | |
| ICG15 (%) | 13.0 (6.6) | 13.3 (5.9) | 0.82 b | 8.4–15.3 | |
| Total bilirubin (mg/dL) | 1.64 (1.26) | 0.96 (0.73) | 0.13 b | 0.60–1.92 | |
| Albumin (g/dL) | 3.73 (0.48) | 4.02 (0.40) | 0.04b | 3.68–4.20 | |
| Platelet (1010 l−1) | 22.9 (11.9) | 19.9 (10.1) | 0.17b | 14.3–25.5 | |
| Prothrombin time (s) | 11.9 (0.8) | 12.1 (1.2) | 1.00b | 11.4–12.3 | |
| Prothrombin activity (%) | 95.1 (18.4) | 98.3 (26.8) | 0.66b | 95.3–111.8 | |
| FLRCT (ml) | 413.6 (104.4) | 431.9 (210.4) | 0.80b | 381.9–489.2 | |
| % FLRCT (%) | 33.7 (9.1) | 31.4 (8.2) | 0.44b | 26.0–36.9 | |
| %FLRSPECT (%) | 32.8 (9.4) | 28.8 (9.5) | 0.16b | 24.0–38.2 | |
| FLRCT /BS (ml/m2) | 267.4 (67.0) | 263.1 (110.3) | 0.50b | 202.5–328.2 | |
| After PVE | ICG15 | 11.1 (6.1) | 11.5 (6.0) | 0.87b | 6.7–15.0 |
| Total bilirubin (mg/dL) | 0.95 (0.55) | 0.73 (0.34) | 0.21b | 0.50–1.20 | |
| Albumin (g/dL) | 3.41 (0.52) | 3.65 (0.39) | 0.10b | 3.30–3.90 | |
| Platelet (1010 l−1) | 27.8 (11.5) | 22.7 (7.4) | 0.09b | 18.2–33.6 | |
| Prothrombin time (s) | 12.1 (0.9) | 12.1 (1.3) | 0.96b | 11.4–12.4 | |
| Prothrombin activity (%) | 90.1 (15.5) | 95.8 (23.2) | 0.36b | 79.5–108.2 | |
| FLRCT (ml) | 518.5 (100.9) | 600.2 (228.4) | 0.25b | 438.6–607.8 | |
| %FLRCT (%) | 45.7 (9.2) | 42.6 (8.9) | 0.36b | 37.9–51.5 | |
| %FLRSPECT (%) | 446.4 (8.5) | 47.9 (9.1) | 0.80 b | 42.0–52.4 | |
| FLRCT /BS (ml/m2) | 340.5 (74.4) | 368.7 (113.9) | 0.84b | 291.0–382.3 | |
| ΔFLRCT (%) | 11.2 (6.4) | 8.7 (3.9) | 0.15b | 17.1–60.4 | |
| Δ%FLRCT (%) | 8.3 (4.7) | 11.2 (6.4) | 0.25b | 6.3–13.3 | |
| Δ%FLRSPECT (%) | 19.2 (7.3) | 15.4 (7.2) | 0.09b | 16.0–22.4 | |
| ΔFLRCT /BS (%) | 47.1 (31.3) | 33.6 (29.1) | 0.19b | 17.2–60.4 | |
| Post-right lobectomy | Child-Pugh score | 7.00 (1.60) | 6.10 (1.07) | 0.08b | 5.0–8.0 |
| Total bilirubin (mg/dL) | 0.72 (0.31) | 0.78 (0.27) | 0.31b | 0.50–0.90 | |
| Albumin (g/dL) | 3.30 (0.65) | 3.47 (0.58) | 0.40b | 2.90–3.80 | |
| Platelet (1010 l−1) | 16.7 (10.7) | 15.9 (5.4) | 0.69b | 11.8–17.3 | |
| Prothrombin time (s) | 12.5 (0.9) | 13.2 (2.2) | 0.69b | 11.8–13.3 | |
| Prothrombin activity (%) | 80.7 (13.8) | 80.4 (19.5) | 0.95b | 68.2–90.3 | |
| Major complications | 2 (9%) | 1 (5%) | 0.61a | ||
| 90-day mortality | 3 (13%) | 0 (0%) | 0.09a |
%FLRCT, the ratio of FLR volume calculated using CT (%); FLRCT, future liver remnant volume calculated using CT (ml); (%), FLRCT / BS, FLRCT / body surface (ml/m2); %FLRSPECT, the ratio of FLR volume calculated using SPECT; ICG15, indocyanine green test; PTPE, percutaneous trans-hepatic portal embolization; PVE, portal vein embolism ; TIPE, trans-ileocecal portal embolization; ΔFLR/BS (%), 100× [ FLR/BS(after PVE) - FLR/BS (before PVE)]/ FLR/BS (before PVE); ΔFLRCT (%), 100×[ FLRCT (after PVE) - FLRCT (before PVE)]/ FLRCT (before PVE); Δ%FLRSPECT, %FLRSPECT (after PVE) - %FLRSPECT (before PVE).
χ2 test
Mann–Whitney U test
Table 3.
Clinical results and FLR values before and after portal embolization
| Pre-PVE | Post-PVE | p- value | Z value | ||
|---|---|---|---|---|---|
| Mean (SD) | Mean (SD) | ||||
| TIPE | ICG15 | 13.0 (6.6) | 11.1 (6.1) | 0.25 | −1.16 |
| Total bilirubin (mg/dL) | 1.64 (1.26) | 0.95 (0.55) | <0.01 | −3.04 | |
| Albumin (g/dL) | 3.73 (0.48) | 3.41 (0.52) | <0.01 | −2.98 | |
| Platelet (1010 l−1) | 22.9 (11.9) | 27.8 (11.5) | <0.01 | −2.78 | |
| Prothrombin time (s) | 11.9 (0.8) | 12.1 (0.9) | 0.66 | −0.44 | |
| Prothrombin activity (%) | 95.1 (18.4) | 90.1 (15.5) | 0.10 | −1.65 | |
| FLRCT (ml) | 413.6 (104.4) | 518.5 (100.9) | <0.01 | −3.05 | |
| % FLRCT (%) | 33.8 (9.1) | 45.7 (9.2) | <0.01 | −3.73 | |
| %FLRSPECT (%) | 32.8 (9.4) | 46.4 (8.5) | <0.01 | −3.73 | |
| FLRCT / body surface (ml/m2) | 267.4 (67.0) | 340.5 (74.4) | <0.01 | −3.10 | |
| PTPE | ICG15 | 13.3 (5.9) | 11.5 (6.0) | 0.35 | −0.93 |
| Total bilirubin (mg/dL) | 0.96 (0.73) | 0.73 (0.34) | 0.09 | −1.70 | |
| Albumin (g/dL) | 4.02 (0.40) | 3.65 (0.39) | <0.01 | −3.17 | |
| Platelet (1010 l−1) | 19.9 (10.1) | 22.7 (7.4) | 0.06 | −1.89 | |
| Prothrombin time (s) | 12.1 (1.2) | 12.1 (1.3) | 0.74 | −0.33 | |
| Prothrombin activity (%) | 98.3 (26.8) | 95.8 (23.2) | 0.94 | −0.08 | |
| FLRCT (ml) | 431.9 (210.4) | 600.2 (228.4) | <0.01 | −3.92 | |
| % FLRCT (%) | 31.4 (8.2) | 42.6 (8.9) | <0.01 | −3.92 | |
| %FLRSPECT (%) | 28.8 (9.5) | 47.9 (9.1) | <0.01 | −3.92 | |
| FLRCT / body surface (ml/m2) | 263.1 (110.3) | 368.7 (113.9) | <0.01 | −3.92 |
%FLRCT, the ratio of FLR volume calculated using CT (%); FLRCT , future liver remnant volume calculated using CT (ml); %FLRSPECT, the ratio of FLR volume calculated using SPECT (%); ICG15, indocyanine green test; PTPE, percutaneous transhepatic portal embolization; SD, standard deviation; TIPE, trans-ileocecal portal embolization.
The procedure time during PTPE was defined as the interval between the time when the patient entered the angiography room and the time when the patient left, and that of TIPE was defined as the interval between the initiation of general anesthesia in the operating room and the time when the patient recovered from general anesthesia. The procedure time was significantly shorter in the PTPE group (108.7 ± 24.9 min) than in the TIPE group (181.4 ± 40.6 min) (p < 0.01 [25–75 percentile:103.3–193.5 min]) (Table 4).
Table 4.
Procedure time, hospital stay and embolic material between PTPE and TIPE
| TIPE (n = 22) | PTPE (n = 20) | p- value | 25–75 percentile | |
|---|---|---|---|---|
| Procedure time (minutes) | 181.4 (40.6) | 108.7 (24.9) | <0.01a | 103.3–193.5 |
| Interval between PVE and operation (days) | 24.0 (10.8) | 38.1 (20.2) | <0.01a | 20.8–33.3 |
| Hospital stay (days) | 46.5 (40.2) | 19.4 (20.5) | 0.01a | 6.2–50.6 |
| The number and ratio of one-stop operation | 8 (36.4%) | 1 (5%) | <0.01b | |
| Embolic material | 0.89b | |||
| Absolute ethanol+coil | 18 (81.8%) | 18 (90.0%) | ||
| GS+coil | 1 (4.5%) | 1 (5.0%) | ||
| Absolute ethanol+GS | 3 (13.6%) | 0 (0%) | ||
| Absolute ethanol+GS + coil | 0 (0%) | 1 (5.0%) |
GS, gelatin sponge; PTPE, percutaneous transhepatic portal embolization; TIPE, trans-ileocecal portal embolization.
Mann–Whitney U test
χ2 test
There were no significant differences in the kinds of embolic materials used during PVE, including absolute ethanol, gelatin sponge and metallic coils (p = 0.89) (Table 4). The hospital stay during PVE was significantly longer and the interval between PVE and right hepatectomy shorter in the TIPE group than in PTPE group, as a one-step operation was performed without the patient leaving the hospital after PVE due to abdominal pain in 8 of 22 TIPE patients (36.4%). A two-step operation (PVE and right hepatectomy carried out during different admissions) was selected in the remaining 14 patients (63.6%).
After right lobectomy, portal vein stenosis occurred in 1 of the 20 PTPE patients (5%) and 2 of the 22 TIPE patients (9.1%) (Table 2: p = 0.61). Three patients died within 90 days after right lobectomy in the TIPE group due to intraperitoneal bleeding caused by bile leakage (n = 2) and liver dysfunction after liver infarction (n = 1) (Table 2).
Discussion
PVE leads to hypertrophy of the FLR in patients with a normal liver and FLRCT is currently the established method for determining whether or not a patient can safely undergo liver resection. However, the incidence of hypertrophy of the FLR is significantly reduced in patients with chronic liver disease. 17 In patients with HCC, surgical resection remains a standard curative therapy; however, clinicians are sometimes hesitant to recommend major hepatic resection, especially in patients with a marginal FLR volume. 18 Before PVE, three of nine patients with HCC underwent neoadjuvant chemotherapy in this study with Child-Pugh scores ranging from 5 to 7. The %FLRSPECT and FLRCT /BS values significantly increased after PVE. However, the increase ratios in the %FLRCT, %FLRSPECT and FLRCT/BS (6.1%, 16.2 and 27.3%, respectively) in HCC patients were smaller than in patients with other liver malignancies with normal liver parenchyma (11.6–15.2%, 16.4–19.8% and 42.6–45.7%, respectively) (Table 1), as a result of liver cirrhosis or chronic liver diseases. 17 However, the %FLRCT values in patients with HCC and other malignancies (43.9 and 44.2%) were larger than those previous reported (35 and 31%) after PVE in Table 5. 17 An additional use of coil embolization after administration of absolute ethanol led to large FLR values in this study. High FLR values were achieved after PVE in HCC patients, but its increased ratio of %FLRCT was smaller than those in other malignancies (p = 0.04, Table 1), because the morphologic atrophy of the right lobe with hypertrophy of the left lobe is usually noted in the compensated stage of liver cirrhosis. 22
Table 5.
Future liver remnant based on approach site and the presence of liver cirrhosis (LC)
| %FLRCT (%) | Number | Reference | ||
|---|---|---|---|---|
| Laparotomy (general anesthesia) |
TIPE | 37.4 | 14 | 10 |
| 45.7 | 22 | * | ||
| PVL | 38.5 | 123 | 19 | |
| 31.2 | 12 | 20 | ||
| Percutaneous (local anesthesia) |
PTPE | 48.3 | 19 | 21 |
| 43.2 | 1953 | 19 | ||
| 32.4 | 51 | 20 | ||
| 42.6 | 20 | * | ||
| Based on the presence of LC | LC | 35 | 13 | 17 |
| 43.9 | 9 | * | ||
| non-LC | 31 | 14 | 17 | |
| 44.2 | 32 | * |
*, the result in this study; %FLRCT, the ratio of FLR volume calculated using CT after portal vein embolization or ligation (%); LC, liver cirrhosis; PTPE, percutaneous transhepatic portal embolization; PVL, portal vein ligation; TIPE, trans-ileocecal portal embolization.
In this study, 5 of 47 patients (10.6%) were excluded due to disease progression after PVE. To prevent patient dropout during the waiting period for FLR regeneration, dual embolization of pre-operative PVE and transarterial chemoembolization may facilitate tumor control. 23 PVE remains the gold-standard strategy for increasing the FLR. However, up to 30% of patients with liver malignancies still cannot undergo surgery after PVE due to tumor progression and/or insufficient FLR regeneration during the waiting period. 23 Indeed, 11 of 12 patients in the present study with metastatic liver tumors (PTPE, n = 8; TIPE, n = 4) underwent neoadjuvant chemotherapy, and their %FLRSPECT and FLRCT/BS values increased from 30.1% and 253.0 ml/m2 to 49.3% and 358.6 ml/m2, with the largest increase ratio of 19.8 and 45.7%, respectively, after PVE (Table 1). In patients with biliary tumors of the bile duct, gallbladder cancer, or hilar cholangiocarcinoma, pre-operative biliary drainage was carried out as the pre-operative management to prevent cholestasis-associated toxic effects and improve liver regeneration before PVE and major hepatectomy. The patients with biliary tumors had low %FLRSPECT and FLRCT/BS values (before PVE: 29.4% and245.5 ml/m2; after: 44.8% and 335.0 ml/m2, respectively) before and after PVE. However, the increase ratios of %FLRSPECT and FLRCT/BS were larger than those of patients with patients with HCC (16.4 and 42.6%, respectively) (Table 1). The selection of patients with biliary tumors for PVE is a challenge, since the obstructive cholestasis and accompanying biliary drainage and cholangitis are associated with a loss of liver regeneration. 24 The growth ratio of FLR exceeds 50% in patients with HCC and liver metastasis (52 and 58%, respectively) compared to those with biliary tumors (37%). 25 However, FLR using HBS and CT volumetry showed that the smallest growth ratio was in patients with HCC in this study (Table 1), as PVE provokes tumor progression, and liver cirrhosis decreases the FLR regeneration capacity, thereby doubling the risk for patient dropout.
Three patients died within 90 days after right lobectomy in the TIPE group due to intraperitoneal bleeding (n = 2) and liver dysfunction after liver infarction (n = 1) (Table 2). One patient with a low %FLRSPECT value of 25% (<30%) and marginal %FLRCT value of 33.5% died 18 days after right hepatectomy due to liver insufficiency. The most frequently used remnant volume cut-off value is 40%, 26 but literature is equivocal and liver volume alone has insufficient predictive value for accurate patient selection for PVE. 24,26,27 The assessment of the liver function with HBS had a better predictive value for post-hepatectomy liver failure than that for liver volume in patients with perihilar cholangiocarcinoma. 27 When the FLR is <30%, the rates of hepatic insufficiency and fatal situation from liver failure are significantly higher among even patients with pre-operative cholangitis. 28
The choice of approach site (ipsilateral or contralateral) can depend on the type of surgery planned after PTPE. In our institution, the ipsilateral approach was chosen to reduce residual liver damage. There were no significant differences in the embolic materials that were used (Table 4); however, the ipsilateral technique in PTPE requires the operator be experienced. Cannulation into the right portal vein branches is technically difficult in the ipsilateral approach due to retrograde manner because of the acute angles between the anterior or posterior branches via the punctured tract, and the risk of migration of embolic material or catheter removal during embolization. 29 PTPE is not appropriate in cases with multiple or large hepatic tumors considering the risk of puncturing tumors that result in cancer cell seeding during portal access. TIPE can be applied under laparotomy and enables the examination of extrahepatic diseases during direct cannulation into the ileocolic vein. However, TIPE should be chosen when a PTPE approach is not considered feasible or when additional treatment is needed during surgical exploration. 30 In this study, the ratio of biliary tumor in the TIPE group (59.1%) was larger than that in the PTPE group (40.0%) (Table 1). This study showed no significant difference in the FLR between the PTPE and TIPE groups based on the different approach sites; however, PTPE was associated with a shorter procedure than TIPE (Table 4) and could be performed under local anesthesia. Table 5 summarizes the FLR ratio after PVE or portal vein ligation (PVL). There is no significant difference in FLR hypertrophy between PTPE and portal vein ligation or TIPE. 10,19–21 However, PVE is recommended as preferred strategy because of its minimal invasive nature. 19 Selection of each approach may principally be based on each operator’s preference, but must be decided according to each patient’s condition.
A significantly longer hospital stay was needed after TIPE (46.5 ± 40.1 days) than after PTPE (19.4 ± 29.5 days) (p = 0.01). In the TIPE group, 8 patients (36.4%) had a one-step operation, with PVE and hepatectomy performed during the same hospital stay, because of persistent abdominal discomfort or pain after PVE under laparotomy. In most PTPE patients (95%), a two-step operation was performed with a shorter total hospital stay.
Except for one case in each group, an absolute ethanol and metallic coils were used as embolic materials for PVE (Table 4). Absolute ethanol is a reliable embolic material with a strong coagulative effect and low risk of recanalization after PVE. Absolute ethanol also has the advantage of being readily available, cheap, and easily administered due to its low viscosity. 31 Coil embolization was added after coagulation with an absolute ethanol to completely cut-off the target portal flow. However, attention should be paid to coil migration, which can lead to the unexpected occlusion of non-target vessels. 32
The incidence of complications after PVE is reported to be 12.8%, and these complications include transient liver failure, thrombosis or migration of embolic material, hemoperitoneum, subcapsular hematoma, hemobilia, abscess formation, cholangitis and sepsis, arterioportal shunt, arterioportal fistula, and pneumothorax, among others. 30,33 Hepatic arterial injury during PVE is a life-threatening complication that occurs in 2.6–8.5% of cases, and hepatic arterial embolization was added to stop intraperitoneal bleeding during PTPE. 34–37 A case of hepatic arterial injury occurred during PTPE due to repeated liver puncture, and the damaged hepatic artery was embolized with a metallic coil. The puncture site was converted to a transileocecal vein approach on a continuing basis (Figure 4). The rates of PVE-related morbidity (2.3%) and mortality (0%) in this study were similar to those in a previous report (2.2 and 0%, respectively). 37
Figure 4.
A 66-year-old female with hilar bile duct cancer. The hepatic A6 branch was injured during the ipsilateral percutaneous transhepatic portal approach and urgent embolization was carried out.
The rate of operative mortality, which was defined as death occurring during the same hospital admission or within 90 days, was 3.9%. 38 In our study population, the rates of 30- and 90 day mortality were 4.7% [2/42; mean, 21.5 days (18–25 days)] and 7.1% [3/42; mean, 35.7 days (18–64 days)], respectively. Two patients with bile duct cancer died within 30 days after major right hepatectomy, and one patient with gall bladder cancer died 64 days after right hepatectomy following TIPE. However, combined therapy of pancreaticoduodenectomy and hepatectomy was applied to these patients with biliary tumors, which might have affected the mortality.
The present study was associated with several limitations. First, this study was performed in a single center. Second, the period between TIPE and PTPE was different, and TIPE was carried out slightly earlier than PTPE. TIPE requires surgical guidance and this invasiveness might have been associated with the increase rates of complications or mortality after major hepatectomy in this study, as the TIPE group included more patients with bile duct cancer than the PTPE group, and these patients underwent pancreaticoduodenectomy in addition to major hepatectomy. Finally, the definition of procedure time was different between PTPE and TIPE, because PTPE was carried out under local anesthesia, and TIPE was under general anesthesia. If the procedure time was defined as the interval between needle puncture and pull-out of introducer, it might be very short in TIPE, because target portal branches could be easily selected and embolized in antegrade manner. However, ipsilateral PTPE will require a longer procedure time due to retrograde manner.
Conclusion
Pre-operative PVE is an effective method of increasing the FLR, regardless of approach site. However, TIPE was associated with a longer procedure time and an increased hospitalization period compared to PTPE.
Footnotes
Acknowledgments: We gratefully acknowledge the work of previous members of Radiology and Surgery in Yamaguchi University Hospital and present members of the National Hospital Organization, Kanmon Medical Center.
Funding: The authors state that this work has not received any funding.
Ethical Statement: This study was approved by the Institutional Review Board of our institution.
Author contribution: M.O contributed to the study concepts and design, a literature research and manuscript preparation. K.M. and S.N contributed to data acquisition and data analysis and interpretation. M.O, K. I. and M.T. contributed to the interventional procedure of portal embolization. Y.T, E.H., K.S. and H N contributed to surgical operation and patient’s care. K.I. and H.N. contributed to manuscript editing.
Disclosures of Conflicts of Interest: The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.
Informed Consent: Written informed consent was waived by the Institutional Review Board.
Contributor Information
Munemasa Okada, Email: okada.munemasa.wn@mail.hosp.go.jp, Department of Radiology, National Hospital Organization, Kanmon Medical Center, Shimonoseki, Japan .
Kenichiro Ihara, Email: k_ihara@yamaguchi-u.ac.jp, Department of Radiology, Yamaguchi University Graduate School of Medicine, Ube, Japan .
Keisuke Miyoshi, Email: kei1999x1234@gmail.com, Department of Radiology, Yamaguchi University Graduate School of Medicine, Ube, Japan .
Sei Nakao, Email: snakao-ygc@umin.ac.jp, Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan .
Masahiro Tanabe, Email: masa-ygc@umin.ac.jp, Department of Radiology, Yamaguchi University Graduate School of Medicine, Ube, Japan .
Yukio Tokumitsu, Email: yt790604@yamaguchi-u.ac.jp, Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan .
Eijiro Harada, Email: eharada@yamaguchi-u.ac.jp, Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan .
Kazuhiko Sakamoto, Email: sakamoto.kazuhiko.ky@mail.hosp.go.jp, Department of Surgery, National Hospital Organization, Kanmon Medical Center, Shimonoseki, Japan .
Hiroaki Nagano, Email: hnagano@yamaguchi-u.ac.jp, Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
Katsuyoshi Ito, Email: itokatsu@yamaguchi-u.ac.jp, Department of Radiology, Yamaguchi University Graduate School of Medicine, Ube, Japan
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