Risk Factors of Complications from Central Bisectionectomy (H458) for Hepatocellular Carcinoma: A Multi-Institutional Single-Arm Analysis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients, Research Collaborators, and Ethics
2.2. Study Design and Parameters
2.3. Statistical Analysis
3. Results
3.1. Study Population and Selected Patient Characteristics
3.2. Relationship between Variables and Postoperative Morbidities and Mortality
3.3. Postoperative Patient Outcomes for Three Years
4. Discussion
Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variables (n = 142) | n, (%), Median Value [Minimum–Maximum] |
---|---|
Age (years) | 73 [36–87] * |
Sex (Male/Female) | 118 (83)/24 (17) |
ASA-PS (n = 137) | |
1/2/3 | 30 (22)/93 (68)/14 (10) |
Background liver status | |
Chronic liver injury, non/chronic hepatitis/cirrhosis | 39/103 (73) |
non-BC (NAFLD 22, PBC 1, other 7) | 72 (51) |
B | 21 (15) |
C | 49 (34) # |
Portal hypertension, yes | 4 (3) |
Ascites, yes | 2 (1) (controllable, mild) |
Splenomegaly, no/mild/moderate or more | 122 (85)/19 (14)/1 (1) |
Preoperative liver functions | |
Child–Pugh classification | A 138/B 4 (3) |
Liver damage grade | A 121/B 14 (10) |
ICGR15 (%) | 11.2 [1.3–25] |
Total bilirubin (mg/dL) | 0.7 [0.3–2.6] |
Albumin (g/dL) | 4.1 [2.3–4.9] |
Prothrombin activity (%) | 95 [44–139] |
Platelet counts (× 104/mm3) | 18.2 [9.8–77] |
C-reactive protein (mg/dL) | 0.19 [0.02–10.1] |
Alfa-feto protein (ng/mL) | 13.3 [1.1–383,541] |
PIVKA-II (mAU/mL) | 323 [9–269,391] |
Tumor location diagnosed before operation | |
Main location, S8/S4/S5 | 25 (18)/107 (75)/10 (7) |
S1 involved, yes | 9 (6) |
Number of HCC | 1.2 [range 1–6] * |
1/2/3/4/5/6 | 103 (73)/24 (17)/8 (6)/2 (1)/2 (1)/3 (2) |
Size | 6.0 [range 4–14] * |
0–4.9/5–9.9/over 10 cm | 1 (1)/10 (6)/160 (93) |
Macrovascular involvement no/yes § | 130 (92)/12 (8) |
Portal vein no/yes | 136 (96)/6 (4) |
Hepatic venous no/yes | 134 (94)/8 (6) |
Distance to major vessels | |
Hilar Glisson, >10/10- >0/0 mm | 106 (75)/24 (17)/11 (8); Stenosis, 7 |
MHV, >10/10- >0/0 mm | 96 (68)/13 (9)/32 (23) |
RHV, >10/10- >0/0 mm | 115 (82)/12 (8)/14 (10) |
IVC >10/10- >0/0 mm | 131 (93)/7 (5)/3 (2) |
Right diaphragm involvement, yes | 26 (19) |
Qiu’s classification system of centrally located HCC ¶ | |
Type I/II/III/IV | 7 (5)/49 (35)/75 (53)/5 (3)/6 (4) |
Preoperative cancer treatment | |
TAE/chemotherapy/brachytherapy | 15 (11)/1 (1)/2 (2) |
Surgical records | |
Additional resection except H4581, yes | 8 (6) |
S1 combined resection, yes | 8 (6) |
Estimated resection volume (cm3) | 380 [28–1243] |
Expose hilar plate Glisson sheath, yes | 93 (66) |
root of MHV/entire RHV/front of IVC | 125 (87)/100 (71)/51 (36) |
Hepatic inflow occlusion (Pringle), no/yes | 13/129 (91) |
Time (min) | 115 [15–322] |
Taping of main HV root, yes | 18 (13) |
CVP before transection (mmHg) (n = 88) | 6.0 [1–11] |
Operating time (min) | 475 [282–1807] |
Intraoperative blood loss factors (iBL) | |
Intraoperative blood loss (mL) | 852 [42–23,336] |
Red cell transfusion, no/yes | 88/54 (38) |
Injury of preserved main vessels, yes | 15 (11) |
Histology | |
Diagnosis (HCC, combined type HCC) | 136/6 (4) |
Occupied location | |
Main location, S8/S4/S5 | 25 (18)/107 (75)/10 (7) |
S1 involved, yes | 9 (6) |
Histological tumor findings | |
F (fibrotic grade) ‡ 0/1/2/3/4 (n = 98) | 15 (11)/50 (37)/28 (21)/25 (18)/18 (13) |
Normal liver/chronic hepatitis/cirrhosis | 1 (11)5/109 (76)/18 (13) |
A (necro-inflammatory grade) ‡ 0/1/2/3 | 15 (15)/56 (57)/24 (25)/3 (3) |
Surgical margin (mm) | 4.0 [0–26] |
0/0.1–5/>5 mm | 29/58/55 |
Postoperative outcomes | |
Complications | |
Liver failure (PHLF), no/A/B/C ** | 85 (60)/39/12/6 |
Bile leakage (PHBL), no/A/B/C ** | 87 (61)/28/26/1 |
Prolonged ascites >7 days, yes | 18 (13) |
Post-hepatectomy hemorrhage (PHH) | |
Radiological or surgical intervention, yes | nil |
Organ space SSI, yes | 21 (15) |
Others | 32 |
Mortality, yes | 4 (3) |
Within 30 days, yes | 1 (0.5) |
Hospital stay (days) | 26 [8–176] |
Prognosis within 3 years | |
1st cancer recurrence, yes | 71 (51); liver 60, extra-liver 10, lung 1 |
Relapse-free survival period (days) | 1362 ± 139 (mean ± standard deviation) |
rate (1-, 2-, 3-year) | 70%, 56%, 48% |
Prognosis | |
Cancer-free survival | 109 |
Dead, in-hospital/HCC/other disease | 4/25/4 |
Overall survival period (days) | 4838 ± 216 (mean ± standard deviation) |
rate (1-, 2-, 3-year) | 90%, 86%, 81% |
Variables | PHLF | PHBL | Total Morbidity # | |||||||
---|---|---|---|---|---|---|---|---|---|---|
None | A | B | C | None | A | B | C | No | Yes | |
Demographics | ||||||||||
ASA-PS | ||||||||||
1 | 0 | 5 | 0 | 1 | 5 | 0 | 1 | 0 | 6 | 5 |
2 | 3 | 16 | 3 | 2 | 5 | 15 | 4 | 0 | 15 | 9 |
3 | 68 | 16 | 8 | 1 | 65 | 12 | 15 | 1 | 56 | 37 |
4 | 9 | 2 | 1 | 2 ** | 8 | 1 | 5 | 0 ** | 5 | 9 |
Liver functions | ||||||||||
Liver damage grade | ||||||||||
A | 78 | 30 | 9 | 4 | 73 | 25 | 22 | 1 | 74 | 8 |
B | 6 | 4 | 3 | 1 | 8 | 3 | 3 | 0 | 8 | 6 |
ICGR15 (%) | 12.2 (6.6) | 12.6 (6.6) | 24.5 (16.9) | 9.7 (3.8) | 13.6 (8.3) | 14.9 (10.6) | 11.1 (6.8) | 4.1 | 14.0 (8.2) | 12.5 (9.2) |
Bilirubin (mg/dL) | 0.80 (0.3) | 0.83 (0.4) | 0.84 (0.4) | 0.77 (0.3) | 0.80 (0.3) | 0.81 (0.3) | 0.85 (0.5) | 0.6 | 0.79 (0.3) | 0.83 (0.4) |
Albumin (g/dL) | 4.0 (0.4) | 4.2 (0.4) | 3.9 (0.5) | 3.8 (0.9) | 4.0 (0.4) | 4.3 (0.3) | 3.9 (0.6) * | 3.7 | 4.1 (0.4) | 3.9 (0.5) ** |
PT (%) | 95 (17) | 94 (11) | 87 (13) | 90 (10) | 94 (15) | 93 (10) | 94 (19) | 88 | 94 (15) | 94 (15) |
Platelet (/mm3) | 19.6 (7.2) | 20.4 (7.5) | 24.3 (17.3) | 20.9 (7.3) | 20.1 (9.6) | 20.9 (6.7) | 19.8 (6.7) | 29.2 | 20.7 (9.9) | 19.7 (6.2) |
CRP (mg/dL) | 0.57 (1.5) | 0.39 (0.4) | 0.27 (0.3) | 2.23 (2.8) * | 0.57 (1.5) | 0.35 (0.4) | 0.8 (1.5) | 0.55 | 0.50 (1.4) | 0.65 (1.3) |
Imaging of tumor | ||||||||||
Location (main) | ||||||||||
S8 | 13 | 11 | 1 | 0 | 15 | 10 | 0 | 0 | 20 | 5 |
S4 | 64 | 27 | 11 | 5 | 65 | 17 | 24 | 1 | 56 | 51 * |
S5 | 8 | 1 | 0 | 1 | 7 | 1 | 2 | 0 | 6 | 4 |
S1 involvement (H4581), yes | 5 | 1 | 2 | 2 * | 8 | 1 | 1 | 0 | 3 | 7 |
Number of tumors | ||||||||||
1 | 61 | 30 | 9 | 3 | 62 | 22 | 18 | 1 | 57 | 46 |
2 | 15 | 5 | 1 | 3 | 14 | 5 | 5 | 0 | 16 | 8 |
3≤ | 9 | 4 | 2 | 0 | 11 | 1 | 3 | 0 | 9 | 6 |
Tumor size (mm) | ||||||||||
0–5 | 37 | 6 | 4 | 1 | 37 | 5 | 5 | 1 | 29 | 19 |
5–10 | 38 | 24 | 3 | 2 | 37 | 15 | 15 | 0 | 39 | 28 |
10< | 10 | 9 | 5 | 3 ** | 13 | 8 | 6 | 0 | 14 | 13 |
Vascular invasion | ||||||||||
0 | 73 | 23 | 11 | 3 | 76 | 15 | 19 | 0 | 61 | 49 |
1 | 4 | 14 | 1 | 1 | 5 | 11 | 3 | 1 | 13 | 7 |
2 and 3 | 7 | 1 | 0 | 2 ** | 6 | 1 | 3 | 0 ** | 8 | 4 |
Portal vein | ||||||||||
0 | 78 | 27 | 12 | 3 | 80 | 19 | 21 | 0 | 68 | 52 |
1 | 5 | 10 | 0 | 1 | 6 | 7 | 2 | 1 | 11 | 5 |
2 and 3 | 2 | 2 | 0 | 2 ** | 1 | 2 | 3 | 0 ** | 3 | 3 |
Hepatic vein | ||||||||||
0 | 76 | 31 | 11 | 5 | 80 | 22 | 20 | 1 | 70 | 53 |
1 | 2 | 8 | 1 | 0 | 2 | 6 | 3 | 0 | 7 | 4 |
2 and 3 | 7 | 0 | 0 | 1 | 5 | 0 | 3 | 0 | 5 | 3 |
Glisson pedicle stenosis | ||||||||||
no | 81 | 37 | 11 | 5 | 84 | 27 | 23 | 0 | 79 | 55 |
yes | 4 | 2 | 1 | 1 | 3 | 1 | 3 | 1 ** | 3 | 5 |
Compression of LMHV root | ||||||||||
no | 83 | 32 | 8 | 6 | 81 | 24 | 23 | 1 | 74 | 55 |
yes | 2 | 7 | 4 | 0 ** | 6 | 4 | 3 | 0 | 8 | 5 |
RHV root | ||||||||||
no | 80 | 36 | 10 | 3 | 77 | 27 | 24 | 1 | 76 | 53 |
yes | 5 | 3 | 2 | 3 ** | 10 | 1 | 2 | 0 | 6 | 7 |
IVC | ||||||||||
no | 84 | 38 | 10 | 5 | 84 | 26 | 26 | 1 | 79 | 58 |
yes | 1 | 1 | 2 | 1* | 3 | 2 | 0 | 0 | 3 | 2 |
Diaphragm | ||||||||||
no | 75 | 29 | 9 | 3 | 74 | 21 | 20 | 1 | 68 | 48 |
yes | 10 | 10 | 3 | 3* | 13 | 7 | 6 | 0 | 14 | 12 |
Qiu’s CLLTs type | ||||||||||
I | 4 | 2 | 1 | 0 | 3 | 1 | 2 | 1* | 4 | 3 |
II | 25 | 18 | 4 | 2 | 29 | 12 | 8 | 0 | 30 | 19 |
III | 55 | 17 | 5 | 2 | 52 | 13 | 14 | 0 | 47 | 32 |
IV | 1 | 2 | 2 | 2* | 3 | 2 | 2 | 0 | 1 | 6 |
Treatment related factors | ||||||||||
Resected volume (cm3) | 355 (253) | 505 (223) | 563 (395) | 723 (485) | 62.9 (32.3) | 70.9 (36.3) | 73.9 (28.3) | 709 | 419 (293) | 420 (275) |
Segment 1 partial resection | ||||||||||
no | 81 | 37 | 11 | 5 | 83 | 27 | 23 | 1 | 79 | 55 |
yes | 4 | 2 | 1 | 1 | 4 | 1 | 3 | 0 | 3 | 5 |
Occlusion time (min) | 110 (57) | 87 (66) | 124 (91) | 116 (84) | 374 (289) | 546 (275) | 440 (239) | 99 (62) | 114 (67) | |
Operating time (min) | ||||||||||
<480 | 45 | 22 | 5 | 2 | 49 | 14 | 11 | 0 | 42 | 32 |
≥480 | 40 | 17 | 7 | 4 | 38 | 14 | 15 | 1 | 40 | 28 |
Blood loss (mL) | ||||||||||
<1500 | 68 | 25 | 5 | 1 | 66 | 18 | 15 | 0 | 61 | 38 |
≥1500 | 17 | 14 | 7 | 5 ** | 21 | 10 | 11 | 1 | 21 | 22 |
Histological factors | ||||||||||
Fibrotic grade | ||||||||||
0 | 7 | 8 | 0 | 0 | 6 | 5 | 4 | 0 | 8 | 7 |
1 | 31 | 12 | 6 | 1 | 33 | 11 | 5 | 1 | 31 | 19 |
2 | 18 | 5 | 3 | 2 | 17 | 2 | 9 | 0 | 16 | 12 |
≥3 | 25 | 12 | 3 | 3 | 28 | 8 | 7 | 0 | 22 | 21 |
Necroinflammatory grade (n = 98) | ||||||||||
0 | 9 | 6 | 0 | 0 | 9 | 3 | 3 | 0 | 8 | 7 |
1 | 32 | 15 | 5 | 4 | 35 | 12 | 9 | 0 | 36 | 20 |
≥2 | 16 | 5 | 4 | 2 | 19 | 4 | 4 | 0 | 14 | 13 |
Background liver status | ||||||||||
normal | 7 | 8 | 0 | 0 | 6 | 5 | 4 | 0 | 8 | 7 |
chronic hepatitis | 64 | 28 | 11 | 6 | 67 | 21 | 20 | 1 | 64 | 45 |
cirrhosis | 14 | 3 | 1 | 0 | 14 | 2 | 2 | 0 | 10 | 8 |
Postoperative outcomes | ||||||||||
Hospital stay (days) | 30 (24) | 35 (29) | 39 (22) | 66 (56) † | 27 (14) | 27 (30) | 64 (37) ‡ | 74 | 23 (10) | 49 (36) ** |
Complications | ||||||||||
Organ SSI | ||||||||||
no | 76 | 31 | 11 | 3 | 85 | 27 | 9 | 0 | - | - |
yes | 9 | 8 | 1 | 3 * | 2 | 1 | 17 | 1 ** | ||
Prolonged ascites | ||||||||||
no | 79 | 35 | 7 | 3 | 78 | 25 | 21 | 0 | - | - |
yes | 6 | 4 | 5 | 3 ** | 9 | 3 | 5 | 1 ** | ||
Mortality | ||||||||||
no | 85 | 39 | 12 | 2 | 86 | 28 | 23 | 1 | - | - |
yes | 0 | 0 | 0 | 4 ** | 1 | 0 | 3 | 0 |
Variables | Significance | RR | 95% Confidence Interval | |
---|---|---|---|---|
(p Value) | Lower Limit | Upper Limit | ||
PHLF | ||||
CRP ≥ 0.2 mg/dL | 0.379 | 1.43 | 0.644 | 3.171 |
Tumor size ≥ 10 cm | 0.556 | 1.473 | 0.405 | 5.356 |
Segment 1 resection, yes | 0.254 | 2.347 | 0.541 | 10.18 |
Vascular involvement of tumor, yes | 0.475 | 0.629 | 0.177 | 2.242 |
Compression of middle & left HV confluence, yes | 0.05 | 6.818 | 0.995 | 46.93 |
Compression of RHV, yes | 0.928 | 1.073 | 0.236 | 4.886 |
Compression of IVC, yes | 0.472 | 0.338 | 0.018 | 6.502 |
iBL ≥ 1500 mL | 0.025 | 2.791 | 1.14 | 6.826 |
PHBL | ||||
Albumin < 4 g/dL | 0.009 | 2.994 | 1.31 | 6.849 |
Tumor size ≥ 10 cm | 0.255 | 1.809 | 0.651 | 5.028 |
Glissonean pedicle stenosis, yes | 0.128 | 6.976 | 0.572 | 85.05 |
Segment 1 resection, yes | 0.092 | 2.662 | 0.852 | 8.319 |
Inflow hepatic occlusion ≥ 120 min | 0.914 | 1.045 | 0.472 | 2.314 |
iBL ≥ 1500 mL | 0.099 | 2.072 | 0.871 | 4.93 |
Total severe morbidities # | ||||
Step 1 | ||||
Total bilirubin ≥ 0.8 mg/dL | 0.776 | 1.208 | 0.329 | 4.432 |
Albumin < 4 g/dL | 0.291 | 0.498 | 0.136 | 1.816 |
CRP ≥ 0.2 mg/dL | 0.159 | 2.795 | 0.669 | 11.674 |
Segment 1 resection, yes | 0.057 | 10.2 | 0.933 | 111.43 |
Tumor size ≥ 6 cm | 0.071 | 3.562 | 0.897 | 14.14 |
Vascular involvement of tumor, yes | 0.799 | 1.345 | 0.138 | 13.15 |
Glissonean pedicle stenosis, yes | 0.205 | 7.149 | 0.341 | 150.04 |
Compression of middle & left HV confluence, yes | 0.02 | 33.59 | 1.76 | 642.92 |
Compression of RHV root, yes | 0.255 | 3.602 | 0.397 | 32.7 |
Compression of IVC, yes | 0.037 | 0.008 | 0 | 0.755 |
Inflow hepatic occlusion ≥ 120 min | 0.972 | 1.023 | 0.292 | 3.589 |
Operation time ≥ 480 min | 0.164 | 0.367 | 0.089 | 1.506 |
iBL ≥ 750 mL | 0.132 | 2.968 | 0.72 | 12.23 |
Red cell blood transfusion, yes | 0.847 | 0.853 | 0.169 | 4.299 |
Step 6 * | ||||
Segment 1 resection, yes | 0.037 | 5.67 | 1.11 | 29.056 |
Tumor size ≥ 6 cm | 0.013 | 3.749 | 1.33 | 10.589 |
Glissonean pedicle stenosis, yes | 0.053 | 6.505 | 0.976 | 43.331 |
Compression of middle & left HV confluence, yes | 0.032 | 8.948 | 1.21 | 66.002 |
Compression of IVC, yes | 0.049 | 19.61 | 1.01 | 333.33 |
iBL ≥ 1500 mL | ||||
---|---|---|---|---|
Significance | RR | 95% Confidence Interval | ||
Variables | (p Value) | Lower Limit | Upper Limit | |
Step (1) | ||||
Albumin <4 g/dL | 0.18 | 5.139 | 1.328 | 19.895 |
PT < 90% | 0.559 | 0.691 | 0.2 | 2.392 |
CRP ≥ 0.2 mg/dL | 0.028 | 4.901 | 1.188 | 20.213 |
Estimated liver volume ≥ 500 cm3 * | 0.065 | 4.745 | 0.907 | 24.824 |
Tumor size ≥ 6.2 cm | 0.043 | 6.25 | 1.058 | 37.037 |
≥10 cm | 0.04 | 10.47 | 1.114 | 98.36 |
Compression of RHV root, yes | 0.942 | 1.137 | 0.036 | 36.258 |
Diaphragm compression by HCC, yes | 0.054 | 0.105 | 0.011 | 1.042 |
Operating time > 480 min, yes | 0.169 | 3.414 | 0.594 | 19.618 |
Resection of segment 1, yes | 0.051 | 9.598 | 0.988 | 93.254 |
Step (11) ** | ||||
Albumin < 4 g/dL | 0.017 | 3.795 | 1.267 | 11.374 |
CRP ≥ 0.2 mg/dL | 0.03 | 3.74 | 1.137 | 12.304 |
Tumor size ≥ 6.2 cm | 0.025 | 6.25 | 1.309 | 29.412 |
≥10 cm | 0.002 | 7.178 | 2.358 | 37.346 |
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Nanashima, A.; Eguchi, S.; Hisaka, T.; Kawasaki, Y.; Yamashita, Y.-i.; Ide, T.; Kuroki, T.; Yoshizumi, T.; Kitahara, K.; Endo, Y.; et al. Risk Factors of Complications from Central Bisectionectomy (H458) for Hepatocellular Carcinoma: A Multi-Institutional Single-Arm Analysis. Cancers 2023, 15, 1740. https://doi.org/10.3390/cancers15061740
Nanashima A, Eguchi S, Hisaka T, Kawasaki Y, Yamashita Y-i, Ide T, Kuroki T, Yoshizumi T, Kitahara K, Endo Y, et al. Risk Factors of Complications from Central Bisectionectomy (H458) for Hepatocellular Carcinoma: A Multi-Institutional Single-Arm Analysis. Cancers. 2023; 15(6):1740. https://doi.org/10.3390/cancers15061740
Chicago/Turabian StyleNanashima, Atsushi, Susumu Eguchi, Toru Hisaka, Yota Kawasaki, Yo-ichi Yamashita, Takao Ide, Tamotsu Kuroki, Tomoharu Yoshizumi, Kenji Kitahara, Yuichi Endo, and et al. 2023. "Risk Factors of Complications from Central Bisectionectomy (H458) for Hepatocellular Carcinoma: A Multi-Institutional Single-Arm Analysis" Cancers 15, no. 6: 1740. https://doi.org/10.3390/cancers15061740
APA StyleNanashima, A., Eguchi, S., Hisaka, T., Kawasaki, Y., Yamashita, Y. -i., Ide, T., Kuroki, T., Yoshizumi, T., Kitahara, K., Endo, Y., Utsunomiya, T., Kajiwara, M., Sakoda, M., Okamoto, K., Nagano, H., Takami, Y., & Beppu, T. (2023). Risk Factors of Complications from Central Bisectionectomy (H458) for Hepatocellular Carcinoma: A Multi-Institutional Single-Arm Analysis. Cancers, 15(6), 1740. https://doi.org/10.3390/cancers15061740