Not all reoperative laparoscopic liver resection procedures are feasible for hepatolithiasis patients with a history of biliary surgery

Abstract

BACKGROUND

Laparoscopic hepatectomy (LH) has been applied in the treatment of hepatolithiasisa in patients with a history of biliary surgery and has already achieved good clinical outcomes. However, reoperative LH (rLH) includes multiple procedures, and the no studies have examined the clinical value of individual laparoscopic procedures.

AIM

To evaluate the safety and feasibility of each rLH procedure for hepatolithiasisa in patients with a history of biliary surgery.

METHODS

Patients with previous biliary surgery who underwent reoperative hepatectomy for hepatolithiasis were studied. Liver resection procedures were divided into three categories: (1) Laparoscopic/open left lateral sectionectomy [reoperative laparoscopic left lateral sectionectomy (rLLLS)/reoperative open left lateral sectionectomy (rOLLS)]; (2) Laparoscopic/open left hemihepatectomy [reoperative laparoscopic left hemihepatectomy (rLLH)/reoperative open left hemihepatectomy (rOLH)]; and (3) Laparoscopic/open complex hepatectomy [reoperative laparoscopic complex hepatectomy (rLCH)/reoperative open complex hepatectomy (rOCH)]. The clinical outcomes were compared between the rLLLS, rLLH, and rLCH groups, and subgroup analyses were performed for the rLLLS/rOLLS, rLLH/rOLH, and rLCH/rOCH subgroups.

RESULTS

A total of 185 patients were studied, including 101 rLH patients (40 rLLLS, 50 rLLH, and 11 rLCH) and 84 reoperative open hepatectomy (40 rOLLS, 33 rOLH, and 11 rOCH). Among the three types of rLH procedure, rLLLS required the shortest operation time (240.0 minutes vs 325.0 minutes vs 350.0 minutes, P = 0.001) and the lowest blood transfusion rate (10.0% vs 22.0% vs 54.5%, P = 0.005), followed by rLLH. The rLCH had the highest conversion rate (P < 0.05) and postoperative intensive care unit stay rate (P = 0.001). Most clinical outcomes in rLLLS and rLLH were superior or similar to those in the corresponding open surgery, while there were no differences in all outcomes between the rLCH and rOCH subgroups.

CONCLUSION

The rLH is safe for hepatolithiasis patients with a history of biliary surgery. The rLLLS and rLLH can be recommended for these patients, whereas rLCH should be applied with caution.

Key Words: Hepatolithiasis; Laparoscopic hepatectomy; Previous biliary surgery; Reoperation; Conversion

Core Tip: This study aimed to evaluate the safety and feasibility of three types of reoperative laparoscopic hepatectomy procedures in patientsfor with hepatolithiasis and a history of biliary surgery. Among the three procedures, reoperative laparoscopic left lateral sectionectomy (rLLLS) had the most favorable clinical outcomes, followed by reoperative laparoscopic left hemihepatectomy (rLLH). However, reoperative laparoscopic complex hepatectomy (rLCH) had the lowest clinical value. The majority of clinical outcomes in rLLLS and rLLH patients were either superior or equivalent to those in the corresponding open procedures, while rLCH did not offer any advantages over the corresponding open surgery. Therefore, rLLLS and rLLH are recommended for these patients, while rLCH should be used with caution.

INTRODUCTION

Hepatolithiasis is common in Southeast Asia but rare in Western countries[1]. Patients with hepatolithiasis often have a history of biliary surgery. A survey from Japan showed that the proportion of patients who underwent previous biliary surgery is as high as 61%[2]. When the patients develop liver parenchymal lesions such as liver fibrosis, liver atrophy, liver abscesses, and even cholangiocarcinoma, hepatectomy is still the most effective treatment method in addition to liver transplantation, as it can simultaneously remove intrahepatic stones and concomitant liver lesions. Open hepatectomy (OH) can be performed in nearly all patients with a success rate of almost 100%[3].

With the development of minimally invasive techniques and devices, laparoscopic hepatectomy (LH) has been applied in the treatment of patients with hepatolithiasis and a history of biliary or upper abdominal surgery in the last 20 years and has already achieved good clinical outcomes[4,5]. However, reoperative LH (rLH) includes multiple procedures, and the above studies did not examine individual laparoscopic procedures. Different procedures have their own clinical and technical characteristics; therefore, their clinical values may vary. It remains unclear whether each rLH procedure is suitable for patients with hepatolithiasis and a history of biliary surgery. This is an important clinical issue that should not be ignored by hepatobiliary surgeons. If applied properly, the procedure alleviates pain in patients and promotes recovery. Otherwise, it may increase the surgical risk and even endanger the patient's life. Therefore, it is essential to perform a clinical evaluation of each rLH procedure.

This study aimed to evaluate the safety and feasibility of different rLH procedures for hepatolithiasis patients with a history of biliary surgery using clinical comparisons and subgroup analysis.

MATERIALS AND METHODS

Patients and study design

This study was approved by the Institutional Review Board of The First Affiliated Hospital (Yijishan Hospital) of Wannan Medical College (No. [2022]106) on 3 January 2023, performed at the same institution, and conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was part of a clinical trial (www.chictr.org.cn, ChiCTR2300072545). Informed consent forms were signed by all study subjects and investigators of the study. The study design and preparation of the original manuscript were performed according to the Consolidated Standards of Reporting Trials statement[6].

Patients with a history of biliary surgery who underwent liver resection for hepatolithiasis between January 2015 and December 2022 were included in the study. Their clinical data of these patients were collected. Left lateral sectionectomy and left hemihepatectomy were the two most commonly performed surgical procedures. Other procedures were less commonly used and were collectively called complex liver resections, which included right posterior sectionectomy, right hemihepatectomy, left lateral sectionectomy in combination with right posterior sectionectomy, and hepatectomy with caudal lobe resection. These procedures are relatively complex, time-consuming, and associated with considerable risks. Based on the above classification, we categorized all procedures into three types: (1) Laparoscopic or open left lateral sectionectomy [reoperative laparoscopic left lateral sectionectomy (rLLLS) or reoperative open left lateral sectionectomy (rOLLS)]; (2) Laparoscopic or open left hemihepatectomy [reoperative laparoscopic left hemihepatectomy (rLLH) or reoperative open left hemihepatectomy (rOLH)]; and (3) Laparoscopic or open complex hepatectomy [reoperative laparoscopic complex hepatectomy (rLCH) or reoperative open complex hepatectomy (rOCH)]. The clinical outcomes of the three types of reoperative laparoscopic procedures ( rLLLS, rLLH, and rLCH) were compared to explore the differences in the safety and feasibility. Each rLH procedure was then compared with the corresponding open surgery procedure to evaluate its relative clinical value.

Inclusion and exclusion criteria

The following inclusion criteria were used for patient selection: (1) Multiple stones in the intrahepatic bile duct identified by ultrasound, computed tomography (CT), and/or magnetic resonance imaging (MRI); (2) A history of biliary surgery before hepatectomy regardless of whether it is a recurrent or residual stone; (3) With or without concomitant benign liver lesions at the same site as most stones, including liver atrophy, chronic liver abscess, intrahepatic bile duct stenosis or dilation, hepatic hemangioma, papilloma, etc.; (4) Child-Pugh class A or B and serum albumin > 30 g/L; (5) Anatomical hepatectomy followed by a biliary exploration as the main treatment for hepatolithiasis; and (6) Typical histological changes of hepatolithiasis verified by postoperative pathological examination.

The exclusion criteria included: (1) Secondary intrahepatic stones due to anastomotic stenosis of a previous biliary-enteric anastomosis; (2) Stones combined with intrahepatic cholangiocarcinoma (ICC) or other hepatobiliary malignancy; (3) Non-anatomical hepatectomy; (4) Hepatectomy without biliary exploration (as all OH patients underwent concomitant bile duct exploration, while a few LH patients did not undergo biliary exploration, patients who did not undergo concomitant biliary exploration were excluded to balance the types of surgical procedures between the two groups); and (5) Other therapies such as pure percutaneous choledochoscopic lithotomy, biliary exploration, or biliary-enteric anastomosis as the main treatment measure for stones.

Surgical procedure

Following control of cholangitis and improvement of liver function, the patient underwent elective liver resection under general anesthesia with tracheal intubation. For OH patients, an oblique incision or an inverted L-shaped incision of the right upper abdomen was usually made. When the liver and hepatoduodenal ligaments were adequately mobilized, liver resection and bile duct exploration were performed according to previous reports[4,7].

All rLHs were performed by senior surgeons with more than three years of experience in laparoscopic liver resection. Patients were placed in the supine position with legs apart. A five-hole method was employed. The Veress needle was inserted directly at the lower edge of the umbilicus in patients with a history of laparoscopic cholecystectomy or open surgery whose previous incision site was more than 3 cm from the umbilicus. If the previous incision site was less than 3 cm away from the umbilicus, an open Hasson technique was applied to enter to the peritoneal cavity[8]. After CO₂ artificial pneumoperitoneum was established, a 30-degree camera (Karl Storz Endoscopy, Tuttlingen, Germany) was inserted into the abdomen to observe any visible organs or adhesion. The first operating port was made in the nonadhesive region to avoid damaging the intestinal tract under direct visualization, and an electrocoagulator or harmonic scalpel (Ethicon Endo-Surgery, Cincinnati, OH, United States) was inserted into the abdomen to separate the adhesions. The remaining 3 operating ports were then made in the appropriate positions. The subsequent processes, including liver resection and bile duct exploration, were performed according to previous reports[4,7]. If the observation hole or any other operation could not be completed, it was necessary to convert to open surgery.

Postoperative management and follow-up

Postoperative monitoring, drug administration, drainage tube management, and follow-up were performed according to a previously published report[7]. The final follow-up date was June 30, 2023.

End points

Intraoperative outcomes included the choice of hepatic blood inflow occlusion, operation duration, estimated blood loss, blood transfusion, and conversion to OH. The short-term outcomes were postoperative intensive care unit (ICU) stay, postoperative hospital stay, 90-day complications, 90-day major complications, re-intervention for complications, initial stone clearance, re-treatment for residual stones, final calculi clearance, readmission, and 90-day mortality. Long-term outcomes included stone recurrence, late complications, secondary ICC, and late death.

Baseline and outcome definitions

Baseline variables included gender, age, body mass index (BMI), American Society of Anesthesiologists score, obstructive jaundice, benign liver lesions, number of previous surgeries, types of previous procedure, types of previous approach, and interval between the last two surgeries. Previous biliary surgeries, including cholecystectomy, biliary exploration, and liver resection, were performed using an open or laparoscopic approach. Major complications were defined as Clavien-Dindo grade III or higher[9], with the most severe complication accounting for the complication rate. Short-term re-interventions were defined as endoscopic, radiological, or surgical treatments within 90 days after surgery due to complications. Readmission meant a second hospitalization within 3 months after surgery due to complications or residual stones. Residual stones were defined as the presence of stones in the intrahepatic or extrahepatic bile duct detected by postoperative T-tube cholangiography, ultrasonography, CT,or MRI within 3 months after surgery[10]. Re-treatment for residual stones included subsequent choledochoscopy or endoscopic retrograde cholangiopancreatography. Late complications were limited to uncontrolled or new-onset events that occurred more than 3 months after reoperation. Late death was defined as death due to late complications or secondary ICC.

Statistical analysis

Normally distributed continuous variables were expressed as mean (SD) and nonnormally distributed variables as median (interquartile ranges). Categorical variables were reported as absolute number (percentage). Missing data were imputed using a regularized expectation maximization algorithm. One-way analysis of variance, Kruskal-Wallis test, and χ² test were performed to analyze the differences among the three rLHs, and the P values of the multiple comparisons were adjusted with the Bonferroni correction to control Type I errors. Comparisons between two subgroups were analyzed using the Student’s t-test, Mann-Whitney test, and χ² test. All analyses were performed using IBM Statistical Package for the Social Sciences statistics (version 26.0; IBM Corporation, Armonk, NY, United States). A 2-sided P < 0.05 was considered statistically significant.

RESULTS

Baseline characteristics

A total of 447 patients underwent hepatectomy for hepatolithiasis. After exclusion, 185 patients with a history of biliary surgery who underwent anatomical liver resection combined with biliary exploration for pure hepatolithiasis were identified, including 101 patients who underwent rLH and 84 underwent rOH (Figure 1). The rLH patients included 40 cases of rLLLS, 50 of rLLH, and 11 of rLCH, while rOH patients included 40 of rOLLS, 33 of rOLH, and 11 of rOCH. There were no missing preoperative data, except for BMI [69 (37.3%)]. Data imputation led to completion of the variables. There were no significant differences in the demographic characteristics between the rLLLS, rLLH, and rLCH groups (all P > 0.05) (Table 1). There were no significant differences in the baseline characteristics between each pair of laparoscopic and open reoperations in the three subgroups (rLLLS/rOLLS, rLLH/rOLH, and rLCH/rOCH) (Supplementary Tables 1, 2, and 3).

Figure 1 Flowchart depicting the number of patients included in this study. rLCH: Reoperative laparoscopic complex hepatectomy; rLLLS: Reoperative laparoscopic left lateral sectionectomy; rLLH: Reoperative laparoscopic left hemihepatectomy; rOCH: Reoperative open complex hepatectomy; rOLH: Reoperative open left hemihepatectomy; rOLLS: Reoperative open left lateral sectionectomy.

Table 1 Baseline characteristics of the three subgroups, n (%).

Characteristic	Reoperative laparoscopic left lateral sectionectomy (n = 40)	Reoperative laparoscopic left hemihepatectomy (n = 50)	Reoperative laparoscopic complex hepatectomy (n = 11)	χ²/F value	P value
Male	9 (22.5)	16 (32.0)	4 (36.4)	1.333	0.5141
Age, mean (SD), years	62.3 (11.5)	61.8 (7.8)	60.0 (7.7)	0.261	0.7712
Body mass index > 21.5 kg/m2	18 (45.0)	25 (50.0)	6 (54.5 )	0.402	0.8181
American Society of Anesthesiologists score 2-3	21 (52.5)	19 (38.0)	5 (45.5)	1.895	0.3881
Obstructive jaundice	6 (15.0)	11 (22.0)	2 (18.2)	0.716	0.6991
Benign liver lesions	32 (80.0)	43 (86.0)	9 (81.8)	0.588	0.7451
Number of previous surgeries > 2	2 (5.0)	1 (2.0)	0 (0.0)	N/A3	0.706
Types of previous procedure				N/A3	0.250
cholecystectomy	29 (72.5)	28 (56.0)	9 (81.8)
Choledochotomy with exploration	11 (27.5)	19 (38.0)	2 (18.0)
Hepatectomy	0 (0.0)	3 (6.0)	0 (0.0)
Types of previous approach				N/A3	0.789
Open surgery	30 (75.0)	40 (80.0)	9 (81.8)
Laparoscopic surgery	9 (22.5)	7 (14.0)	2 (18.0)
Unclear	1 (2.5)	3 (6.0)	0 (0.0)
Interval between last two surgeries				N/A3	0.608
≤ 2 years	3 (7.5)	8 (16.0)	2 (18.2)
> 2 years	30 (75.0)	37 (74.0)	8 (72.7)
Unknown time-interval	7 (17.5)	5 (10.0)	1 (9.1)

¹χ² test was used.

²One-way analysis of variance was used.

³No χ² value was reported for Fisher's exact test.

N/A: Not applicable.

Comparison of three types of laparoscopic reoperation

The clinical outcomes of the three types of laparoscopic reoperations are shown in Table 2. There were significant differences in the use of selective hepatic blood flow occlusion (20.0% vs 94.0% vs 63.6%, P < 0.001), median operation duration (240.0 minutes vs 325.0 minutes vs 350.0 minutes, P = 0.001), blood transfusion rate (10.0% vs 22.0% vs 54.5%, P = 0.005), and postoperative ICU stay rate (12.5% vs 20.0% vs 63.6%, P = 0.001) among the rLLLS, rLLH, and rLCH groups. The rLLLS group required the shortest operation duration and the lowest blood transfusion rate (both P < 0.05). In contrast, the rLCH group had the longest operation duration, most blood transfusions, and highest ICU stay rate (all P < 0.05). Surprisingly, the laparoscopic conversion rate of rLCH was still significantly higher than that of rLLLS (36.4% vs 7.5%, P < 0.05), although no difference was found between the three groups. There were no differences in any of the postoperative outcomes, except for postoperative ICU stay.

Table 2 Clinical outcomes of the three types of laparoscopic reoperation.

Characteristic	Reoperative laparoscopic left lateral sectionectomy (n = 40)	Reoperative laparoscopic left hemihepatectomy (n = 50)	Reoperative laparoscopic complex hepatectomy (n = 11)	χ²/H value	P value
Selective hepatic blood flow occlusion	8/40 (20.0)	47/50 (94.0)6	7/11 (63.6)6,7	51.364	< 0.0011
Operation duration, median (IQR), minute	240.0 (196.3-322.5)	325.0 (254.5-387.8)6	350.0 (295.0-460.0)6	14.508	0.0012
Blood loss, median (IQR), mL	200.0 (75.0-281.2)	200.0 (100.0-400.0)	400.0 (200.0-800.0)	5.837	0.0542
Blood transfusion	4/40 (10.0)	11/50 (22.0)6	6/11 (54.5)6	10.483	0.0051
Conversion to open surgery	3/40 (7.5)	8/50 (16.0)	4/11 (36.4)6	5.787	0.0551
Postoperative intensive care unit stay	5/40 (12.5)	10/50 (20.0)	7/11 (63.6)6,7	13.426	0.0011
Postoperative stay, median (IQR), days	8.0 (6.0-10.0)	8.0 (7.0-12.3)	10.0 (7.0-13.0)	2.211	0.3312
Early complications within 90 days	17/40 (42.5)	27/50 (54.0)	7/11 (63.6)	2.028	0.3631
Major complications within 90 days	2/40 (5.0)	3/50 (6.0)	0/11 (0.0)	N/A3	1.000
Reinterventions within 90 days	2/40 (5.0)	3/50 (6.0)	0/11 (0.0)	N/A3	1.000
Readmission within 90 days	6/40 (15.0)	10/50 (20.0)	3/11 (27.3)	0.942	0.6241
90-day mortality	0/40 (0.0)	0/50 (0.0)	0/11 (0.0)	-	-
Initial stone clearance4	33/40 (82.5)	36/48 (75.0)	8/11 (72.7)	0.893	0.6401
Re-treatment for residual stones4	2/40 (5.0)	6/48 (12.5)	1/11 (9.1)	N/A3	0.412
Final stone clearance4	34/40 (85.0)	39/48 (81.3)	8/11 (72.7)	0.894	0.6401
Stone recurrence5	2/34 (5.9)	2/39 (5.1)	0/8 (0.0)	N/A3	1.000
Late complications4	1/40 (2.5)	3/48 (6.3)	1/11 (9.1)	N/A3	0.411
Late major complications4	0/40 (0.0)	1/48 (2.1)	0/11 (0.0)	N/A3	1.000
Secondary ICC4	1/40 (2.5)	0/48 (0.0)	0/11 (0.0)	N/A3	0.515
Late death due to complications or ICC4	1/40 (2.5)	0/48 (0.0)	0/11 (0.0)	N/A3	0.515

¹χ² test was used.

²Kruskal-Wallis test was used.

³No χ² value was reported for Fisher's exact test.

⁴Two patients in the laparoscopic left hemihepatectomy subgroup had no postoperative imaging data and were excluded.

⁵Six patients in the reoperative laparoscopic left lateral sectionectomy subgroup, 11 in the reoperative laparoscopic left hemihepatectomy subgroup, and 3 in ther laparoscopic complex hepatectomy subgroup were excluded due to no follow-up data and residual stone.

⁶compared with the reoperative laparoscopic left lateral sectionectomy subgroup, P < 0.05.

⁷compared with the reoperative laparoscopic left hemihepatectomy subgroup, P < 0.05.

Data are presented as number/total number (percentage) of patients unless otherwise indicated. IQR: Interquartile range; ICC: Intrahepatic cholangiocarcinoma; N/A: Not applicable.

Subgroup analysis

To further understand the safety and feasibility of different reoperative laparoscopic procedures for hepatolithiasis, we compared them with corresponding open procedures. The clinical outcomes in the rLLLS/rOLLS subgroups are shown in Table 3. The median operation duration in the rLLLS subgroup was longer than that in the rOLLS subgroup (240.0 minutes vs 200.0 minutes, P = 0.002). However, the blood transfusion rate (10.0% vs 30.0%, P = 0.025), median postoperative hospital stay (8.0 days vs 13.0 days, P = 0.001), and stone recurrence rate (5.9% vs 28.1%, P = 0.015) in the rLLLS subgroup were lower or shorter than those in the rOLLS subgroup. No differences were found in the other outcomes.

Table 3 Clinical outcomes of the two subgroups of reoperative left lateral sectionectomy.

Clinical outcomes	Reoperative open left lateral sectionectomy (n = 40)	Reoperative laparoscopic left lateral sectionectomy (n = 40)	χ²/Z value	P value
Selective hepatic blood flow occlusion	5/40 (12.5)	8/40 (20.0)	0.827	0.3631
Operation duration, median (IQR), minute	200.0 (180.0-240.0)	240.0 (196.3-322.5)	-3.073	0.0022
Blood loss, median (IQR), mL	200.0 (81.3-300.0)	200.0 (75.0-281.2)	-0.743	0.4572
Blood transfusion	12/40 (30.0)	4/40 (10.0)	5.000	0.0251
Conversion to open surgery	-	3/40 (7.5)	-	-
Postoperative intensive care unit stay	5/40 (12.5)	5/40 (12.5)	0.000	1.0001
Postoperative hospital stay, median (IQR), days	10.0 (8.0-17.0)	8.0 (6.0-10.0)	-3.332	0.0012
Early complications within 90 days	16/40 (40.0)	17/40 (42.5)	0.052	0.8201
Major complications within 90 days	1/40 (2.5)	2/40 (5.0)	N/A3	1.000
Reinterventions within 90 days	1/40 (2.5)	2/40 (5.0)	N/A3	1.000
Readmission within 90 days	5/40 (12.5)	6/40 (15.0)	0.105	0.7451
90-day mortality	0/40 (0.0)	0/40 (0.0)	-	-
Initial stone clearance rate4	29/39 (74.4)	33/40 (82.5)	0.775	0.3791
Re-treatment of residual stones4	4/39 (10.3)	2/40 (5.0)	N/A3	0.432
Final stone clearance rate4	32/39 (85.0)	34/40 (85.0)	0.125	0.7241
Stone recurrence5	9/32(28.1 )	2/34 (5.9)	5.872	0.0151
Late complications4	1/39 (2.6)	1/40 (2.5)	N/A3	1.000
Late major complications4	1/39 (2.6)	0/40 (0.0)	N/A3	0.494
Secondary ICC4	4/39 (10.3)	1/40 (2.5)	N/A3	0.201
Late death due to complications or ICC4	4/39 (10.3)	1/40 (2.5)	N/A3	0.201

¹χ² test was used.

²Mann-Whitney U test was used.

³No χ² value was reported for Fisher's exact test.

⁴One patients in the reoperative open left lateral sectionectomy group had no postoperative imaging and was excluded.

⁵Seven patients in the reoperative open left lateral sectionectomy group and 6 in the reoperative laparoscopic left lateral sectionectomy group were further excluded due to residual stone.

Data are presented as number/total number (percentage) of patients unless otherwise indicated. IQR: Interquartile range; ICC: Intrahepatic cholangiocarcinoma; N/A: Not applicable.

The outcomes in the rLLH/rOLH subgroups are shown in Table 4. There was no significant difference in the transfusion rate between the two subgroups. The remaining outcomes in the rLLH/rOLH subgroups were similar to those in the rLLS/rOLLS subgroups. Unlike the rLLH/rOLH and rLLLS/rOLLS subgroups, there were no differences in all outcomes between the rLCH/rOCH subgroups (Supplementary Table 4); however, the rLCH subgroup had a high conversion rate (36.4%).

Table 4 Clinical outcomes of the two subgroups of reoperative left hemihepatectomy.

Clinical outcomes	Reoperative open left hemihepatectomy (n = 33)	Reoperative laparoscopic left hemihepatectomy (n = 50)	χ²/t/Z value	P value
Selective hepatic blood flow occlusion	29/33 (87.9)	47/50 (94.0)	0.956	0.3261
Operation duration, mean (SD), minute	244.7 (84.7)	318.9 (88.5)	-3.800	0.0002
Blood loss, median (IQR), mL	235.7 (150.0-400.0)	200.0 (100.0-400.0)	-1.411	0.1583
Blood transfusion	13/33 (39.4)	11/50 (22.0)	2.926	0.0871
Conversion to open surgery	-	8/50 (16.0)	-	-
Postoperative intensive care unit stay	5/33 (15.2)	10/50 (20.0)	0.316	0.5741
Postoperative hospital stay, median (IQR), days	13.0 (8.0-21.0)	8.0 (7.0-12.3)	-3.237	0.0013
Early complications within 90 days	21/33 (63.6)	27/50 (54.0)	0.757	0.3841
Major complications within 90 days	1/33 (3.0)	3/50 (6.0)	N/A4	1.000
Reinterventions within 90 days	1/33 (3.0)	3/50 (6.0)	N/A4	1.000
Readmission within 90 days	6/33 (18.2)	10/50 (20.0)	0.042	0.8371
90-day mortality	0/33 (0.0)	0/50 (0.0)	-	-
Initial stone clearance rate5	25/32 (78.1)	36/48 (75.0)	0.104	0.7481
Re-treatment of residual stones5	4/32 (12.5)	6/48 (12.5)	N/A3	1.000
Final stone clearance rate5	26/32 (81.3)	39/48 (81.3)	0.000	1.0001
Stone recurrence6	8/26(30.8 )	2/39 (5.1)	N/A4	0.011
Late complications5	4/32 (12.5)	3/48 (6.3)	N/A4	0.429
Late major complications5	2/32 (6.3)	1/48 (2.1)	N/A4	0.561
Secondary ICC5	0/32 (0.0)	0/48 (0.0)	-	-
Late death due to complications or ICC5	1/32 (3.1)	0/48 (0.0)	N/A4	0.400

¹χ² test was used.

²Student t-test was used.

³Mann-Whitney U test was used.

⁴No χ² value was reported for Fisher's exact test.

⁵One patients in the reoperative open left hemihepatectomy group and 2 in the reoperative laparoscopic left hemihepatectomy group had no postoperative imaging and were excluded.

⁶Six patients in the reoperative open left hemihepatectomy group and 9 in the reoperative laparoscopic left hemihepatectomy group were further excluded due to residual stone.

Data are presented as number/total number (percentage) of patients unless otherwise indicated. IQR: Interquartile range; ICC: Intrahepatic cholangiocarcinoma; N/A: Not applicable.

DISCUSSION

This multi-cohort study systematically analyzed the clinical differences between multiple rLH procedures and their relative advantages over rOH for pure hepatolithiasis in patients with a history of biliary surgery. Of the three types of rLH, rLLLS patients had the best clinical outcomes, followed by rLLH patients, whereas rLCH showed the lowest clinical value. Most clinical outcomes in the rLLLS and rLLH subgroups were better than or equal to those undergoing the corresponding rOH procedures, while rLCH had no advantage over rOCH with a high conversion rate. To our knowledge, this study is the first to systematically investigate the clinical characteristics of each rLH procedure for hepatolithiasis in patients with a history of biliary surgery. In the absence of international guidelines, our study provides meaningful clinical evidence for the rational application of each rLH procedure for recurrent or residual intrahepatic stones.

To understand the differences in the safety and feasibility of different rLH procedures, we first compared the clinical outcomes of the three types of rLH procedures and found that the differences were mainly related to intraoperative indicators and postoperative ICU stay. The rLLLS had the shortest operation duration and the lowest blood transfusion rate. Selective hepatic blood flow occlusion is most commonly performed in rLLH patients. However, the rLCH group had the longest median operation duration, most blood transfusions, and the highest laparoscopic conversion rate. No significant differences were found in other clinical outcomes, and no patients in any of the groups died within 90 days post-surgery. These results suggest that all three procedures are safe for hepatolithiasis patients with a history of biliary surgery, with rLLLS having the greatest clinical advantage and rLCH having relatively low feasibility. LLLS has been recognized as the gold standard for the treatment of liver cancer and some benign liver lesions due to its good clinical outcome and cost-effectiveness[11-13]. Based on the results of this study, we also believe that rLLLS is the preferred option for hepatolithiasis patients with a history of biliary surgery if left lateral sectionectomy is required.

To further evaluate the safety and feasibility of each rLH procedure, we compared each procedure with the corresponding open reoperation, as rOH can still be performed in almost every patient with a success rate of nearly 100%[3]. As a result, most clinical outcomes of rLLLS and rLLH were equal to or better than those of their corresponding rOH, except for prolonged operation duration. Laparoscopic repeat hepatectomy has been reported to have a similar[14] or shorter[15-17] operative time than open repeat liver resection for recurrent and metastatic liver cancers. However, due to previous surgery, multiple stones, dense perihepatic adhesions, and severe inflammation, rLH is more difficult to perform than rOH for hepatolithiasis patients with a history of biliary surgery. In patients with recurrent and metastatic liver tumors, this inflammation does not exist, but can seriously affect the surgical process of hepatolithiasis patients with a history of biliary surgery. Therefore, rLLLS and rLLH required longer operation durations in this study. As reported in the literature[4,5], rLLLS and rLLH did not significantly reduce the intraoperative blood loss in this study. However, rLLLS and rLLH have significant advantages over their corresponding open procedures in reducing intraoperative blood transfusion, shortening postoperative hospital stay, and decreasing stone recurrence. The complication and mortality rates in the two subgroups were the same or similar to their corresponding open surgeries. These results suggest that rLLLS and rLLH are highly safe and feasible for hepatolithiasis patients with a history of biliary surgery.

Inexplicably, there was no difference in all clinical outcomes including operation duration and postoperative hospital stay between the rLCH and rOCH subgroups. The main reason for this is that both subgroups had relatively small sample sizes. Therefore, subgroup analysis did not show any advantages of rLCH. Furthermore, the rLCH subgroup had a high conversion rate (36.4%). In this study, rLCH is a general term for multiple technically demanding laparoscopic procedures that require specific skills, require patient selection, and carry a risk of bleeding and unsuccessful resection. Therefore, a high conversion rate is inevitable or understandable, which once again indicates that the feasibility of LCH is relatively low. From the perspective of safety and feasibility, rLCH and even rLLH should be performed by skilled surgeons in well-equipped medical centers.

This study has several limitations. First, owing to the retrospective study design, we do not know the reasons why surgeons choose rOH or rLH. Generally speaking, surgeons may choose patients with relatively mild liver lesions for laparoscopic surgery. Second, some information or data were lacking or incomplete, such as partial BMI and individual previous procedures. Expectation maximization imputation had to be performed for BMI in 37.3% of the 185 patients. The data processing may have caused bias. However, the differences between the two groups can be ignored as all P values were more than 0.05. Third, the sample sizes in the three groups were small, especially in the rLCH group. Therefore, the results of this study should be interpreted with caution. In addition, reoperative laparoscopic liver resection should be limited to patients with a history of 1-2 biliary surgeries. For those with a history of multiple surgeries, laparoscopic surgery is no longer suitable due to safety and feasibility issues.

CONCLUSION

All three procedures are safe for hepatolithiasis patients with a history of biliary surgery. The rLLLS and rLLH can be recommended as their overall clinical efficacy is superior to or similar to their corresponding open surgery, while rLCH should be performed with caution due to its relatively low feasibility.

ACKNOWLEDGEMENTS

The authors thank all the patients who took part in this study and our colleagues in the Department of Hepatobiliary Surgery of our hospital for their contributions to surgical procedures and patient management.