Influence of laparoscopic radical cholecystectomy for early gallbladder cancer on surgical performance, postoperative recuperation, and complication rates

Abstract

BACKGROUND

Laparoscopic surgery is the standard therapy for gastrointestinal (GI) cancers; however, its application in gallbladder cancer (GBC) remains cautious, and its clinical advantages require further validation.

AIM

To compare surgical performance, postoperative recovery, and complication rates between patients with early GBC undergoing laparoscopic radical cholecystectomy (LRC) and those receiving open radical cholecystectomy.

METHODS

A total of 89 patients treated between July 2022 and July 2024 were assigned to a control group (open radical cholecystectomy, n = 40) or a research group (LRC, n = 49). Outcomes included surgical performance (intraoperative bleeding, incision length, and surgical duration); pathological indicators (lymph node yield and surgical margins); recovery indices (time of ambulation, GI function recovery, and length of hospital stay); postoperative complications (wound infection, biliary fistula, intra-abdominal infection); stress markers (adrenaline, cortisol, and norepinephrine); and quality-of-life assessed using the Generic Quality-of-Life Inventory-74.

RESULTS

Compared with the control group, the research group had reduced blood loss, smaller incisions, shorter operative time, faster postoperative recovery (earlier ambulation, quicker GI function recovery, and shorter hospital stay), and fewer complications. Postoperative adrenaline, cortisol, and norepinephrine levels increased in both groups but remained significantly lower in the research group. Postoperative Generic Quality-of-Life Inventory-74 scores across psychological, physical, social, and material domains were significantly higher in the research group. No significant between-group differences were observed in lymph node yield or surgical margins.

CONCLUSION

LRC offers patents with early GBC improved surgical performance, enhanced postoperative recovery, and reduced complication rates.

Key Words: Laparoscopic radical cholecystectomy; Early gallbladder cancer; Surgical performance; Postoperative recovery; Complications

Core Tip: This study compared two surgical approaches for early gallbladder cancer and demonstrated that laparoscopic radical cholecystectomy provides superior clinical outcomes compared with open surgery. Specifically, laparoscopic radical cholecystectomy significantly improves surgical performance, promote postoperative recovery, reduces overall postoperative complications, alleviates surgical stress, and enhance patients’ quality-of-life.

INTRODUCTION

Gallbladder cancer (GBC) is a highly aggressive and often lethal malignancy, ranking as the sixth most common gastrointestinal (GI) cancer and a leading biliary tract tumor[1]. More than 90% of cases are adenocarcinomas arising from epithelial cells[2]. Early-stage GBC is typically asymptomatic and progresses insidiously; consequently, most cases are diagnosed at an advanced stage, with a five-year survival rate of only 5%-15%[3,4]. Advanced GBC cases may present with jaundice, unexplained weight loss, abdominal discomfort, and metastatic spread[5]. The therapeutic potential of early GBC (eGBC) has been increasingly recognized, as timely surgical resection can substantially improve prognosis[6]. Conventional open radical cholecystectomy (ORC) is associated with considerable surgical trauma. Prolonged abdominal exposure during ORC increases the risk of infection and may delay postoperative recovery[7]. Although laparoscopic surgery is been widely accepted as the standard approach for many GI malignancies, its use in GBC remains cautious due to concerns regarding intraoperative tumor dissemination, the adequacy of laparoscopic lymphadenectomy, and uncertainty regarding long-term oncological outcomes[8]. Emerging evidence supports the safety and feasibility of this treatment in eGBC, demonstrating noninferiority to ORC in short-term and long-term survival outcomes[9]. However, consensus has not been reached, as some studies suggest that laparoscopic radical cholecystectomy (LRC) may confer superior short-term and long-term efficacy compared with ORC[10].

To provide additional evidence regarding the clinical advantages of LRC for eGBC, we conducted a comprehensive comparative evaluation, the details of which are presented below.

MATERIALS AND METHODS

Case selection

Eligible patients met the following criteria: (1) Histologically confirmed eGBC[11]; (2) TNM stage I or II based on preoperative clinical assessment and postoperative pathological staging according to the 8^th edition of American Joint Committee on Cancer[12]; (3) Clear indications for radical surgery; (4) First diagnosis and initial treatment; (5) Absence of psychiatric disorders with intact cognitive and communication abilities; and (6) Complete clinical records. Exclusion criteria included systemic infection, severe organ dysfunction, hematological disease, thrombocyte dysfunction, autoimmune or coagulation disorders, concomitant malignancy, infectious diseases, long-term use of psychoactive medications, or pregnancy or lactation.

Following ethics committee approval, 89 eligible patients with eGBC who underwent surgical treatment at our institution between July 2022 and July 2024 were enrolled. Of these, 40 patients were assigned to the control group (ORC) and 49 to the research group (LRC). No significant differences in baseline characteristics were observed between groups (P > 0.05), indicating comparability.

Intervening methods

Patients in the control group underwent ORC as follows: After induction of general anesthesia, patients were placed in the supine position, and a 10-cm incision was made along the right upper rectus abdominis. The skin and subcutaneous tissues were dissected layer by layer, followed by abdominal exploration. Standard resection of the gallbladder and partial liver was performed, along with lymph node dissection of the pancreaticoduodenal region and surrounding tissue. Hemostasis was achieved using electrocautery; after which the abdominal cavity was irrigated, a drainage tube was placed, and the incision was closed.

Patients in the research group underwent LRC. Anesthesia and positioning were identical to those in the control group. A subumbilical incision was used to insert the trocar, and pneumoperitoneum was established at approximately 12 mmHg. Additional 5-mm and 12-mm trocars were placed at the xiphoid process and right costal margin, respectively. After comprehensive abdominal exploration and standard cholecystectomy, intraoperative frozen-section analysis was performed, and further procedures were continued only after confirmation. Lymphadenectomy of the hepatoduodenal ligament was then conducted, with additional hepatic segment or biliary tract resection performed when necessary. Patients requiring extrahepatic bile duct resection underwent bilioenteric anastomosis. During partial hepatectomy, ductal structures were isolated, clamped, and transected using electrocautery. Hemostasis via electrocautery was performed before pneumoperitoneum release, followed by abdominal cavity irrigation, drainage tube placement, and wound closure. All patients received postoperative antibiotic prophylaxis.

Data collection and outcome measurement

Surgical performance: (1) Intraoperative blood loss; (2) Incision length; and (3) Operative time were recorded.

Tumor pathological indexes: Lymph node yield and surgical margin status (R0/R1 resection) were evaluated. R0 resection was defined as the absence of microscopic tumor infiltration at all margins (bile duct, liver, peripheral soft tissue, and lymph node capsules). R1 resection was defined as microscopic tumor infiltration at any of these abovementioned margins.

Postoperative recuperation: Time to ambulation, recovery of GI function, and length of hospital stay were recorded.

Complications: The incidence of postoperative complications, including wound infection, biliary fistulas, and intra-abdominal infection, were monitored.

Stress response: Fasting venous blood samples (5 mL) were collected preoperatively and postoperatively in the morning. After serum separation via centrifugation, levels of adrenaline (Ad), cortisol (Cor), and norepinephrine (NE) were measured using an automated analyzer.

Quality-of-life: Quality-of-life was assessed preoperatively and postoperatively using the Generic Quality-of-Life Inventory-74 questionnaires[13], covering psychological, physical, social, and material domains. Scores were converted to a 100-point scale, with higher scores indicating better quality-of-life.

Statistical analysis

Measurement data with normal distributions are presented as mean ± SD and were analyzed using independent-sample and paired t-tests for between-group and within-group comparisons, respectively. Count data are expressed as n (%) and were analyzed using χ² tests. Statistical analyses were performed using SPSS 22.0, with P < 0.05 considered statistically significant.

RESULTS

Analysis of demographic characteristics

Comparison of baseline demographic data (Table 1) demonstrated no significant between-group differences in sex distribution, mean age, body mass index, disease duration, clinical staging, or tumor diameter (P > 0.05), indicating good baseline comparability.

Table 1 Patient demographics, n (%)/mean ± SD.

Indicators	Control group (n = 40)	Research group (n = 49)	χ2/t	P value
Male	15 (37.50)	14 (28.57)	0.799	0.371
Average age (years)	52.42 ± 6.48	53.31 ± 6.38	0.650	0.517
Body mass index (kg/m2)	22.75 ± 2.96	22.10 ± 2.66	1.090	0.279
Disease duration (months)	8.55 ± 2.23	9.39 ± 2.01	1.867	0.065
Clinical staging			0.074	0.786
I	16 (40.00)	21 (42.86)
II	24 (60.00)	28 (57.14)
Tumor diameter (cm)	2.56 ± 0.53	2.47 ± 0.57	0.765	0.447

Comparative analysis of surgical performance

As shown in Figure 1, patients treated with LRC exhibited significantly improved surgical performance compared with those undergoing ORC, including reduced intraoperative bleeding, shorter incision length, and decreased operative time (P < 0.01).

Figure 1 Surgical performance analysis. A: Intraoperative blood loss in two groups; B: Incision length measurements; C: Operation time of two patient groups. ^bP < 0.01 vs the control group.

Analysis of tumor pathological indexes

Tumor pathological indexes are summarized in Table 2. No significant differences were observed between the two groups with respect to lymph node yield or surgical margin status (P > 0.05).

Table 2 Tumor pathological indexes, n (%)/mean ± SD.

Indicators	Control group (n = 40)	Research group (n = 49)	χ2/t	P value
Lymph node yield	7.45 ± 2.46	7.57 ± 2.06	0.250	0.803
Surgical margin			0.267	0.606
R0	30 (75.00)	39 (79.59)
R1	10 (25.00)	10 (20.41)

Analysis of postoperative recuperation

Evaluation of postoperative recovery parameters (Figure 2) showed that the LRC group achieved earlier ambulation, faster GI function recovery, and shorter hospital stays compared with the ORC group (P < 0.05).

Figure 2 Postoperative recuperation assessment in two patient cohorts. A: Time to ambulation; B: Time to gastrointestinal function recovery; C: Length of hospital stay. ^aP < 0.05, ^bP < 0.01 vs control group.

Comparative complication assessment

Complication rate data (Table 3) demonstrated a significantly lower overall incidence of postoperative complications, including wound infection, biliary fistulas, and intra-abdominal infection, in the LRC group than in the ORC group (P < 0.001).

Table 3 Complications, n (%).

Indicators	Control group (n = 40)	Research group (n = 49)	χ2	P value
Wound infection	8 (20.00)	3 (6.12)
Biliary fistula	5 (12.50)	4 (8.16)
Intra-abdominal infection	6 (15.00)	0 (0.00)
Total	19 (47.50)	7 (14.29)	11.749	< 0.001

Comparative stress response evaluation

Stress-related biomarkers are presented in Table 4. Postoperative levels of Ad, Cor, and NE were comparable between groups (P > 0.05). Postoperatively, levels of all three markers increased in both groups; however, the increases were significantly lower in the LRC group than in the ORC group (P < 0.05).

Table 4 Surgical stress responses, mean ± SD.

Indicators	Control group (n = 40)	Research group (n = 49)	t value	P value
Adrenaline (pg/mL)
Preoperative	13.70 ± 4.46	13.71 ± 3.89	0.011	0.991
Postoperative	22.88 ± 4.43c	17.92 ± 3.88b	5.628	< 0.001
Cortisol (ng/mL)
Preoperative	339.57 ± 48.63	336.29 ± 54.34	0.297	0.767
Postoperative	407.50 ± 62.79c	372.88 ± 53.43b	2.810	0.006
Norepinephrine (pg/mL)
Preoperative	355.93 ± 54.27	368.92 ± 62.60	1.033	0.305
Postoperative	431.02 ± 49.97c	401.57 ± 76.79b	2.090	0.040

^bP < 0.01 (within-group comparison vs preoperative measurement).

^cP < 0.001 (within-group comparison vs preoperative measurement).

Assessment of life quality metrics

Quality-of-life assessment using the Generic Quality-of-Life Inventory-74 (Table 5) showed no significant differences in baseline psychological, physical, social, or material domains between groups (P > 0.05). Postoperative scores improved across all domains in both groups, with significantly higher scores observed in the LRC group (P < 0.05).

Table 5 Quality-of-life analysis, mean ± SD.

Indicators	Control group (n = 40)	Research group (n = 49)	t value	P value
Psychological well-being (points)
Preoperative	62.73 ± 5.21	63.92 ± 5.98	0.989	0.326
Postoperative	72.58 ± 5.61b	75.67 ± 7.34c	2.190	0.031
Physical well-being (points)
Preoperative	61.25 ± 5.72	59.45 ± 6.68	1.348	0.181
Postoperative	71.78 ± 5.38b	77.67 ± 7.68c	4.097	< 0.001
Social well-being (points)
Preoperative	64.85 ± 6.68	64.59 ± 6.02	0.193	0.848
Postoperative	72.08 ± 8.07b	81.39 ± 6.02c	6.229	< 0.001
Material well-being (points)
Preoperative	57.45 ± 5.36	57.00 ± 5.73	0.379	0.705
Postoperative	70.12 ± 6.93b	73.98 ± 7.48c	2.502	0.014

^bP < 0.01 (within-group comparison vs preoperative measurement).

^cP < 0.001 (within-group comparison vs preoperative measurement).

DISCUSSION

This study showed that LRC was superior to ORC in patients with eGBC, as evidenced by reduced intraoperative blood loss, shorter incision length, and decreased operative duration. These advantages are likely attributable to improved visualization during laparoscopy, which enhances anatomical precision and limits injury to surrounding normal tissues, thereby reducing bleeding risk[14]. Agarwal et al[15] reported similar findings, noting lower median blood loss in patients with primary GBC treated with LRC compared with ORC. With respect to tumor pathological indexes, no significant differences were observed between groups in lymph node yield or surgical margin status, consistent with findings reported by Vrabie et al[16]. Regarding postoperative recovery, LRC was associated with earlier ambulation, faster recovery of GI function, and shorter hospital stays, suggesting a role in accelerating postoperative recovery. Feng et al[17] likewise reported significantly reduced hospitalization in patients with eGBC treated with LRC, supporting the present results. These benefits may be related to precise resection of diseased tissues and surrounding lymph nodes, combined with reduced surgical trauma and stress.

In terms of safety, the overall incidence of postoperative complications – including wound infection, biliary fistula, and intra-abdominal infection – was significantly lower in the LRC group. Notably, six cases of intra-abdominal infection occurred in the ORC group, whereas no such events were observed following LRC. Although pneumoperitoneum establishment during laparoscopy has raised concerns regarding infection risk, its impact remains controversial[18]. As a minimally invasive technique, LRC has certain clinical advantages, including smaller abdominal incisions, reduced tissue traction, and minimal abdominal exposure, which collectively mitigate surgical trauma and postoperative inflammatory responses, thereby minimizing infection risk. Although LRC carries potential risks, including port-site metastasis, no such events were observed in this study. This may be related to the low risk of peritoneal dissemination in the patients with stage I and II GBC included in this study. Supporting this interpretation, Hale et al[19] reported that LRC can serve as an effective alternative to ORC, with lower blood transfusion and superficial surgical site infection rates. Together, these findings reinforce the advantages of LRC in improving surgical performance and clinical safety. Furthermore, postoperative stress responses were attenuated in the LRC group, as reflected by smaller postoperative increases in Ad, Cor, and NE levels. This effect is likely linked to the minimally invasive nature of LRC[20], as well as its associated reductions in blood loss, incision size, and operative duration. Finally, patients undergoing LRC demonstrated superior postoperative quality-of-life across psychological, physical, social, and material domains. These improvements may result from enhanced surgical outcomes, accelerated postoperative recovery, and reduced complication risk, collectively facilitating better postoperative quality-of-life.

Previous studies have similarly evaluated the clinical effectiveness of laparoscopic cholecystectomy in GBC management. Chan et al[21] reported satisfactory surgical outcomes, low port-site tumor recurrence rates, and noninferior 5-year survival in eGBC patients treated with laparoscopic approaches compared with ORC. A meta-analysis further indicated comparable long-term prognoses between LRC and ORC[22]. Additionally, Shirobe and Maruyama[23] demonstrated that LRC combined with lymphadenectomy yielded safe and effective outcomes in T1b/T2 GBC, with 5-year survival rates of 100.0% for T1b and 83.3% for T2 disease.

CONCLUSION

For eGBC cases, LRC should be preferred because it optimizes the surgical outcomes, accelerates postoperative recovery, improves safety, reduces stress response, and positively affects the quality-of-life, making it worthy of wider clinical application.