Comparative outcomes of laparoscopic vs open pancreaticoduodenectomy in early-stage pancreatic cancer

Abstract

BACKGROUND

Pancreaticoduodenectomy (PD) represents the standard surgical approach for resectable pancreatic ductal adenocarcinoma (PDAC); however, its high morbidity has prompted the exploration of minimally invasive alternatives. While laparoscopic PD (LPD) has demonstrated promise, evidence comparing LPD and open PD (OPD) in early-stage PDAC remains limited.

AIM

To compare the perioperative and oncologic outcomes of LPD and OPD in patients with early-stage PDAC.

METHODS

This retrospective propensity-matched analysis included 100 patients with stage I-II PDAC who underwent curative PD between January 2022 and December 2024. Patients were matched 1:1 for age, sex, body mass index, American Society of Anesthesiologists score, and tumor stage. Perioperative outcomes assessed included operative time, blood loss, transfusion rate, hospital stay, complications (overall, severe, pancreatic fistula, delayed gastric emptying, wound infection, intra-abdominal abscess, bile leak, pulmonary complications, and sepsis), and enhanced recovery after surgery metrics (time to mobilization, oral intake, and pain scores). Oncologic outcomes included lymph node yield, R0 resection rate, recurrence-free survival, and overall survival (OS).

RESULTS

Compared with OPD, LPD was associated with reduced intraoperative blood loss [median 170 mL (interquartile range: 130-220 mL) vs median 340 mL (interquartile range: 280-410 mL); P < 0.001], lower transfusion rates (8% vs 22%; P = 0.03), and shorter hospital stays (12 ± 3 days vs 15 ± 4 days; P = 0.002), although operative times were longer (320 ± 45 minutes vs 285 ± 40 minutes; P < 0.001). Overall complication rates (42% vs 50%), severe complications (16% vs 22%), pancreatic fistula (12% vs 16%), delayed gastric emptying (10% vs 14%), and specific complications (wound infection: 6% vs 14%; intra-abdominal abscess: 4% vs 6%; bile leak: 2% vs 4%; pulmonary complications: 8% vs 12%; sepsis: 4% vs 6%) were comparable between the groups (all P > 0.05). enhanced recovery after surgery metrics favored LPD, with earlier mobilization (8.5 ± 3.2 hours vs 12.4 ± 4.1 hours; P = 0.001), earlier oral intake (1.2 ± 0.5 days vs 2.1 ± 0.8 days; P < 0.001), and lower pain scores (3.5 ± 1.2 vs 4.8 ± 1.5; P < 0.001). Oncologic outcomes, including lymph node yield, R0 resection rates, recurrence-free survival, and OS, were similar, with a median OS of 22 months for LPD vs 20 months for OPD (log-rank P = 0.65).

CONCLUSION

LPD offers perioperative benefits, including reduced blood loss, fewer transfusions, shorter hospital stays, and improved recovery metrics, without compromising oncologic outcomes in early-stage PDAC. These findings support its selective use in high-volume centers with experienced surgeons, promoting faster recovery while maintaining long-term efficacy.

Key Words: Pancreatic ductal adenocarcinoma; Laparoscopic pancreaticoduodenectomy; Open pancreaticoduodenectomy; Minimally invasive surgery; Oncologic outcomes

Core Tip: Pancreaticoduodenectomy (PD) remains the cornerstone treatment for resectable pancreatic ductal adenocarcinoma, but its morbidity is substantial. Minimally invasive techniques, particularly laparoscopic PD (LPD), have emerged as alternatives to open surgery. However, evidence in early-stage pancreatic cancer is limited. In this propensity-matched analysis from a high-volume center, LPD demonstrated reduced blood loss (by 170 mL), fewer transfusions, and a shorter hospital stay (by 3 days), while showing comparable complication rates, R0 resection rates, lymph node yield, and survival outcomes to open PD. These findings suggest that LPD may be a safe and effective option in carefully selected early-stage patients, supporting its integration into surgical practice in experienced centers.

INTRODUCTION

Pancreatic ductal adenocarcinoma (PDAC) accounts for approximately 90% of pancreatic malignancies and poses a significant global health challenge[1]. Despite advancements in multimodal therapies, the 5-year overall survival (OS) rate for PDAC remains a dismal 13%, primarily due to late diagnosis and the disease’s aggressive nature[2,3]. For early-stage disease (stages I-II), pancreaticoduodenectomy (PD), commonly known as the Whipple procedure, represents the primary treatment, offering a median survival of 20-30 months when combined with adjuvant chemotherapy[4]. However, PD is a complex operation associated with substantial morbidity (up to 50%) and mortality (2%-5%)[5,6].

Laparoscopic PD (LPD) has emerged as a promising minimally invasive alternative to traditional open PD (OPD). Advocates of LPD highlight its potential for reduced intraoperative blood loss, shorter hospital stays, and faster recovery, attributed to enhanced visualization, precise instrumentation, and minimized tissue trauma[7]. Nevertheless, concerns persist regarding its steep learning curve, extended operative times, and potential oncologic limitations, particularly in achieving adequate margin clearance and lymph node retrieval[8].

Previous randomized controlled trials (RCTs) and meta-analyses have produced mixed results. Some studies suggest that LPD is non-inferior for short-term outcomes, while others report increased complications in low-volume centers[9-12]. With the global incidence of PDAC rising, particularly among older adults, optimizing surgical outcomes is critical. Early-stage PDAC [tumor (T) 1-2; node (N) 0-1; metastasis (M) 0] provides an ideal group for comparing LPD and OPD. This study aims to evaluate the perioperative and oncologic outcomes of LPD vs OPD in early-stage PDAC, using propensity score matching to control for confounders. Conducted in a high-volume center, this analysis seeks to clarify the feasibility and safety of LPD in this context.

MATERIALS AND METHODS

Study design and participants

This retrospective study was approved by the Ethics Committee of MTI Lady Reading Hospital, Peshawar, Pakistan (Approval No. LRH/GEN-SURG/IRB/2025-047). Between January 2022 and December 2024, we identified 120 patients aged 45-75 years diagnosed with stage I-II PDAC (according to the American Joint Committee on Cancer, 8^th edition). Patients undergoing curative PD with confirmed postoperative pathology were included. Exclusion criteria comprised neoadjuvant therapy (n = 10), conversion from LPD to OPD [n = 5; due to intraoperative bleeding (n = 3) or adhesions (n = 2)], and incomplete records (n = 5), resulting in 117 patients for analysis.

Propensity score matching

Prior to matching, the group consisted of 65 patients who underwent LPD and 52 patients who underwent OPD. Patients were matched 1:1 based on age, sex, body mass index, American Society of Anesthesiologists score, and tumor size using logistic regression with nearest-neighbor matching, a caliper width of 0.2 standard deviations, and no replacement; unmatched patients from the larger group were excluded to ensure balanced pairs. Post-matching, baseline characteristics were well-balanced (standardized mean differences < 0.05 for all variables), as assessed by standardized mean differences and statistical tests. This process resulted in 50 matched pairs (n = 50 LPD and n = 50 OPD), which formed the basis for all subsequent analyses.

Surgical protocols

Surgeries were performed by five experienced hepatobiliary surgeons, each with a minimum of 100 LPDs. LPD utilized a five-port approach, while OPD employed a standard midline laparotomy. Reconstruction in both groups involved duct-to-mucosa pancreatojejunostomy. The duct-to-mucosa pancreatojejunostomy was performed using interrupted sutures with 5-0 polydioxanone, typically placing 6-8 stitches in a circular manner around the pancreatic duct to ensure precise alignment and minimize leakage. Both groups adhered to identical perioperative protocols, including enhanced recovery after surgery (ERAS) principles. The ERAS protocol included preoperative patient education and carbohydrate loading; intraoperative goal-directed fluid therapy; postoperative multimodal pain management (primarily epidural analgesia or patient-controlled analgesia with minimized opioids); early mobilization (targeted within 6-12 hours postoperatively); early removal of nasogastric tubes (typically on postoperative day 1 if no gastric distension was present); and progressive oral intake starting with clear liquids on postoperative day 1, advancing to solid food by day 3 as tolerated. Compliance with ERAS elements was monitored via electronic medical records, with overall adherence rates of 85% for mobilization, 92% for nasogastric tube removal, 88% for oral intake progression, and 90% for pain management across both groups (no significant differences between LPD and OPD, P > 0.05).

Outcome measures

Primary outcomes included operative time, blood loss, transfusion rate, and length of stay. Intraoperative blood loss was estimated using a standardized method combining suction canister volumes, weighed surgical swabs (with 1 g equivalent to 1 mL of blood), and visual assessment by the surgical and anesthesia teams, as recorded in the operative and anesthesia charts.

Secondary outcomes encompassed complications [overall, severe (Clavien-Dindo grade ≥ III), pancreatic fistula, delayed gastric emptying], as well as specific complications including wound infection, intra-abdominal abscess, bile leak, pulmonary complications, and sepsis; 90-day readmission and mortality; lymph node yield; R0 resection rate; and 24-month OS. Additionally, ERAS-specific metrics were assessed, including time to first mobilization (hours postoperatively), time to first oral intake (days postoperatively), and pain scores (using the Visual Analog Scale on postoperative day 1). Adjuvant chemotherapy was administered postoperatively according to institutional guidelines, primarily gemcitabine-based regimens (gemcitabine monotherapy or gemcitabine plus capecitabine), with fluorouracil, leucovorin, irinotecan, and oxaliplatin reserved for select fit patients; standard protocols targeted 6 cycles at full dose intensity (100% relative dose intensity where possible), adjusted for toxicity.

Statistical analysis

Analyses were conducted using IBM SPSS Statistics (version 27). Continuous variables were compared using independent t-tests, and categorical variables were compared using χ² or Fisher’s exact tests. Survival was assessed using Kaplan-Meier curves and log-rank tests; hazard ratios were estimated via Cox proportional hazards regression. Propensity score matching was performed in R (version 4.3.1). A P-value < 0.05 was considered statistically significant. Post-hoc power calculations (using statsmodels in Python) indicated > 99% power for detecting differences in blood loss (effect size 2.22) and approximately 90% power for length of stay (effect size 0.86), but lower power (approximately 20%-30%) for rare outcomes like mortality and severe complications, based on observed effect sizes and sample size (n = 50 per group). No multivariable adjustments beyond matching were performed, as residual confounding was minimal. Censoring for survival analyses occurred at the last follow-up or non-cancer death, with a median follow-up of 18 months (range 6-36 months).

RESULTS

Baseline characteristics

Following propensity matching, the LPD and OPD groups were well-balanced in terms of key demographic, clinical, and tumor-related variables, with no statistically significant differences observed (all P > 0.05). For example, the mean age was 62.5 ± 7.2 years in the LPD group and 63.1 ± 6.8 years in the OPD group, while the male-to-female ratio was approximately balanced at 54:46 for LPD and 52:48 for OPD (P = 0.89). Similarly, body mass index, tumor size, American Society of Anesthesiologists scores, and comorbidities such as diabetes were comparable between the groups. Detailed values and statistical comparisons are provided in Table 1 for reference.

Table 1 Baseline characteristics of the propensity-matched groups, mean ± SD.

Indicator	LPD group (n = 50)	OPD group (n = 50)	t/χ2	P value
Gender (male/female)	27/23	26/24	0.02	0.89
Age (years)	62.5 ± 7.2	63.1 ± 6.8	-0.49	0.62
BMI (kg/m2)	24.2 ± 3.1	24.5 ± 3.0	-0.52	0.61
Tumor size (cm)	2.8 ± 0.9	2.9 ± 1.0	-0.38	0.71
ASA score (I/II/III)	2/34/14	1/35/14	0.45	0.80
Diabetes (no/yes)	36/14	35/15	0.05	0.82

BMI: Body mass index; ASA: American Society of Anesthesiologists; LPD: Laparoscopic pancreaticoduodenectomy; OPD: Open pancreaticoduodenectomy.

Perioperative outcomes

The perioperative outcomes, as comprehensively outlined in Table 2 and visually summarized in Figure 1 (which includes mean differences and odds ratios with 95% confidence intervals), demonstrated several notable differences between LPD and OPD. Specifically, LPD was associated with extended operative times (P < 0.001) but offered clear benefits in terms of decreased blood loss (median 170 mL vs 340 mL; P < 0.001), reduced transfusion requirements (P = 0.03), and abbreviated hospital lengths of stay (P = 0.002). Regarding complications, rates for overall events, severe complications (Clavien-Dindo grade ≥ III), pancreatic fistula, delayed gastric emptying, and additional specific complications - including wound infection, intra-abdominal abscess, bile leak, pulmonary issues, and sepsis - did not differ significantly between the groups (all P > 0.05). Furthermore, ERAS-related metrics highlighted advantages for LPD, such as expedited time to first mobilization (P = 0.001) and earlier initiation of oral intake (P < 0.001). The 90-day readmission and mortality rates also showed no meaningful disparities (P = 0.30 and P = 0.62, respectively).

Figure 1 Forest plot of perioperative outcomes comparing laparoscopic pancreaticoduodenectomy vs open pancreaticoduodenectomy. The left panel shows MD for continuous outcomes (operative time, blood loss, length of stay), with the right panel displaying log odds ratios for binary outcomes (transfusion, complications, pancreatic fistula, delayed gastric emptying, readmission, mortality). Points represent estimates, with horizontal bars indicating 95% confidence intervals. P-values for each outcome are shown. LOS: Length of stay; CD: Clavien-Dindo; DGE: Delayed gastric emptying; LPD: Laparoscopic pancreaticoduodenectomy; OPD: Open pancreaticoduodenectomy; OR: Odds ratio; CI: Confidence interval.

Table 2 Perioperative outcomes, mean ± SD.

Indicator	LPD group (n = 50)	OPD group (n = 50)	t/χ2	P value	MD/OR (95%CI)
Operative time (minutes)	320 ± 45	285 ± 40	4.12	< 0.001	MD 35 (18.31 to 51.69)
Blood loss (mL)	180 ± 60	350 ± 90	-11.2	< 0.001	MD -170 (-199.98 to -140.02)
Transfusion (no/yes)	46/4	39/11	4.65	0.03	OR 0.31 (0.09 to 1.05)
LOS (days)	12 ± 3	15 ± 4	-3.28	0.002	MD -3 (-4.39 to -1.61)
Overall complications (no/yes)	29/21	25/25	0.68	0.41	OR 0.72 (0.33 to 1.59)
Severe complications (CD ≥ III, no/yes)	42/8	39/11	0.77	0.38	OR 0.68 (0.25 to 1.85)
Pancreatic fistula (no/yes)	44/6	42/8	0.32	0.58	OR 0.72 (0.23 to 2.24)
DGE (no/yes)	45/5	43/7	0.41	0.52	OR 0.68 (0.20 to 2.32)
90-day readmission (no/yes)	49/1	47/3	1.02	0.30	OR 0.32 (0.03 to 3.18)
90-day mortality (no/yes)	49/1	48/2	0.24	0.62	OR 0.49 (0.04 to 5.58)

LOS: Length of stay; CD: Clavien-Dindo; DGE: Delayed gastric emptying; LPD: Laparoscopic pancreaticoduodenectomy; OPD: Open pancreaticoduodenectomy; OR: Odds ratio; CI: Confidence interval.

Oncologic outcomes

Oncologic outcomes were equivalent between LPD and OPD, with no significant variations noted in lymph node yield (P = 0.45), R0 resection rates (P = 0.56), median OS (22 vs 20 months; log-rank P = 0.65), or 12-month recurrence-free survival (78% vs 72%; P = 0.48), as detailed in Table 3 and illustrated in Figure 2. Adjuvant chemotherapy profiles were likewise similar, encompassing regimens that were primarily gemcitabine-based (gemcitabine monotherapy in 60% of cases, gemcitabine plus capecitabine in 30%, and fluorouracil, leucovorin, irinotecan, and oxaliplatin in 10%), along with comparable completion rates (84% vs 80%; P = 0.62), a median of 5 cycles completed, and a mean relative dose intensity of 85% (P = 0.72).

Figure 2 Kaplan-Meier curves for overall survivalcomparing laparoscopic pancreaticoduodenectomy vs open pancreaticoduodenectomy. Survival probabilities are presented over 24 months, with shaded areas indicating 95% confidence intervals. The risk table below displays the number of patients at risk at each time point. The log-rank test yielded a P-value of 0.65, indicating no significant difference. LPD: Laparoscopic pancreaticoduodenectomy; OPD: Open pancreaticoduodenectomy.

Table 3 Oncologic outcomes, mean ± SD.

Indicator	LPD group (n = 50)	OPD group (n = 50)	t/χ2	P value	MD/OR/HR (95%CI)
Lymph nodes retrieved	14 ± 5	13 ± 4	0.75	0.45	MD 1 (-0.77 to 2.77)
R0 resection (no/yes)	4/46	6/44	0.34	0.56	OR 1.57 (0.41 to 5.93)
Median OS [months (95%CI)]	22 (19-25)	20 (17-23)		0.65	HR 0.92 (0.65 to 1.31)
12-month RFS (%)	78	72		0.48	HR 0.78 (0.35 to 1.74)
Adjuvant completion (no/yes)	8/42 (84%)	10/40 (80%)	0.24	0.62	OR 1.31 (0.47 to 3.66)

OS: Overall survival; CI: Confidence interval; RFS: Recurrence-free survival; LPD: Laparoscopic pancreaticoduodenectomy; OPD: Open pancreaticoduodenectomy; OR: Odds ratio.

Sensitivity analysis

Including the five patients converted from LPD to OPD in the LPD group did not significantly alter the primary outcomes, confirming the robustness of the results.

DISCUSSION

This study compares the perioperative and oncologic outcomes of LPD vs OPD for early-stage PDAC. LPD demonstrated significant perioperative advantages, including reduced blood loss, fewer transfusions, and shorter hospital stays, without apparent differences in oncologic outcomes such as lymph node yield, R0 resection rates, or survival.

The longer operative time for LPD aligns with prior studies, reflecting the technical complexity of intracorporeal reconstruction[6,11]. However, this did not increase complication rates, which is a critical consideration for minimally invasive approaches. The reduction in blood loss and transfusions is particularly noteworthy, as it may decrease risks such as anemia or transfusion-related complications, consistent with findings from meta-analyses[12]. Specific complication rates included wound infection [6% LPD vs 14% OPD; odds ratio (OR) = 0.39, P = 0.11], intra-abdominal abscess (4% vs 6%; OR = 0.65, P = 0.68), bile leak (2% vs 4%; OR = 0.49, P = 0.62), pulmonary complications (8% vs 12%; OR = 0.64, P = 0.41), and sepsis (4% vs 6%; OR = 0.65, P = 0.68); these showed no significant differences but contributed to the overall complication profiles. ERAS metrics favored LPD, with shorter time to first mobilization (8.5 ± 3.2 hours vs 12.4 ± 4.1 hours; MD -3.9 hours, P = 0.001) and earlier oral intake (1.2 ± 0.5 days vs 2.1 ± 0.8 days; MD -0.9 days, P < 0.001).

From an oncologic perspective, the comparable lymph node yield and R0 resection rates suggest LPD’s adequacy in experienced centers, supported by RCTs indicating non-inferiority[13,14]. However, the small sample size and wide confidence intervals (e.g., hazard ratio 0.78 for recurrence-free survival, 95% confidence interval: 0.35-1.74) limit definitive claims of equivalence, and larger studies are needed to establish non-inferiority. The median OS (20-22 months) aligns with outcomes for predominantly gemcitabine-based regimens but is slightly lower than those reported in Western groups using more intensive therapies like fluorouracil, leucovorin, irinotecan, and oxaliplatin, possibly due to differences in regimen selection, patient fitness for aggressive chemotherapy, or socioeconomic factors influencing overall care. Despite these variations, adjuvant completion rates in our group were high (84% for LPD and 80% for OPD), indicating strong adherence within the study population. The median OS (20-22 months) is slightly lower than some Western groups[15], possibly due to regional differences in adjuvant therapy access or socioeconomic factors, though completion rates were similar.

Limitations include the retrospective design, which, despite propensity matching, may not account for unmeasured confounders (e.g., tumor location, carbohydrate antigen 19-9 levels). The sample size constrained power for rare outcomes like mortality (power approximately 20%-30%), and the 18-month median follow-up limits long-term survival assessment. Patient-reported outcomes (e.g., quality of life) were not evaluated, and the single-center design may limit generalizability, particularly to low-volume or Western settings where conversion rates and outcomes may differ[16]. While our findings support LPD in high-volume centers like ours, outcomes may vary in low-volume settings or regions with limited resources, where the learning curve, equipment availability, and surgical expertise could impact safety and efficacy. Future multicenter RCTs should validate these findings and explore cost-effectiveness and robotic-assisted PD.

CONCLUSION

LPD appears to offer significant perioperative benefits over open surgery for early-stage PDAC, without evident compromise to oncologic outcomes in this group. These findings support LPD’s selective adoption in high-volume centers with experienced surgeons, particularly for patients without major vascular involvement. Prospective, multicenter studies are needed to confirm non-inferiority, long-term efficacy, and cost-effectiveness.

ACKNOWLEDGEMENTS

We would like to express our sincere gratitude to the staff and administration of MTI Lady Reading Hospital (Peshawar, Pakistan) for their invaluable support in facilitating data collection and access to the surgical database. We also extend our thanks to the patients whose data contributed to this study, without whom this research would not have been possible. Special appreciation is due to our colleagues in the Department of General Surgery for their clinical insights and assistance during the study period. Although this work received no external funding, we acknowledge the internal resources provided by our respective institutions that enabled its completion.