Zhang JZ, Guo XY, Zhang ZW, Zhu DS, Zhang Z, Zheng H, Guo T, Yu YH, Huang XR. Textbook oncologic outcomes following pancreatoduodenectomy in patients with pancreatic adenocarcinoma: A high-volume center study. World J Gastroenterol 2026; 32(20): 119062 [DOI: 10.3748/wjg.v32.i20.119062]
Corresponding Author of This Article
Xiao-Rui Huang, MD, Doctor, Division of Hepato-Pancreato-Biliary Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430000, Hubei Province, China. xiaoruihuang826@163.com
Research Domain of This Article
Surgery
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Jing-Zhao Zhang, Xin-Yi Guo, Zhi-Wei Zhang, Deng-Sheng Zhu, Zhen Zhang, Huan Zheng, Tong Guo, Ya-Hong Yu, Xiao-Rui Huang, Division of Hepato-Pancreato-Biliary Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
Co-corresponding authors: Ya-Hong Yu and Xiao-Rui Huang.
Author contributions: Zhang JZ was responsible for data curation, conceptualization, methodology, and drafting of the original manuscript; Guo XY performed the formal data analysis; Zhang ZW and Zhu DS contributed to case collection; Zhang Z and Zheng H were responsible for patient follow-up and preliminary data organization; Guo T critically revised the manuscript and provided clinical expertise; Huang XR and Yu YH contributed equally to supervision, funding acquisition, and manuscript review and editing.
AI contribution statement: AI-assisted tools may have been used only for language polishing, grammar correction, and improvement of English readability. No AI tool was used for data analysis, statistical processing, generation of scientific content, creation of references, or development of the study conclusions.
Institutional review board statement: The study was approved by the Medical Ethics Committee of the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (approval No. TJ-IRB202512058).
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent. The acquisition and use of these clinical data were approved by the Institutional Review Board.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.
Corresponding author: Xiao-Rui Huang, MD, Doctor, Division of Hepato-Pancreato-Biliary Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430000, Hubei Province, China. xiaoruihuang826@163.com
Received: January 20, 2026 Revised: January 31, 2026 Accepted: February 26, 2026 Published online: May 28, 2026 Processing time: 122 Days and 22 Hours
Abstract
BACKGROUND
The concept of textbook oncologic outcome (TOO), serving as an integrated composite measure, has emerged to evaluate the overall standard of oncologic care. Its utilization now spans various cancer types, supported by growing evidence linking successful TOO achievement to improved long-term patient survival. However, the role of TOO in pancreatic cancer patients undergoing pancreaticoduodenectomy (PD), particularly via open surgery, remains unclear. Additionally, differences in TOO achievement rates and associated factors between open PD (OPD) and laparoscopic PD (LPD) have not been systematically investigated.
AIM
To compare the achievement rates and influencing factors of TOO between OPD and LPD.
METHODS
We retrospectively reviewed patient records from our institution for those who received PD due to tumors located in the pancreatic head from January 2012 to June 2022. Patients meeting specific criteria were enrolled and grouped according to the type of surgical approach employed, either LPD or OPD. Propensity score matching techniques were employed to control for baseline differences between cohorts. Subsequently, multivariate logistic regression analysis was performed to identify factors independently associated with achieving TOO.
RESULTS
Overall, 78 patients achieved TOO, including 45 in the LPD group and 33 in the OPD group (P = 0.112). Achieving TOO was associated with significantly longer median overall survival in both groups (all P < 0.05). In the LPD group, independent risk factors negatively associated with TOO were high Clavien-Dindo grade [odds ratio (OR) = 0.22; 95% confidence interval (CI): 0.07-0.68] and prolonged postoperative hospital stay (OR = 0.94; 95%CI: 0.88-1.00). In the OPD group, independent risk factors included elevated aspartate aminotransferase (OR = 0.39; 95%CI: 0.16-0.92) and high Clavien-Dindo grade (OR = 0.32; 95%CI: 0.13-0.78) (all P < 0.05).
CONCLUSION
TOO achievement did not differ between LPD and OPD but was strongly correlated with superior long-term survival, with distinct risk factors across surgical approaches.
Core Tip: As an emerging composite endpoint, textbook oncologic outcome (TOO) reflects both the quality and effectiveness of oncologic surgery, although its role in pancreaticoduodenectomy (PD) has not been fully elucidated. In this propensity score matching-based analysis, no significant difference in TOO achievement was observed between laparoscopic PD and open PD. Nevertheless, achieving TOO was consistently associated with improved long-term survival regardless of surgical approach. Moreover, the factors influencing TOO attainment differed between surgical strategies, underscoring the impact of postoperative complications, recovery patterns, and hepatic function. These findings support TOO as a meaningful quality indicator and advocate for individualized perioperative strategies to optimize PD outcomes.
Citation: Zhang JZ, Guo XY, Zhang ZW, Zhu DS, Zhang Z, Zheng H, Guo T, Yu YH, Huang XR. Textbook oncologic outcomes following pancreatoduodenectomy in patients with pancreatic adenocarcinoma: A high-volume center study. World J Gastroenterol 2026; 32(20): 119062
Pancreatic cancer (PC) remains one of the most aggressive and lethal malignancies within the digestive system, characterized by insidious onset, rapid progression, and high metastatic potential. Despite advancements in diagnosis and treatment, the prognosis remains poor, with reported five-year overall survival (OS) rates ranging merely from 10% to 25% across various studies[1-3]. Given PC’s notably poor prognosis, early detection and effective treatment strategies are critically important. Surgical intervention remains the cornerstone for curative intent among patients eligible for resection. Pancreaticoduodenectomy (PD), which includes both the traditional Whipple procedure and its pylorus-preserving variant, remains the established surgical option for tumors of the pancreatic head. Since its systematic description by Whipple in the 1930s[4], PD has undergone extensive refinement, evolving into a highly standardized procedure with established perioperative management protocols. More recently, minimally invasive techniques, including laparoscopic and robotic PD, have been increasingly adopted alongside conventional open surgery, owing to their potential benefits such as reduced operative trauma, accelerated postoperative recovery, and improved cosmetic results[5,6].
PD is widely considered the most technically challenging abdominal operation. Its primary goal is to achieve a safe yet radical tumor resection, transforming significant perioperative risk into meaningful postoperative survival gains. Traditional metrics for surgical outcomes assessment, including R0 resection status, lymph node yield, and hospital stay duration, offer only partial insights into oncologic care quality and provide limited benchmarking value across institutions or techniques.
To address these limitations, the Dutch PC Group proposed a procedure-specific composite outcome in 2020 known as textbook outcome (TO). In pancreatic resection, TO is achieved only when a patient experiences no clinically relevant pancreatic fistula, bile leak, post-pancreatectomy hemorrhage (all International Study Group of Pancreatic Surgery grade B/C), severe morbidity (Clavien-Dindo grade ≥ III), hospital readmission, or in-hospital mortality[7]. This definition has since demonstrated effectiveness in several large national cohorts[8-10], establishing TO as a robust quality indicator for pancreatic surgery. However, TO remains focused exclusively on the surgical episode without considering postoperative adjuvant therapy. Consequently, it does not fully capture multidisciplinary oncologic care.
A truly comprehensive assessment of oncologic effectiveness, encompassing operative technical quality, perioperative management, and timely delivery of adjuvant therapy, is essential for accurate prognostication, evidence-based treatment refinement, and durable survival improvement. Building on the TO concept, textbook oncologic outcome (TOO) expands this perspective by integrating surgical quality metrics with the delivery of adjuvant chemotherapy, creating a multidimensional measure for entire cancer-treatment trajectories[11]. Therefore, TOO serves as a critical instrument for auditing the complete continuum of complex oncologic care and has been validated in gastric, hepatic, colorectal, and ovarian cancers[11-14]. In PC, TOO reportedly correlates closely with long-term survival following PD[15].
Nevertheless, uncertainty remains regarding potential differences in TOO achievement rates between surgical approaches to PD, independent factors influencing TOO in each surgical context, and the relationship between TOO attainment and patient survival. These gaps highlight the need for further research to refine TOO as a tool for evaluating and improving the quality of comprehensive oncologic care.
Using a retrospectively maintained, single-institution database of consecutive patients who underwent open PD (OPD) or laparoscopic PD (LPD) for pancreatic-head adenocarcinoma, we conducted a systematic, propensity-adjusted analysis comparing baseline characteristics, perioperative outcomes, TOO achievement, and long-term survival across surgical approaches. Additionally, we developed cohort-specific multivariable models to identify independent determinants of TOO achievement within each surgical context. This study expands the application of TOO to PD and offers actionable insights into optimizing perioperative management, enhancing adherence to adjuvant therapy, and ultimately improving overall treatment outcomes. These findings enrich the existing evidence base and reinforce TOO as a valuable benchmark for assessing and standardizing PC care across different surgical techniques.
MATERIALS AND METHODS
Research cohort
In this study, we analyzed consecutive cases undergoing PD for malignant pancreatic head lesions at Division of Hepato-Pancreato-Biliary Surgery, Tongji Hospital between January 2012 and June 2022. Eligible cases satisfied the following conditions: (1) Age ≥ 18 years; (2) Undergoing PD via open or laparoscopic techniques; and (3) No previous exposure to neoadjuvant therapies. Exclusion criteria involved: (1) Incomplete patient follow-up data; (2) Presence of concurrent or previously treated malignancies; and (3) Postoperative pathological diagnosis other than pancreatic ductal adenocarcinoma. Eligible participants were grouped according to surgical modality into LPD and OPD.
Ethical approval for this research was granted by the Institutional Review Board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (approval No. TJ-IRB202512058).
Data collection
Collected variables included baseline demographics (sex, age, height, and weight), American Society of Anesthesiologists (ASA) classification, and comorbidities (including diabetes, hypertension, and coronary artery disease). Laboratory parameters at admission comprised neutrophil, lymphocyte, platelet, and monocyte counts; alanine aminotransferase, aspartate aminotransferase (AST), alkaline phosphatase, γ-glutamyl transferase, serum albumin, total bilirubin, direct bilirubin, total cholesterol, and serum levels of carbohydrate antigen 19-9 and carcinoembryonic antigen (CEA). Preoperative biliary drainage status, including percutaneous transhepatic cholangial drainage and endoscopic retrograde cholangiopancreatography, as well as operative time, were recorded. Pathological variables included resection margin status, number of lymph nodes retrieved, maximum tumor diameter, histological type, tumor differentiation grade, and American Joint Committee on Cancer (AJCC) 8th edition tumor node metastasis (TNM) stage[16]. Postoperative complications assessed included bile leakage[17], gastrointestinal fistula, delayed gastric emptying (DGE)[18], post-pancreatectomy hemorrhage[19], postoperative pancreatic fistula (POPF) (grade B/C)[20], postoperative abdominal infection[21], pulmonary infection[21], liver failure[22], and kidney injury[23]. Postoperative length of stay (LOS) and Clavien-Dindo complication grade[24] were also documented. Follow-up data included receipt of postoperative adjuvant therapy and survival status. Patients were followed every 3 months via telephone or text messaging, with follow-up censored on June 30, 2023.
Calculation of relevant inflammation and nutritional indicators
Neutrophil to lymphocyte ratio = neutrophil count (× 109/L)/Lymphocyte count (× 109/L). Platelet to lymphocyte ratio = platelet count (× 109/L)/Lymphocyte count (× 109/L). Prognostic nutritional index (PNI) = serum albumin (g/L) + 5 × lymphocyte count (× 109/L). Systemic immune inflammation index (SII) = platelet count (× 109/L) × neutrophil count (× 109/L)/Lymphocyte count (× 109/L).
The Naples prognostic score (NPS)[25] incorporated albumin, total cholesterol, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio. Parameters received scores of either 0 or 1 based on established thresholds, producing cumulative scores ranging from 0 to 4. Higher NPS values indicated increased systemic inflammation and poorer nutritional status.
The controlling nutritional status score[26] was derived from albumin, total cholesterol levels, and lymphocyte count, providing a scoring scale from 0 to 12, with higher scores denoting poorer nutritional condition.
Definition of TOO
TOO is not merely an extension of TO; rather, it emphasizes a comprehensive tumor treatment process involving surgical intervention, quality of recovery, and adjuvant therapy administration. This approach underscores its significant relationship with patients' long-term survival. R0 resection is a critical indicator for evaluating the completeness of tumor removal[27], whereas comprehensive lymph node dissection is closely associated with improved patient survival[28]. Likewise, adjuvant therapy is essential for the comprehensive management of PC[29]. Accordingly, TOO was defined by simultaneously meeting all the following criteria: R0 resection, adequate lymphadenectomy (LAD), no prolonged LOS, no unplanned 30-day readmission, no 30-day mortality, and appropriate adjuvant chemotherapy administered within 12 weeks post-surgery based on tumor stage[30,31]. For patients who underwent PD from 2012 to 2015, adequate LAD was assessed using the AJCC 7th edition TNM staging system[32], requiring retrieval of ≥ 12 lymph nodes. For patients treated from 2016 onward, updated recommendations required retrieval of ≥ 15 lymph nodes[33,34]. Prolonged LOS was defined as a postoperative stay exceeding the 75th percentile[35].
Propensity score matching
A 1:1 nearest-neighbor matching strategy was utilized in propensity score matching (PSM), incorporating preoperative oncologic and demographic factors [age, sex, body mass index (BMI), ASA, physical status classification, comorbidities, tumor size, TNM stage, preoperative biliary drainage, PNI, and SII]. The R package “MatchIt” facilitated the matching procedure, and covariate balance post-matching was assessed through standardized mean differences (SMDs), calculated using the “tableone” package. An SMD below 0.1 was indicative of sufficient balance between matched. All procedures were performed by surgeons who had completed their learning curve for PD. All patients in the LPD cohort successfully underwent laparoscopic surgery (Figure 1).
Figure 1 Flowchart of case selection.
OPD: Open pancreaticoduodenectomy; LPD: Laparoscopic pancreaticoduodenectomy; ASA: American Society of Anesthesiologists; BMI: Body mass index; SII: Systemic immune inflammation index; PNI: Prognostic nutritional index; TNM: Tumor node metastasis; PSM: Propensity score matching.
Statistical analysis
Continuous variables that followed a normal distribution were expressed as means ± SD and evaluated using independent-sample t-tests. Conversely, continuous variables with non-normal distributions were reported as medians (interquartile ranges) and compared through the Wilcoxon rank-sum test. Categorical data were presented as n (%) and analyzed using χ2 or Fisher’s exact tests as appropriate. Ordinal variables, such as the Clavien-Dindo classification, were evaluated by the Cochran-Armitage test for trend. Receiver operating characteristic curves determined optimal thresholds for selected variables, which were subsequently employed for patient grouping. Univariate logistic regression identified variables potentially predictive of TOO attainment, and statistically significant factors (P < 0.05) proceeded to multivariate logistic regression analyses. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and statistical significance was set at P < 0.05. All statistical evaluations and PSM were performed with R software (version 4.5.0; R Foundation for Statistical Computing, Vienna, Austria).
RESULTS
TOO results and cohort characteristics
A total of 478 patients with pancreatic malignancies fulfilled the inclusion criteria, among whom 147 underwent LPD and 331 received OPD. Following PSM, each surgical group comprised 144 matched cases for subsequent analysis. TOO was successfully achieved in 78 patients overall, with 45 cases in the LPD cohort and 33 in the OPD cohort. The total TOO achievement rate was 27.1%, with subgroup achievement rates of 31.2% for LPD and 22.9% for OPD, respectively. Individual indicator achievement rates are detailed in Figure 2. Among these indicators, adherence to postoperative adjuvant therapy was lowest (49.31%), followed by adequate LAD (71.18%). Conversely, indicators such as absence of 30-day readmission (98.26%) and absence of 30-day mortality (95.49%) exhibited the highest achievement frequencies.
Figure 2 Distribution of textbook oncologic outcome components.
LOS: Length of stay; LAD: Lymphadenectomy; TOO: Textbook oncologic outcome.
Baseline characteristics and perioperative outcomes
There were no significant differences in demographic characteristics (sex, BMI, age, comorbidities, and ASA classification). Regarding laboratory tests, the overall serum CEA level was higher in the OPD group [3.3 (2.1-5.3) ng/mL vs 2.8 (1.8-4.0) ng/mL, P = 0.013], but remained within the normal range (< 5 ng/mL). Other laboratory parameters, including neutrophil, lymphocyte, monocyte, and platelet counts, serum albumin, liver function indices, and nutritional and inflammatory markers derived from these variables, did not significantly differ between cohorts.
Regarding perioperative results, preoperative biliary drainage rates were similar across both groups, without significant differences in tumor-specific characteristics (TNM stage and differentiation). Additionally, complication distributions according to the Clavien-Dindo classification did not significantly differ between groups. However, the OPD group exhibited a higher frequency of postoperative complications, notably increased incidences of POPF, DGE, and pulmonary infection (all P < 0.05). The median postoperative hospital stay appeared shorter in the LPD group, though this difference did not achieve statistical significance (P = 0.052). Furthermore, median OS did not differ between the surgical approaches (15.4 months vs 14.5 months, P = 0.134) (Tables 1 and 2).
Table 1 Demographic data and clinical characteristics of open pancreaticoduodenectomy and laparoscopic pancreaticoduodenectomy patients, mean ± SD/n (%).
Characteristic
LPD (n = 144)
OPD (n = 144)
Total (n = 288)
P value
Sex (male)
84 (58.3)
87 (60.4)
171 (59.4)
0.719
Age (years)
59.6 ± 8.3
58.5 ± 9.2
59.1 ± 8.8
0.307
BMI (kg/m2)
21.9 ± 2.4
21.9 ± 3.0
21.9 ± 2.7
0.987
Diabetes
17 (11.8)
18 (12.5)
35 (12.2)
0.857
Cardiovascular disease
32 (22.2)
31 (21.5)
63 (21.9)
0.887
ASA score
I
9 (6.2)
8 (5.6)
17 (5.9)
0.955
II
92 (63.9)
94 (65.3)
186 (64.6)
III
43 (29.9)
42 (29.2)
85 (29.5)
Neutrophil count (× 109/L), median (IQR)
3.4 (2.6, 4.3)
3.2 (2.6, 4.7)
3.4 (2.6, 4.4)
0.937
Lymphocyte count (× 109/L), median (IQR)
1.3 (1.1, 1.7)
1.3 (1.0, 1.7)
1.3 (1.0, 1.7)
0.661
Mononuclear cell count (× 109/L), median (IQR)
0.4 (0.4, 0.6)
0.5 (0.4, 0.6)
0.5 (0.4, 0.6)
0.293
Platelet count (× 109/L), median (IQR)
211.0 (167.0, 266.5)
218.5 (181.5, 259.5)
214.0 (176.0, 265.0)
0.529
Serum albumin (g/L), median (IQR)
38.5 (36.5, 40.8)
38.0 (35.6, 40.4)
38.2 (35.9, 40.5)
0.155
PLR, median (IQR)
160.5 (120.0, 216.4)
161.7 (124.6, 226.3)
160.8 (123.1, 222.2)
0.659
NLR, median (IQR)
2.5 (1.8, 3.4)
2.6 (1.8, 3.7)
2.6 (1.8, 3.4)
0.517
PNI, median (IQR)
45.6 (42.2, 48.3)
45.0 (42.3, 48.0)
45.4 (42.2, 48.1)
0.371
SII, median (IQR)
516.9 (363.3, 780.5)
549.4 (354.5, 836.6)
535.5 (359.5, 809.5)
0.557
NPS, median (IQR)
2.0 (2.0, 3.0)
3.0 (2.0, 3.0)
2.0 (2.0, 3.0)
0.240
CONUT score, median (IQR)
2.0 (1.0, 3.0)
2.0 (1.0, 3.0)
2.0 (1.0, 3.0)
1.000
ALT (U/L), median (IQR)
124.5 (43.0, 266.5)
115.0 (52.5, 245.0)
118.5 (50.0, 254.5)
0.558
AST (U/L), median (IQR)
82.0 (36.0, 188.0)
77.0 (36.5, 140.0)
78.0 (36.0, 165.5)
0.548
ALP (U/L), median (IQR)
254.0 (119.5, 454.5)
296.0 (143.5, 476.0)
277.0 (131.5, 462.0)
0.331
γ-GT (U/L), median (IQR)
460.5 (134.0, 764.0)
463.0 (141.5, 908.0)
462.5 (136.0, 832.0)
0.494
TBIL (μmol/L), median (IQR)
100.1 (17.9, 203.2)
123.2 (34.5, 198.2)
118.5 (24.2, 201.2)
0.373
DBIL (μmol/L), median (IQR)
85.0 (9.9, 163.7)
109.3 (24.5, 162.4)
95.4 (16.0, 163.6)
0.397
Serum total cholesterol level (mmol/L), median (IQR)
In the LPD group, patients achieving TOO demonstrated longer median OS (32.2 months vs 13.3 months, P < 0.0001). Corresponding 1-, 3-, and 5-year survival rates were 88.8%, 40.4%, and 23.6%, respectively (Figure 3A). Similarly, in the OPD cohort, achieving TOO was associated with significantly improved median OS (23.4 months vs 11.7 months, P = 0.0083). The 1- and 3-year survival rates in the TOO group were 81.8% and 10.8%, respectively (Figure 3B).
Figure 3 Kaplan-Meier survival curves stratified by textbook oncologic outcomes.
A: Kaplan-Meier survival curves for patients in the laparoscopic pancreaticoduodenectomy group stratified by achievement of textbook oncologic outcomes; B: Kaplan-Meier survival curves for patients in the open pancreaticoduodenectomy group stratified by achievement of textbook oncologic outcomes. TOO: Textbook oncologic outcome.
Risk factors associated with TOO
Univariate and multivariable logistic regression analyses were separately conducted in the LPD and OPD groups. Within the LPD cohort, independent negative predictors for TOO achievement included postoperative complications classified as Clavien-Dindo grade II or above (OR = 0.22; 95%CI: 0.07-0.68; P = 0.008) and extended postoperative LOS (OR = 0.94; 95%CI: 0.88-1.00; P = 0.048). Additionally, serum albumin levels ≥ 37.95 g/L exhibited a positive association with TOO attainment, although this was marginally non-significant (OR = 2.65; 95%CI: 1.00-7.00; P = 0.050) (Table 3). Comparable results emerged in the OPD group, where independent factors negatively impacting TOO achievement were identified as Clavien-Dindo complication grades ≥ II (OR = 0.32; 95%CI: 0.13-0.78; P = 0.012) and elevated AST concentrations (OR = 0.39; 95%CI: 0.16-0.92; P = 0.031) (Table 4).
Table 3 Univariate and multivariable logistic regression analysis of textbook oncologic outcome achievement in the laparoscopic pancreaticoduodenectomy cohort.
Table 4 Univariate and multivariable logistic regression analysis of textbook oncologic outcome achievement in the open pancreaticoduodenectomy cohort.
Previous studies[11,13,14] demonstrated that TOO serves as a robust prognostic indicator across multiple malignancies. In PC, achieving TOO among patients undergoing LPD reportedly conferred significant survival advantages, with improved median OS (P = 0.034) and recurrence-free survival (P =0.053)[15]. However, the influence of surgical approach on TOO achievement remains unclear, and evidence regarding TOO attainment after OPD and its association with long-term survival is limited. By including both OPD and LPD cohorts, this study directly compared TOO achievement rates between surgical approaches and further explored its association with long-term outcomes, addressing important gaps in existing literature.
TOO integrates postoperative adjuvant therapy as a crucial indicator, highlighting comprehensive and effective oncologic care. The overall rate of TOO achievement at our institution was 27.1%, without a statistically significant difference observed between surgical approaches (31.2% vs 22.9%, P = 0.112). This rate is comparable to findings from a previous LPD study[15]. However, compared to other malignancies, the TOO achievement rate for pancreatic head cancer remains relatively low. For example, studies on hepatocellular carcinoma reported overall TOO achievement rates as high as 69%[13]. Similarly, an analysis using the National Cancer Database indicated a TOO achievement rate of 54.8% following colon adenocarcinoma resection[35]. Among individual TOO criteria, postoperative adjuvant chemotherapy had the lowest fulfillment rate (49.3%), substantially limiting overall TOO success. Given its importance in postoperative management, timely initiation of adjuvant chemotherapy significantly reduces mortality risk, enhances survival outcomes, and contributes to better long-term prognosis in PC patients[36].
Furthermore, patients who achieved TOO exhibited notably improved OS compared to those who did not, regardless of surgical technique, consistent with previous studies in various malignancies[11,13,14]. As a comprehensive indicator, TOO may reflect improved perioperative recovery and quality of care, subsequently influencing long-term survival. Therefore, TOO likely represents the impact of patients’ physical condition and postoperative recovery on survival rather than directly determining survival itself. Consequently, initiation of adjuvant chemotherapy within the recommended 12-week postoperative interval emerges as a critical determinant for TOO achievement and enhanced survival. Nonetheless, multiple factors, including patient-specific conditions, postoperative morbidity, and hospital- or healthcare system-related circumstances, may influence the timely administration of adjuvant therapies[37,38]. Thus, meticulous surgical planning, adequate postoperative nutritional support, and referral to experienced centers are crucial to increasing adjuvant chemotherapy uptake and optimizing outcomes.
POPF, a frequent complication following pancreatic surgery, may result in severe adverse outcomes. A recent meta-analysis indicated comparable rates of POPF (OR = 0.93, P = 0.29) and severe complications (OR = 0.97, P = 0.74) between LPD and OPD procedures[39]. However, Hong et al[40] reported significantly reduced POPF incidence in PC patients undergoing LPD when pancreatic texture was soft and pancreatic duct diameter was under 2 mm. Previous research identified pancreatic duct diameter and texture as independent risk factors for POPF occurrence[41]. Therefore, although overall pancreatic fistula incidence does not differ significantly between LPD and OPD, surgical approach may influence its occurrence under specific pancreatic conditions. Compared to OPD, LPD provides a clearer operative field and facilitates precise surgical manipulation. Thus, for patients with high-risk features for pancreatic fistula, LPD might offer significant advantages and improved outcomes.
Consistent with previous findings, our study identified a notably elevated incidence of POPF within the OPD cohort (P < 0.001). Although this could potentially relate to inherent pancreatic features, further research is warranted to confirm this hypothesis. Additionally, OPD patients exhibited higher rates of DGE, pulmonary infections, and severe postoperative morbidity, aligning with prior studies[39,42]. While the LPD group demonstrated a trend towards reduced postoperative hospitalization duration, this advantage did not achieve statistical significance (P = 0.052). Nonetheless, this observation implies that LPD might facilitate quicker postoperative recovery.
To align with contemporary oncologic standards, the criteria for adequate lymph node retrieval in the TOO definition evolved during the study period. These criteria were based on the AJCC staging systems and relevant studies prevalent at the time of surgery[32-34]. However, these changes may have introduced temporal bias and influenced observed TOO achievement rates. Future research could evaluate the impact of varying lymph node dissection standards on TOO outcomes through segmented analyses at different intervals.
Moreover, complications classified as Clavien-Dindo grade II or higher emerged as significant independent predictors negatively impacting TOO attainment in both surgical groups. Severe postoperative adverse events typically lead to prolonged hospital stays, delayed physical recovery, postponed initiation of adjuvant therapy, and occasionally render patients unsuitable for chemotherapy due to their deteriorated condition. Specifically, multivariate logistic regression in the LPD group revealed that prolonged postoperative hospitalization reduced the likelihood of achieving TOO (OR = 0.94; 95%CI: 0.88-1.00; P = 0.048), consistent with OPD group findings. Thus, reducing the incidence of serious postoperative complications (Clavien-Dindo grade ≥ II) through comprehensive preoperative assessment, meticulous surgical techniques, and optimized perioperative management is a crucial determinant in achieving TOO.
Serum albumin levels (≥ 37.95 g/L) showed a marginal association with TOO achievement in the LPD group (P = 0.050). Although statistically borderline, this finding is biologically plausible, indicating preoperative nutritional status may significantly influence postoperative recovery and treatment quality. Serum albumin reflects nutritional and inflammatory status, is closely associated with postoperative complications, and may serve as a prognostic indicator, either independently or in combination with other clinical factors[43-45]. In the OPD group, an AST level ≥ 77.5 U/L was also identified as an independent factor negatively associated with TOO achievement (P = 0.031). Elevated AST levels usually reflect biliary obstruction caused by tumors. Persistent obstruction further elevates bilirubin and impairs liver function, worsening patients’ nutritional and inflammatory conditions. This deterioration can impede postoperative recovery, hinder adjuvant chemotherapy administration, and adversely affect long-term prognosis. Therefore, for patients with elevated preoperative AST levels, preoperative drainage to relieve obstruction and improve liver function may significantly enhance TOO achievement.
Several limitations merit consideration. Firstly, the single-center, retrospective design confines external validity; inter-institutional differences in case volume and surgical expertise will inevitably shift TOO rates; therefore, each center should calibrate the TOO definition to its own performance profile before benchmarking. Second, the choice between OPD and LPD for pancreatic head cancer patients involves preoperative multidisciplinary discussions. Surgeons typically prefer OPD for large tumors, significant pancreatic inflammation, complex vascular reconstruction, or limited surgical exposure. Consequently, selection bias is inherently present. To reduce surgeon preference bias, PSM accounted for patient demographics, preoperative nutritional status, and oncologic characteristics. However, residual confounding due to unmeasured variables cannot be fully excluded. Third, patients receiving neoadjuvant therapy were excluded from this study. Neoadjuvant therapy influences critical pathological parameters, such as R0 resection likelihood and lymph node retrieval number. Therefore, excluding these patients may overestimate TOO rates and limit applicability to current multimodal treatment approaches. Future multicenter studies, including prospective randomized controlled trials, are necessary to refine subgroup analyses and broaden the applicability of TOO in oncologic care.
CONCLUSION
Although TOO achievement rates showed no statistically significant difference between LPD and OPD, patients undergoing OPD were more susceptible to developing postoperative complications, such as POPF, DGE, pulmonary infection, and complications categorized as Clavien-Dindo grade II or above. Determinants of TOO achievement differed by surgical approach, whereas severe postoperative complications consistently reduced the likelihood of achieving TOO in both groups. Implementing optimized treatment strategies to reduce severe postoperative complications (Clavien-Dindo ≥ II), including enhanced recovery programs, refined surgical techniques, and improved perioperative management, may enhance the likelihood of achieving an optimal oncologic pathway fulfilling TOO criteria.
ACKNOWLEDGEMENTS
We are grateful to all patients who contributed to this study.
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Footnotes
Peer review: Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: China
Peer-review report’s classification
Scientific quality: Grade B, Grade B, Grade B
Novelty: Grade B, Grade B, Grade B
Creativity or innovation: Grade B, Grade B, Grade B
Scientific significance: Grade B, Grade B, Grade B
P-Reviewer: Chen YX, PhD, Academic Fellow, China; Zhang JL, MD, Academic Fellow, China S-Editor: Fan M L-Editor: A P-Editor: Zhang L
