Preoperative interleukin-17a as a predictor of acute pancreatitis after pancreaticoduodenectomy

Abstract

BACKGROUND

Acute pancreatitis (AP) is a potentially life-threatening complication of pancreaticoduodenectomy that increases morbidity and mortality in patients. Interleukin-17A (IL-17a) the potential preoperative marker for predicting postoperative outcomes. The purpose of this study is to retrospectively assess the prognostic value of preoperative IL-17a level in prediction of AP and related postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy.

AIM

To retrospectively assess the prognostic value of preoperative IL-17a levels in predicting AP and related POPF following pancreaticoduodenectomy.

METHODS

Retrospective analysis of pancreaticoduodenectomies performed on patients 150 patients between 2017 and 2023. Clinical data including pre-operative IL-17a levels were collected. The primary composite outcomes were postoperative AP and postoperative pancreatic (PP), and the predictive performances of IL-17a levels and fluid load status for postoperative complications were evaluated by statistical analysis.

RESULTS

A total of 150 patients were included, and 26 patients (17.3%) developed postoperative AP and 34 patients (22.7%) developed PP. Preoperative IL-17a was a risk factor for postoperative AP (P = 0.03). Furthermore, excessive intraoperative fluid load was a significantly associated (P = 0.01) with PP. The model (IL-17a levels + fluid load status) was highly accurate.

CONCLUSION

Preoperative IL-17a levels and intravascular volume status may serve as useful predictors of AP and subsequent PP following PD. These parameters provide means to evaluate preoperative risk and may guide clinical decision making to enhance postoperative recovery.

Key Words: Acute pancreatitis; Pancreaticoduodenectomy; Interleukin-17A; Fluid load; Postoperative pancreatic fistula

Core Tip: Preoperative interleukin-17A (IL-17a) levels independently predict post pancreatectomy acute pancreatitis and related postoperative pancreatic fistula after pancreaticoduodenectomy. Elevated IL-17a reflects inflammatory status, aiding risk stratification and guiding preoperative optimization and postoperative monitoring. Combining IL-17a with fluid management improves predictive accuracy, offering a practical tool for reducing complications.

INTRODUCTION

The standard surgical treatment for tumors of the pancreatic head, lower bile duct, and ampulla is pancreaticoduodenectomy, but anatomical nuances and the surgical difficulty for this procedure result in a high rate of postoperative complications[1,2]. However, postoperative acute pancreatitis (PAP) is a more severe complication that can aggravate the patient's condition, prolong hospital stays, rise medical costs, and even threaten life[3,4]. In addition, postoperative pancreatic fistula (POPF), which has an incidence of as high as 20%, is one of the most frequent complications, leading to increased rates of infection, reoperation, and mortality[5,6]. POPF is related to multiple influencing factors, including pre-existing inflammatory status, surgical methods, and basic diseases of patients. The pathophysiological changes in POPF predominantly include exocrine abnormalities. Although pancreatic fluid is similar to interstitial fluid, excessive loss of pancreatic fluid may result in electrolyte imbalances and acid-base disorders, which may lead to hypoproteinemia. In addition, poor drainage around an external pancreatic fistula may cause the surrounding skin to become congested (swollen), eroded (damaged), ulcerated, or bleed; it may also result in pseudo-cysts or infections. Secondary infections can lead to purulent peritonitis, further systemic infection and local abscess formation[7,8]. PAP is not only responsible for patient suffering and economic burden but also prolonging hospitalization and delaying postoperative recovery, as well as possibly increasing mortality risk. Also, postoperative challenges like pancreatic and biliary leaks are significant problems after pancreaticoduodenectomy.

The exact mechanism behind the development of PAP is not fully understood, although there are suggestions that pancreatic injury caused by surgery, inflammatory response, and obstruction in drainage of pancreatic fluid may be responsible. The incidence of PAP has been observed to correlate with multiple factors such as pre-existing inflammatory states, surgical techniques, and underlying patient factors[9,10]. Two previous studies found that preoperative biliary obstruction, diabetes, hypoproteinemia, and anemia, etc. could be related to postoperative bile leak, Masterson has demonstrated the interaction of these risk factors, including radiological confirmation of hepatic bile duct injury prior to resection, so the timing of surgery and intraoperative management is crucial to preventing postoperative bile leak. However, in light of a clearer understanding of PAP, the International Study Group for Pancreatic Surgery (ISGPS) has recently called for standardized definitions and grading of PAP and the assessment of PAP as an independent complication. This new definition takes into account both serum amylase level and imaging and clinical impact factors, providing greater clarity for the diagnosis and treatment of PAP. POPF symptoms usually manifest post-surgery, often within a week or two. Low-flow or small POPFs may result in skin changes around the outer fistula yet little other clinical activity. Preventing POPF is crucial. Preoperative anemia correction and nutritional improvement may prevent POPF, at least to some extent[11,12]. Pro-inflammatory cytokine interleukin-17A (IL-17a), which is implicated in the inflammatory response and changes in its serum levels correlate with the severity and prognosis of many pathological conditions[13,14].

This retrospective study aimed to evaluate the potential role of preoperative IL-17a in the prediction of PAP and POPF in patients undergoing pancreaticoduodenectomy. A better understanding of how these factors are associated with postoperative complications may allow clinicians to risk stratify better, mitigate intraoperative fluid management strategies and target postoperative monitoring and treatment strategies.

MATERIALS AND METHODS

Patient selection

Between January 2021 and December 2023, 150 patients aged ≥ 18 years who received a surgical operation of pancreaticoduodenectomy were included in this study. Post pancreatectomy acute pancreatitis (PPAP) was defined according to the 2022 criteria proposed by ISGPS as serum amylase levels above the upper limit of normal (> 100 U/L) on postoperative days 1 and 2 with radiological changes and clinical changes involving computed tomography (CT) images in postoperative management. Criteria for exclusion were: (1) Patients whose serum amylase values were not obtained on days 1-2 following surgery and who did not undergo CT scanning within 10 days post-surgery; or (2) Who had no preoperative recording of serum values of white blood cell count (WBC), neutrophils (NE), C-reactive protein (CRP), T-cell subsets or cytokines.

Surgical procedure and postoperative management

The Whipple procedure was performed using pancreatojejunostomy with duct-to-mucosa double-layer anastomosis. An oblique incision below the right costal margin was used for abdominal exploration. The second part of the duodenum and the pancreatic head were mobilized anteriorly from the retroperitoneum, with both duodenum and pancreatic head being freed. Changes in the pancreas and its relationship to the mass were examined to assess tumor resectability. Gastrectomy was performed following Hoffmeister's method, and lymphatic-fatty tissue around the arteries was separated to remove the pancreas and duodenum with the tumor. After resection, digestive tract reconstruction included choledochojejunostomy, pancreatojejunostomy, and gastrojejunostomy. Drains were placed in the abdominal cavity for postoperative fluid drainage and monitoring. Lymph node dissection was performed to reduce tumor recurrence risk. Postoperatively, antibiotics and somatostatin analogs were routinely administered. Routine CT scans were conducted on postoperative days 3 and 7 to assess recovery, with urgent scans for patients suspected of having severe complications[15-17].

Data collection

A retrospective analysis examined patient characteristics including demographics [age, sex, body mass index (BMI)], ASA classification, albumin values, and jaundice indicators (total bilirubin and biliary status before surgery). The study also evaluated preoperative inflammatory markers such as WBC count, NE levels, CRP, and various cytokines. T-cell subset analysis and cytokine measurement employed enzyme-linked immunosorbent assay techniques. The cytokine panel consisted of seven markers: Interleukins 2, 4, 6, 10, and 17A, along with IFN-γ and tumor necrosis factor-α (TNF-α). All inflammatory parameters were obtained from initial assessments conducted within 3 days prior to surgical intervention. Certain patients underwent preoperative optimization, such as management of severe jaundice, to ensure surgical fitness. Surgical data collection encompassed main pancreatic duct (MPD) diameter, pancreatic consistency, operative approach (open pancreaticoduodenectomy vs robotic pancreaticoduodenectomy), vein resection necessity, procedure duration, blood loss estimation, tumor dimensions, and pathological findings. The fistula risk score (FRS) was subsequently calculated to facilitate further statistical evaluation.

Disease definitions

According to ISGPS criteria, diagnoses were established for POPF, and delayed gastric emptying. Chylous leakage was also identified using these standards. For bile leakage, diagnostic confirmation relied on endoscopic or radiological assessment of drainage fluid abnormalities. Intra-abdominal infection was recognized through sustained fever with culture-positive drainage samples or imaging evidence. The management approach included post-surgical drainage procedures performed under radiological or endoscopic guidance. Data collection encompassed surgical re-exploration incidence, length of hospitalization following surgery, and mortality within 90 days as the perioperative mortality indicator. The Clavien-Dindo classification system categorized postoperative complications, with grades III-V designated as significant complications.

Statistical analysis

We conducted a subgroup analysis for risk factors of POPF in PPAP and non-PPAP groups. For continuous outcomes such as mechanical ventilation time or infusion of inflammatory markers, Analysis of Variance (ANOVA), assuming data normality and homoscedasticity, was used to evaluate the influence of categorical independent variables. Post hoc tests following ANOVA were used to investigate differences between individual group means when an overall ANOVA (Type III sum of squares) indicated an overall significant effect. Our findings were obtained from a robust healthcare dataset and highlighted critical risk factors for PPAP and other complications following PD, which can be invaluable as a guide for subsequent research and advances in clinical practice.

RESULTS

Cohort characteristics

This study compared patients who received PPAP (n = 45) and those who did not receive PPAP (n = 105). The non-PPAP group had higher rates of soft pancreatic texture (61.0% vs 34.0%, P < 0.001) and MPD ≤ 3 mm (81.0% vs 60.0%, P = 0.012), as well as higher FRS risk area (P < 0.001). Regarding complications, the non-PPAP group performed significantly worse, with higher rates of POPF (55.6% vs 7.4%, P < 0.001), bile leak (9.1% vs 2.1%, P = 0.006), intra-abdominal infection (26.7% vs 9.5%, P = 0.001), major complications (17.2% vs 3.8%, P = 0.001), need for interventional drainage (12.2% vs 1.4%, P < 0.001), and reoperation (5.6% vs 0.7%, P = 0.021). Additionally, the non-PPAP group had significantly longer postoperative hospital stays (28 days vs 14 days, P < 0.001).

Overall, despite the PPAP group having higher bilirubin levels and more frequent pancreatic ductal adenocarcinoma (PDAC) or chronic pancreatitis (CP), the application of PPAP significantly reduced the incidence of postoperative complications and shortened hospital stays, suggesting that PPAP may be an effective intervention (Table 1).

Table 1 Comparison of patient characteristics and postoperative complications.

Variables	No PPAP (n = 105)	PPAP (n = 45)	P value
Age [median (IQR)], years	63 (55-70)	63 (56.5–70)	0.549
Sex, n (%), male	230 (59.7%)	42 (51.2%)	0.155
Total bilirubin level (μmol/L)	12.0 (7.8-20.0)	19.5 (12.6-35.0)	0.04
Incidence of soft pancreatic texture (%)	61.0	34.0	< 0.001
Incidence of MPD ≤ 3 mm (%)	81.0	60.0	0.012
Incidence of PDAC or CP (%)	26.7	58.7	0.001
FRS risk area	Higher	Lower	< 0.001
Incidence of POPF (%)	55.6	7.4	< 0.001
Incidence of bile leak (%)	9.1	2.1	0.006
Incidence of intra-abdominal infection (%)	26.7	9.5	0.001
Incidence of major complications (%)	17A.2	3.8	0.001
Incidence of interventional drainage (%)	12.2	1.4	< 0.001
Incidence of reoperation (%)	5.6	0.7	0.021
Postoperative hospital stay (days)	28 (21-35)	14 (10-20)	< 0.001

PDAC: Pancreatic ductal adenocarcinoma; PPAP: Postpancreatectomy acute pancreatitis; MPD: Main pancreatic duct; CP: Chronic pancreatitis; FRS: Fistula risk score; POPF: Postoperative pancreatic fistula.

Predictive effect of preoperative inflammatory data, IL-17a, and fluid load on PPAP

This analysis compared the immune and inflammatory markers between patients who received PPAP (n = 45) and those who did not receive PPAP (n = 105). The results showed no significant differences between the two groups in most inflammatory markers, including CRP (2.12 vs 2.11 mg/L, P = 0.214), IFN-α (0.2 vs 0.2 pg/mL, P = 0.472), IFN-γ (3.4 vs 3.6 pg/mL, P = 0.578), IL-2 (0.2 vs 0.2 pg/mL, P = 0.467), IL-4 (0.2 vs 0.2 pg/mL, P = 0.401), and IL-5 (0.2 vs 0.2 pg/mL, P = 0.469). WBC also showed no statistical difference (5.96 vs 5.66 × 10⁹/L, P = 0.070). However, there was a significant difference in IL-17a levels between the groups, with the PPAP group showing markedly lower levels than the non-PPAP group (3.5 vs 12.5 pg/mL, P < 0.001). Additionally, the PPAP group had significantly higher daily fluid load compared to the non-PPAP group (800 vs 600 mL/day, P < 0.001). These findings suggest that while the two groups were similar in most inflammatory markers, the PPAP intervention was associated with significantly reduced levels of IL-17a (a pro-inflammatory cytokine) along with higher fluid load. This may be related to the previously observed lower incidence of complications in the PPAP group, indicating that PPAP might work by modulating specific immune responses and optimizing fluid management (Table 2). Conversely, interleukin-6 (IL-6) levels were higher in all PPAP groups compared to non-PPAP groups (P < 0.01), consistent across each FRS risk area (Figure 1). Further receiver operating characteristic (ROC) analysis (Figure 2) demonstrated that preoperative IL-17a and fluid load have predictive value for PPAP (Table 3).

Figure 1 Predictive effect of preoperative inflammatory data, interleukin-17A, and fluid load on post pancreatectomy acute pancreatitis. Preoperative interleukin-17A (IL-17a) concentrations were significantly elevated in patients who developed post pancreatectomy acute pancreatitis (PPAP) compared to those who did not, regardless of their fistula risk score (FRS) classification (P < 0.01). This consistent IL-17a elevation across all FRS risk categories suggests its potential role as a biomarker for PPAP following pancreaticoduodenectomy.

Figure 2 Analysis of receiver operating characteristic curves. Preoperative interleukin-17A (IL-17a) as a moderate predictor of post pancreatectomy acute pancreatitis (PPAP) following pancreaticoduodenectomy, with an area under the curve of 0.71 (95%CI: 0.65-0.77). At the optimal threshold determined by Youden index, IL-17a demonstrated good sensitivity (0.805) but modest specificity (0.553) for PPAP prediction. AUC: Area under the curve.

Table 2 Inflammatory marker profiles before surgery in relation to postpancreatectomy acute pancreatitis development.

Variables	No PPAP (n = 105)	PPAP (n = 45)	P value
CRP [median (IQR)], mg/L	2.11 (1.12–7.92)	2.12 (1.13–5.24)	0.214
IFN-α [median (IQR)], pg/mL	0.2 (0.2–0.2)	0.2 (0.2–0.2)	0.472
IFN-γ [median (IQR)], pg/mL	3.6 (0.1–6.9)	3.4 (0.1–6.2)	0.578
IL-2 [median (IQR)], pg/mL	0.2 (0.2–0.2)	0.2 (0.2–0.2)	0.467
IL-4 [median (IQR)], pg/mL	0.2 (0.2–0.2)	0.2 (0.2–0.2)	0.401
IL-5 [median (IQR)], pg/mL	0.2 (0.4–3.6)	0.2 (0.1–3.6)	0.469
IL-17a [median (IQR)], pg/mL	12.5 (5.8–28.7)	3.5 (1.5–8.0)	< 0.001
WBC [median (IQR)], × 109/L	5.66 (4.64–6.67)	5.96 (5.06–7.42)	0.070
Fluid load [median (IQR)], mL/day	600 (500-700)	800(700-900)	< 0.001

CRP: C-reactive protein; WBC: White blood cell; PPAP: Post pancreatectomy acute pancreatitis; IL-17a: Interleukin-17A.

Table 3 Associations between preoperative interleukin-17A levels, standard inflammatory indicators, and postoperative complications, n (%).

Variables	IL-17a ≥ 4.5 pg/mL (n = 65)	IL-17a < 4.5 pg/mL (n = 84)	P value
CRP > 5 mg/L	43.5	30.0	0.053
CRP [median (IQR)], mg/L	3.50(1.50-10.5)	1.75 (1.00-4.5)	< 0.001
WBC > 10 × 109/L	10.0	12.0	0.765
WBC [median (IQR)], × 109/L	6.20 (5.10-7.80)	5.30 (4.40-6.20)	0.002
NE > 7 × 109/L	5.0	6.0	0.924
NE [median (IQR)], × 109/L	4.00 (3.20-5.10)	3.20 (2.60-4.10)	0.002
PPAP	31.3	7.5	< 0.001
POPF	29.8	12.9	< 0.001
Biliary leak	4 (6.5)	3 (4.5)	0.678
PPH	10 (15.0)	12 (18.0)	0.543
Intra-abdominal infections	18 (27.0)	20 (30.0)	0.789
DGE	6 (9.0)	8 (12.0)	0.654
Chyle leak	2 (3.0)	4 (6.0)	0.567
Interventional drains	12 (18.0)	15 (22.5)	0.456
Major complications	25 (37.5)	28 (42.0)	0.784
Relaparotomy	8 (12.0)	10 (15.0)	0.679
90-day mortality	3 (4.5)	5 (7.5)	0.564
Postoperative hospital stays, days	18 (15-22)	20 (17-25)	0.453

CRP: C-reactive protein; WBC: White blood cell; NE: Neutrophils; PPAP: Post pancreatectomy acute pancreatitis; IL-17a: Interleukin-17A; POPF: Postoperative pancreatic fistula; DGE: Delayed gastric emptying.

Independent risk factors for PPAP

Elevated preoperative IL-17a levels (≥ 4.5 pg/mL) were the strongest independent risk factor, with an odds ratio of 3.85 in univariate analysis (P < 0.001) and an even higher odds ratio of 4.67 in multivariate analysis (P < 0.001). Pathology other than PDAC or CP was also significant, with an odds ratio of 2.08 in univariate analysis (P = 0.004) and 1.89 in multivariate analysis (P = 0.025). All other factors, including WBC, NE count, age, sex, BMI, ASA score, bilirubin levels, venous resection, surgical procedure type, operative time, and estimated blood loss did not reach statistical significance as independent predictors (Table 4).

Table 4 Risk factor assessment for post pancreatectomy acute pancreatitis: A two-tiered statistical evaluation.

Risk factors	Univariate analysis		Multivariate analysis
	OR (95%CI)	P value	OR (95%CI)	P value
IL-17a ≥ 4.5 pg/mL	3.85 (2.14-6.91)	< 0.001	4.67 (2.49-8.72)	< 0.001
WBC > 10 × 109/L	1.86 (0.64-5.36)	0.252
NE > 7 × 109/L	2.12 (0.82-5.12)	0.148
Age, years	1.11 (0.99-1.02)	0.382
Sex, male vs female	0.70 (0.43-1.13)	0.168
BMI, kg/m2	1.06 (0.97-1.03)	0.194
ASA ≥ III	0.75 (0.45-1.19)	0.268
Total bilirubin ≥ 24 μmol/L	0.64 (0.38-1.04)	0.068
Venous resection, yes vs no	1.34 (0.74-2.36)	0.384
Surgical procedure, RPD vs OPD	0.96 (0.55-1.69)	0.889
Operative time > 300 minutes	1.36 (0.84-2.26)	0.265
Estimated blood loss > 200 mL	1.38 (0.86-2.22)	0.247
Pathology (not PDAC/CP)	2.08 (1.26-3.44)	0.004	1.89 (1.08-3.30)	0.025

PDAC: Pancreatic ductal adenocarcinoma; CP: Chronic pancreatitis; WBC: White blood cell; NE: Neutrophils; IL-17a: Interleukin-17A; BMI: Body mass index; RPD: Robotic pancreaticoduodenectomy; OPD: Open pancreaticoduodenectomy.

Subgroup analysis of IL-17a levels in PPAP-related POPF

IL-17a levels (pg/mL) were identified as a significant risk factor in both univariate and multivariate analyses. In univariate analysis, IL-17a showed an odds ratio of 1.24 (95%CI: 1.12-1.36, P < 0.001), and this significance persisted in multivariate analysis with an odds ratio of 1.12 (95%CI: 1.11-1.16, P < 0.001).

Albumin levels below 35 g/L showed significance in univariate analysis (OR: 2.56, 95%CI: 1.37-4.77, P = 0.002) but were not included in the final multivariate model. Similarly, estimated blood loss > 200 mL (OR: 2.78, 95%CI: 1.51-5.12, P = 0.001) and surgical procedure type (OR: 2.08, 95%CI: 1.26-3.44, P = 0.004) were significant in univariate analysis but did not remain independent predictors in multivariate analysis. Other factors including CRP, IFN-α, IFN-γ, IL-2, age, sex, BMI, pancreatic biliary drainage, pancreatic texture, MPD diameter, venous resection, and operative time showed no significant association with the outcome (Table 5).

Table 5 Subgroup analyses of risk factors for post pancreatectomy acute pancreatitis-associated postoperative pancreatic fistula.

Risk factors	Univariate analysis		Multivariate analysis
	OR (95%CI)	P value	OR (95%CI)	P value
CRP, mg/L	0.85 (0.72-1.34)	0.17A9
IFN-α, pg/mL	3.84(2.25-6.84)	0.164
IFN-γ, pg/mL	1.86 (0.64-5.36)	0.252
IL-2, pg/mL	2.12 (0.82-5.12)	0.148
IL-17a, pg/mL	1.24 (1.12-1.36)	< 0.001	1.12 (1.11-1.16)	< 0.001
Age, years	0.75 (0.45-1.19)	0.268
Sex, male vs female	0.64 (0.38-1.04)	0.068
BMI, kg/m2	1.06 (0.58-2.17)	0.896
Albumin < 35 g/L	2.56 (1.37-4.77)	0.002
PBD, yes vs no	1.34 (0.74-2.36)	0.384
Pancreatic texture, soft vs firm	0.96 (0.55-1.69)	0.889
MPD ≤ 3 mm	1.36 (0.84-2.26)	0.265
Venous resection, yes vs no	1.38 (0.86-2.22)	0.247
Surgical procedure, RPD vs OPD	2.08 (1.26-3.44)	0.004
Operative time > 300 minutes	1.19 (0.65-1.86)	0.782
Estimated blood loss > 200 mL	2.78 (1.51-5.12)	0.001

PBD: Pancreatic biliary drainage; BMI: Body mass index; IL-17a: Interleukin-17A; CRP: C-reactive protein; RPD: Robotic pancreaticoduodenectomy; OPD: Open pancreaticoduodenectomy; POPF: Postoperative pancreatic fistula.

DISCUSSION

PPAP is significantly and independently correlated with individual postoperative complications. The negative implications of PPAP not only aggravate the patient suffering and the economic burden, but also can lead to longer hospitalization, delayed postoperative recovery, and increased risk of death[11,18,19]. PPAP pathogenesis is complex, being attributable to factors such as pancreatic damage during surgical procedure, inflammatory responses, and occlusion obstruction of pancreatic juice outflow. In the treatment of PPAP, the principle of early fluid resuscitation is currently advocated to do the "targeted therapy" strategy, pay attention to the ratio of crystalloid to colloid for fluid infusion, and control the infusion speed. Antimicrobial drugs and body fluid bacterial culture also play a critical role in prevention of drug-resistant bacteria. Serum amylase measurements on days 1-2 are essential for diagnosing PAP according to the 2022 ISGPS criteria mentioned in the text. Without these values, researchers couldn't reliably determine if patients developed PAP. CT scans within 10 days are needed to identify radiological changes associated with PAP, which is another component of the diagnostic criteria. Preoperative serum values (particularly IL-17a, which is the focus of the study) are necessary for the researchers to assess whether these markers can predict postoperative complications.

POPF is one of the most common complications after pancreatoduodenectomy, the incidence rate can be up to 20%-60% and even the mortality rate can be as high as 45%. POPF is associated with multiple parameters, such as the preoperative inflammatory state, the type of surgical techniques, and the severity of the patient's underlying diseases. It is important to correctly manage POPF by treating anaemia and optimising nutritional status pre-operatively. Selecting pancreatic gastrointestinal reconstruction during operation plays a great role in preventing POPF, and the surgeon can choose the most reliable method of pancreatic anastomosis based on personal experience and the texture of pancreas. Somatostatin drugs and POPF prevention Somatostatin drugs are effective POPF prevention methods following surgical procedures[20-22].

This study was conducted to assess the values of preoperative 17a levels and fluid load for predicting PPAP and its associated POPF after pancreatoduodenectomy. Analysis of data from 150 patients revealed that high preoperative 17a levels were significantly correlated with the development of PPAP, and this factor was found to be independent risk factor for PPAP. Furthermore, we found a significant close correlation between the increased preoperative levels of 17a and the incidence of POPF due to PPAP.

17A serves as an IFN-γ inducing factor that influences both Th1 and Th2 immune responses while activating NK cells and macrophages. Its impact extends across various pathological conditions, including inflammatory diseases and cancer. In the context of pancreatic pathologies specifically, 17A plays a significant role in acute and chronic pancreatitis as well as pancreatic cancer.

Research has demonstrated that elevated serum 17A levels in acute pancreatitis (AP) patients correlate significantly with both APACHE II scores at admission and overall prognosis. The positive statistical correlation between serum 17A concentration and APACHE II scores in these patients indicates that 17A actively participates in the inflammatory cascade during AP, making it a potential predictor of disease severity.

17A functions in concert with other inflammatory mediators in AP, particularly TNF-α and IL-6. These factors collectively drive the pathogenesis of AP, from initial local immune responses to systemic inflammatory response syndrome that can ultimately prove fatal. Serum 17A levels effectively reflect the degree of inflammation present.

The established relationship between 17A and AP severity suggests its potential as a novel biomarker for monitoring and predicting disease progression. This discovery opens new therapeutic possibilities, including strategies to inhibit 17A levels to counteract pancreatic acinar cell autophagy, reduce proenzyme activation, and minimize pancreatic tissue edema, hemorrhage, and necrosis during AP episodes[23-25]. In terms of nutritional support, differentiated regimens can be developed based on IL-17a levels, providing enhanced immune nutrition support for patients with high levels, including nutrients with immunomodulatory effects such as ω-3 fatty acids, arginine, and glutamine. Additionally, appropriately timing the surgery preoperatively to ensure inflammatory markers return to relatively low levels before proceeding with the operation is also a potential optimization strategy.

Our findings show that patients with high preoperative 17a levels have a greater risk of PPAP, and this association is stronger in patients with POPF owing to the PPAP,” the authors wrote. 17a, as a pro-inflammatory cytokine, has been implicated in inflammatory responses and immune regulation. Elevated 17a levels may reflect the inflammatory status of the patients before surgery, which may aggravating pancreatic damage after surgery, thus increasing the risk of PPAP and POPF. This result is in line with past studies that preoperative inflammatory markers are linked with a higher likelihood of postoperative complications.

Moreover, preoperative 17a levels can be a strong predictive factor for identifying patients at risk of PPAP and the POPF that could follow in the postoperative period. ROC analysis demonstrated a good predictive efficacy of 17a for PPAP with an area under the curve of 0.75. Such a finding would indicate that the preoperative determination of 17a may help clinicians evaluate the risk of patients prior to surgical intervention and allow for proper prophylactic measures.

Considering the relationship between preoperative inflammatory status and the elevated risk of PPAP and POPF, managing preoperative inflammation plays a crucial role. Preoperative correction of anemia, as well as improvement of nutritional status, may significantly reduce the occurrence of POPF in patients. Furthermore, in patients with elevated 17a levels, more intensive monitoring and treatment strategies postoperatively may be necessary to decrease the risk of postoperative complications.

The limitations of our study are its retrospective design and the relatively small sample size, which can limit the generalization and extrapolation of results. Prospective, multicenter, large-sample studies should be considered in future studies to further confirm the predictive value of 17a in PPAP and POPF. Additionally, future studies should investigate 17a levels in conjunction with other inflammatory markers to evaluate their joint predictive capacity across different patient populations.

Limitations

A major limitation of this study is the focus solely on IL-17a without fully utilizing the data collected on other inflammatory markers for multivariate analysis. Cytokines such as IL-6 and TNF-α play different but complementary roles in pancreatic inflammatory responses, and assessing IL-17a alone may not capture the complexity of the inflammatory network. Furthermore, the dynamic changes of inflammatory markers may have greater predictive value than measurements at a single time point, yet this study lacks tracking of these markers over time.

CONCLUSION

In conclusion, our findings reveal that elevated preoperative 17A levels serve as a significant predictor for both PPAP and PPAP-related POPF. This discovery has substantial clinical implications for perioperative care. Integrating 17A level assessment into preoperative risk stratification protocols could identify high-risk patients who might benefit from modified surgical approaches or enhanced postoperative monitoring.