Navigating the Spectrum of Pancreatic Surgery Complications: A Review

Abstract

Background: Despite advances in surgical techniques and perioperative care, pancreatic resections such as pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) remain high-risk procedures. Postoperative complications significantly impact morbidity, mortality, and patient quality of life. Methods: This narrative review summarizes recent literature on major complications following pancreatic surgery, including postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), and post-pancreatectomy hemorrhage (PPH), with an emphasis on incidence, risk factors, outcomes, and current preventive strategies. Results: POPF is a leading complication, occurring in 5–22% of cases and often linked with sepsis and hemorrhage. Key risk factors include high BMI, soft pancreatic texture, and small duct size. Preventive measures like Pasireotide, modified anastomosis techniques, and neoadjuvant therapy show variable success. DGE affects up to 57% of PD patients and is associated with prolonged recovery; antecolic reconstruction and erythromycin may reduce incidence. PPH, though less frequent (3–13%), can be life-threatening, particularly when secondary to POPF. Endovascular approaches are now favored for late arterial bleeding. Other complications include wound infections, abscesses, bile leaks, and pulmonary issues, all contributing to extended hospital stays and diminished quality of life. Conclusions: Pancreatic surgery continues to carry significant risks, with POPF, DGE, and PPH being the most impactful complications. While multiple interventions have shown promise, standardized protocols and predictive tools are still needed. Surgery should be performed in high-volume centers with experienced multidisciplinary teams to optimize outcomes.

1. Introduction

Pancreatic resection, especially pancreaticoduodenectomy (PD), is considered a formidable procedure given it is a demanding and highly complex operation with a risk of major complications. Pancreaticoduodenectomy, also referred to as a Whipple operation, includes several variants depending on the extent of resection, including classic PD, pylorus preserving PD, and, rarely, duodenum preserving PD [1]. Resection of the pancreatic tail, often with the body, is broadly referred to as a distal pancreatectomy (DP) and often also involves a concomitant splenectomy. Despite improvement in morbidity and mortality with advanced intensive care and surgical techniques, postoperative complications remain high [2]. Major postoperative complications include delayed gastric emptying (DGE), post-pancreatectomy hemorrhage (PPH) requiring radiological or operative intervention, postoperative pancreatic fistula (POPF), intra-abdominal abscess, bile leak, and surgical site complications like wound dehiscence and infection [2]. Surgical resection is the main cure for pancreatic cancer. A pancreaticoduodenectomy is also the surgery of choice for many periampullary tumors, including duodenal adenocarcinoma as well as extrahepatic cholangiocarcinoma. Ho et al. report surgical resection as the sole key factor in determining outcomes for patients with pancreatic adenocarcinoma [1]. Finally, pancreatic surgery is also offered for many patients with other lesions of the pancreas, including pancreatic neuroendocrine tumors, pancreatic cystic neoplasms including intraductal papillary mucinous neoplasm (IPMN), and even chronic pancreatitis. Despite surgical management and histological differences in tumors, many patients have poor survival, making quality of life an important consideration in their remaining time. The grade, severity, and frequency of postoperative complications significantly alter surgical outcomes, survival, and quality of life [3]. In this narrative review, we aim to briefly discuss the possible complications that occur post pancreatic surgery to allow for prediction of patients at highest risk, and to ensure adequate management after surgery to improve patient outcomes.

2. Methods

We conducted a focused literature search using PubMed and Google Scholar with the keywords “pancreas surgery,” “pancreatectomy,” “pancreatic surgery complications,” “postoperative pancreatic fistula (POPF),” “delayed gastric emptying (DGE),” and “postpancreatectomy hemorrhage (PPH).” The search included peer-reviewed original studies, meta-analyses, clinical guidelines, and relevant narrative reviews published in English between 2005 and 2023. Boolean operators (AND, OR) were used to refine searches where applicable. Articles were selected based on their clinical relevance, contribution to understanding the most common and significant complications following pancreatic resection, and presence in citation networks. This review prioritizes POPF, DGE, and PPH due to their frequency, impact on patient outcomes, and evolving evidence base. Less common complications such as portal vein thrombosis or anatomical variation-related injuries are only briefly discussed given their lower incidence and limited data. A narrative review was planned from the outset.

3. Postoperative Pancreatic Fistula

3.1. Definition and Classification

POPF, a major complication of pancreatic surgery, is defined by the International Study Group on Pancreatic Fistulas (ISGPF) as amylase-rich fluid from a drain >3 times the upper limit of normal serum amylase on or after postoperative day 3 [4,5]. POPF is classified into three grades based on severity: grade A is a biochemical leak that is asymptomatic and requires no intervention, grade B requires clinical management, and grade C involves severe complications that necessitate invasive treatment [5]. In pancreatectomy, clinically relevant POPFs (grade B or C) occur in 5–10% of cases [6], with some series reporting rates up to 22% [7]. For distal pancreatectomy, POPF incidence ranges from 0 to 64% [8], with this wide variation largely due to inconsistent definitions until the ISGPF’s 2016 update. This update separated isolated biochemical leaks from clinically relevant fistulas [6]. These fistulas can cause severe complications including sepsis and hemorrhage, leading to mortality rates of 20–40%, longer hospital stays, and higher healthcare costs [7].

3.2. Risk Factors for the Development of POPF

The development of POPF is influenced by both patient-specific and surgical factors (

Table 1. Summary of post-pancreatectomy clinical complications and their associated complications, risk factors, and prevention.

Complication Type	Definition	Classification	Incidence	Risk Factors	Associated Complications	Prevention Strategies
Postoperative Pancreatic Fistula (POPF)	Amylase-rich fluid from drain > 3× upper limit of normal serum amylase on or after POD 3	Grade A: Biochemical leak, asymptomatic Grade B: Requires clinical management Grade C: Severe complications requiring invasive treatment	PD: 5–10% (up to 22%) DP: 0–64%	Patient-related: High BMI, preoperative jaundice, hypoalbuminemia Surgical: Soft pancreatic texture, narrow pancreatic duct, excessive blood loss, prolonged operative time	Intra-abdominal abscesses, DGE, PPH, sepsis, organ failure, longer hospital stays, higher 90-day mortality, death.	External pancreatic duct drainage, Pasireotide, ulinastatin, invagination pancreatojejunostomy, neoadjuvant therapy.
Delayed Gastric Emptying (DGE)	Inability to return to standard diet by end of first postoperative week and includes prolonged nasogastric intubation	Grade A: NGT between POD 4–7 or reinsertion after POD 3 Grade B: NGT between POD 8–14 or reinsertion after POD 7 Grade C: NGT after POD 14 or reinsertion before POD 14	PD: 16.6–57%	Male sex, age ≥ 65 years, ASA Class ≥ 3, BMI ≥ 30, longer surgery duration, pylorus preservation, POPF	Prolonged hospital stay, reduced quality of life, mental health implications up to 90 days post-op, physical health impacts up to 180 days post-op.	Preoperative risk stratification, IVF restriction, reduced narcotic dependence, early NGT removal, early mobilization, erythromycin, antecolic reconstruction, Braun enteroenterostomy.
Post-pancreatectomy Hemorrhage (PPH)	Bleeding after pancreatic surgery, classified by timing (early vs. late) and severity	Grade A: Mild, self-limiting Grade B: Requires intervention Grade C: Life-threatening	Post-pancreatectomy: 3–13%	Male sex, BMI ≥ 25 kg/m2, normal HbAlc ≤ 6.2% hypoalbuminemia, PD, CR-POPF grades B/C	Mortality, significant impact on long-term survival in oncology patients.	Endovascular interventions, covered stents, primary interventional angiography, multidisciplinary approach.

PD—Pancreaticoduodenectomy, DP—distal pancreatectomy, BMI—body mass index, POD—post-op day, ASA—American Society of Anesthesiologists, NGT—nasogastric tube, CR-POPF—clinically relevant postoperative pancreatic fistula.

). Patient-related risk factors include high body mass index (BMI), preoperative jaundice, and hypoalbuminemia, while surgical risk factors comprise soft pancreatic texture, narrow pancreatic duct, excessive intraoperative blood loss, and prolonged operative time [7,9,10]. A predictive risk score using BMI and preoperative duct width has proven useful in predicting POPF risk [11]. Potential techniques to decrease POPF have been explored. For instance, prophylactic endoscopic pancreatic duct interventions, such as sphincterotomy or stenting, aim to reduce ductal back pressure and have been shown to lower POPF rates in select patients [12]; however, randomized trials and meta-analyses report inconsistent benefits with stenting [13]. Similarly, modified suture techniques like the Blumgart method [14,15] and reinforced pancreatic stump closures using secure drain fixation or bioabsorbable materials have demonstrated promise, yet their superiority over traditional methods remains unproven [16,17].

3.3. POPF-Associated Complications and Outcomes

When POPF occurs, it can lead to serious complications including intra-abdominal abscesses, delayed gastric emptying, postoperative hemorrhage, and systemic inflammation resulting in sepsis, organ failure, or death [18]. A large study of 2752 patients demonstrated that infected POPF significantly increased the rates of various complications compared to non-infected POPF: post-pancreatectomy hemorrhage (42% vs. 22%), sepsis (38% vs. 7%), wound infection (30% vs. 7%), and reoperation (48% vs. 11%) [19]. Additionally, infected POPF was associated with higher 90-day mortality (20% vs. 4%) and longer hospital stays (median 42 vs. 26 days) and was identified as an independent risk factor for sepsis, wound infection, and reoperation [19].

3.4. Prevention and Management Strategies

Various prevention strategies for POPF have been studied, with a 2022 meta-analysis showing that external pancreatic duct drainage reduces clinically relevant POPF (CR-POPF) by 28.6% and all POPF by 29.6%. Medications such as Pasireotide, a somatostatin analog, reduce pancreatic exocrine secretions and may prevent postoperative pancreatic fistula, significantly lowering the risk of fistula, leak, or abscess [20]. Additionally, ulinastatin, a human glycoprotein clinically used for the treatment of acute or chronic recurrent inflammation, reduced CR-POPF rates by 19.4%, while invagination pancreatojejunostomy lowered all-POPF rates by 37.5% [21,22].

3.5. Impact of Neoadjuvant Therapy

Neoadjuvant therapy, now commonly used for borderline and locally advanced pancreatic cancer, also impacts POPF risk. A single-center study of 753 patients demonstrated that CR-POPF rates were significantly lower with neoadjuvant therapy compared to upfront resection (3.8% vs. 13.8%, a 3.6-fold reduction) [23]. However, this study found that CR-POPF in patients who received neoadjuvant therapy was associated with worse overall survival (17 vs. 34 months) [23], suggesting that, while neoadjuvant therapy reduces POPF risk through pancreatic fibrosis, persistent soft parenchyma might indicate poor therapeutic response and worse outcomes. In summary, despite advancements in prevention and management, POPF remains a significant challenge in pancreatic surgery, contributing to increased morbidity, mortality, and healthcare costs.

4. Delayed Gastric Emptying

4.1. Definition and Classification

The rationale behind DGE is multifactorial and has not been fully understood. Possible explanations include reduced plasma motilin concentrations due to duodenal resection, nerve supply disruption of sympathetic and vagal to the antrum and pylorus, devascularization of the pylorus, and transient pancreatitis [24]. The ISGPS defines DGE as the inability to return to a standard diet by the end of the first postoperative week and includes prolonged nasogastric intubation of the patient [24]. Wente et al. reported that 19–57% of patients had delayed gastric emptying (DGE) as a common post-op complication after PD [24]. DGE can be classified by severity and grade as mild, moderate, and severe and A, B, and C based on clinical assessment. Requirement of nasogastric tube (NGT) between POD 4 and 7, reinsertion after POD 3, and inability to tolerate solid oral intake before POD 7 are classified as DGE grade A. Requirement of NGT between POD 8 and 14, reinsertion after POD 7, and inability to tolerate solid oral intake before POD 14 are classified as DGE grade B. Requirement of NGT after or reinsertion before POD 14 and inability to tolerate solid oral intake before POD 21 are classified as DGE grade C. DGE grade A does not prolong hospital stay but grade B might need nutritional and prokinetic support and prolonged hospital stay. DGE grade C is associated with pancreatic fistula or intra-abdominal abscesses and other complications and requires nutritional and prokinetic support leading to prolonged hospital stay [24].

4.2. Risk Factors for the Development of DGE

DGE is associated with a couple of risk factors (Table 1). Büchler et al. report that, although DGE infrequently occurs after distal pancreatectomy and duodenum preserving pancreatic head resection, 23% of their patients had DGE after PD [25]. The rate of DGE was reported as 16.6% in a study conducted by Snyder et al. involving a retrospective cohort of patients with data from the ACS NSQIP who underwent PD from 2014 to 2016. Multivariable (MV) regression was used to determine perioperative risk factors for DGE. Male sex, age ≥ 65 years, ASA Class ≥ 3, BMI > 30, longer surgery duration, and pylorus preservation were the risk factors associated with DGE. Preoperative chemotherapy surprisingly turned out to reduce the risk of DGE, with a 23% reduction in Odds in their study [26]. Tsutaho et al. conducted a study with 188 patients who underwent subtotal stomach preserving PD and performed a propensity score matching between two cohorts who underwent gastrojejunostomy (GJ), i.e., end-to-end and side-to-side group. The incidence of DGE grade C turned out to be significant (p = 0.04) [27]. Damanakis et al. reported men with pancreatic head resections were more likely than women to experience clinically relevant DGE, but while analyzing the reasons outside intra-abdominal complications like POPF, male sex did not contribute as a risk factor [28].

4.3. Impact on Quality of Life and Hospital Stay

An observational cohort study of patients who underwent elective pancreatectomy between 2020 and 2022 reported DGE had a significant impact on health-related quality of life for uncomplicated post-op patients, with mental health implications up to 90 days and physical health implications up to 180 days post-op, as reported by Pecorelli et al. [29]. Smits et al. quantified the population attributable fractions (PAF) post-PD (2014–2017) in their study to determine which complication was more likely associated with mortality, hospital stay, readmission, and other postoperative outcomes. DGE had a huge impact on hospital stay, with a PAF of 27.6% [30].

4.4. Prevention and Management Strategies

Arango et al. (2021) tailored preoperative risk stratified pathways that aligned with standardized care for PD patients that included IVF restriction, reduced narcotic dependence, early NGT removal with initiation of a diet, and frequent and early patient mobilization, among other features which were associated with a dramatically lower rate of DGE [31]. Ohwada et al. (2001) reported that erythromycin was associated with a significant decrease of around 75% of the incidence of DGE in their study compared to the control group (14.3% vs. 57.1%, p = 0.04) [32].

4.5. Surgical Reconstruction Techniques and DGE Incidence

Types of resections or techniques have also affected the incidence of DGE. There is a type of gastrojejunostomy where a flange technique was associated with a marked reduction in PD [33]. Hwang et al. [34] reported that Braun enteroenterostomy did not lead to a difference in the incidence of DGE post pylorus preserving PD, whereas Watanabe et al. (2023) and Hochwald et al. (2010) reported it can be performed safely in patients undergoing PD and reduces the incidence of DGE [35,36]. Ho et al. also report a 16% drop in DGE incidence from adopting an antecolic reconstruction approach [1].

5. Post-Pancreatectomy Hemorrhage

5.1. PPH Incidence and Timing

PPH remains a rare but critical complication after pancreatoduodenectomy, with an incidence below 5% in high-volume centers [37]. The overall occurrence ranges from 3 to 13% across pancreatic surgeries, reflecting variations in surgical complexity and patient populations [38,39]. Understanding the timing of PPH is crucial, as late hemorrhage, occurring beyond 24 h post-surgery, represents 3–16% of cases, with a 5% weighted mean incidence. These late events typically manifest as arterial bleeding with pseudoaneurysm formation, presenting unique management challenges [40].

5.2. Definition and Classification

The ISGPS has established a comprehensive classification system that guides clinical decision-making. This framework categorizes PPH into grade A (mild, self-limiting), grade B (requiring intervention), and grade C (life-threatening), with mortality rates spanning from 21 to 88%, underscoring the critical nature of this complication [37,41]. PPH is classified into two types based on the 24 h cutoff into early and late. Early PPH occurs due to blood vessels being ligated non-securely whereas late PPH stems from the pseudoaneurysm or erosion of major arteries [41].

5.3. Risk Factors for the Development of PPH

The development of PPH is influenced by several well-documented risk factors (Table 1). In a meta-analysis the following risk factors were highly predictive of PPH: male sex (69.9%), elevated BMI ≥ 25 kg/m² (78.7%), normal HbA1c ≤ 6.2% (78.4%), and hypoalbuminemia (63.9%). From a surgical perspective, pancreatoduodenectomy (75.35%) and the development of CR-POPF grades B/C (96.9%) play crucial roles. Among these factors, pancreatic fistula emerges as the leading predictor, as it creates conditions favorable for vessel erosion and subsequent pseudoaneurysm formation [42,43]. In analyzing the anatomical distribution of PPH, the gastroduodenal artery stump emerges as the predominant source of bleeding (29%), with the common hepatic artery (19%) and splenic artery (12%) representing other common sites of hemorrhage [40].

5.4. Management Strategies and Outcomes

Modern management has evolved significantly through technological advances, with endovascular interventions, including embolization and covered stents, achieving success rates above 90%. Notably, covered stents demonstrate superior outcomes with reduced re-bleeding risk compared to embolization alone [40,44,45,46]. The selection of initial intervention substantially influences patient outcomes, as evidenced by the marked difference in mortality rates between primary interventional angiography (16%) and relaparotomy (37%). This disparity underscores the importance of endovascular-first approaches [40]. Diagnostic efficacy varies by imaging modality, with angiography identifying bleeding sources in 69% of cases and CT imaging showing effectiveness in 56–67% of cases [40]. The implementation of a coordinated multidisciplinary approach, involving surgeons, interventional radiologists, and critical care specialists, has further enhanced patient outcomes [44,47]. The severity of PPH is reflected in short-term mortality rates of 15–30%, with particularly significant implications for long-term survival among oncology patients [38,40,48]. Despite these advances in management techniques and improved outcomes, important challenges remain. The absence of prospective studies and standardized treatment protocols continues to limit the optimization of care across institutions [44], highlighting the need for further research and protocols.

6. Other Potential Complications

Overview of Less Common Complications

There are other less common complications seen after pancreas resection. Yeo et al. (1997) reported that, post-PD, they observed the following complications: wound infections (10%), intra-abdominal abscesses (5%), cholangitis (5%), pneumonia (3%), bile leaks (3%), pancreatitis (2%), and marginal ulcers (1%) [49]. Karim et al. reported a 23.5% rate of complications including superficial, deep infections, and wound dehiscence and a 17.3% rate of pulmonary complications, such as pulmonary embolism, pleural effusion, pneumonia, and reintubation [2]. Ho et al. report a 1–12% incidence in intra-abdominal fluid collection post pancreatic surgery commonly from an anastomotic leak at the hepatico, gastro, duodenojejunostomy, or pancreaticoenterostomy site [1]. It is important to remain vigilant after surgery for the development of other complications that can impact a patient’s hospital course and quality of life.

7. Impact of Surgical Approaches on Complications

Pancreatic surgery has always been challenging, with minimally invasive approaches, including laparoscopic and robotic surgery, commonly employed to reduce complications [50]. Kamarajah SK, et al. reported in their meta-analysis and systematic review that both laparoscopic and robotic techniques for PD did not have any significant differences in their overall (48% vs. 47%) and major (42% vs. 41%) complication rates [51]. Another study by Kamarajah SK highlighted that neither of the approaches had a significant difference in overall (40% vs. 49%) and major complications (12% vs. 15%) after a DP as well [52].

8. Future Directions for Predicting Post-Pancreatectomy Complications

With the current speed of technology and innovation, artificial intelligence is dominating (AI) in every field, especially healthcare. The role of AI has been very useful preoperatively in predicting pancreatic complications. In a study by Han IW et al., they utilized an AI-driven algorithm to detect multiple risk factors of POPF incidence using patient data [53]. Another study by Miyamoto R et al. reports the use of a semi-automated simulation AI tool that is used to segment pancreatic parenchyma and peripancreatic vessels [54]. This is highly useful in cases with tumor encasement around vasculature, in which AI can help surgeons pre map and rationalize an operative plan accordingly to minimize complications.

9. Conclusions

Pancreatic surgery remains a high-risk procedure, with complications such as postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), and post-pancreatectomy hemorrhage (PPH) significantly impacting patient outcomes. Advances in surgical techniques, perioperative management, and risk stratification have improved complication rates, yet challenges persist. While strategies like optimized anastomotic techniques and pharmacologic interventions show promise, standardized approaches for prevention and management remain an area of ongoing research.