Learning Curve of a Laparoscopic Pancreaticoduodenectomy Program at a Second Institution.

BACKGROUND: Historically, pancreaticoduodenectomy (PD) has been performed via a laparotomy, but increasingly, laparoscopic and robotic platforms are being employed for PD. Laparoscopic PD has a steep surgeon specific learning curve and programmatic elements that must be optimized. These factors may limit a surgeon who is proficient at laparoscopic PD to develop a program at another institution. We hypothesize that the learning curve for a surgeon transferring a program to a second institution is shorter than the initial laparoscopic PD learning curve for the same surgeon. METHODS: A retrospective review of patients who underwent laparoscopic PD for any indication at the first institution (FI) from 2012 to 2017 and the second institution (SI) from 2018 to 2021 was conducted. Standard statistical analysis was performed. The learning curve was identified using one-sided CUSUM analysis of operative times. RESULT: We identified 110 participants, 90 from the FI and 20 from the SI. More patients at the FI were diagnosed with periampullary adenocarcinoma on final pathology compared to the SI (65.6% vs 40.0%, P = .0132). FI operative times stabilized after the 25th laparoscopic PD and SI operative times stabilized after the 5th operation. No statistically significant difference was identified in postoperative complications. CONCLUSIONS: The learning curve and average operative time of an SI laparoscopic PD program was shorter than the initial learning curve for a single surgeon with comparable outcomes. This suggests that complex minimally invasive surgical programs can be safely transferred to another high-volume institution without significant loss of progress.

Cancer-associated fibroblast-derived acetate promotes pancreatic cancer development by altering polyamine metabolism via the ACSS2-SP1-SAT1 axis.

The ability of tumour cells to thrive in harsh microenvironments depends on the utilization of nutrients available in the milieu. Here we show that pancreatic cancer-associated fibroblasts (CAFs) regulate tumour cell metabolism through the secretion of acetate, which can be blocked by silencing ATP citrate lyase (ACLY) in CAFs. We further show that acetyl-CoA synthetase short-chain family member 2 (ACSS2) channels the exogenous acetate to regulate the dynamic cancer epigenome and transcriptome, thereby facilitating cancer cell survival in an acidic microenvironment. Comparative H3K27ac ChIP-seq and RNA-seq analyses revealed alterations in polyamine homeostasis through regulation of SAT1 gene expression and enrichment of the SP1-responsive signature. We identified acetate/ACSS2-mediated acetylation of SP1 at the lysine 19 residue that increased SP1 protein stability and transcriptional activity. Genetic or pharmacologic inhibition of the ACSS2-SP1-SAT1 axis diminished the tumour burden in mouse models. These results reveal that the metabolic flexibility imparted by the stroma-derived acetate enabled cancer cell survival under acidosis via the ACSS2-SP1-SAT1 axis.

Intraoperative Imaging in Hepatopancreatobiliary Surgery.

Hepatopancreatobiliary surgery belongs to one of the most complex fields of general surgery. An intricate and vital anatomy is accompanied by difficult distinctions of tumors from fibrosis and inflammation; the identification of precise tumor margins; or small, even disappearing, lesions on currently available imaging. The routine implementation of ultrasound use shifted the possibilities in the operating room, yet more precision is necessary to achieve negative resection margins. Modalities utilizing fluorescent-compatible dyes have proven their role in hepatopancreatobiliary surgery, although this is not yet a routine practice, as there are many limitations. Modalities, such as photoacoustic imaging or 3D holograms, are emerging but are mostly limited to preclinical settings. There is a need to identify and develop an ideal contrast agent capable of differentiating between malignant and benign tissue and to report on the prognostic benefits of implemented intraoperative imaging in order to navigate clinical translation. This review focuses on existing and developing imaging modalities for intraoperative use, tailored to the needs of hepatopancreatobiliary cancers. We will also cover the application of these imaging techniques to theranostics to achieve combined diagnostic and therapeutic potential.

Combination therapies for cancer: challenges and opportunities.

BACKGROUND: Gastrointestinal cancers represent a major challenge to public health. Pancreatic cancer is the most lethal cancer among all gastrointestinal cancers. Most patients cannot meet the criteria of resection at diagnosis, indicating these patients will have dismal prognosis. MAIN TEXT: Neoadjuvant chemotherapy helps some patients regain the opportunity of radical resection. An optimal regimen of chemotherapy is one that maximizes the anti-tumor efficacy while maintaining a relatively manageable safety profile. The development of surgical procedures further improves the outcomes of these patients. CONCLUSIONS: Combination therapies in a multidisciplinary manner that involves modified chemotherapy regimen, radical resection, and intestine auto-transplantation may provide the currently best possible care to patients with locally advanced pancreatic cancer.

Innovative Imaging Techniques Used to Evaluate Borderline-Resectable Pancreatic Adenocarcinoma.

A diagnosis of pancreatic cancer carries a 5-y survival rate of less than 10%. Furthermore, the detection of pancreatic cancer occurs most often in later stages of the disease due to its location in the retroperitoneum and lack of symptoms (in most cases) until tumors become more advanced. Once diagnosed, cross-sectional imaging techniques are heavily utilized to determine the tumor stage and the potential for surgical resection. However, a major determinant of resectability is the extent of local vascular involvement of the mesenteric vessels and critical tributaries; current imaging techniques have limited capacity to accurately determine vascular involvement. Surrounding inflammation and fibrosis can be difficult to discriminate from viable tumor, making determination of the degree of vascular involvement unreliable. New innovations in fluorescence and optoacoustic imaging techniques may overcome these limitations and make determination of resectability more accurate. These imaging modalities are able to more clearly discern between viable tumor tissue and non-neoplastic inflammation or desmoplasia, allowing clinicians to more reliably characterize vascular involvement and develop individualized treatment plans for patients. This review will discuss the current imaging techniques used to diagnose pancreatic cancer, the barriers that current techniques raise to accurate staging, and novel fluorescence and optoacoustic imaging techniques that may provide more accurate clinical staging of pancreatic cancer.

Nanotheranostics for Image-Guided Cancer Treatment.

Image-guided nanotheranostics have the potential to represent a new paradigm in the treatment of cancer. Recent developments in modern imaging and nanoparticle design offer an answer to many of the issues associated with conventional chemotherapy, including their indiscriminate side effects and susceptibility to drug resistance. Imaging is one of the tools best poised to enable tailoring of cancer therapies. The field of image-guided nanotheranostics has the potential to harness the precision of modern imaging techniques and use this to direct, dictate, and follow site-specific drug delivery, all of which can be used to further tailor cancer therapies on both the individual and population level. The use of image-guided drug delivery has exploded in preclinical and clinical trials although the clinical translation is incipient. This review will focus on traditional mechanisms of targeted drug delivery in cancer, including the use of molecular targeting, as well as the foundations of designing nanotheranostics, with a focus on current clinical applications of nanotheranostics in cancer. A variety of specially engineered and targeted drug carriers, along with strategies of labeling nanoparticles to endow detectability in different imaging modalities will be reviewed. It will also introduce newer concepts of image-guided drug delivery, which may circumvent many of the issues seen with other techniques. Finally, we will review the current barriers to clinical translation of image-guided nanotheranostics and how these may be overcome.

Anti-IL-8 antibody activates myeloid cells and potentiates the anti-tumor activity of anti-PD-1 antibody in the humanized pancreatic cancer murine model.

Pancreatic ductal adenocarcinoma(PDAC) does not respond to single-agent immune checkpoint inhibitor therapy, including anti-PD-1 antibody(aPD-1) therapy. Higher plasma levels of IL-8 are associated with poorer outcomes in patients who receive aPD-1 therapies, providing a rationale for combination immunotherapy with an anti-IL-8 antibody(aIL-8) and aPD-1. We thus investigated whether human aIL-8 therapy can potentiate the antitumor activity of aPD-1 and further investigated how the combination affects the immune response by regulating myeloid cells in the tumor microenvironment in a humanized murine model of PDAC with a reconstituted immune system consisting of human T cells and a combination of CD14+ and CD16+ myeloid cells. The results show that the combination of aIL-8 and aPD-1 treatment significantly enhanced antitumor activity following the infusion of myeloid cells. Our results further showed that the target of IL-8 is mainly present in CD16+ myeloid cells and is likely to be granulocytes. FACS analysis showed that aIL-8 treatment increased granulocytic myeloid cells in tumors. Consistently, single-nuclear RNA-sequencing analysis of tumor tissue showed that the innate immune response and cytokine response pathways in the myeloid cell cluster were activated by aIL-8 treatment. This is the first preclinical study using a humanized mouse model for new combination immunotherapeutic development and supports the further clinical testing of aIL-8 in combination with aPD-1 for PDAC treatment. This study also suggests that peripherally derived myeloid cells can potentiate the antitumor response of T cells, likely through the innate immune response, and aIL-8 re-educates tumor-infiltrating myeloid cells by activating the innate immune response.

Blockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapy.

The immature and dysfunctional vascular network within solid tumors poses a substantial obstacle to immunotherapy because it creates a hypoxic tumor microenvironment that actively limits immune cell infiltration. The molecular basis underpinning this vascular dysfunction is not fully understood. Using genome-scale receptor array technology, we showed here that insulin-like growth factor binding protein 7 (IGFBP7) interacts with its receptor CD93, and we subsequently demonstrated that this interaction contributes to abnormal tumor vasculature. Both CD93 and IGFBP7 were up-regulated in tumor-associated endothelial cells. IGFBP7 interacted with CD93 via a domain different from multimerin-2, the known ligand for CD93. In two mouse tumor models, blockade of the CD93/IGFBP7 interaction by monoclonal antibodies promoted vascular maturation to reduce leakage, leading to reduced tumor hypoxia and increased tumor perfusion. CD93 blockade in mice increased drug delivery, resulting in an improved antitumor response to gemcitabine or fluorouracil. Blockade of the CD93 pathway triggered a substantial increase in intratumoral effector T cells, thereby sensitizing mouse tumors to immune checkpoint therapy. Last, analysis of samples from patients with cancer under anti-programmed death 1/programmed death-ligand 1 treatment revealed that overexpression of the IGFBP7/CD93 pathway was associated with poor response to therapy. Thus, our study identified a molecular interaction involved in tumor vascular dysfunction and revealed an approach to promote a favorable tumor microenvironment for therapeutic intervention.

Vaccine-Induced Intratumoral Lymphoid Aggregates Correlate with Survival Following Treatment with a Neoadjuvant and Adjuvant Vaccine in Patients with Resectable Pancreatic Adenocarcinoma.

PURPOSE: Immunotherapy is currently ineffective for nearly all pancreatic ductal adenocarcinomas (PDAC), largely due to its tumor microenvironment (TME) that lacks antigen-experienced T effector cells (Teff). Vaccine-based immunotherapies are known to activate antigen-specific Teffs in the peripheral blood. To evaluate the effect of vaccine therapy on the PDAC TME, we designed a neoadjuvant and adjuvant clinical trial of an irradiated, GM-CSF-secreting, allogeneic PDAC vaccine (GVAX). PATIENTS AND METHODS: Eighty-seven eligible patients with resectable PDAC were randomly assigned (1:1:1) to receive GVAX alone or in combination with two forms of low-dose cyclophosphamide. Resected tumors following neoadjuvant immunotherapy were assessed for the formation of tertiary lymphoid aggregates (TLA) in response to treatment. The clinical endpoints are disease-free survival (DFS) and overall survival (OS). RESULTS: The neoadjuvant treatment with GVAX either alone or with two forms of low-dose cyclophosphamide is safe and feasible without adversely increasing the surgical complication rate. Patients in Arm A who received neoadjuvant and adjuvant GVAX alone had a trend toward longer median OS (35.0 months) than that (24.8 months) in the historical controls who received adjuvant GVAX alone. However, Arm C, who received low-dose oral cyclophosphamide in addition to GVAX, had a significantly shorter DFS than Arm A. When comparing patients with OS > 24 months to those with OS < 15 months, longer OS was found to be associated with higher density of intratumoral TLA. CONCLUSIONS: It is safe and feasible to use a neoadjuvant immunotherapy approach for PDACs to evaluate early biologic responses. In-depth analysis of TLAs is warranted in future neoadjuvant immunotherapy clinical trials.

Serum discrimination and phenotype assessment of coronary artery disease patents with and without type 2 diabetes prior to coronary artery bypass graft surgery.

Diabetes Mellitus (DM) accelerates coronary artery disease (CAD) and atherosclerosis, the causes of most heart attacks. The biomolecules involved in these inter-related disease processes are not well understood. This study analyzes biomolecules in the sera of patients with CAD, with and without type (T) 2DM, who are about to undergo coronary artery bypass graft (CABG) surgery. The goal is to develop methodology to help identify and monitor CAD patients with and without T2DM, in order to better understand these phenotypes and to glean relationships through analysis of serum biomolecules. Aorta, fat, muscle, and vein tissues from CAD T2DM patients display diabetic-related histologic changes (e.g., lipid accumulation, fibrosis, loss of cellularity) when compared to non-diabetic CAD patients. The patient discriminatory methodology utilized is serum biomolecule mass profiling. This mass spectrometry (MS) approach is able to distinguish the sera of a group of CAD patients from controls (p value 10-15), with the CAD group containing both T2DM and non-diabetic patients. This result indicates the T2DM phenotype does not interfere appreciably with the CAD determination versus control individuals. Sera from a group of T2DM CAD patients however are distinguishable from non-T2DM CAD patients (p value 10-8), indicating it may be possible to examine the T2DM phenotype within the CAD disease state with this MS methodology. The same serum samples used in the CAD T2DM versus non-T2DM binary group comparison were subjected to MS/MS peptide structure analysis to help identify potential biochemical and phenotypic changes associated with CAD and T2DM. Such peptide/protein identifications could lead to improved understanding of underlying mechanisms, additional biomarkers for discriminating and monitoring these disease conditions, and potential therapeutic targets. Bioinformatics/systems biology analysis of the peptide/protein changes associated with CAD and T2DM suggested cell pathways/systems affected include atherosclerosis, DM, fibrosis, lipogenesis, loss of cellularity (apoptosis), and inflammation.

International expert consensus on laparoscopic pancreaticoduodenectomy.

IMPORTANCE: While laparoscopic pancreaticoduodenectomy (LPD) is being adopted with increasing enthusiasm worldwide, it is still challenging for both technical and anatomical reasons. Currently, there is no consensus on the technical standards for LPD. OBJECTIVE: The aim of this consensus statement is to guide the continued safe progression and adoption of LPD. EVIDENCE REVIEW: An international panel of experts was selected based on their clinical and scientific expertise in laparoscopic and open pancreaticoduodenectomy. Statements were produced upon reviewing the literature and assessed by the members of the expert panel. The literature search and its critical appraisal were limited to articles published in English during the period from 1994 to 2019. The Web of Science, Medline, and Cochrane Library and Clinical Trials databases were searched, The search strategy included, but was not limited to, the terms 'laparoscopic', 'pancreaticoduodenectomy, 'pancreatoduodenectomy', 'Whipple's operation', and 'minimally invasive surgery'. Reference lists from the included articles were manually checked for any additional studies, which were included when appropriate. Delphi method was used to establish expert consensus and the AGREE II-GRS Instrument was applied to assess the methodological quality and externally validate the final statements. The statements were further discussed during a one-day face-to-face meeting at the 1st Summit on Minimally Invasive Pancreatico-Biliary Surgery in Wuhan, China. FINDINGS: Twenty-eight international experts from 8 countries constructed the expert panel. Sixteen statements were produced by the members of the expert panel. At least 80% of responders agreed with the majority (80%) of statements. Other than three randomized controlled trials published to date, most evidences were based on level 3 or 4 studies according to the AGREE II-GRS Instrument. CONCLUSIONS AND RELEVANCE: The Wuhan international expert consensus meeting on LPD has produced a set of clinical practice statements for the safe development and progression of LPD. LPD is currently in its development and exploration stages, as defined by the international IDEAL framework for surgical innovation. More robust randomized controlled trial and registry study are essential to proceed with the assessment of LPD.

Actively Targeted Nanodelivery of Echinomycin Induces Autophagy-Mediated Death in Chemoresistant Pancreatic Cancer In Vivo.

Pancreatic cancer remains a recalcitrant neoplasm associated with chemoresistance and high fatality. Because it is frequently resistant to apoptosis, exploiting autophagic cell death could offer a new treatment approach. We repurpose echinomycin, an antibiotic encapsulated within a syndecan-1 actively targeted nanoparticle, for treatment of pancreatic cancer. Tumor-specific uptake, biodistribution, efficacy of nanodelivered echinomycin, and mechanism of cell death were assessed in aggressive, metastatic models of pancreatic cancer. In these autophagic-dependent pancreatic cancer models, echinomycin treatment resulted in autophagic cell death noted by high levels of LC3 among other autophagy markers, but without hallmarks of apoptosis, e.g., caspase activation and chromatin fragmentation, or necrosis, e.g., plasma membrane degradation and chromatin condensation/degrading. In vivo, biodistribution of syndecan-1-targeted nanoparticles indicated preferential S2VP10 or S2CP9 tumor uptake compared to the liver and kidney (S2VP10 p = 0.0016, p = 0.00004 and S2CP9 p = 0.0009, p = 0.0001). Actively targeted nanodelivered echinomycin resulted in significant survival increases compared to Gemzar (S2VP10 p = 0.0003, S2CP9 p = 0.0017) or echinomycin only (S2VP10 p = 0.0096, S2CP9 p = 0.0073). We demonstrate that actively targeted nanodelivery of echinomycin results in autophagic cell death in pancreatic and potentially other high-autophagy, apoptosis-resistant tumors. Collectively, these findings support syndecan-1-targeted delivery of echinomycin and dysregulation of autophagy to induce cell death in pancreatic cancer.

The Miami International Evidence-based Guidelines on Minimally Invasive Pancreas Resection.

OBJECTIVE: The aim of this study was to develop and externally validate the first evidence-based guidelines on minimally invasive pancreas resection (MIPR) before and during the International Evidence-based Guidelines on Minimally Invasive Pancreas Resection (IG-MIPR) meeting in Miami (March 2019). SUMMARY BACKGROUND DATA: MIPR has seen rapid development in the past decade. Promising outcomes have been reported by early adopters from high-volume centers. Subsequently, multicenter series as well as randomized controlled trials were reported; however, guidelines for clinical practice were lacking. METHODS: The Scottisch Intercollegiate Guidelines Network (SIGN) methodology was used, incorporating these 4 items: systematic reviews using PubMed, Embase, and Cochrane databases to answer clinical questions, whenever possible in PICO style, the GRADE approach for assessment of the quality of evidence, the Delphi method for establishing consensus on the developed recommendations, and the AGREE-II instrument for the assessment of guideline quality and external validation. The current guidelines are cosponsored by the International Hepato-Pancreato-Biliary Association, the Americas Hepato-Pancreato-Biliary Association, the Asian-Pacific Hepato-Pancreato-Biliary Association, the European-African Hepato-Pancreato-Biliary Association, the European Association for Endoscopic Surgery, Pancreas Club, the Society of American Gastrointestinal and Endoscopic Surgery, the Society for Surgery of the Alimentary Tract, and the Society of Surgical Oncology. RESULTS: After screening 16,069 titles, 694 studies were reviewed, and 291 were included. The final 28 recommendations covered 6 topics; laparoscopic and robotic distal pancreatectomy, central pancreatectomy, pancreatoduodenectomy, as well as patient selection, training, learning curve, and minimal annual center volume required to obtain optimal outcomes and patient safety. CONCLUSION: The IG-MIPR using SIGN methodology give guidance to surgeons, hospital administrators, patients, and medical societies on the use and outcome of MIPR as well as the approach to be taken regarding this challenging type of surgery.

Safe implementation of minimally invasive pancreas resection: a systematic review.

BACKGROUND: Minimally invasive pancreas resection (MIPR) has been expanding in the past decade. Excellent outcomes have been reported, however, safety concerns exist. The aim of this study was to define prerequisites for performing MIPR with the objective to guide safe implementation of MIPR into clinical practice. METHODS: This systematic review was conducted as part of the 2019 Miami International Evidence-Based Guidelines on Minimally Invasive Pancreas Resection (IG-MIPR). PubMed, Embase and Cochrane databases were searched for literature concerning the implementation of MIPR between 1946 and November 2018. Quality assessment was according to The Scottish Intercollegiate Guidelines Network (SIGN). RESULTS: Overall, 1150 studies were screened, of which 32 studies with 8519 patients were included in this systematic review. Training programs for minimally invasive distal pancreatectomy, laparoscopic pancreatoduodenectomy and robotic pancreatoduodenectomy have been described with acceptable outcomes during the learning curve and improved outcomes after training. Learning curve studies have revealed an association between growing experience and improving perioperative outcomes. In addition, the association between higher center volume and lower mortality and morbidity has been reported by several studies. CONCLUSION: When embarking on MIPR, it is recommended to participate in a dedicated training program, to assure a sufficient volume, especially when implementing minimally invasive pancreatoduodenectomy, (20 procedures recommended annually), and prospectively collect and closely monitor outcomes for continuous quality assessment, this can be achieved through institutional databases and participation in national or international registries.

ZIP4 Increases Expression of Transcription Factor ZEB1 to Promote Integrin α3ß1 Signaling and Inhibit Expression of the Gemcitabine Transporter ENT1 in Pancreatic Cancer Cells.

BACKGROUND & AIMS: Pancreatic tumors undergo rapid growth and progression, become resistant to chemotherapy, and recur after surgery. We studied the functions of the solute carrier family 39 member 4 (SLC39A4, also called ZIP4), which regulates concentrations of intracellular zinc and is increased in pancreatic cancer cells, in cell lines and mice. METHODS: We obtained 93 pancreatic cancer specimens (tumor and adjacent nontumor tissues) from patients who underwent surgery and gemcitabine chemotherapy and analyzed them by immunohistochemistry. ZIP4 and/or ITGA3 or ITGB1 were overexpressed or knocked down with short hairpin RNAs in AsPC-1 and MIA PaCa-2 pancreatic cancer cells lines, and in pancreatic cells from KPC and KPC-ZEB1-knockout mice, and pancreatic spheroids were established; cells and spheroids were analyzed by immunoblots, reverse transcription polymerase chain reaction, and liquid chromatography tandem mass spectrometry. We studied transcriptional regulation of ZEB1, ITGA3, ITGB1, JNK, and ENT1 by ZIP4 using chromatin precipitation and luciferase reporter assays. Nude mice were given injections of genetically manipulated AsPC-1 and MIA PaCa-2 cells, and growth of xenograft tumors and metastases was measured. RESULTS: In pancreatic cancer specimens from patients, increased levels of ZIP4 were associated with shorter survival times. MIA PaCa-2 cells that overexpressed ZIP4 had increased resistance to gemcitabine, 5-fluorouracil, and cisplatin, whereas AsPC-1 cells with ZIP4 knockdown had increased sensitivity to these drugs. In mice, xenograft tumors grown from AsPC-1 cells with ZIP4 knockdown were smaller and more sensitive to gemcitabine. ZIP4 overexpression significantly reduced accumulation of gemcitabine in pancreatic cancer cells, increased growth of xenograft tumors in mice, and increased expression of the integrin subunits ITGA3 and ITGB1; expression levels of ITGA3 and ITGB1 were reduced in cells with ZIP4 knockdown. Pancreatic cancer cells with ITGA3 or ITGB1 knockdown had reduced proliferation and formed smaller tumors in mice, despite overexpression of ZIP4; spheroids established from these cells had increased sensitivity to gemcitabine. We found ZIP4 to activate STAT3 to induce expression of ZEB1, which induced expression of ITGA3 and ITGB1 in KPC cells. Increased ITGA3 and ITGB1 expression and subsequent integrin α3ß1 signaling, via c-Jun-N-terminal kinase (JNK), inhibited expression of the gemcitabine transporter ENT1, which reduced gemcitabine uptake by pancreatic cancer cells. ZEB1-knockdown cells had increased sensitivity to gemcitabine. CONCLUSIONS: In studies of pancreatic cancer cell lines and mice, we found that ZIP4 increases expression of the transcription factor ZEB1, which activates expression of ITGA3 and ITGB1. The subsequent increase in integrin α3ß1 signaling, via JNK, inhibits expression of the gemcitabine transporter ENT1, so that cells take up smaller amounts of the drug. Activation of this pathway might help mediate resistance of pancreatic tumors to chemotherapeutic agents.

Blame it on the injury: Trauma is a risk factor for pancreatic fistula following distal pancreatectomy compared with elective resection.

BACKGROUND: Postoperative pancreatic fistula (POPF) remains a significant source of morbidity following distal pancreatectomy (DP). There is a lack of information regarding the impact of trauma on POPF rates when compared with elective resection. We hypothesize that trauma will be a significant risk factor for the development of POPF following DP. METHODS: A retrospective, single-institution review of all patients undergoing DP from 1999 to 2017 was performed. Outcomes were compared between patients undergoing DP for traumatic injury to those undergoing elective resection. Univariate and multivariable analyses were performed using SAS (version 9.4). RESULTS: Of the 372 patients who underwent DP during the study period, 298 met inclusion criteria: 38 DPs for trauma (TDP), 260 elective DPs (EDP). Clinically significant grade B or C POPFs occurred in 17 (44.7%) of 38 TDPs compared with 41 (15.8%) of 260 EDPs (p < 0.0001). On multivariable analysis, traumatic injury was found to be independently predictive of developing a grade B or C POPF (odds ratio, 4.3; 95% confidence interval, 2.10-8.89). Age, sex, and wound infection were highly correlated with traumatic etiology and therefore were not retained in the multivariable model. When analyzing risk factors for each group (trauma vs. elective) separately, we found that TDP patients who developed POPFs had less sutured closure of their duct, higher infectious complications, and longer hospital stays, while EDP patients that suffered POPFs were more likely to be male, younger in age, and at a greater risk for infectious complications. Lastly, in a subgroup analysis involving only patients with drains left postoperatively, trauma was an independent predictor of any grade of fistula (A, B, or C) compared with elective DP (odds ratio, 8.6; 95% confidence interval, 3.09-24.15), suggesting that traumatic injury is risk factor for pancreatic stump closure disruption following DP. CONCLUSION: To our knowledge, this study represents the largest cohort of patients comparing pancreatic leak rates in traumatic versus elective DP, and demonstrates that traumatic injury is an independent risk factor for developing an ISGPF grade B or C pancreatic fistula following DP. LEVEL OF EVIDENCE: Prognostic study, Therapeutic, level III.