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.

Molecular disparities in colorectal cancers of White Americans, Alabama African Americans, and Oklahoma American Indians.

In the US, the majority of cancer samples analyzed are from white people, leading to biases in racial and ethnic treatment outcomes. Colorectal cancer (CRC) incidence and mortality rates are high in Alabama African Americans (AAs) and Oklahoma American Indians (AIs). We hypothesized that differences between racial groups may partially explain these disparities. Thus, we compared transcriptomic profiles of CRCs of Alabama AAs, Oklahoma AIs, and white people from both states. Compared to CRCs of white people, CRCs of AAs showed (a) higher expression of cytokines and vesicle trafficking toward modulated antitumor-immune activity, and (b) lower expression of the ID1/BMP/SMAD axis, IL22RA1, APOBEC3, and Mucins; and AIs had (c) higher expression of PTGS2/COX2 (an NSAID target/pro-oncogenic inflammation) and splicing regulators, and (d) lower tumor suppressor activities (e.g., TOB2, PCGF2, BAP1). Therefore, targeting strategies designed for white CRC patients may be less effective for AAs/AIs. These findings illustrate needs to develop optimized interventions to overcome racial CRC disparities.

G-CSF Is a Novel Mediator of T-Cell Suppression and an Immunotherapeutic Target for Women with Colon Cancer.

PURPOSE: G-CSF enhances colon cancer development. This study defines the prevalence and effects of increased G-CSF signaling in human colon cancers and investigates G-CSF inhibition as an immunotherapeutic strategy against metastatic colon cancer. EXPERIMENTAL DESIGN: Patient samples were used to evaluate G-CSF and G-CSF receptor (G-CSFR) levels by IHC with sera used to measure G-CSF levels. Peripheral blood mononuclear cells were used to assess the rate of G-CSFR+ T cells and IFNγ responses to chronic ex vivo G-CSF. An immunocompetent mouse model of peritoneal metastasis (MC38 cells in C57Bl/6J) was used to determine the effects of G-CSF inhibition (αG-CSF) on survival and the tumor microenvironment (TME) with flow and mass cytometry. RESULTS: In human colon cancer samples, the levels of G-CSF and G-CSFR are higher compared to normal colon tissues from the same patient. High patient serum G-CSF is associated with increases in markers of poor prognosis, (e.g., VEGF, IL6). Circulating T cells from patients express G-CSFR at double the rate of T cells from controls. Prolonged G-CSF exposure decreases T cell IFNγ production. Treatment with αG-CSF shifts both the adaptive and innate compartments of the TME and increases survival (HR, 0.46; P = 0.0237) and tumor T-cell infiltration, activity, and IFNγ response with greater effects in female mice. There is a negative correlation between serum G-CSF levels and tumor-infiltrating T cells in patient samples from women. CONCLUSIONS: These findings support G-CSF as an immunotherapeutic target against colon cancer with greater potential benefit in women.

The Effect of Body Mass Index on the Creation of an End-Colostomy in Rectal Cancer Patients.

With the increasing prevalence of obesity, there has been a parallel increase in the incidence of rectal cancer. The association of body mass index (BMI) and end-colostomy creation versus primary anastomosis in patients undergoing proctectomy for rectal cancer has not been described. This is a retrospective study of patients with rectal cancer from 2012 to 2018 using data from the National Surgical Quality Improvement Project. 16,446 (92.1%) underwent primary anastomosis and 1,418 (7.9%) underwent creation of an end-colostomy. Patients with a BMI of 25-29.9 (overweight) comprised the most frequent group to have a proctectomy (reference group), but the least likely to have an end-colostomy. Patients with severe obesity (BMI 50+) had an adjusted odds ratio for end-colostomy of 2.7 (95% CI 1.5-4.7) compared to the reference group. Patients who have severe obesity should be counseled regarding the likelihood of an end-colostomy and may benefit from medical weight management or weight-loss surgery.

Association of Age and Overall Survival in Surgically Resected Colorectal Cancer Patients.

INTRODUCTION: Incidence of colorectal cancer (CRC) among young patients has increased in the last 20 y often with more aggressive tumor biology. It is unclear if age < 50 y is an independent factor for shorter overall survival in CRC patients. Our objective was to determine if younger age at diagnosis was associated with worse overall survival. METHODS: This study used the National Cancer Data Base (2004-2016), retrospectively reviewing patients who underwent surgical resection for CRC. Patients were limited to only those without comorbidities and primary outcome was overall survival for all patients. RESULTS: Older patients have worse overall survival as compared to younger patients at a lower stage of disease (I and II) after adjusting for tumor location, gender, histology, stage, and systemic chemotherapy (< 36 y old versus 36-55 y old hazard ratio [HR] 1.16, confidence interval [CI] 1.03-1.29). This survival benefit is eliminated at a higher stage of disease, stage III in 36-55 y old versus < 36 y old (HR 0.96 [CI 0.90-1.03.99]) and stage IV (HR 0.94 [CI 0.89-0.99]). CONCLUSIONS: Older patients (aged > 36 y) have worse overall survival at a lower stage of disease, but the survival among all age groups was similar for stage III or IV disease in CRC.

An analysis of sexual dimorphism in the tumor microenvironment of colorectal cancer.

Women with colorectal cancer (CRC) have survival advantages over men, yet the underlying mechanisms are unclear. T cell infiltration within the CRC tumor microenvironment (TME) correlates strongly with survival. We hypothesized that women with CRC have increased T cell infiltration and differential gene expression in the TME compared to men. Tissue microarrays comprising primary tumor, tumor infiltrated lymph nodes, and uninvolved colon were created from CRC patients. Proportions of CD4 positive (CD4+) and CD8 positive (CD8+) T cells were identified using immunohistochemistry. TME immune- and cancer-related genetic expression from primary and metastatic CRC tumor were also evaluated via the NanoStringIO360 panel and The Cancer Genome Atlas Project database. CD4+ was higher in tumor samples from women compared to men (22.04% vs. 10.26%, p=0.002) and also in lymph node samples (39.54% vs. 8.56%, p=0.001). CD8+ was increased in uninvolved colon from women compared to men (59.40% vs. 43.61%, p=0.015), and in stage I/II tumors compared to III/IV in all patients (37.01% vs. 23.91%, p=0.009). Top CD8+ tertile patients survived longer compared to the bottom (43.9 months vs. 25.3 months, p=0.007). Differential gene expression was observed in pathways related to Treg function, T cell activity, and T cell exhaustion, amongst several others, in women compared to men. Thus, significant sexual dimorphism exists in the TME that could contribute to survival advantages observed in female patients with CRC.

A review of granulocyte colony-stimulating factor receptor signaling and regulation with implications for cancer.

Granulocyte colony-stimulating factor receptor (GCSFR) is a critical regulator of granulopoiesis. Studies have shown significant upregulation of GCSFR in a variety of cancers and cell types and have recognized GCSFR as a cytokine receptor capable of influencing both myeloid and non-myeloid immune cells, supporting pro-tumoral actions. This systematic review aims to summarize the available literature examining the mechanisms that control GCSFR signaling, regulation, and surface expression with emphasis on how these mechanisms may be dysregulated in cancer. Experiments with different cancer cell lines from breast cancer, bladder cancer, glioma, and neuroblastoma are used to review the biological function and underlying mechanisms of increased GCSFR expression with emphasis on actions related to tumor proliferation, migration, and metastasis, primarily acting through the JAK/STAT pathway. Evidence is also presented that demonstrates a differential physiological response to aberrant GCSFR signal transduction in different organs. The lifecycle of the receptor is also reviewed to support future work defining how this signaling axis becomes dysregulated in malignancies.

Retrospective Cohort Analysis of the Effect of Age on Lymph Node Harvest, Positivity, and Ratio in Colorectal Cancer.

Introduction: Colon cancer among young patients has increased in incidence and mortality over the past decade. Our objective was to determine if age-related differences exist for total positive nodes (TPN), total lymph node harvest (TLH), and lymph node ratio (LNR). Material and Methods: A retrospective review of stage III surgically resected colorectal cancer patient data in the National Cancer Database (2004−2016) was performed, reviewing TPN, TLH, and LNR (TPN/TLH). Results: Unadjusted analyses suggested significantly higher levels of TLH and TPN (p < 0.0001) in younger patients, while LNR did not differ by age group. On adjusted analysis, TLH remained higher in younger patients (<35 years 1.56 (CI 95 1.54, 1.59)). The age-related effect was less pronounced for LNR (<35 years 1.16 (CI 95 1.13, 1.2)). Conclusion: Younger patients have increased TLH, even after adjusting for known confounders, while age does not have a strong independent impact on LNR.

Development of a Risk Score to Predict Post-Discharge Rehabilitation Care After Liver Metastasectomy.

INTRODUCTION: Need for discharge to intermediate care (DCIC) can increase length of stay and be a source of stress to patients. Estimating risk of DCIC would allow earlier involvement of case managers, improve length of stay and patient satisfaction by setting realistic expectations. The aim was to use National Surgical Quality Improvement Program dataset to develop a prediction model for DCIC after undergoing liver metastasectomy. METHODS: Data were obtained from National Surgical Quality Improvement Program 2011-2018 covering liver metastasectomy. Recursive partitioning narrowed potential predictors and identified thresholds for categorization of continuous variables. Logistic regression identified a predictive model, internally validated by using 200 bootstrap samples with replacement. A risk score was derived using Framingham Study methodology by dividing all regression coefficients by the smallest model coefficient. Receiver operating characteristic analysis identified the score that maximized sensitivity/specificity, defining low/high risk. Finally, recursive partitioning identified categories low/medium/high. RESULTS: The most parsimonious model predicting DCIC area under the curve (, 0.722, 95%CI: 0.705-0.739) identified five independent predictors including age >60, procedure type, hypertension requiring medication, albumin <3.5 mg/dL and hematocrit <30%. Internal validation resulted in expected bias-corrected area under the curve of 0.717, 95% CI: 0.698-0.732. The maximum score was 17.9 and 5.8 maximized sensitivity (sn) and specificity (sp) [sn = 81%, sp = 51%) predicting DCIC. Stratified into three groups, a score ≥9.5 identified highest risk (12.8%), ≥4.3 medium (6.1%) and <4.3 lowest risk (1.5%). CONCLUSIONS: Determining risk of DCIC benefits shared decision making and patient care. This evidence may enhance discharge planning after liver metastasectomy expediting the process. Age >60 contributed the most weight to the score, but the use of additional variables in three groups allowed further discrimination between patients.

Risk Factors Associated With Readmission After Pancreatectomy: A Single-Institution Retrospective Cohort Study.

BACKGROUND: Pancreatectomy has a significant rate of procedure-specific morbidity which can result in readmission. Readmission has been proposed as a measure of quality. The goal of this study is to determine what factors are associated with readmission after pancreatectomy and whether readmission can be prevented. METHODS: A retrospective review of a single institution's pancreatectomies between January 2011 and April 2015 was performed. Demographic, perioperative, and outpatient data were collected from the medical record. Primary outcome was 90-day readmission. Univariate and multivariable analyses were performed to determine which factors were associated with increased risk for readmission. RESULTS: A total of 257 patients met inclusion criteria; the 90-day readmission rate was 32.7%. The median time to readmission was 13 days. Readmitted patients were more likely to have a postoperative pancreatic fistula (POPF) on univariate analysis. Surgical site infections were more common in readmitted patients (18% vs 6.4%, P = .0138). Upon multivariable adjustment, only POPF (P = .0005) remained significant. A positive dose-response relationship was noted between POPF grade and the odds of readmission with odds ratios (ORs) ranging from 1.6 (95% Confidence Interval (CI): .6-4.1) for grade A to 16.7 (95% CI: 1.8-156.8) for grade C, albeit with limited precision. CONCLUSIONS: Readmission after pancreatectomy is a common occurrence despite the many advancements in perioperative care. Our data suggest that POPF is a risk factor for readmission after pancreatectomy. Presently, this factor is not clearly preventable. This suggests that readmission may not be the best measure of quality to utilize in the evaluation of pancreatic surgery.

Isolation of extra-cellular vesicles in the context of pancreatic adenocarcinomas: Addition of one stringent filtration step improves recovery of specific microRNAs.

microRNAs (miRNA) in extracellular vesicles (EVs) have been investigated as potential biomarkers for pancreatic ductal adenocarcinoma (PDAC). However, a mixed population of EVs is often obtained using conventional exosome isolation methods for biomarker development. EVs are derived from different cellular processes and present in various sizes, therefore miRNA expression among them is undoubtedly different. We developed a simple protocol utilizing sequential filtration and ultracentrifugation to separate PDAC EVs into three groups, one with an average diameter of more than 220 nm, named operational 3 (OP3); one with average diameters between 100-220 nm, named operational 2 (OP2); and another with average diameters around 100 nm, named operational 1 (OP1)). EVs were isolated from conditioned cell culture media and plasma of human PDAC xenograft mice and early stage PDAC patients, and verified by nanoparticle tracking, western blot, and electronic microscopy. We demonstrate that exosome specific markers are only enriched in the OP1 group. qRT-PCR analysis of miRNA expression in EVs from PDAC cells revealed that expression of miR-196a and miR-1246, two previously identified miRNAs highly enriched in PDAC cell-derived exosomes, is significantly elevated in the OP1 group relative to the other EV groups. This was confirmed using plasma EVs from PDAC xenograft mice and patients with localized PDAC. Our results indicate that OP1 can be utilized for the identification of circulating EV miRNA signatures as potential biomarkers for PDAC.

Inflammatory Mediators and Gut Microbial Toxins Drive Colon Tumorigenesis by IL-23 Dependent Mechanism.

Obesity-associated chronic inflammation predisposes colon cancer risk development. Interleukin-23 (IL-23) is a potential inflammatory mediator linking obesity to chronic colonic inflammation, altered gut microbiome, and colon carcinogenesis. We aimed to elucidate the role of pro-inflammatory eicosanoids and gut bacterial toxins in priming dendritic cells and macrophages for IL-23 secretion to promote colon tumor progression. To investigate the association of IL-23 with obesity and colon tumorigenesis, we utilized TCGA data set and colonic tumors from humans and preclinical models. To understand IL-23 production by inflammatory mediators and gut microbial toxins, we performed several in vitro mechanistic studies to mimic the tumor microenvironment. Colonic tumors were utilized to perform the ex vivo experiments. Our findings showed that IL-23 is elevated in obese individuals, colonic tumors and correlated with reduced disease-free survival. In vitro studies showed that IL-23 treatment increased the colon tumor cell self-renewal, migration, and invasion while disrupting epithelial barrier permeability. Co-culture experiments of educated dendritic cells/macrophages with colon cancer cells significantly increased the tumor aggression by increasing the secretory levels of IL-23, and these observations are further supported by ex vivo rat colonic tumor organotypic experiments. Our results demonstrate gut microbe toxins and eicosanoids facilitate IL-23 production, which plays an important role in obesity-associated colonic tumor progression. This newly identified nexus represents a potential target for the prevention and treatment of obesity-associated colon cancer.

Women survive longer than men undergoing cytoreductive surgery and HIPEC for appendiceal cancer.

BACKGROUND: We hypothesize that women undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis from appendiceal cancer will have a survival advantage compared to men. METHODS: The National Cancer Database (NCDB) public user file (2004-2014) was used to select patients with PC undergoing CRS and HIPEC from appendiceal cancer. Univariate and multivariable analyses were performed. RESULTS: 1,190 patients with PC from appendiceal cancer underwent HIPEC and CRS. OS was significantly longer for women than for men, with mean and median OS being 73.8 months and 98.2 months for women vs 58.7 months and 82.5 months for men, respectively (p = 0.0032). On multivariable analysis, male sex (HR: 1.444, 95% CI: 1.141-1.827, p = 0.0022) and increasing age (HR: 1.017, 95% CI: 1.006-1.027, p = 0.0017) were both found to be independent risk factors for worse OS. CONCLUSION: Women undergoing CRS and HIPEC for PC from appendiceal origin live longer than men undergoing the same treatment. Increasing age was also found to be independent risk factors for worse survival.

Colony-stimulating factor 3 signaling in colon and rectal cancers: Immune response and CMS classification in TCGA data.

Colorectal cancer is the 2nd leading cause of cancer-related deaths in the world. The mechanisms underlying CRC development, progression, and resistance to treatment are complex and not fully understood. The immune response in the tumor microenvironment has been shown to play a significant role in many cancers, including colorectal cancer. Colony-stimulating factor 3 (CSF3) has been associated with changes to the immune environment in colorectal cancer animal models. We hypothesized that CSF3 signaling would correlate with pro-tumor tumor microenvironment changes associated with immune infiltrate and response. We utilized publicly available datasets to guide future mechanistic studies of the role CSF3 and its receptor (CSF3R) play in colorectal cancer development and progression. Here, we use bioinformatics data and mRNA from patients with colon (n = 242) or rectal (n = 92) cancers, obtained from The Cancer Genome Atlas Firehose Legacy dataset. We examined correlations of CSF3 and CSF3R expression with patient demographics, tumor stage and consensus molecular subtype classification. Gene expression correlations, cell type enrichment, Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data scores and Gene Ontology were used to analyze expression of receptor and ligand, tumor microenvironment infiltration of immune cells, and alterations in biological pathways. We found that CSF3 and CSF3R expression is highest in consensus molecular subtype 1 and consensus molecular subtype 4. Ligand and receptor expression are also correlated with changes in T cell and macrophage signatures. CSF3R significantly correlates with a large number of genes that are associated with poor colorectal cancer prognosis.

Molecular Imaging of Inflammatory Disease.

Inflammatory diseases include a wide variety of highly prevalent conditions with high mortality rates in severe cases ranging from cardiovascular disease, to rheumatoid arthritis, to chronic obstructive pulmonary disease, to graft vs. host disease, to a number of gastrointestinal disorders. Many diseases that are not considered inflammatory per se are associated with varying levels of inflammation. Imaging of the immune system and inflammatory response is of interest as it can give insight into disease progression and severity. Clinical imaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI) are traditionally limited to the visualization of anatomical information; then, the presence or absence of an inflammatory state must be inferred from the structural abnormalities. Improvement in available contrast agents has made it possible to obtain functional information as well as anatomical. In vivo imaging of inflammation ultimately facilitates an improved accuracy of diagnostics and monitoring of patients to allow for better patient care. Highly specific molecular imaging of inflammatory biomarkers allows for earlier diagnosis to prevent irreversible damage. Advancements in imaging instruments, targeted tracers, and contrast agents represent a rapidly growing area of preclinical research with the hopes of quick translation to the clinic.

17α-Estradiol prevents ovariectomy-mediated obesity and bone loss.

Menopause is a natural physiological process in older women that is associated with reduced estrogen production and results in increased risk for obesity, diabetes, and osteoporosis. 17α-estradiol (17α-E2) treatment in males, but not females, reverses several metabolic conditions associated with advancing age, highlighting sexually dimorphic actions on age-related pathologies. In this study we sought to determine if 17α-E2 could prevent ovariectomy (OVX)-mediated detriments on adiposity and bone parameters in females. Eight-week-old female C57BL/6J mice were subjected to SHAM or OVX surgery and received dietary 17α-E2 during a six-week intervention period. We observed that 17α-E2 prevented OVX-induced increases in body weight and adiposity. Similarly, uterine weight and luminal cell thickness were decreased by OVX and prevented by 17α-E2 treatment. Interestingly, 17α-E2 prevented OVX-induced declines in tibial metaphysis cancellous bone. And similarly, 17α-E2 improved bone density parameters in both tibia and femur cancellous bone, primarily in OVX mice. In contrast, to the effects on cancellous bone, cortical bone parameters were largely unaffected by OVX or 17α-E2. In the non-weight bearing lumbar vertebrae, OVX reduced trabecular thickness but not spacing, while 17α-E2 increased trabecular thickness and reduced spacing. Despite this, 17α-E2 did improve bone volume/tissue volume in lumbar vertebrae. Overall, we found that 17α-E2 prevented OVX-induced increases in adiposity and changes in bone mass and architecture, with minimal effects in SHAM-operated mice. We also observed that 17α-E2 rescued uterine tissue mass and lining morphology to control levels without inducing hypertrophy, suggesting that 17α-E2 could be considered as an adjunct to traditional hormone replacement therapies.

Obesity is an Independent Risk Factor for Mortality in Otherwise Healthy Patients After Hepatectomy.

BACKGROUND: Obesity is often associated with comorbidities that limit remnant liver recovery after hepatectomy. The extent to which obesity, in the absence of comorbidities, impacts surgical risk after hepatectomy is unknown. We hypothesized that an obese population without major comorbidities would not be at increased risk of adverse outcomes after hepatectomies. METHODS: We performed a retrospective analysis identifying patients who underwent hepatectomies from the American College of Surgeons National Surgical Quality Improvement Program data set 2005-2017. Outcomes of interest included the following: mortality, any morbidity, critical care complications, and failure to discharge home. Body mass index (BMI) was the primary variable of interest, grouped as ≥35 and <35 based on bivariate tests of associations with candidate cut-off points. In attempt to isolate the effect of obesity on outcomes among patients "without major comorbidities" (WOC), we included patients without diabetes, chronic obstructive pulmonary disease, renal insufficiency, and nonsmokers; remaining patients were grouped as "with major comorbidities" (WC). Multivariable logistic regression was used to test whether obesity is independently associated with the outcomes of interest after adjustment for other covariates. RESULTS: A total of 36,396 patients were included. There were 13,754 patients in the WOC group and 22,642 in the WC group. Among patients in the WOC group, the adjusted odds of mortality were 2.2 times higher for patients with a BMI ≥35 versus a BMI <35. Among the patients in the WC group, a BMI ≥35 was not a statistically significant predictor of mortality after adjustment for other covariates. Obese patients had increased odds of each outcome among the WOC group. CONCLUSIONS: Our hypothesis was refuted by these data. In fact, the adverse effect of obesity was more evident among healthy patients.

The role of sex in the innate and adaptive immune environment of metastatic colorectal cancer.

BACKGROUND: Women with colorectal cancer (CRC) have a significant survival advantage over men. Sex influences on the tumour microenvironment (TME) are not well characterised, despite the importance of immune response in CRC. We hypothesised that sex-divergent immune responses could contribute to survival. METHODS: Using a murine model of metastatic CRC, we examined T cells, macrophages, and cytokines locally and systemically. TME and serum cytokines were measured by multiplex bead-based arrays, while FCA was used to identify cells and phenotypes. IHC provided spatial confirmation of T cell infiltration. RESULTS: Females had increased survival and T cell infiltration. CD8, CD4 and Th2 populations correlated with longer survival. Males had increased serum levels of chemokines and inflammation-associated cytokines. Within the TME, males had lower cytokine levels than females, and a shallower cytokine gradient to the periphery. Female tumours had elevated IL-10+ macrophages, which correlated with survival. CONCLUSIONS: These data demonstrate survival-associated differences in the immune response of males and females to metastatic CRC. Females showed changes in cytokine production accompanied by increased immune cell populations, biased toward Th2-axis phenotypes. Key differences in the immune response to CRC correlated with survival in this model. These differences support a multi-faceted shift across the TME.

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.