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Background The aim of this study was to analyze the associations between the degree of postoperative leukocytosis and major morbidity after elective distal pancreatectomy with splenectomy (DPS). Methods Retrospective review of patients undergoing DPS for pancreatic diseases (2013–2016). Receiver operating characteristic curves, Youden’s index, and area under the curve were used to identify ideal lab cut-off values and discriminatory ability of postoperative white blood cell count to detect complications. Results 158 patients underwent DPS. Median age was 57 years (range, 22–90) and 53% of patients were male. POD3 absolute WBC count ≥16 × 109/L or an increase in WBC count ≥9 × 109/L from preoperative baseline was associated with major morbidity after DPS (AUC 0.7 and 0.7, respectively). Conclusion Postoperative day three leukocytosis ≥16 × 109/L or an increase in WBC of ≥9 × 109/L from preoperative baseline should raise clinical awareness for major postoperative complication after DPS.

Biliary fistula after pancreatoduodenectomy (PD) is associated with significant morbidity and mortality. The aim of this study was to determine the risk of early postoperative biliary fistula for developing biliary anastomotic stricture after PD. Retrospective review of all PD performed for various indications at a single institution between 2013 and 2018. Postoperative biliary fistulae were graded according to the International Study Group of Liver Surgery (ISGLS) as grade A–C. Multivariable analysis was performed for all comparative patient subgroups. A total of 843 patients underwent PD for malignant (68%) and benign (32%) indications. Postoperative biliary fistula developed in 66 (8%) patients; ISGLS grade A in 29 (3%), grade B in 32 (4%), and grade C in 5 (0.6%). Ninety-day mortality was 3% (25 patients). The remaining 818 patients were evaluated with a median follow-up of 16 months (IQR, 5–32 months). Biliary anastomotic stricture developed in 41 (5%) patients at a median of 10 months (IQR, 6–18 months) postoperatively. Strictures were managed with percutaneous (27 patients, 66%) or endoscopic (14 patients, 34%) stenting. No biliary stricture required operative anastomotic revision. Postoperative biliary fistula (HR, 4.4; 95% CI, 2.0–9.9; P = 0.0002) was associated with biliary anastomotic stricture; an increased risk for biliary anastomotic stricture was seen in patients with grade A (HR, 6.4; 95% CI, 2.4–16.9; P = 0.0002) and grade B (HR, 3.6; 95% CI, 1.2–10.9; P = 0.02) postoperative biliary fistula. Postoperative biliary fistula after pancreatoduodenectomy, including clinically insignificant, transient biliary fistula, is associated with an increased risk of a late biliary anastomotic stricture requiring stenting.

GLUT4, an insulin-sensitive glucose transporter, plays a major role of postprandial glucose disposal. We previously reported that human GLUT4 promoter-driven insulin receptor knockout (GIRKO) mice have reduced insulin signaling in central and peripheral tissues and develop hyperglycemia, albeit at a lower rate in an age-dependent manner on normal chow diet. Long-term high fat diet (HFD) feeding is well established for causing adiposity gain, increased inflammation, and insulin resistance. We hypothesized that HFD feeding will exacerbate the insulin resistance and result in rapid progression to overt diabetes in GIRKO mice. To test this, we examined the physiological response of euglycemic GIRKO mice to HFD in a time course study. We used indirect calorimetry analysis and found that GIRKO mice showed differences in energy partitioning shortly after HFD feeding started. The majority of GIRKO mice cohorts had 5-fold higher circulating insulin and 1.5-fold elevated blood glucose after 1 month of HFD feeding. In addition to the hyperglycemia and hyperinsulinemia, GIRKO mice also exhibited impaired glucose tolerance and islet hyperplasia, suggesting extreme insulin resistance exceeded the compensatory increase of insulin production. After 3 months on HFD, GIRKO mice had increased relative liver size, elevated hepatic triglycerides, and reduced hepatic glycogen, demonstrating impaired hepatic insulin signaling to stimulate glycogen synthesis and inhibit gluconeogenesis. We also confirmed the increase of key hepatic gluconeogenic gene expression, which likely contributed to hyperglycemia. The rapid progression of metabolic defects of GIRKO mice on HFD is not due to excessive weight or adiposity gain. In conclusion, our studies of HFD-fed GIRKO mouse will offer insights in the role of the dietary contribution to diabetes disease progression without the confounding factor of increased adiposity. Disclosure A. Reilly: None. S. Yan: None. A.J. Loncharich: None. H. Ren: None. Funding Indiana University Diabetes and Obesity Research Training Program (T32DK064466); National Institute of Diabetes and Digestive and Kidney Diseases (R01DK120772, R00DK098294); Indiana Diabetes Center (P30DK097512); Indiana Clinical and Translational Sciences Institute (UL1TR002529)

Biliary fistula after pancreatoduodenectomy (PD) is associated with significant morbidity and mortality. The aim of this study was to determine the risk of early postoperative biliary fistula for developing biliary anastomotic stricture after PD.Retrospective review of all PD performed for various indications at a single institution between 2013 and 2018. Postoperative biliary fistulae were graded according to the International Study Group of Liver Surgery (ISGLS) as grade A-C. Multivariable analysis was performed for all comparative patient subgroups.A total of 843 patients underwent PD for malignant (68%) and benign (32%) indications. Postoperative biliary fistula developed in 66 (8%) patients; ISGLS grade A in 29 (3%), grade B in 32 (4%), and grade C in 5 (0.6%). Ninety-day mortality was 3% (25 patients). The remaining 818 patients were evaluated with a median follow-up of 16 months (IQR, 5-32 months). Biliary anastomotic stricture developed in 41 (5%) patients at a median of 10 months (IQR, 6-18 months) postoperatively. Strictures were managed with percutaneous (27 patients, 66%) or endoscopic (14 patients, 34%) stenting. No biliary stricture required operative anastomotic revision. Postoperative biliary fistula (HR, 4.4; 95% CI, 2.0-9.9; P = 0.0002) was associated with biliary anastomotic stricture; an increased risk for biliary anastomotic stricture was seen in patients with grade A (HR, 6.4; 95% CI, 2.4-16.9; P = 0.0002) and grade B (HR, 3.6; 95% CI, 1.2-10.9; P = 0.02) postoperative biliary fistula.Postoperative biliary fistula after pancreatoduodenectomy, including clinically insignificant, transient biliary fistula, is associated with an increased risk of a late biliary anastomotic stricture requiring stenting.

Background and Hypothesis: Metabolic diseases, including type 2 diabetes (T2D), have become increasingly prevalent and their associated medical costs have skyrocketed. Furthermore, recent epidemiological evidence suggests links between metabolic defects and neurodegenerative diseases, such as Alzheimer’s Disease (AD). The increasing coincidence of AD and T2D, and unmet treatment needs, necessitates research investigating potential shared mechanisms. To study glucose and lipid metabolism defects and neurocognitive deficits, we have generated non-obese insulin resistant mouse models, named GLUT4-mediated Insulin Receptor KnockOut (GIRKO). Insulin-responsive glucose transporter, Glut4, is expressed in muscle, fat, and a subset of neurons in the brain. Our previous publications show that GIRKO mice are highly insulin resistant and insulin sensitive GLUT4 neurons are critical mediators for glucose metabolism. We hypothesize that central insulin resistance in GIRKO mice instigates neurocognitive defects. Experimental Design: We will measure the neurocognitive function of 3- to 4-month old GIRKO mice using Morris water maze (MWM) test. Results: GIRKO mice exhibited increased escape latency. Additionally, they spent less time in the target quadrant in the probe trial, in which the platform is removed. GIRKO performed equally compared to control mice in raised platform tests, which demonstrates that motor competencies do not confound our findings. Conclusion and Potential Impact: GIRKO mice have learning and memory deficits, which illustrates a possible link between neurocognition and metabolism. Our results support the notion that insulin resistance precedes cognitive decline and necessitates early intervention therapy to treat insulin resistance and protect cognitive function.