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Objective: To evaluate the efficacy of transanastomotic pancreatic duct internal stenting in the reduction of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy. Design: Retrospective study. Setting: Mayo Clinic. Patients: Between January 1, 1999, and September 30, 2010, 553 patients underwent pancreaticoduodenectomy by a single surgeon. Main Outcome Measures: Rates of POPF, morbidity, and mortality between stent and no-stent groups. Results: The clinically relevant POPF (International Study Group on Pancreatic Fistula definition grade B or C) rates in the stent and no-stent groups were similar (9.6% [43 of 449 patients] and 12.5% [13 of 104 patients], respectively; P=.38). Postoperative outcomes and morbidity were also similar between the 2 groups. Mortality was 0.7% (3 of 449 patients) for the stent group and 1.0% (1 of 104 patients) for the no-stent group. Four patients (0.9%) required endoscopic retrieval of the anastomotic stent. In subset analysis, the clinically relevant POPF rates in patients with a small pancreatic duct (⩽3 mm; n=167) were similar in the stent and no-stent groups (17.7% [23 of 130 patients] and 24.3% [9 of 37 patients], respectively; P=.38). In patients with a soft pancreatic gland (n=64), rates of clinically relevant pancreatic fistulae were also similar in the stent and no-stent groups (31.7% [13 of 41 patients] and 17.4% [4 of 23 patients], respectively; P=.20). Conclusions: Internal transanastomotic pancreatic duct stenting does not decrease the frequency or severity of POPF. The effect of stenting on long-term anastomotic patency warrants further investigation. [ABSTRACT FROM AUTHOR]

Intestinal organoids (IO), known as "mini-guts", derived from intestinal crypts, are self-organizing three-dimensional (3D) multicellular ex vivo models that recapitulate intestine epithelial structure and function and have been widely used for studying intestinal physiology, pathophysiology, molecular mechanisms of host-pathogen interactions, and intestinal disease in mammals. However, studies on avian IO are limited and the development of long-term cultures of IO model for poultry research is lacking. Therefore, the objectives of this study were to generate crypt-derived organoids from chicken intestines and to optimize conditions for cell growth and enrichments, passages, and cryopreservation. Crypts were collected from the small intestines of birds at embryonic d-19 and ceca from layer and broiler chickens with ages ranging from d 1 to 20 wk, embedded in a basement membrane matrix, and cultured with organoid growth media (OGM) prepared in house. The crypt-derived organoids were successfully grown and propagated to form 3D spheres like structures that were cultured for up to 3 wk. Organoids were formed on d one, budding appeared on d 3, and robust budding was observed on d 7 and beyond. For cryopreservation, dissociated organoids were resuspended in a freezing medium. The characteristics of IO upon extended passages and freeze-thaw cycles were analyzed using reverse transcription (RT)-PCR, immunoblotting, and live cell imaging. Immunoblotting and RT-PCR using E-cadherin (the marker for epithelial cells), leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5, the marker for stem cells), chromogranin A (the marker for enteroendocrine cells), lysozyme (the marker for Paneth cells), and mucin (the biomarker for goblet cells) confirmed that IO were composed of heterogeneous cell populations, including epithelial cells, stem cells, enteroendocrine cells, Paneth cells, and goblet cells. Furthermore, OGM supplemented with both valproic acid and CHIR99021, a glycogen synthase kinase 3β inhibitor and a histone deacetylase inhibitor, increased the size of the avian IO (P < 0.001). To the best of our knowledge, this is the first comprehensive report for establishing long-term, organoid culture models from small intestines and ceca of layer and broiler chickens. This model will facilitate elucidation of the mechanisms impacting host-pathogen interactions, eventually leading to the discovery of pathogen intervention strategies in poultry., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The U.S. swine industry is currently inadequately prepared to counteract the increasing threat of high-consequence diseases. Although approved and preferred depopulation guidelines exist, ventilation shutdown (VSD+) is currently the only method being deployed during a state of emergency to depopulate large swine populations. However, the permitted use of VSD+ during constrained circumstances has been criticized due to raised swine welfare concerns. The objective of this study was to investigate the effectiveness of carbon dioxide gas (CO 2 ), nitrogen gas (N 2 ), compressed air foam (CAF), compressed nitrogen foam (CAF-N 2 ) and aspirated foam (AF) during a 15-min dwell time on adult swine in an emergency depopulation situation. A small-scale trial using 12 sows per depopulation method showed the highest efficiency to induce cessation of movement for AF and CO 2 (186.0 ± 48 vs. 202.0 ± 41, s ± SD). The ease of implementation and safety favored AF for further investigation. A large-scale field study using AF to depopulate 134 sows in modified rendering trailers showed a mean fill time of 103.8 s (SD: 5.0 s) and cessation of movement of 128.0 s (SD: 18.6 s) post filling. All sows were confirmed dead post-treatment for both trials. The implementation of AF in modified rendering trailers may allow for a safe and reliable method that allows for the expedient and mobile depopulation of both small and large numbers of sows during an emergency.

Salmonella Heidelberg (SH) on contaminated poultry causes economic and health risks to producers and consumers. We hypothesized that sodium bisulfate (SBS) would decrease SH biofilm on polyvinyl chloride (PVC) coupons and decrease the horizontal transfer of SH in broilers. Experiment 1: Salmonella Heidelberg biofilm was cultured with PVC coupons, which were treated with SBS at a pH of 3.5 for 10 min, 8 h, and 24 h. Experiment 2: Nine replicate pens per treatment were divided between two rooms. A seeder contact model was used to mimic a natural infection environment. Treatments consisted of tap water or sodium bisulfate in water at a pH of 3.5. Salmonella Heidelberg incidence and enumeration were measured in crops and ceca. Sodium bisulfate significantly reduced biofilm by 2.16 and 1.04 logs when treated for 8 and 24 h, respectively. Crop colonization was significantly decreased in trials 1 and 2 by 0.29 and 0.23 logs, respectively. Crop pH was significantly decreased in trial 2. Ceca colonization was significantly decreased in trial 1 by 0.39 logs. The results from the present study suggest that SBS may be administered to drinking water to decrease SH gut colonization and to reduce biofilm.

Newly hatched male layer chicks are considered as "by-products" in the egg industry and must be humanely euthanized at the hatchery. Instantaneous mechanical destruction (maceration) is the predominant euthanasia method applied in poultry hatcheries and is approved by the American Veterinary Medical Association (AVMA). However, maceration is not perceived by the public to be a humane means of euthanasia. The effects of alternative euthanasia methods, including carbon dioxide (CO 2 ) or nitrogen (N 2 ) inhalation, and a commercial negative pressure stunning system on behavioral and physiological responses of day-of-hatch male layer chicks, were evaluated in a field trial. Chick behaviors, including ataxia, loss of posture, convulsions, cessation of vocalization, and cessation of movement, were monitored. Serum hormones were assessed at the end of each of the alternative euthanasia treatments, including a control group allowed to breathe normal atmospheric air. The N 2 method induced unconsciousness and death later than the CO 2 and negative pressure methods, and increased serum corticosterone concentrations of neonatal chicks. Carbon dioxide inhalation increased serotonin concentrations as compared to controls, as well as the N 2 and the negative pressure methods. The behavioral and physical responses observed in this study suggest that both CO 2 inhalation and negative pressure stunning can be employed to humanely euthanize neonatal male layer chicks.

Monitoring antimicrobial resistance of foodborne pathogens in poultry is critical for food safety. We aimed to compare antimicrobial resistance phenotypes in Salmonella isolated from poultry samples as influenced by isolation and antimicrobial susceptibility testing methods. Salmonella isolates were cultured from a convenience sample of commercial broiler ceca with and without selective broth enrichment, and resistance phenotypes were determined for 14 antimicrobials using the Sensititre ® platform and a qualitative broth breakpoint assay. The broth breakpoint method reported higher resistance to chloramphenicol, sulfisoxazole, and the combination of trimethoprim and sulfamethoxazole, and lower resistance to streptomycin as compared to the Sensititre ® assay in trial one. Selective enrichment of samples containing Salmonella in Rappaport-Vassiliadis broth reported lowered detectable resistance to amoxicillin/clavulanic acid, ampicillin, azithromycin, cefoxitin, ceftriaxone, nalidixic acid, and meropenem, and increased resistance to streptomycin and tetracycline than direct-plating samples in trial one. Using matched isolates in trial two, the Sensititre ® assay reported higher resistance to chloramphenicol and gentamicin, and lower resistance to nalidixic acid as compared to the broth breakpoint method. These results suggest methodology is a critical consideration in the detection and surveillance of antimicrobial resistance phenotypes in Salmonella isolates from poultry samples and could affect the accuracy of population or industry surveillance insights and intervention strategies.

As the demand for alternatives to antibiotic growth promoters (AGP) increases in food animal production, phytobiotic compounds gain popularity because of their ability to mimic the desirable bioactive properties of AGP. Chestnut tannins (ChT) are one of many phytobiotic compounds used as feed additives, particularly in South America, for broilers because of its favorable antimicrobial and growth promotion capabilities. Although studies have observed the microbiological and immunologic effects of ChT, there is a lack of studies evaluating the metabolic function of ChT. Therefore, the objective of this study was to characterize the cecal metabolic changes induced by ChT inclusion and how they relate to growth promotion. A total of 200 day-of-hatch broiler chicks were separated into 2 feed treatment groups: control and 1% ChT. The ceca from all the chicks in the treatment groups were collected on day 2, 4, 6, 8, and 10 after hatch. The cytokine mRNA quantitative RT-PCR was determined using TaqMan gene expression assays for IL-1B, IL-6, IL-8, IL-10, and interferon gamma quantification. The cytokine expression showed highly significant increased expressions of IL-6 and IL-10 on day 2 and 6, whereas the other proinflammatory cytokines did not have significantly increased expression. The results from the kinome array demonstrated that the ceca from birds fed with 1% ChT had significant (P < 0.05) metabolic alterations based on the number of peptides when compared with the control group across all day tested. The increased expression of IL-6 appeared to be strongly indicative of altered metabolism, whereas the increased expression of IL-10 indicated the regulatory effect against other proinflammatory cytokines other than IL-6. The ChT initiate a metabolic mechanism during the first 10 d in the broiler. For the first time, we show that a phytobiotic product initially modulates metabolism while also potentially supporting growth and feed efficiency downstream. In conclusion, a metabolic phenotype alteration in the ceca of chickens fed ChT may indicate the importance of enhanced broiler gut health., (Copyright © 2020. Published by Elsevier Inc.)

Background: A triple-row stapler is widely used to divide the pancreas in distal pancreatectomy (DP). However, the selection criteria of the stapler cartridge to prevent postoperative pancreatic fistula (POPF) remain unclear. The objective of this study was to determine if factors concerning pancreatic thickness or staple size affect POPF after DP., Methods: Datasets of patients from the Mayo Clinic and National Cancer Center Hospital East who underwent DP using a triple-row stapler were merged. Risk of POPF was analyzed using clinicopathological variables, including data for pancreatic thickness and staple height. A compression index was defined as the designated staple height (mm) after closure divided by the pancreatic thickness (mm)., Results: Among the 277 patients, POPF occurred in 65 (23%) patients. The median pancreatic thickness was 13.7 mm and the median compression index was 0.137. Multivariable logistic models showed that a greater pancreatic thickness (odds ratio, 1.190, P < 0.001) and a compression index ≤0.160 (odds ratio, 4.754, P < 0.001) were independently related with POPF., Conclusion: In patients undergoing DP using a triple-row stapler, the thickness of the pancreas was related with the occurrence of POPF. Selection of the stapler cartridge with a compression index of ≤0.160 may reduce the occurrence of POPF., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Limited research has been performed to evaluate the effects of high-frequency electrical stunning (ES) methods on the lipid oxidative stability of the meat goose livers. This study was conducted to evaluate the effects of high-frequency-ES current intensities on lipid oxidative stability and antioxidant capacity in the liver of Yangzhou goose ( Anser cygnoides domesticus ). Forty 92-day-old male Yangzhou geese were randomly divided into five treatments ( n = 8). Geese were not stunned (control) or exposed to ES for 10 s with alternating current (AC) at 500 Hz in a water bath. Current intensities were set at 30 V/20 mA (E30V), 60 V/40 mA (E60V), 90 V/70 mA (E90V), or 120 V/100 mA (E120V), respectively. The malondialdehyde level at day 0 was the highest in 120 V ( p < 0.05). Antioxidant enzymes' activity on day 2 was the highest in E60V. The 1, 1-diphenyl-2-picrylhydrazyl free radical (DPPH·) elimination ability was lower in the E120V than that in the E60V at two days and four days postmortem ( p < 0.05). A combination of 60 V/40 mA/ 500 Hz/ 10 s per bird could be applied in the ES of Yangzhou geese to improve the lipid oxidative stability and antioxidant capacity in the livers.

Background and Objectives: Conclusive evidence in favor of neoadjuvant therapy for those with non-metastatic pancreatic ductal adenocarcinoma (PDAC) is still lacking. The objective of this study was to evaluate the survival benefit of neoadjuvant therapy vs upfront surgery for patients with non-metastatic PDAC., Methods: The study involved 565 patients undergoing neoadjuvant therapy or upfront surgery as the primary treatment for PDAC. Propensity score matching was performed between the neoadjuvant therapy group (NAT group) and the upfront surgery group (UFS group) using 20 clinical variables at diagnosis. Overall survival and surgical pathology were compared between the two treatment groups on an intent-to-treat basis., Results: In the matched cohort, the NAT group (n = 91) had a longer median overall survival than the UFS group (n = 91) (23.1 months vs 18.5 months, P = .043). The rate of patients undergoing surgical resection was lower in the NAT group (58% vs 80%, P = .001). Regarding surgical pathology, the NAT group had smaller tumor size (2.8 cm vs 4.0 cm, P = .001), lower incidence of positive surgical margins (8% vs 30%, P < .002), and less lymph node metastasis (45% vs 78%, P < .001)., Conclusions: The strategy of neoadjuvant therapy before surgical resection appears to offer pathologic effect and survival benefit for the patients presenting with non-metastatic PDAC., (© 2019 Wiley Periodicals, Inc.)

Background: Pancreatectomy with arterial resection (AR) is performed infrequently. As indications evolve, we evaluated indications, outcomes, and predictors of mortality, morbidity, and survival after AR., Study Design: We performed a single-institution review of elective pancreatectomies with AR (from July1990 to July 2017). Univariate and multivariate analyses were performed for predictors of outcomes and survival., Results: A total of 111 patients underwent pancreatectomy with AR including any hepatic (54%), any celiac (44%), any superior mesenteric (14%), or multiple ARs (14%), with revascularization in 55%. The majority of cases were planned (77%) and performed post-2010 (78%). Overall 90-day major morbidity (≥grade III) and mortality were 54% and 13%, respectively, due to post-pancreatectomy hemorrhage (PPH), postoperative pancreatic fistula (POPF), or ischemia in the majority of cases. There was a significant decrease in mortality post-2010 (9% vs 29%, p = 0.02), and this was protective on multivariate analysis (odds ratio [OR] 0.1, p = 0.004); PPH increased mortality (OR 6.1, p < 0.001). Post-pancreatectomy hemorrhage was associated with major morbidity (OR 5.1, p = 0.005), reoperation (OR = 23.0, p = 0.004), ICU (OR 5.5, p < 0.001), and readmission (OR 2.6, p = 0.004). Other morbidity predictors were AR with graft (OR 4.0, p = 0.031) and POPF (OR 3.1, p = 0.003). Median survival was 28.5 months and improved for ductal adenocarcinoma after neoadjuvant chemotherapy (p = 0.038). There were no differences in survival based on AR type., Conclusions: Regardless of indication or type, pancreatectomy with AR is associated with risks greater than standard resections. Mortality has decreased in the modern era; however, morbidity remains high from hemorrhagic, fistula, or ischemia-related complications. Mitigation measures are needed if advanced resections are considered with increasing frequency given the potential oncologic benefit of AR in selected cases after modern chemotherapy., (Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to investigate the impact of decreased skeletal muscle (SM) volume on survival outcomes in patients undergoing surgical resection for pancreatic ductal adenocarcinoma (PDAC)., Methods: Between March 2000 and February 2015, 323 patients who underwent upfront surgical resection for PDAC were identified from the Mayo Clinic SPORE in Pancreatic Cancer. Body composition data, including SM area, subcutaneous adipose tissue area, and visceral adipose tissue area were calculated using an abdominal computed tomography (CT) image at the third lumbar spinal level. The body composition data were normalized by patients' height (e.g., SM index, cm 2 /m 2 ) and analyzed as continuous variables. Clinicopathological findings and body composition data at initial diagnosis were evaluated for association with overall survival and recurrence-free survival., Results: Because the median SM index was significantly different between males vs. females (49.9 cm 2 /m 2 [range, 32.0-70.3] vs. 39.4 cm 2 /m 2 [range, 29.2-66.2], P < 0.001), it was standardized for each sex and used for further analyses. Parameters independently associated with a shorter overall survival were a larger tumor size (P = 0.007), a greater tumor extent (P = 0.037), a higher carbohydrate antigen 19-9 level (P < 0.001), and a smaller sex-standardized SM index (P = 0.011). Parameters independently associated with a shorter recurrence-free survival were female sex (P = 0.029), a larger tumor size (P < 0.001), a higher carbohydrate antigen 19-9 level (P = 0.001), and a smaller sex-standardized SM index (P = 0.007)., Conclusions: A smaller sex-standardized SM index is a predictive factor for shorter overall and recurrence-free survival in PDAC patients undergoing surgery.

Background: Morbidity and costs after pancreatoduodenectomy remain increased, driven by postoperative pancreatic fistula (POPF). A risk-based pathway for pancreatoduodenectomy (RBP-PD) was implemented and the clinical and cost outcomes compared with that of our historic practice., Methods: Prospective clinical and cost outcomes for our RBP-PD cohort treated from September 2014 to September 2015 were compared with a previously published cohort of pancreatoduodenectomies from January 2007 to February 2014., Results: A total of 128 RBP-PD cases were compared with 808 historic controls. Apart from less blood loss, there were no significant clinical differences between the 2 groups. Overall POPF rate did not change. Average duration of stay decreased to 10 days from 12 (P < .001) despite similar readmission rates. Postsurgical interventional radiology procedures decreased to 18.0% from 26.4% (P = .048). Utilization of and duration of stay in monitored care decreased to 23.4% from 35.6% (P < .01) and to 1 day from 3 (P < .01). On multivariable analysis RBP-PD was independently associated with decreased odds of higher postoperative pancreatic fistula grade, monitored care, and prolonged duration of stay. Inpatient cost of care decreased $6,387 per patient (-11.1%, P = .016), and total 30-day costs decreased $8,565 per patient (-13.7%, P = .01), representing a total 30-day cost savings of $1.1 million., Conclusion: RBP-PD significantly improved patient outcomes, decreased costs of care, and likely has applicability for surgical care beyond pancreatoduodenectomy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background and Aims: Among the greatest hurdles to pancreatic cancer (PC) therapy is the limited tissue penetration of systemic chemotherapy because of tumor desmoplasia. The primary study aim was to determine the toxicity profile of EUS-guided fine-needle injection (EUS-FNI) with gemcitabine. Secondary endpoints included the ability to disease downstage leading to an R0 resection and overall survival (OS) at 6 months, 12 months, and 5 years after therapy., Methods: In a prospective study from a tertiary referral center, gemcitabine (38 mg/mL) EUS-FNI was performed in patients with PC before conventional therapy. Initial and delayed adverse events (AEs) were assessed within 72 hours and 4 to 14 days after EUS-FNI, respectively. Patients were followed for ≥5 years or until death., Results: Thirty-six patients with stage II (n = 3), stage III (n = 20), or stage IV (n = 13) disease underwent gemcitabine EUS-FNI with 2.5 mL (.7-7.0 mg) total volume of injectate per patient. There were no initial or delayed AEs reported. Thirty-five patients (97.2%) were deceased at the time of analysis with a median 10.3 months of follow-up (range, 3.1-63.9). OS at 6 months and 12 months was 78% and 44%, respectively. The median OS was 10.4 months (range, 2.7-68). Among patients with stage III unresectable disease, 4 (20%) were downstaged and underwent an R0 resection., Conclusions: Our study suggests the feasibility, safety, and potential efficacy of gemcitabine EUS-FNI for PC. Additional data are needed to verify these observations and to determine the potential role relative to conventional multimodality therapy., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Malignant vascular invasion usually results from gross direct infiltration from a primary tumor and impacts cancer staging, prognosis, and therapy. However, patients may also develop a remote malignant thrombi (RMT), defined as a malignant intravascular thrombus located remote and noncontiguous to the primary tumor. Our aim was to compare EUS, CT, and magnetic resonance imaging (MRI) findings of RMT and to explore the potential impact on cancer staging., Methods: Patients with RMT were identified from a prospectively maintained EUS database. Retrospective chart review was performed to obtain EUS, CT/MRI, clinical, and outcome data., Results: A median of 3 FNAs (range, 1-8) was obtained from RMT in 17 patients (60 ± 14.1 years, 56% men) between April 2003 and August 2016, with the finding of malignant cytology in 12 patients (70.6%; 10 positive, 2 suspicious). CT/MRI detected the RMT in 5 patients (29.4%), 4 of whom had positive or suspicious EUS-FNA cytology. Among the 8 newly diagnosed pancreatic adenocarcinoma (PaC) patients, CT did not detect the RMT in 5 (63%), of whom 3 patients had positive or suspicious intravascular EUS-FNA cytology. For newly diagnosed PaC patients (n = 8), the EUS-FNA diagnosis of a biopsy specimen-proven RMT upstaged 3 patients (37.5%) and converted 2 patients (25%) from CT resectable to unresectable disease. No adverse events were reported. The mean follow-up was 18.9 ± 27.7 months., Conclusions: Our study demonstrates the ability and potential safety of intravascular FNA to detect radiographically occult RMT, which substantially impacts cancer staging and resectability., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Introduction: Adjuvant chemotherapy improves survival after curative intent resection for localized pancreatic adenocarcinoma (PDAC). Given the differences in perioperative morbidity, we hypothesized that patients undergoing distal partial pancreatectomy (DPP) would receive adjuvant therapy more often those undergoing pancreatoduodenectomy (PD)., Methods: The National Cancer Data Base (2004-2012) identified patients with localized PDAC undergoing DPP and PD, excluding neoadjuvant cases, and factors associated with receipt of adjuvant therapy were identified. Overall survival (OS) was analyzed using multivariable Cox proportional hazards regression., Results: Overall, 13,501 patients were included (DPP, n = 1933; PD, n = 11,568). Prognostic characteristics were similar, except DPP patients had fewer N1 lesions, less often positive margins, more minimally invasive resections, and shorter hospital stay. The proportion of patients not receiving adjuvant chemotherapy was equivalent (DPP 33.7%, PD 32.0%; p = 0.148). The type of procedure was not independently associated with adjuvant chemotherapy (hazard ratio 0.96, 95% confidence interval 0.90-1.02; p = 0.150), and patients receiving adjuvant chemotherapy had improved unadjusted and adjusted OS compared with surgery alone. The type of resection did not predict adjusted mortality (p = 0.870)., Conclusion: Receipt of adjuvant chemotherapy did not vary by type of resection but improved survival independent of procedure performed. Factors other than type of resection appear to be driving the nationwide rates of post-resection adjuvant chemotherapy in localized PDAC.

Synchronous primary pancreatic adenocarcinoma, defined as the simultaneous presence of 2 or more newly identified and anatomically separate primary adenocarcinomas within the pancreas, is reported rarely. We compared endoscopic ultrasound (EUS) and computed tomography (CT) and magnetic resonance imaging (MRI) findings from patients with synchronous primary pancreatic adenocarcinoma and their effects on cancer staging and treatment. We performed a retrospective analysis of the EUS database at the Mayo Clinic, from September 2008 through May 2016, to collect EUS, CT, MRI, and clinical data from patients with synchronous primary pancreatic adenocarcinoma. EUS and separate fine-needle aspiration of both tumors detected synchronous primary pancreatic adenocarcinoma in 11 patients (70.9 ± 10.4 y; 64% men). Of the 22 cancers, CT (n = 9) and MRI (n = 2) detected 9 (41%) cancers; in only 2 patients did CT detect both cancers. EUS increased cancer stage for 7 of the 11 (64%) patients and changed the status from resectable to unresectable for 3 of the 9 (33%) patients, compared with CT or MRI. EUS findings altered the likely extent of surgical resection for 3 patients. Synchronous primary pancreatic adenocarcinoma is reported rarely and may be undetected by CT or MRI; this could account for the false presumption of early tumor recurrence, rather than actual residual second tumor, leading to incomplete resection., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Workers are exposed to dust in broiler chicken production during daily work activities. Poultry dust may contain inflammatory agents (e.g., endotoxin) and inhalation exposure has been associated with pulmonary symptoms. Current practice to reduce worker exposure to poultry dust is the use of respiratory protection (e.g., elastomeric face-piece respirator with a P100 and ammonia chemical cartridge). Limited research has been conducted to evaluate engineering controls to reduce dust and ammonia concentrations in broiler chicken production; therefore, the purpose of this research was to evaluate the effectiveness of a water sprinkling system to reduce inhalable dust and ammonia concentrations in a broiler chicken house. Inhalable dust and ammonia concentrations were measured daily for the production cycle of a flock of broiler chickens (63 days). Inhalable dust was measured gravimetrically using an inhalable sampler and ammonia was measured by a direct reading sensor. Sampling was performed on a stationary mannequin inside two broiler chicken houses. One house used a sprinkler cooling system to deliver a water mist throughout the house and the second house was an untreated control. The sprinkler system activated after day 5 of chicken placement, releasing water periodically from 6 am to 10 pm. The amount of sprinkling increased at day 10 and day 15 as recommended by the manufacturer. Geometric mean (GM) inhalable dust concentrations measured in the treatment house (5.5 mg/m 3 ) were not different (p = 0.33) than those found in the control house (6.0 mg/m 3 ). The GM ammonia concentrations were also not different (p = 0.34) across the treatment and control house [10.6 ppm (GSD: 1.80); GM 9.51 ppm (GSD: 1.77)], respectively. The use of cost effective engineering, administrative and personal exposure controls are needed in the poultry industry to effectively reduce worker's exposure to hazardous concentrations of dust and ammonia.

Background: Intrahepatic lesions of mixed hepatocellular (HCC) and intrahepatic cholangiocellular carcinoma (ICC) histology are rare. The aim was to describe the natural history of these tumors relative to monomorphic ICC or HCC utilizing the National Cancer Data Base (NCDB)., Methods: Patients with ICC, HCC, and mixed histology (cHCC-CCA) were identified in the NCDB (2004-2012). Inter-group comparisons were made. Kaplan-Meier and multivariable Cox Proportional Hazards analyzed overall survival., Results: The query identified 90,499 patients with HCC; 14,463 with ICC; and 1141 with cHCC-CCA histology. Patients with cHCC-CCA histology were relatively young (61 vs. 62 (HCC, p = 0.877) and 67 (ICC, p < 0.001) years) and more likely to have poorly differentiated tumor (29.2% vs. 10.3% (HCC) and 17.2% (ICC) p < 0.001). Median overall survival for cHCC-CCA was 7.9 months vs. 10.8 (HCC) and 8.2 (ICC, all p < 0.001). Stage-specific survival for mixed histology tumors was most similar to that of HCC for all stages. cHCC-CCA were transplanted at a relatively high rate, and transplant outcomes for mixed tumors were substantially worse than for HCC lesions., Discussion: cHCC-CCA demonstrate stage-specific survival similar to HCC, but post-surgical survival more consistent with ICC. Patients with a pre-operative diagnosis of cHCC-CCA should undergo resection when appropriate., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Pancreatic leak is common after distal pancreatectomy. This trial sought to compare TissueLink closure of the pancreatic stump to that of SEAMGUARD., Methods: A multicenter, prospective, trial of patients undergoing distal pancreatectomy randomized to either TissueLink or SEAMGUARD., Results: Enrollment was closed early due to poor accrual. Overall, 67 patients were enrolled, 35 TissueLink and 32 SEAMGUARD. The two groups differed in American Society of Anesthesiologist class and diagnosis at baseline and were relatively balanced otherwise. Overall, 37 of 67 patients (55%) experienced a leak of any grade, 15 (46.9%) in the SEAMGUARD arm and 22 (62.9%) in the TissueLink arm (P = 0.19). The clinically significant leak rate was 17.9%; 22.9% for TissueLink and 12.5% for SEAMGUARD (P = 0.35). There were no statistically significant differences in major or any pancreatic fistula-related morbidity between the two groups., Conclusions: This is the first multicentered randomized trial evaluating leak rate after distal pancreatectomy between two common transection methods. Although a difference in leak rates was observed, it was not statistically significant and therefore does not provide evidence of the superiority of one technique over the other. Choice should remain based on surgeon comfort, experience, and pancreas characteristics., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Outcomes of neoadjuvant systemic therapy versus an upfront operation for clinical, stage III pancreatic adenocarcinoma remain poorly defined. Our aim was to compare survival among patients receiving neoadjuvant chemotherapy versus surgery-first with an intention-to-treat analysis., Methods: The National Cancer Data Base was reviewed from 2002-2011 for patients with clinical, stage III adenocarcinoma of the head or body of the pancreas. Patients were categorized as neoadjuvant or surgery-first. The intention-to-treat analysis included all neoadjuvant therapy patients in whom a potentially curative operation was planned and all surgery-first patients for whom adjuvant therapy was recommended. Intention-to-treat overall survival was compared by Kaplan-Meier and Cox proportional hazards multivariable regression., Results: A total of 593 patients were identified: 377 (63.6%) in the neoadjuvant cohort, wherein 104 (27.6%) experienced preoperative attrition, and 216 (36.4%) in the surgery-first cohort, of whom 30 (13.9%) failed to receive intended adjuvant chemotherapy. Intention-to-treat Kaplan-Meier analysis demonstrated superior survival for neoadjuvant compared to surgery-first (median overall survival 20.7 months vs 13.7 months, log rank P < .001). Intention-to-treat multivariable regression analysis revealed a decreased mortality hazard (hazard ratio = 0.68, 95% confidence interval 0.53-0.86, P = .0012) for neoadjuvant compared to surgery-first., Conclusion: Despite preoperative attrition, neoadjuvant therapy in clinical, stage III pancreatic cancer patients is associated with improved overall survival when compared to patients receiving surgery-first., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Optimal management of patients with intrahepatic cholangiocarcinoma (ICCA) and elevated CA19-9 remains undefined. We hypothesized CA19-9 elevation above normal indicates aggressive biology and that inclusion of CA19-9 would improve staging discrimination., Methods: The National Cancer Data Base (NCDB-2010-2012) was reviewed for patients with ICCA and reported CA19-9. Patients were stratified by CA19-9 above/below normal reference range. Unadjusted Kaplan-Meier and adjusted Cox-proportional-hazards analysis of overall survival (OS) were performed., Results: A total of 2,816 patients were included: 938 (33.3%) normal; 1,878 (66.7%) elevated CA19-9 levels. Demographic/pathologic and chemotherapy/radiation were similar between groups, but patients with elevated CA19-9 had more nodal metastases and less likely to undergo resection. Among elevated-CA19-9 patients, stage-specific survival was decreased in all stages. Resected patients with CA19-9 elevation had similar peri-operative outcomes but decreased long-term survival. In adjusted analysis, CA19-9 elevation independently predicted increased mortality with impact similar to node-positivity, positive-margin resection, and non-receipt of chemotherapy. Proposed staging system including CA19-9 improved survival discrimination over AJCC 7th edition., Conclusion: Elevated CA19-9 is an independent risk factor for mortality in ICCA similar in impact to nodal metastases and positive resection margins. Inclusion of CA19-9 in a proposed staging system increases discrimination. Multi-disciplinary therapy should be considered in patients with ICCA and CA19-9 elevation. J. Surg. Oncol. 2016;114:475-482. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Patient triage in anatomically resectable, early stage pancreatic ductal adenocarcinoma (PDAC) with elevated carbohydrate antigen 19-9 (CA 19-9) remains unclear. We hypothesized that any CA 19-9 elevation indicates biologically borderline resectability., Study Design: The National Cancer Data Base (NCDB 2010 to 2012) was reviewed for PDAC patients with reported CA 19-9. Nonsecretors were analyzed separately. Early stage (I/II) patients were stratified by CA 19-9 above or below normal (37 U/mL). Unadjusted Kaplan-Meier and adjusted Cox proportional hazards survival modeling were performed., Results: Of 113,145 patients, only 28,074 (24.8%) had CA 19-9 measured and reported, and this proportion was stage independent. Among early stage patients (n = 10,806), there were 957 (8.8%) nonsecretors, 2,708 (25.1%) with normal levels, and 7,141 (66.1%) with elevated levels. Demographics and perioperative outcomes were similar between these groups. Survival was worse in all stages in patients with CA 19-9 elevation. Nonsecretors had survival similar to that of patients with normal levels. Early stage patients with elevated CA 19-9 had decreased survival at 1, 2, and 3 years (56% vs 68%, 30% vs 42%, 15% vs 25%, all p < 0.001) relative to patients with normal levels. Adjusted modeling confirmed this finding (hazard ratio [HR] 1.26, p < 0.001). Repeat modeling in the neoadjuvant cohort demonstrated this to be the only treatment sequence to completely abrogate increased mortality due to CA 19-9 elevation (p = 0.11)., Conclusions: The minority of PDAC patients have CA 19-9 measured and reported in NCDB. The CA 19-9 nonsecretors and normal-level patients achieve equivalent survival. Elevation of CA 19-9 is associated with decreased stage-specific survival, with the greatest difference in early stages. Neoadjuvant systemic therapy followed by curative intent surgery best mitigates the increased mortality hazard. Patients with PDAC who have elevated CA 19-9 levels at diagnosis are biologically borderline resectable regardless of anatomic resectability, and neoadjuvant systemic therapy is suggested., (Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Efficacy and outcomes of resection for pancreatic neuroendocrine tumors (pNET) are well established; specific data on outcomes for pancreaticoduodenectomy (PD), either alone or with combined procedures, are limited. A retrospective review of PDs for pNET (1998-2014) at our institution was conducted. Patients were categorized into standard PD (SPD) alone or combined PD (CPD) defined as patients undergoing concurrent vascular reconstruction or additional organ resection for curative intent. Kaplan-Meier survival analyses were performed. PD for pNET was performed for 95 patients. Tumors were functional in 11 patients (9 %). Twenty-six patients (28 %) underwent CPD. The 30/90-day mortality was 1.1/5.3 % respectively and similar between SPD and CPD (p = 0.61/p = 0.24). Five-year overall survival after PD for pNET was 85.1/71.9 % and similar between SPD/CPD groups (p = 0.17). Recurrence-free and overall survival for low-grade tumors was 74.7/93.9 % at 5 years compared to only 14.8/49.7 % for high-grade tumors (p < 0.001) and not predicted by extent of resection (SPD/CPD, respectively). PD with or without concurrent resection provides an acceptable, perioperative and long-term oncologic, outcome for pNET. CPD is justified treatment modality, particularly for patients with low-grade tumors. The need for combinatorial procedures during PD is not contraindication alone for otherwise resectable patients with pNET.

Objective: Autoimmune pancreatitis (AIP) responds dramatically to corticosteroids treatment. We reviewed our experience to determine the safety and effectiveness of treating obstructive jaundice in definitive AIP with corticosteroids alone without biliary stenting., Methods: From our AIP database, we retrospectively identified type 1 AIP subjects whose jaundice was treated with corticosteroids alone without biliary stenting. Their medical records were reviewed and clinical data were evaluated to determine the outcomes., Results: Fifteen AIP subjects (87% male, mean age 68.4 years) were treated with corticosteroids at initial presentation (n = 8), first (n = 5) or subsequent (n = 2) relapse. Mean values (upper limit of normal, ULN) of liver tests prior to corticosteroids were aspartate aminotransferase (AST) 203.5u/l (4 × ULN), alanine aminotransferase (ALT) 325.8u/l (6 × ULN), alkaline phosphatase (ALP) 567.4u/l (5 × ULN), and total bilirubin (TB) 5.9 mg/dl (5.9 × ULN). At first follow-up (mean 4 days) the decrease was 54.9% for AST, 51.6% for ALT, 33% for ALP and 47.2% for TB (all p < 0.05). After 15-45 days, all patients had normal AST, 3/15 had ALT > 1.5 × ULN, 1/15 had ALP > 1.5 × ULN, 1/15 had TB > 1.5 × ULN. No patient required biliary stent placement, or developed cholangitis or other infectious complications during steroid treatment., Conclusion: Under the supervision of an experienced pancreatologist and with close monitoring of patients, obstructive jaundice secondary to definitive AIP can be safely and effectively managed with corticosteroids alone, without the need for biliary stenting., (Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Purpose: In patients undergoing elective partial pancreatectomy, our aim was to evaluate the effect of metabolic syndrome (MS) on postoperative mortality, morbidity, and utilization of hospital resources. Our hypothesis was that MS is associated with worse surgical outcomes after pancreatectomy., Methods: Fifteen thousand eight hundred thirty-one patients undergoing elective pancreatectomy from 2005 to 2012 were identified in the Participant User File of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Univariable and multivariable analyses were performed examining the association of MS (defined as body mass index ≥30 kg/m(2), hypertension requiring medications, and diabetes requiring medications and/or insulin) and risk of 30-day mortality, morbidity, and utilization of hospital resources (risk of blood transfusion in the first 72 h after pancreatectomy and prolonged hospital stay, defined as ≥13 days, which was the 75th percentile of this cohort). Multivariable logistic regression models controlled for age, sex, race, pancreatectomy type (distal versus proximal), smoking status, alcohol consumption, functional status, dyspnea, cardiovascular disease, hematocrit, INR, serum albumin, bilirubin, and creatinine. Stratified analyses were conducted by type of pancreatectomy and indication for pancreatectomy (benign versus malignant)., Results: On univariate analysis, 1070 (6.8%) patients had MS. MS was associated with increased postoperative morbidity, major morbidity, surgical site infection, septic shock, cardiac event, respiratory failure, pulmonary embolism, blood transfusion, and prolonged duration of hospital stay (P < 0.05 for all analyses). After controlling for potentially confounding variables, there was a 26% increased odds of postoperative morbidity (P < 0.001), 17% increased odds of major morbidity (P = 0.034), 32% increased odds of surgical site infection (P < 0.001), 34% increased odds of respiratory failure (P = 0.023), 68% increased odds of pulmonary embolism (P = 0.045), 26% increased odds of blood transfusion (P = 0.018), and 21% increased odds of prolonged hospital stay (P = 0.011) in patients with MS compared to patients without MS. MS was not associated with 30-day mortality after elective pancreatectomy (P = 0.465). When stratified by distal versus proximal pancreatectomy and benign versus malignant disease, the effect of MS on outcomes appears to be modified by type of pancreatectomy and indication with poorer outcomes observed for distal pancreatectomies and benign indications for resection., Conclusion: MS is an under-emphasized predictor of increased postoperative morbidity and utilization of hospital resources in patients undergoing elective pancreatectomy. The effect of MS on these postoperative outcomes appears to be more pronounced for patients with benign rather than malignant indications for pancreatectomy and in patients undergoing distal rather than proximal pancreatectomy. These results may inform patient selection, optimization of comorbidities prior to elective pancreatectomy, and strategies for postoperative management.

Background: Over the last 30 years, numerous developments in the management of chronic pancreatitis have occurred, leading to multiple surgical and non-surgical options., Patients and Methods: All patients who underwent pancreatoduodenectomy for chronic pancreatitis from January 1976 to July 2013 were reviewed. Surviving patients were contacted for a follow-up questionnaire and Short Form (SF)-12 Quality of Life Survey administration., Results: A total of 166 patients were identified (cohort 1:1976-1997(N = 105) and cohort 2:1998-2013(N = 61)). Prior to pancreatoduodenectomy, a higher proportion of patients in cohort 2 had undergone endoscopic stenting, 67 vs 10 % (p < 0.001) and/or celiac plexus block 15 and 5 % (p = 0.026). Median follow-up for all survey respondents was 15 years. On the SF-12, mean physical component score was 43.8 ± 11.8 and mental component score was 54.3 ± 7.9. Patients were significantly lower on the physical component score (p < 0.001) and significantly better on the mental component score (p = 0.001) than the general US population. Mean pain score out of 10 was significantly lower after surgery 1.6 ± 2.6 than before surgery 7.9 ± 3.5 (p < 0.001). Diabetes developed in 28 % of patients who were not diabetic prior to surgery., Conclusion: Although practice has changed so that patients have a longer time from presentation until surgery as less-invasive techniques are attempted, pancreatoduodenectomy appears to provide effective long-term pain relief and acceptable quality of life in appropriately selected patients with chronic pancreatitis and intractable pain.

Background: Elderly patients undergoing open pancreatoduodenectomy (OPD) are at increased risk for surgical morbidity and mortality. Whether totally laparoscopic pancreatoduodenectomy (TLPD) mitigates these risks has not been evaluated., Methods: A retrospective review of outcomes in patients submitted to pancreatoduodenectomy during 2007-2014 was conducted (n = 860). Outcomes in elderly patients (aged ≥70 years) were compared with those in non-elderly patients with respect to risk-adjusted postoperative morbidity and mortality. Differences in outcomes between patients submitted to OPD and TLPD, respectively, were evaluated in the elderly subgroup., Results: In elderly patients, the incidences of cardiac events (odds ratio [OR] 3.21, P < 0.001), respiratory events (OR 1.68, P = 0.04), delayed gastric emptying (DGE) (OR 1.73, P = 0.003), increased length of stay (LoS, 1 additional day) (P < 0.001), discharge disposition other than home (OR 8.14, P < 0.001) and blood transfusion (OR 1.48, P = 0.05) were greater than in non-elderly patients. Morbidity and mortality did not differ between the OPD and TLPD subgroups of elderly patients. In elderly patients, OPD was associated with increased DGE (OR 1.80, P = 0.03), LoS (1 additional day; P < 0.001) and blood transfusion (OR 2.89, P < 0.001) compared with TLPD., Conclusions: Elderly patients undergoing TLPD experience rates of mortality, morbidity and cardiorespiratory events similar to those in patients submitted to OPD. In elderly patients, TLPD offers benefits by decreasing DGE, LoS and blood transfusion requirements., (© 2015 International Hepato-Pancreato-Biliary Association.)

Background: A clinical risk score for pancreatic fistula (CRS-PF) was recently reported to predict postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD). An independent external validation has not been performed. Our hypothesis was that CRS-PF predicts POPF after both laparoscopic and open PD., Study Design: The CRS-PF was calculated from a retrospective review of patients undergoing PD from January 2007 to February 2014. Postoperative pancreatic fistula was graded using International Study Group of Pancreatic Fistula criteria. Grade B and C leaks were defined as clinically significant. Performance was measured based on sensitivity, specificity, positive and negative predictive value, accuracy, and R(2)., Results: There were 808 patients who met inclusion criteria; 539 (66.7%) had open and 269 (33.3%) had laparoscopic PD. The CRS-PF was high risk in 134 patients, intermediate in 492, low in 135, and negligible in 47. Postoperative pancreatic fistula occurred in 191 (23.6%) patients (grade A, 3.8%; B, 14.2%; and C, 5.6%), and it increased with risk category (R(2) = 0.935 all, 0.898 open, and 0.968 laparoscopic). High and intermediate risk categories were combined and classified as "test positive," and negligible and low risk categories were combined and classified "test negative," resulting in a CRS-PF with a sensitivity of 95% and a negative predictive value of 96% for predicting POPF. Contrary to previous studies, grade A POPF increased with increasing CRS-PF and POPF did not correlate with estimated blood loss (R(2) = 0.04)., Conclusions: The CRS-PF was validated independently by predicting POPF for both laparoscopic and open PD. Predictive performance was at least as good for laparoscopic PD as for open PD. Lack of correlation with estimated blood loss suggests CRS-PF might be tailored for improved performance. The CRS-PF is a clinically useful tool for POPF risk stratification after PD and allows for targeted intra- and postoperative measures to address patients at increased risk., (Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background and Study Aims: Pancreas cyst fluid analysis does not provide optimal discrimination between mucinous and nonmucinous cysts. The aim of this study was to assess the performance characteristics of the "string sign" - a test performed at the time of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), for the diagnosis of mucinous pancreatic cysts (branch duct intraductal papillary mucinous neoplasms [bIPMN] and mucinous cystic neoplasms)., Patients and Methods: Patients undergoing EUS-FNA of pancreatic cystic lesions at one referral center between 2003 and 2012 were included. The string sign was performed prospectively, and was considered positive if ≥ 1 cm string formed in cyst fluid and lasted for ≥ 1 second. Performance characteristics of the string sign and a sequential cyst fluid test interpretation model were assessed., Results: For 98 histologically proven cases, the sensitivity, specificity, positive predictive value, and negative predictive value of the string sign for diagnosis of mucinous cysts were 58 % (95 % confidence interval [CI] 44 % - 70 %), 95 % (83 % - 99 %), 94 % (81 % - 99 %), and 60 % (46 % - 72 %), respectively. When string sign results and carcinoembryonic antigen (CEA) concentration (≥ 200 ng/mL) were combined, diagnostic accuracy improved from 74 % and 83 %, respectively, to 89 % (P ≤ 0.03). Among bIPMN, a positive string sign was associated with gastric and intestinal epithelial subtypes. The sequential cyst fluid test interpretation model (including cytology, mucin stain, CEA, and string sign) yielded an overall sensitivity for mucinous lesions of 96 %, with a specificity of 90 %., Conclusions: The string sign is highly specific for diagnosis of mucinous pancreatic cysts, and improves overall diagnostic accuracy of pancreatic cyst fluid analysis. Sequential cyst fluid test interpretation yields high diagnostic sensitivity and specificity for mucinous cysts., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Studies of pancreaticoduodenectomy (PD) frequently overlook diagnosis as a variable when evaluating postoperative outcomes or generically group patients according to whether they have 'benign' or 'malignant' disease. Large multicentre studies comparing postoperative outcomes in PD stratified by diagnosis are lacking. The present study was conducted to verify the hypothesis that postoperative morbidity and length of stay (LoS) following PD vary by diagnosis and that patients may be grouped into low- and high-risk categories., Methods: The database of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) was reviewed for all PDs performed during 2005-2011. Diagnoses were identified using ICD-9 codes and grouped based on the incidence of major morbidity. Univariate and multivariate analyses were utilized to assess the impact of diagnosis on PD outcomes., Results: Of 5537 patients, those with pancreas cancer (n = 3173) and chronic pancreatitis (n = 485) experienced similar incidences of major morbidity (P = 0.95) and were grouped as having low-risk diagnoses. Patients with bile duct and ampullary (n = 1181), duodenal (n = 558) and neuroendocrine (n = 140) disease experienced similar levels of major morbidity (P = 0.78) and were grouped as having high-risk diagnoses. A high-risk diagnosis was identified as an independent risk factor for a prolonged LoS [odds ratio (OR) 1.67], organ space infection (OR 2.57), sepsis or septic shock (OR 1.83), and major morbidity (OR 1.70). Diagnosis did not predict readmission., Conclusions: The high-risk diagnosis is independently associated with postoperative morbidity and prolonged LoS. Patients with PD should be stratified by diagnosis to more accurately reflect their risk for postoperative complications and the complexity of care they will require., (© 2014 International Hepato-Pancreato-Biliary Association.)

Background: The 7th edition of the American Joint Committee on Cancer (AJCC) staging system has recently been validated and shown to predict survival in patients with intrahepatic cholangiocarcinoma (ICC). The present study attempted to investigate the validity of these findings., Methods: A single-centre, retrospective cohort study was conducted. Histopathological restaging of disease subsequent to primary surgical resection was carried out in all consecutive ICC patients. Overall survival was compared using Kaplan-Meier estimates and log-rank tests., Results: A total of 150 patients underwent surgery, 126 (84%) of whom met the present study's inclusion criteria. Of these 126 patients, 68 (54%) were female. The median length of follow-up was 4.5 years. The median patient age was 58 years (range: 24-79 years). Median body mass index was 27 kg/m(2) (range: 17-46 kg/m(2) ). Staging according to the AJCC 7th edition categorized 33 (26%) patients with stage I disease, 27 (21%) with stage II disease, five (4%) with stage III disease, and 61 (48%) with stage IVa disease. The AJCC 7th edition failed to accurately stratify survival in the current cohort; analysis revealed significantly worse survival in those with microvascular invasion, tumour size of >5 cm, grade 4 disease, multiple tumours and positive lymph nodes (P < 0.001). A negative resection margin was associated with improved survival (P < 0.001)., Conclusions: The AJCC 7th edition did not accurately predict survival in patients with ICC. A multivariable model including tumour size and differentiation in addition to the criteria used in the AJCC 7th edition may offer a more accurate method of predicting survival in patients with ICC., (© 2014 International Hepato-Pancreato-Biliary Association.)

Background: Major vascular resection when necessary for margin control during pancreaticoduodenectomy is relatively universal with perioperative and oncological outcomes that are similar to those of patients undergoing a PD without venous involvement. The present study compares total laparoscopic pancreaticoduodenectomy (TLPD) versus open pancreaticoduodenectomy (OPD) with major vascular resection., Methods: We reviewed data for all patients undergoing TLPD or OPD with vascular resection at Mayo Clinic Rochester, between the dates of July 2007 and July 2013., Results: A total of 31 patients undergoing TLPD and 58 patients undergoing OPD with major vascular resection were identified. Mean operative blood loss was significantly less in the laparoscopic (842 cc) compared to the open group (1,452 cc) (p < 0.001), as was median hospital stay, 6 (4-118) versus 9 (6-73) days, respectively (p = 0.006). There was no significant difference in the total number of complications (lap 35%, open 48%) (p = 0.24) or severe complications (≥III) (lap 6.4%, open 3.4%) (p = 0.51) in the two groups. In-hospital mortality or 30-day mortality was not statistically different between the laparoscopic and open groups, 3.2 and 3.4%, respectively (p = 0.96). Patency of the reconstructed vessels on postoperative imaging was not significantly different between the TLPD (93%) and OPD groups (91%) (p = 0.76). In patients with a diagnosis of adenocarcinoma, there was no significant difference in overall survival between the two groups (p = 0.22)., Conclusion: The present study clearly demonstrates that not only is TLPD with major vascular resection feasible and safe but that it can achieve results that are similar in morbidity and mortality as well as oncologic outcome compared to patients undergoing OPD with major vascular resection.

Objective: To directly compare the oncologic outcomes of TLPD and OPD in the setting of pancreatic ductal adenocarcinoma., Background: Total laparoscopic pancreaticoduodenectomy (TLPD) has been demonstrated to be feasible and may have several potential advantages over open pancreaticoduodenectomy (OPD), including lower blood loss and shorter hospital stay. Whether potential advantages could allow patients to recover in a timelier manner and pursue adjuvant treatment options remains to be answered., Methods: We reviewed data for all patients undergoing TLPD (N = 108) or OPD (N = 214) for pancreatic ductal adenocarcinoma at our institution between January 2008 and July 2013., Results: Neoadjuvant therapy, tumor size, node positivity, and margin-positive resection were not significantly different between the 2 groups. Median length of hospital stay was significantly longer in the OPD group (9 days; range, 5-73 days) than in the TLPD group (6 days; range, 4-118 days; P < 0.001). There was a significantly higher proportion of patients in the OPD group (12%) who had a delay of greater than 90 days or who did not receive adjuvant chemotherapy at all compared with that in the TLPD group (5%; P = 0.04). There was no significant difference in overall survival between the 2 groups (P = 0.22). A significantly longer progression-free survival was seen in the TLPD group than in the OPD group (P = 0.03)., Conclusions: TLPD is not only feasible in the setting of pancreatic ductal adenocarcinoma but also has advantages such as shorter hospital stay and faster recovery, allowing patients to recover in a timelier manner and pursue adjuvant treatment options. This study also demonstrated a longer progression-free survival in patients undergoing TLPD than those undergoing OPD.

Aim: Outcomes of patients developing portal vein (PV) thrombosis (PVT) after distal pancreatectomy (DP) are unknown. The goal of this study was to identify risk factors for PVT and describe the long-term outcomes in these patients., Methods: Patients undergoing DP without repair or reconstruction of the PV between 2001 and 2011 were included. Patients that showed evidence of PVT on pre-operative imaging were excluded from the study. Location and extent of thrombosis was determined by post-operative computed tomography or ultrasound imaging in all patients. Evidence of systemic thrombosis (if present) in addition to PVT was also documented., Results: In the study period, 991 patients underwent DP and 21 (2.1%) patients were diagnosed with PVT. Pancreatic neoplasm was the most frequent indication for operation (n = 11). Thrombus occurred in the main PV in 15 and the right branch of the PV in 8 patients. Complete PV occlusion occurred in nine patients with a median time to diagnosis of 16 days (range 5-85 days). Seventeen patients were anticoagulated for a median duration of 6 months (range 3.3-36 months) after the diagnosis of PVT. Over a median follow-up of 22 months, resolution of PVT occurred in seven patients. Predictors of non-resolution of PVT included anesthesia time >180 min (p = 0.025), DM type II (p = 0.03), BMI >30 Kg/m(2) (p = 0.03), occlusive PVT (p < 0.001), or thrombus in a sectoral branch (p = 0.02). Anticoagulation therapy did not influence the frequency of thrombus resolution and was complicated by gastrointestinal hemorrhage in four patients. There was no mortality as a direct result of PVT or anticoagulation., Conclusion: PVT after distal pancreatectomy is a rare complication. Serious complications as a direct result of PVT in this setting are uncommon and are not dependent on thrombus resolution. Although anticoagulation does not appear to influence the rate of PVT resolution in this small retrospective series, we support the use of anticoagulation until larger, controlled studies define clear advantages or disadvantages.

Background: EUS can provide access to the main pancreatic duct (MPD) for therapeutic intervention. The long-term clinical success of EUS-guided MPD interventions is unknown., Objective: To determine technical and clinical success rates, predictors of success, and long-term outcomes of EUS-guided MPD intervention., Design: Retrospective, single-center study., Setting: Tertiary-care referral center., Patients: Forty-five patients., Intervention: EUS-guided MPD stent retrieval or placement., Main Outcome Measurements: Technical and clinical success rates, adverse events, and long-term clinical outcomes., Results: Among the 45 patients, 37 had undergone failed ERCP, and 29 had surgically altered anatomy. Median follow-up after initial EUS-guided intervention was 23 months. Two patients underwent EUS for stent removal, and EUS-guided MPD stent placement was attempted in 43 patients. Technical success was achieved in 32 of 43 patients (74%) with antegrade (n = 18) or retrograde (n = 14) stent insertion. Serious adverse events occurred in 3 patients (6%). Patients underwent a median of 2 (range 1-6) follow-up procedures for revision or removal of stents, without adverse events. Complete symptom resolution occurred in 24 of 29 patients (83%) while stents were in place, including all 6 with nondilated ducts. Stents were removed in 23 patients, who were then followed for an additional median of 32 months; 4 patients had recurrent symptoms. Among the 11 failed cases, most had persistent symptoms or required surgery., Limitations: Retrospective study design, individualized patient management., Conclusion: EUS-guided MPD intervention is feasible and safe, with long-term clinical success in the majority of patients. EUS provides important treatment options, particularly in patients who would otherwise undergo surgery., (Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: We aimed to identify staging parameters associated with survival in patients with hilar cholangiocarcinoma., Methods: Clinicopathologic characteristics were obtained retrospectively for all resected patients with Bismuth-Corlette III cholangiocarcinoma between 1993 and 2011. Patients were stratified by the American Joint Commission on Cancer (AJCC) (7th edition) and Memorial Sloan-Kettering Cancer Center (MSKCC) staging systems. Survival analyses tested the effects of clinicopathologic factors and staging covariates on recurrence-free and overall survival., Results: Eighty patients (mean age 63 ± 11 years, 63% male) underwent anatomic hepatectomy with bile duct resection/reconstruction for Bismuth-Corlette IIIa (53%) and IIIb (47%) cholangiocarcinoma. The median follow-up was 26 months (interquartile range = 12 to 50 months), and the median time to recurrence was 15 months (interquartile range = 6 to 38 months). Neither AJCC nor MSKCC staging systems were associated with recurrence-free survival (all P ≥ .059). MSKCC T-stage but not the AJCC staging system was associated with overall survival (P ≤ .026)., Conclusions: MSKCC T-stage classification but not AJCC staging is independently associated with overall survival for patients after resection of hilar cholangiocarcinoma., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Autoimmune pancreatitis (AIP) is a rare subtype of chronic pancreatitis that may mimic adenocarcinoma of the pancreas. The aim of this study was to evaluate the short-term and long-term outcomes of pancreatectomy for patients with AIP., Methods: In this multi-institutional study, we identified all patients who underwent pancreatectomy for AIP from 1986 to 2011. AIP was confirmed by pathology review. Clinical presentation, operative details, and postoperative outcomes were analyzed., Results: Seventy-four patients (median age, 60 years; 69 % male) with AIP underwent pancreatectomy. The main indication for operation was concern for malignancy (n = 59, 80 %). No patients were found to have pancreatic adenocarcinoma on final pathology. Major complications occurred in ten (14 %) patients, with one perioperative death (1 %). Clinically relevant (grade B/C) pancreatic fistulae occurred in two patients. No patients required reoperation for AIP and 11 (17 %) patients developed recurrent AIP., Conclusion: Although we do not advocate pancreatectomy for AIP, strong suspicion of malignancy may require an operation in selected patients. For patients with AIP, pancreatectomy resulted in few pancreatic fistulae, a low rate of re-intervention, and a 17 % recurrence rate.

Objective: To determine whether remnant pancreatic volume (RPV), subcutaneous/visceral adipose tissue(SAT/VAT) area, and skeletal muscle (SM) area calculated from preoperative computed tomography (CT) can predict the occurrence of pancreatic anastomotic failure (PAF) after pancreatoduodenectomy (PD)., Background: Increased body mass index, small main pancreatic duct, and soft pancreatic texture are well-established predictors of PAF after PD. The impact on PAF of anthropomorphic measurements, such as RPV and body composition, is unknown., Methods: In 173 patients undergoing PD from 2004 to 2009, cross sections of SAT/VAT/SM area were quantitated volumetrically, respectively, from preoperative CT. RPV was calculated from the CT as the sum of pancreatic tissue area to the left of the presumed pancreatic transection site. The predictive ability for multiple models using combinations of body mass index, RPV, SAT/VAT area, SM area, main pancreatic duct size, and pancreatic gland texture was described using a concordance index (c-index)., Results: Clinically relevant PAF occurred in 22 patients (13%). Multivariate logistic regression analysis identified RPV (P = 0.0012), VAT area (P = 0.0003), and SM area (P = 0.0006) as independent predictors of PAF. Using previously identified risk factors, the best 2-predictor model (body mass index and pancreatic duct size) resulted in a c-index of 0.748. Using anthropomorphic factors, however, the 2-predictor model using VAT and SM areas revealed a superior c-index of 0.959., Conclusions: Our 2-predictor model using VAT area and SM area based on volumetric quantification using preoperative CT may offer clinical benefit as an objective prognostic measure to predict clinically relevant PAF after PD.

Background: New-onset diabetes mellitus after a pancreaticoduodenectomy (PD) remains poorly defined. The aim of this study was to define the incidence and predictive factors of immediate post-resection diabetes mellitus (iPRDM)., Methods: Retrospective review of patients undergoing PD from January 2004 through to July 2010. Immediate post-resection diabetes mellitus was defined as diabetes requiring pharmacological treatment within 30 days post-operatively. Logistic regression was conducted to identify factors predictive of iPRDM., Results: Of 778 patients undergoing PD, 214 were excluded owing to pre-operative diabetes (n= 192), declined research authorization (n= 14) or death prior to hospital discharge (n= 8); the remaining 564 patients comprised the study population. iPRDM occurred in 22 patients (4%) who were more likely to be male, have pre-operative glucose intolerance, or an increased creatinine, body mass index (BMI), pre-operative glucose, operative time, tumour size or specimen length compared with patients without iPRDM (P < 0.05). On multivariate analysis, pre-operative impaired glucose intolerance (P < 0.001), pre-operative glucose ≥ 126 (P < 0.001) and specimen length (P= 0.002) were independent predictors of iPRDM. A predictive model using these three factors demonstrated a c-index of 0.842., Discussion: New-onset, post-resection diabetes occurs in 4% of patients undergoing PD. Factors predictive of iPRDM include pre-operative glucose intolerance, elevated pre-operative glucose and increased specimen length. These data are important for patient education and predicting outcomes after PD., (Published 2012. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Primary gastrointestinal stromal tumours (GISTs) of the duodenum are rare. The aim of this study was to review the surgical management of GISTs in this anatomically complex region., Methods: Retrospective review from January 1999 to August 2011 of patients with primary GISTs of the duodenum., Results: Forty-one patients underwent resection of duodenal GISTs. All operations were performed with intent to cure with negative margins of resection. The most common location of origin was the second portion of the duodenum. Local excision (n= 19), segmental resection with primary anastomosis (n= 11) and a pancreatoduodenectomy (n= 11) were performed. Two patients underwent an ampullectomy with local excision. Peri-operative mortality and overall morbidity were 0 and 12, respectively. Patients with high-risk GISTs (P= 0.008) and those who underwent a pancreatoduodenectomy (P= 0.021) were at a greater risk for morbidity. The median follow-up was 18 months. Eight patients developed recurrence. High-risk GISTs and neoplasms with ulceration had the greatest risk for recurrence (P= 0.017, P= 0.029 respectively). The actuarial 3- and 5-year survivals were 85% and 74%, respectively., Conclusion: The choice and type of resection depends on the proximity to the ampulla of Vater, involvement of adjacent organs and the ability to obtain negative margins. The morbidity depends on the type of procedure for GIST., (© 2012 International Hepato-Pancreato-Biliary Association.)

Introduction: We investigated the role of operative therapy in non-cirrhotic patients who developed metastatic hepatocellular carcinoma (HCC)., Methods: This retrospective cohort study included consecutive non-cirrhotic patients with metastatic HCC after a prior hepatectomy treated between 1990 and 2009. Patients were stratified by operative therapy (resection, ablation, transcatheter therapy). Kaplan-Meier analyses with log-rank comparisons tested effects of operative therapy on overall survival (OS) and progression-free survival (PFS)., Results: Of 195 non-cirrhotic patients treated for HCC during the study period, 98 [median age 65, interquartile range (IQR) 53-71; 55 % male] subsequently developed metastatic HCC (55 intrahepatic only). Median time to development of metastases after the index operation was 10 months (IQR 5-20 months); median number of metastases was 3 (IQR 2-7). Half of these patients (n = 50) underwent operative treatment of metastases; 20 (40 %) underwent metastasectomy, 18 (36 %) ablation, and 12 (24 %) transcatheter therapy. Operative therapy was associated with improved OS (p < 0.001). Resection or ablation was associated with improved PFS and OS compared to transcatheter therapy (all p ≤ 0.006). Nine patients (seven resection, two ablation) are disease free at a median of 50 months (IQR 24-80 months) posttreatment., Conclusions: Resection and ablation are associated with an improved PFS and long-term OS and should be considered in select patients with metastatic HCC.

Producing diagnostic antibodies in chicken egg yolk represents an alternate animal system that offers many advantages including high productivity at low cost. Despite being an excellent counterpart to mammalian antibodies, chicken IgG from yolk still represents an underused resource. The potential of agonistic monoclonal anti-CD40 antibodies (mAb) as a powerful immunological adjuvant has been demonstrated in mammals, but not in chickens. We recently reported an agonistic anti-chicken CD40 mAb (designated mAb 2C5) and showed that it may have potential as an immunological adjuvant. In this study, we examined the efficacy of targeting a short peptide to chicken CD40 [expressed by the antigen-presenting cells (APCs)] in enhancing an effective IgG response in chickens. For this purpose, an immune complex consisting of one streptavidin molecule, two directionally biotinylated mAb 2C5 molecules, and two biotinylated peptide molecules was produced. Chickens were immunized subcutaneously with doses of this complex ranging from 10 to 90 μg per injection once, and relative quantification of the peptide-specific IgG response showed that the mAb 2C5-based complex was able to elicit a strong IgG response as early as four days post-immunization. This demonstrates that CD40-targeting antigen to chicken APCs can significantly enhance antibody responses and induce immunoglobulin isotype-switching. This immunization strategy holds promise for rapid production of hapten-specific IgG in chickens., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: The aim of our study was to compare the outcomes of periampullary and extra-ampullary duodenal adenocarcinomas and segmental duodenal resection versus pancreatoduodenectomy and to evaluate prognostic factors., Methods: We performed a retrospective review of all adults treated for duodenal adenocarcinoma by operative resection at a large tertiary referral center from 1994 to 2009., Results: One hundred twenty-four patients had an operation for duodenal adenocarcinoma over a 15-year period (periampullary, n = 25, and extra-ampullary, n = 99). Ninety-nine patients (80%) underwent curative resection, including 24 (96%) with periampullary and 75 (76%) with extra-ampullary carcinomas. The average number of lymph nodes sampled was eight with segmental resection and 12 with pancreatoduodenectomy (p < 0.001). Five-year overall survivals were 37% for the entire cohort (n = 124), 37% in the extra-ampullary group, and 38% in the periampullary group. Tumor size (p = 0.20), positive nodes (p = 0.60), segmental resection versus pancreatoduodenectomy (p = 0.55), adjuvant therapy (p = 0.23), and R(1) versus R(0) resection (p = 0.21) were not associated with survival. In contrast, advanced T stage and pathologic grade were associated with poor survival., Conclusion: Extra-ampullary and periampullary duodenal adenocarcinomas have similar survival after resection. For distal duodenal tumors, survival is improved by curative resection without being compromised by limited resection. The number of lymph nodes sampled was significantly less with segmental resection than pancreatoduodenectomy.