Supplemental Figure S1. Tumor-associated stromal response to pattern recognition receptor ligands. Supplementary Figure S2. Pancreatic cancer cell conditioned media and TLR4 ligation induces expression of antigen presentation machinery and negative co-stimulatory ligands on TAS. Supplemental Figure S3. TAS-mediated T cell suppression is enhanced by neutralization of either IL6 or IL8 and unaffected by TLR4 knockdown in TAS.

Objective: We sought to determine if laparoscopic pancreaticoduodenectomy (LPD) is a cost effective alternative to open pancreaticoduodenectomy (OPD). Methods: Itemized hospital cost data from periampullary cancer patient cohorts of LPD and OPD, previously identified as similar (met NCCN criteria for resectable disease) were compared. This review also included discharge disposition, readmission rates, and readmission costs. Results: The cohorts consisted of 52 and 50 patients in the LPD and OPD cohorts, respectively. The total OR cost was significantly higher in the LPD group (P<0.05) as the laparoscopic equipment and regional blocks had increased cost in the LPD group (P<0.05). Although hospital length of stay was shorter in the LPD group (9 vs 11.9 days), the total hospital cost (average of $36,646 for LPD vs $39,250 for OPD) was not significantly decreased compared to the OPD group. The readmission rates were equal with each group having 23 patients readmitted for a total of 43 readmissions. Readmission costs were not significantly different between groups. More LPD patients were discharged directly home, with or without home health care (P<0.05), and the number discharged to a rehabilitation facility also trended favorably in the LPD group (P=0.054). Conclusion: LPD is cost effective. Total episode-of-care costs may favor LPD via reduced post-hospital needs for skilled nursing and rehabilitation.Tabled 1LPDOPDP value(n=52)(n=50)Expired1 (2%)1 (2%)1To home (with or without HHC)46 (88%)36 (72%)0.046* To home with HHC23 (44%)23 (46%)1 To home without HHC23 (44%)13 (26%)0.064To long term acute care0 (0%)2 (4%)0.24To rehabilitation center0 (0%)4 (8%)0.054To skilled nursing facility5 (10%)7 (14%)0.55Laparoscopic equipment (SEM)$ 450 (31)$ 46 (17)<0.01*Regional block (SEM)$ 1,450 (144)$ 820 (103)<0.01*OR (SEM)$ 13,173 (254)$ 11,770 (539)0.02*Total number of readmissions4343Total hospital days during readmissions282408Average number of readmissions per patient (SEM)0.83 (0.20)0.86 (0.19)0.9Average number of hospital days per patient (SEM)5.42 (1.57)8.16 (2.24)0.28Total readmission costs (SEM)$ 14,722 (2663)$ 20,096 (5983)0.42P values were calculated using Fisher's exact test and unpaired t test.HHC home health care, SEM standard error of the mean. Open table in a new tab P values were calculated using Fisher's exact test and unpaired t test. HHC home health care, SEM standard error of the mean.

490 Background: Despite advances in chemotherapy (CTx), the prognosis for metastatic pancreatic ductal adenocarcinoma (mPDAC) is poor and while hospice is known to improve end-of-life care, referrals are often placed close to death. This may be due to accessibility issues or misconceptions that referral implies abandonment. We hypothesized that utilization of palliative CTx and travel distance to the treatment center impacts hospice referral patterns. Methods: Patients with histologically confirmed or radiographically presumed mPDAC as their initial diagnosis were retrospectively identified in a Veterans Administration Medical Center (VAMC) from 2005-2014. Demographic and clinical data were collected according to timing of hospice referral. Results: Fifty-eight mPDAC patients were identified with a median age of 63yr of which 57 (98.3%) were male. Palliative CTx was used in 26 (44.8%) patients with 32 (55.2%) not treated due to poor performance status (n = 18; 56.3%) or patient refusal (n = 14; 43.8%). Of the 52 (89.7%) patients referred to hospice, the median time from diagnosis to referral and referral to death was 2.4wk (Interquartile Range [IQR] 14.9) and 3.1wk (IQR 6.5), respectively. The median time to hospice referral was 18.7wk for patients treated with CTx vs 1.4wk for those who did not undergo therapy (p < 0.001). The median distance from residence to the VAMC was 58.5mi (IQR 77). Subset analysis for those living > 60mi vs < 60mi to the VAMC, the median time to hospice referral was 1.7wk vs 4.7wk, respectively (p = 0.1). With no significant differences between groups in age, sex, race, or disease burden, univariate analysis demonstrated that those referred to hospice > 2.4wk from diagnosis more often received CTx (p < 0.001) and lived > 60mi from the treatment center (p = 0.05). Conclusions: The majority of patients with mPDAC were enrolled in hospice and while travel distance trended to shorter time to referral, this was not significant. However, receipt of palliative chemotherapy did delay referral and those with this delay lived farther from the hospital. These data suggest that physicians delay hospice care in patients who are able to tolerate treatment and travel long distance to receive it.

Introduction: The role of the microbiome on vascular disease, viral infections, and immune modulating therapy is not well defined. Changes in bacterial signatures are seen in inflammatory vasculiti...

Pneumonia and tracheal aspiration remain problematic following esophagectomy. We hypothesized that the incidence of postesophagectomy pneumonia occurs in part because of swallowing dysfunction and more importantly silent tracheobronchial aspiration. Therefore, we instituted a routine prospective formal swallowing evaluation to determine if the aspiration rate and its associated morbidity can be decreased by early identification of patients with silent or vocal aspiration.

BackgroundTo investigate the outcome of the port-access approach for patent foramen ovale (PFO) closure and to identify the long-term risk of recurrent thromboembolic events in the paradoxical embolus subgroup after closure.MethodsBetween 1997 and 2001, 31 patients underwent PFO closure using the port-access approach. Twelve of the 31 patients underwent PFO closure secondary to at least one paradoxical embolic event leading to either transient ischemic attack or cerebral infarction. All patients were followed longitudinally with office visits and telephone interviews.ResultsThe mean age was 47 years (range 18 to 85 years). All procedures were completed successfully without conversion to median sternotomy. The mean duration of aortic occlusion and cardiopulmonary bypass for all patients (n = 31) was 32 minutes (range 17 to 55 minutes) and 72 minutes (range 40 to 124 minutes), respectively. Postoperative complications included pneumonia/pulmonary embolus (n = 1), transient atrial fibrillation (n = 3, 9.7%), and exploration for bleeding (n = 3, 9.7%). No deaths were recorded. All patients were assessed using transesophageal echocardiography, and the closure of the PFO was documented. The average length of hospital stay was 3.8 days (range 2 to 10 days) for patients with paradoxical emboli. The mean follow-up period for the paradoxical embolus subgroup was 23 months (range 4 to 45 months). One patient was lost to follow-up. Neither transient ischemic attack nor cerebral infarction recurred during follow-up.ConclusionsThe port-access approach to PFO closure is a safe and effective procedure, with acceptable initial experience outcome and excellent low-risk rate of recurrent thromboembolic events.

Several structurally different tumor promoters altered to various degrees both glutathione (GSH) peroxidase (EC 1.11.1.9) and ornithine decarboxylase (ODC, L-ornithine carboxy-lyase, EC 4.1.1.17) activities in mouse epidermis in vivo. At 5 h after their application to the skin, the complete tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and the stage 2 promoter mezerein were the most potent in inhibiting GSH peroxidase activity and inducing ODC activity. In comparison, the effects of anthralin, phorbol-12,13-didecanoate, benzoyl peroxide, H2O2, and phorbol-12,13-dibenzoate were much smaller, whereas the nontumor promoter phorbol, the hyperplastic agent ethyl phenylpropiolate, and the stage 1 promoter 4-O-methyl TPA did not alter GSH peroxidase and ODC activities. Various treatments including i.p. injections of 40 micrograms of Na2SeO3 and 100 mumol of GSH and/or topical applications of 40 mumol of D-alpha-tocopherol (vitamin E) 20 or 15 min, respectively, before tumor promoter treatment inhibited in an additive manner the effects of either TPA or mezerein on both GSH peroxidase activity and ODC induction. Moreover, these Na2SeO3, GSH, and/or vitamin E treatments inhibited in the same additive manner the tumor-promoting activity of TPA in the initiation-promotion protocol. However, when tested in the 2-stage promotion protocol with 4 doses of TPA followed by twice weekly applications of mezerein, Na2SeO3 plus vitamin E and GSH plus vitamin E treatments inhibited remarkably the tumor-promoting activity of mezerein but were ineffective in the first stage of promotion. The sequence and magnitude for the effects of 7,12-dimethylbenz[alpha]anthracene (DMBA) on GSH peroxidase and ODC activities were very different from those of the tumor promoters. In contrast with their antitumor-promoting activity, the treatments with Na2SeO3 plus vitamin E and GSH plus vitamin E failed to inhibit the carcinogenicity of a single large dose of DMBA and even enhanced the induction of skin tumors by repeated applications of subcarcinogenic doses of DMBA. These results suggest that the promoting component of DMBA carcinogenesis may be different from that of TPA. Moreover, the anticarcinogenicity of Na2SeO3, GSH, and vitamin E may be linked to their ability to facilitate or enhance the activity of the natural GSH-dependent antioxidant protective system of the epidermal cells during the later stages of skin tumor promotion.