Pancreatic cancer cells intimately interact with a complex microenvironment that influences pancreatic cancer progression. The pancreas is innervated by fibers of the sympathetic nervous system (SNS) and pancreatic cancer cells have receptors for SNS neurotransmitters which suggests that pancreatic cancer may be sensitive to neural signaling. In vitro and non-orthotopic in vivo studies showed that neural signaling modulates tumour cell behavior. However the effect of SNS signaling on tumor progression within the pancreatic microenvironment has not previously been investigated. To address this, we used in vivo optical imaging to non-invasively track growth and dissemination of primary pancreatic cancer using an orthotopic mouse model that replicates the complex interaction between pancreatic tumor cells and their microenvironment. Stress-induced neural activation increased primary tumor growth and tumor cell dissemination to normal adjacent pancreas. These effects were associated with increased expression of invasion genes by tumor cells and pancreatic stromal cells. Pharmacological activation of β-adrenergic signaling induced similar effects to chronic stress, and pharmacological β-blockade reversed the effects of chronic stress on pancreatic cancer progression. These findings indicate that neural β-adrenergic signaling regulates pancreatic cancer progression and suggest β-blockade as a novel strategy to complement existing therapies for pancreatic cancer.

The CIAO Study (“Complicated Intra-Abdominal infection Observational” Study) is a multicenter investigation performed in 68 medical institutions throughout Europe over the course of a 6-month observational period (January-June 2012).Patients with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study.2,152 patients with a mean age of 53.8 years (range: 4–98 years) were enrolled in the study. 46.3% of the patients were women and 53.7% were men. Intraperitoneal specimens were collected from 62.2% of the enrolled patients, and from these samples, a variety of microorganisms were collectively identified.The overall mortality rate was 7.5% (163/2.152).According to multivariate analysis of the compiled data, several criteria were found to be independent variables predictive of patient mortality, including patient age, the presence of an intestinal non-appendicular source of infection (colonic non-diverticular perforation, complicated diverticulitis, small bowel perforation), a delayed initial intervention (a delay exceeding 24 hours), sepsis and septic shock in the immediate post-operative period, and ICU admission.Given the sweeping geographical distribution of the participating medical centers, the CIAO Study gives an accurate description of the epidemiological, clinical, microbiological, and treatment profiles of complicated intra-abdominal infections (IAIs) throughout Europe.

Scutellaria baicalensis (SB) and SB-derived polyphenols possess anti-proliferative activities in several cancers, including pancreatic cancer (PaCa). However, the precise molecular mechanisms have not been fully defined. SB extract and SB-derived polyphenols (wogonin, baicalin, and baicalein) were used to determine their anti-proliferative mechanisms. Baicalein significantly inhibited the proliferation of PaCa cell lines in a dose-dependent manner, whereas wogonin and baicalin exhibited a much less robust effect. Treatment with baicalein induced apoptosis with release of cytochrome c from mitochondria, and activation of caspase-3 and -7 and PARP. The general caspase inhibitor zVAD-fmk reversed baicalein-induced apoptosis, indicating a caspase-dependent mechanism. Baicalein decreased expression of Mcl-1, an anti-apoptotic member of the Bcl-2 protein family, presumably through a transcriptional mechanism. Genetic knockdown of Mcl-1 resulted in marked induction of apoptosis. The effect of baicalein on apoptosis was significantly attenuated by Mcl-1 over-expression, suggesting a critical role of Mcl-1 in this process. Our results provide evidence that baicalein induces apoptosis in pancreatic cancer cells through down-regulation of the anti-apoptotic Mcl-1 protein.

After 5 years, the two techniques of mesh fixation resulted in similar rates of chronic pain. Whereas recurrence rates were comparable, fixation of the mesh with tissue glue decreased operating room time significantly. Hence, suture less mesh fixation with Histoacryl is a sensible alternative to suture fixation and should be especially considered for patients prone to pain.

Objectives The flavonoid quercetin holds promise as an anti-tumor agent in several preclinical animal models. However, the efficacy of oral administration of quercetin in a pancreatic cancer mouse model is unknown. Methods The anti-proliferative effects of quercetin alone or in combination with gemcitabine were tested in two human pancreatic cancer cell lines using cell count and MTT assays. Apoptosis was evaluated by flow cytometry. Tumor growth in vivo was investigated in an orthotopic pancreatic cancer animal model using bioluminescence. Quercetin was administered orally in the diet. Results Quercetin inhibited the growth of pancreatic cancer cell lines, which was caused by an induction of apoptosis. In addition, dietary supplementation of quercetin attenuated the growth of orthotopically transplanted pancreatic xenografts. The combination of gemcitabine and quercetin had no additional effect compared to quercetin alone. In vivo quercetin caused significant apoptosis and reduced tumor cell proliferation. Conclusions Our data provide evidence that oral administration of quercetin was capable of inhibiting growth of orthotopic pancreatic tumors in a nude mouse model. These data suggest a possible benefit of quercetin in patients with pancreatic cancer.

Clinically relevant fistula after distal pancreatic resection occurs in 5-30% of patients, prolonging recovery and considerably increasing in-hospital stay and costs. We tested whether routine drainage of the pancreatic stump into a Roux-en-Y limb after distal pancreatic resection decreased the incidence of fistula. From October 2001, data of all patients undergoing pancreatic distal resection were entered in a prospective database. From June 2003 after resection, the main pancreatic duct and the pancreatic stump were oversewn, and in addition, anastomosed into a jejunal Roux-en-Y limb by a single-layer suture (n = 23). A drain was placed near the anastomosis, and all patients received octreotide for 5-7 days postoperatively. The volume of the drained fluid was registered daily, and concentration of amylase was measured and recorded every other day. Patient demographics, hospital stay, pancreatic fistula incidence (> or =30 ml amylase-rich fluid/day on/after postoperative day 10), perioperative morbidity, and follow-up after discharge were compared with our initial series of patients (treated October 2001-May 2003) who underwent oversewing only (n = 20). Indications, patient demographics, blood loss, and tolerance of an oral diet were similar. There were four (20%) pancreatic fistulas in the "oversewn" group and none in the anastomosis group (p < 0.05). Nonsurgical morbidity, in-hospital stay, and follow-up were comparable in both groups.

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BACKGROUND AIMS:: Little is known about the pathogenic mechanisms of autoimmune pancreatitis (AIP), an increasingly recognized, immune-mediated form of chronic pancreatitis. Current treatment options are limited and disease relapse is frequent. We investigated factors that contribute to development of AIP and new therapeutic strategies. METHODS:: We used quantitative PCR, immunohistochemical and ELISA analyses to measure expression of cytokines and chemokines in tissue and serum samples from patients with and without AIP. We created a mouse model of human AIP by overexpressing LT and specifically in acinar cells ( Ela1-LTab mice). RESULTS:: mRNA levels of lymphotoxin (LT) and were increased in pancreatic tissues from patients with AIP, compared with controls, and expression of chemokines ( CXCL13, CCL19, CCL21, CCL1 and BAFF) was increased in pancreatic and serum samples from patients. Upregulation of these factors was not affected by corticosteroid treatment. Acinar-specific overexpression of LT (Ela1-LT) in mice led to an autoimmune disorder with various features of AIP. Chronic inflammation developed only in the pancreas but was sufficient to cause systemic autoimmunity. Acinar-specific overexpression of LT did not cause autoimmunity in mice without lymphocytes(Ela1-LTab/Rag1(-/-)); moreover lack of pro-inflammatory monocytes (Ela1-LTab/Ccr2-/-) failed to prevent AIP but prevented early pancreatic tissue damage. Administration of corticosteroids reduced pancreatitis but did not affect production of autoantibodies, such as anti-pancreatic secretory trypsin inhibitor in Ela1-LTab mice. In contrast, inhibition of LTR signaling reduced chemokine expression, renal immune-complex deposition, and features of AIP in Ela1-LTab mice. CONCLUSIONS:: Overexpression of LT specifically in acinar cells of mice causes features of AIP. Reagents that neutralize LT R ligands might be used to treat patients with AIP.