Ziel: Die kontrastverstärkte harmonische endoskopische Sonografie (CEH-EUS) zur Beurteilung der Mikrozirkulation und Ausdehnung pankreatischer Tumoren für deren Charakterisierung und Staging ist erst seit Kurzem auf dem Markt und nur wenige Publikationen behandeln dieses Thema. Ziel der Studie war die qualitative und quantitative digitale Bildanalyse pankreatischer Adenokarzinome mittels konventioneller endoskopischer Sonografie (EUS) und mittels CEH-EUS und die Beurteilung, inwieweit die Anwendung von Kontrastmittel das Staging der Adenokarzinome und deren Management beeinflusste. Material und Methoden: Bei 30 prospektiv untersuchten Patienten mit Verdacht auf einen soliden pankreatischen Tumor wurde CEH-EUS mit der jeweils gleichen Dosis Kontrastmittel (SonoVue) und einem niedrigen mechanischen Index (0,3 – 0,4) durchgeführt; darauf folgte die EUS-FNA. Basierend auf EUS-FNA oder nach Operation lagen folgende Histopathologien vor: pankreatisches Adenokarzinom (n = 15), pseudotumorale chronische Pankreatitis (n = 12), neuroendokriner Tumor (n = 1), Gallengangstumor (n = 1), Lymphknotenmetastase eines Magenkarzinoms (n = 1). Die quantitative Analyse basierte auf Histogrammen, die aus den CEH-EUS-Videoaufzeichnungen erstellt wurden. Ergebnisse: CEH-EUS zeigte ein Muster geringer Kontrastierung in 14 Fällen bei Adenokarzinomen und in 10 Fällen chronischer Pankreatitis. Der Index für die Kontrastmittelaufnahme-Ratio war beim Adenokarzinom signifikant niedriger als bei der raumfordernden chronischen Pankreatitis. Bei einem Grenzwert für die Aufnahme-Ratio von 0,17 zur Diagnose von Adenokarzinomen lag die AUC (KI 95 %) bei 0,86 (0,67 – 1,00) mit einer Sensitivität von 80 %, einer Spezifizität von 91,7 %, einem positiv prädiktiven Wert von 92,8 %, und einem negativ prädiktiven Wert von 78 %. Die Größe der pankreatischen Raumforderung wurde mit CEH-EUS signifikant genauer bestimmt, CEH-EUS hatte aber keinen Einfluss auf das Staging der Adenokarzinome. Schlussfolgerung: Die Mehrzahl der pankreatischen Adenokarzinome und chronischen Pankreatitiden zeigte eine geringe Kontrastierung und eine visuelle Diskriminierung zwischen beiden Entitäten war nicht möglich. Dies ist die erste Studie zur quantitativen Beurteilung pankreatischer Raumforderungen mittels CEH-EUS, die zeigen konnte, dass diese Methode nach Kontrastmittelgabe die Differenzierung zwischen benignen und malignen Läsionen unterstützt, aber keinesfalls die EUS-FNA ersetzen kann. Weder Tumorstadium noch therapeutisches Management änderten sich nach CEH-EUS. Purpose: Contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) for the assessment of microcirculation and the delineation of pancreatic tumors in order to characterize and stage them has only recently become available for commercial use, and few reports have been published. The purpose of the study was the qualitative and quantitative digital image analysis of pancreatic adenocarcinomas using conventional endoscopic ultrasonography (EUS) and CEH-EUS and the evaluation of whether contrast medium injection modified adenocarcinoma staging and patient management. Materials and Methods: In each of 30 prospectively examined patients with suspected pancreatic solid lesions, CEH-EUS was performed using the same quantity of the contrast agent SonoVue and a low mechanical index (0.3 – 0.4), followed by EUS-FNA. The histology, based on EUS-FNA or surgery and 9 months of follow-up, was: pancreatic adenocarcinoma (n = 15), pseudotumoral chronic pancreatitis (n = 12), neuroendocrine tumor (n = 1), common bile duct tumor (n = 1), lymph node metastases of gastric cancer (n = 1). The quantitative analysis was based on histograms obtained from each CEH-EUS video recording. Results: CEH-EUS showed a hypoenhanced pattern in 14 cases of adenocarcinoma and in 10 cases of chronic pancreatitis. The index of the contrast uptake ratio was significantly lower in adenocarcinoma than in mass-forming chronic pancreatitis. A cut-off uptake ratio index value of 0.17 for diagnosing adenocarcinoma corresponded to an AUC (CI 95 %) of 0.86 (0.67 – 1.00) with a sensitivity of 80 %, a specificity of 91.7 %, a positive predictive value of 92.8 %, and a negative predictive value of 78 %. The size of the pancreatic mass was assessed significantly more effectively by CEH-EUS but adenocarcinoma staging was not modified. Conclusion: The majority of cases of both pancreatic adenocarcinoma and chronic pancreatitis were hypoenhanced and visual discrimination was not possible. This is the first study about CEH-EUS for the quantitative assessment of uptake after contrast injection which has shown that it can aid differentiation between benign and malignant masses but cannot replace EUS-FNA. Neither tumor stage nor therapeutic management have changed after contrast medium injection during CEH-EUS.

Patients with pancreatic cancer have a poor prognosis with a median survival of 4-6 mo and a 5-year survival of less than 5%. Despite therapy with gemcitabine, patient survival does not exceed 6 mo, likely due to natural resistance to gemcitabine. Therefore, it is hoped that more favorable results can be obtained by using guided immunotherapy against molecular targets. This review summarizes the new leading targeted therapies in pancreatic cancers, focusing on passive and specific immunotherapies. Passive immunotherapy may have a role for treatment in combination with radiochemotherapy, which otherwise destroys the immune system along with tumor cells. It includes mainly therapies targeting against kinases, including epidermal growth factor receptor, Ras/Raf/mitogen-activated protein kinase cascade, human epidermal growth factor receptor 2, insulin growth factor-1 receptor, phosphoinositide 3-kinase/Akt/mTOR and hepatocyte growth factor receptor. Therapies against DNA repair genes, histone deacetylases, microRNA, and pancreatic tumor tissue stromal elements (stromal extracellular matric and stromal pathways) are also discussed. Specific immunotherapies, such as vaccines (whole cell recombinant, peptide, and dendritic cell vaccines), adoptive cell therapy and immunotherapy targeting tumor stem cells, have the role of activating antitumor immune responses. In the future, treatments will likely include personalized medicine, tailored for numerous molecular therapeutic targets of multiple pathogenetic pathways.

Interleukin (IL)-17 and IL-23 are crucial for mediating gut mucosal inflammation in inflammatory bowel disease (IBD), which has led to new therapeutic strategies. We assessed the relevancy of IL-17 and IL-23 serum levels as potential biomarkers towards severe IBD discrimination and disease-related complications. Sixty-two patients diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC) were included. Serum IL-17 and IL-23 were measured by sandwich enzyme-linked immunosorbent assays (ELISA). IL-23 and fecal calprotectin (FCal) were significantly higher in severe CD (p < 0.001) and UC (p < 0.001 and p = 0.001, respectively), compared to mild or moderate. Elevated C-reactive protein (CRP) was correlated with severe disease only in CD (p = 0.008), whereas for UC, disease severity was associated with increased IL-17 values (p < 0.001). Diagnostic role of IL-23 was superior to FCal in discriminating between severe and mild to moderate CD (p < 0.001). IL-23 levels were also significantly higher in CD patients with intestinal complications (p = 0.04). Both IL-17 and IL-23 correlate with IBD severity, and IL-23 might be a promising novel biomarker for severe CD. Identifying the dominant IL pathway involved in IBD severity could serve as guidance for clinical decision-making on biologic therapy.

Pain in pancreatic cancer is often a major problem of treatment. Administration of opioids is frequently limited by side effects or insufficient analgesia. Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) represents an alternative for the palliative treatment of visceral pain in patients with pancreatic cancer. This review focuses on the indications, technique, outcomes of EUS-CPN and predictors of pain relief. EUS-CPN should be considered as the adjunct method to standard pain management. It moderately reduces pain in pancreatic cancer, without eliminating it. Nearly all patients need to continue opioid use, often at a constant dose. The effect on quality of life is controversial and survival is not influenced. The approach could be done in the central position of the celiac axis, which is easy to perform, or in the bilateral position of the celiac axis, with similar results in terms of pain alleviation. The EUS-CPN with multiple intraganglia injection approach seems to have better results, although extended studies are still needed. Further trials are required to enable more confident conclusions regarding timing, quantity of alcohol injected and the method of choice. Severe complications have rarely been reported, and great care should be taken in choosing the site of alcohol injection. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

In assessing exocrine pancreatic insufficiency (EPI), its diverse etiologies and the heterogeneous population affected should be considered. Diagnosing this condition remains a challenge in clinical practice especially for mild-to-moderate EPI, with the support of the time-consuming breath test or the coefficient of fat absorption. The fecal elastase-1 test, less precise for the diagnosis, cannot be useful for assessing treatment efficacy. Pancreatic enzyme replacement therapy (PERT) is the mainstay of treatment, whereby enteric-coated mini-microspheres are taken with every meal, in progressive doses based on an individual's weight and clinical symptoms. The main indication for PERT is chronic pancreatitis, in patients who have clinically relevant steatorrhea, abnormal pancreatic function test or abnormal function tests associated with symptoms of malabsorption such as weight loss or meteorism. While enzyme replacement therapy is not recommended in the initial stages of acute pancreatitis, pancreatic exocrine function should be monitored for at least 6-18 months. In the case of unresectable pancreatic cancer, replacement enzyme therapy helps to maintain weight and improve overall quality of life. It is also indicated in patients with celiac disease, who have chronic diarrhea (in spite of gluten-free diet), and in patients with cystic fibrosis with proven EPI.

Endoscopic ultrasound in chronic pancreatitis: Where are we now?