Einleitung: Trotz radikaler Operation versterben über 50% aller Patienten mit Magenkarzinom innerhalb von 5 Jahren an den Folgen des Tumors. Neben der radikalen Gastrektomie und erweiterten Lymphadenektomie werden neoadjuvante und adjuvante Therapieansätze bisher nur in Studien durchgeführt. Durch Chemo- und Strahlentherapie oder die Kombination beidere Therapiformen konnten bisher keine wesentlichen Verbesserungen im Überleben erreicht werden. Mit dem humanen monoklonalen Antikörper SC-1 steht erstmals ein apoptoseinduzierendes Immuntherapeutikum zur Verfügung, welches spezifisches gegen Magenkarzinomzellen mit dem SC-1 Rezeptor gerichtet ist.

SC-1 ist ein humaner monoklonaler IgM-Antikörper gegen Magenkarzinomzellen, der aus Milzlymphozyten eines Patienten mit Adenokarzinom des Magens isoliert wurde. Durch Fusion eines antikörperproduzierenden B-Lymphozyten mit einer Heteromyelomzelle kann der Antikörper kontinuierlich produziert werden.

High-resolution manometry (HRM) allows nuanced evaluation of esophageal motor function, and more accurate evaluation of lower esophageal sphincter (LES) function, in comparison with conventional manometry. Pathophysiologic correlates of gastroesophageal reflux disease (GERD) and esophageal peristaltic performance are well addressed by this technique. HRM may alter the surgical decision by assessment of esophageal peristaltic function and exclusion of esophageal outflow obstruction before antireflux surgery . Provocative testing during HRM may assess esophageal smooth muscle peristaltic reserve and help predict the likelihood of transit symptoms following antireflux surgery. HRM represents a continuously evolving new technology that compliments the evaluation and management of GERD.

15559 Background: Reproducible prognostic markers could potentially allow patients with pancreatic cancer to be stratified into treatment groups. In this study, we asked whether EGF, EGFR, erb B2, TGF-α and -β, p53, and PCNA expression might be useful in detecting different aggressive pancreatic cancers and if survival would be worse in high marker expressors. Methods: In this retrospective study a total of 282 patients with histologically verified pancreatic ductal adenocarcinoma were treated at our Department from 1993 to 2003. In addition, 93 patients were selected based on the availability of tissue specimens from the primary tumor and R0-resection (75% head, 13% corpus, 12% caudal). We used Elisa, immunohistochemistry and real time PCR to investigate expression of the different tumor associated factors. The values of morphological and molecular parameters were correlated with clinicopathological characteristics for their predictive value of tumor recurrence using chi-square test, Kaplan-Meier method,...

Advances in the medical treatment of colorectal cancer patients have resulted in considerable improvements through the introduction of new cytotoxic drugs. The significant progress in molecular and tumour biology has produced a great number of targeted, tumour-specific, monoclonal antibodies that are now in various stages of clinical development. Two of these antibodies, cetuximab (Erbitux) und bevacizumab (Avastin), directed against the epidermal growth factor receptor (EGFR) and the vascular epithelial growth factor (VEGF), respectively, have recently been approved for use in metastatic colorectal cancer. The combination of well-known and newly developed cytotoxic agents with monoclonal antibodies makes the medical treatment of colorectal cancer patients considerably more complex, but also provides additional therapeutic strategies for patients in advanced stages of disease.

Objectives. Adult pig islet isolation has greatly improved in the past few years. Islet grafts may now be tested in large animals. Continuous Glucose Monitoring System (CGMS) was applied to diabetic Goettingen Minipigs (GMP) to improve the management of hyperglycemia and hypoglycemia and their welfare before transplantation.Methods. GMP (25-35 kg) received a minipig diet once daily. Diabetes was induced by streptozotocin (STZ; 150 mg/kg intravenous [IV]; n = 5) or by surgical pancreatectomy (PGMP; n = 3). Interstitial glucose concentration (IGC) was monitored continuously with an implanted sensor; CGMS was calibrated using conventional blood glucose tests 3-4 times per day; CGMS data were fed into the monitor memory and analyzed using CGMS software.Results. Glucose sensors were handled accurately. Diabetes occurred 2-3 days after STZ or immediately after pancreatectomy with basal C-peptide secretion of <0.4 ng/mL (measured using intravenous glucose tolerance test) and prompt loss of body weight. Insulin substitution was necessary to keep the GMP in good condition for up to 5-6 months, with stable body weight and normal behavior. Some GMP became hypoglycemic, which was only documented by CGMS, but not by conventional glucose assays. Tight glucose control and substitution of exocrine enzymes (Creon 25,000 E/d) reduced morbidity of the PGMP, which was then comparable with that of STZ-GMP.Conclusions. The CGMS, developed for humans, is equally suitable for the 2 GMP diabetes models. Close-meshed glucose monitoring and insulin treatment improved the general condition of the diabetic GMP, ie, the islet graft recipients, and will thus greatly add to posttransplantation success.

One major obstacle for successful clinical transplantation of isolated pancreatic islets (PI) is their limited survival in vivo. The aim of this study was to analyze the functional and morphological regeneration of PI in diabetic rats by Exendin-4 (Ex4) treatment in vivo. Male Wistar rats (n = 3/group) received 20 nmol/kg Ex4 i.p. for 20 days (day 0 to day +20). Diabetes was induced with 50 mg/kg streptozotocin i.v. on day -3 or on day +5. Diabetic and normal control rats received 0.9% NaCl i.p. instead. Body weight (BW), daily blood glucose (BG) and levels, oral glucose tolerance (OGT) were tested on day -5, day +10, day +20, and on day +22, ie, 48 hours after the last Ex4 injection. Histology of the pancreata ended the study on day +24. In vivo application of Ex4 could not prevent the development of diabetes. Injection of Ex4 led to a significant decrease in postprandial BG levels to 35% for 12 hours. Surprisingly, Ex4 increased postprandial BG levels up to 20% in normal rats. Ex4-treated rats showed better OGT than untreated controls. Interestingly, 48 hours after the last Ex4 injection on day +22 OGT was completely impaired. The Ex4-treated rats lost BW much faster than the untreated controls, and showed signs of gastroparesis at autopsy. Immunohistochemistry of the pancreata documented no signs of islet regeneration. Improvement of OGT in diabetic rats after Ex4 treatment may be explained by increased insulin release from the individual PI, which was confirmed by perifusion studies with isolated PI in vitro (data not shown). Yet, Ex4 may also exert an influence on the gastrointestinal tract as it delays the uptake of glucose during gastroparesis.

15005 Background: The negative regulatory programmed death-1/programmed death-1ligand (PD-1/PD-L) pathway in T-cell activation has been suggested to play an important role in tumor evasion from host immunity. Levels of immune cells expressing PD-1 in clinical colorectal carcinoma (CRC) tumors have not been evaluated. Thus, we investigated whether PD-1 positive T cells were expressed within CRC tumors and the expression of PD-L1 and PD-L2 in human CRC to define their clinical significance in patients’ prognosis after surgery. Methods: Tissue samples from 116 patients operated between 2001 and 2005 were collected in our institution and histologically confirmed CRC were evaluated retrospectively for this study. PD-1 and PD-L gene expression was evaluated by real time quantitative PCR and the samples were immunostained. Outcome analyses were performed. Results: The protein and the mRNA levels of determination by immunohistochemistry and real time quantitative PCR were closely correlated. PD-L expression was inversely correlated with tumor-infiltrating T lymphocytes, particularly CD8+ T cells. T cell infiltration was observed in 105 (90.5%) specimens. 93 (80.2%) specimens were PD-1+ T cells. Intratumoral PD-1+ T cells were associated with advanced tumor stage (p=0.002). Patients with PD-1+ T cells had significantly more PD-L1 tumor cell expression. Multivariate analysis indicated that PD-L positive patients and those with PD-1+ T cells had a significantly poorer prognosis than the negative patients. This was more pronounced in the advanced stage of tumor than in the early stage. Conclusions: These data suggest that interactions of T cells expressing PD-1 and PD-L may promote cancer progression. PD-L1 and PD-L2 status may be a new predictor of prognosis for patients with colorectal carcinoma. No significant financial relationships to disclose.

The programmed death-1/programmed death ligand (PD-1/PD-L) pathway in T cell activation has been suggested to play an important role in tumor evasion from host immunity. However, despite ample evidence from experimental models data in clinical colorectal tumors are scarce. Thus, we investigated the expression of PD-L1 and PD-L2 in human colorectal cancer to define their clinical significance in patients’ prognosis after surgery and asked for the potential role of PD-1 positive T cells within colorectal tumors. Tissue samples from 116 patients operated between 2001 and 2003 with histologically confirmed colorectal carcinoma were evaluated retrospectively for this study. PD-L1 and PD-L2 gene expression together with protein expression were evaluated and outcome analyses were conducted. The protein and mRNA levels as determined by immunohistochemistry and real time PCR were closely correlated. Multivariate analysis indicated that PD-L expression was an independent prognostic factor for colorectal carcinoma. T cell infiltration was observed in 105 (90.5 %) specimens while 67 (63.8 %) out of 105 specimens contained PD-1 positive T cells. Furthermore, patients with PD-1 positive T cells had significantly more PD-L1 expression in their tumor tissue. Presence of tumor infiltrating PD-1 positive T cells was associated with an advanced tumor stage. In addition, patients with PD-L positive tumor tissue and those with tumor infiltrating PD-1 positive T cells had a significantly poorer prognosis than negative patients This was more pronounced in advanced tumor stages than in early stages. These data suggest that interactions of T cells expressing PD-1 may promote cancer progression through a down-regulation of anti-tumor immunity. The PD-L1 and PD-L2 expression may be a new predictor of prognosis for patients with colorectal carcinoma and provide the rationale for developing novel immunotherapies to target the PD-1/PD-L pathway.

The increased rates of resistance associated with antibiotic therapy against Staphylococcus aureus, the dominant cause for nosocomial infections has created renewed interest in using alternative treatment options. An antibody-based therapy approach as an emerging option for the prevention and treatment of serious staphylococcal infections is currently under prae-clinical and clinical investigation. In the presented study, the efficacy of passive immunotherapy was directly tested in vivo in two distinct mouse models of catheter-related sepsis and soft tissue infection. The proposed action of monoclonal antibodies is evoked by antibody-mediated phagocytosis. Overall, the results support the idea that implementation of antibodies to S. aureus can play a role for immunotherapy of staphylococci infections in humans.

The programmed death-1/programmed death ligand (PD-1/PD-L) pathway in T cell activation has been suggested to play an important role in tumor evasion from host immunity. However, despite ample evidence from experimental models data in clinical colorectal tumors are scarce. Thus, we investigated the expression of PD-L1 and PD-L2 in human colorectal cancer to define their clinical significance in patients’ prognosis after surgery and asked for the potential role of PD-1 positive T cells within colorectal tumors. Tissue samples from 116 patients operated between 2001 and 2003 with histologically confirmed colorectal carcinoma were evaluated retrospectively for this study. PD-L1 and PD-L2 gene expression together with protein expression were evaluated and outcome analyses were conducted. The protein and mRNA levels as determined by immunohistochemistry and real time PCR were closely correlated. Multivariate analysis indicated that PD-L expression was an independent prognostic factor for colorectal carcinoma. T cell infiltration was observed in 105 (90.5 %) specimens while 67 (63.8 %) out of 105 specimens contained PD-1 positive T cells. Furthermore, patients with PD-1 positive T cells had significantly more PD-L1 expression in their tumor tissue. Presence of tumor infiltrating PD-1 positive T cells was associated with an advanced tumor stage. In addition, patients with PD-L positive tumor tissue and those with tumor infiltrating PD-1 positive T cells had a significantly poorer prognosis than negative patients This was more pronounced in advanced tumor stages than in early stages. These data suggest that interactions of T cells expressing PD-1 may promote cancer progression through a down-regulation of anti-tumor immunity. The PD-L1 and PD-L2 expression may be a new predictor of prognosis for patients with colorectal carcinoma and provide the rationale for developing novel immunotherapies to target the PD-1/PD-L pathway.

Prognostic information regarding the risk of postoperative tumor recurrence defined by a profile of serological, morphological and/or molecular markers can have potential value particularly for patients with colorectal carcinoma (CRC) of UICC stage II/III, who may benefit from adjuvant chemotherapy after surgery.

Incisional hernias occur in 5–10% of patients who have undergone laparotomy and are associated with a high morbidity and significant socioeconomic costs. Better understanding of the anatomy and improved methods for reinforcement of the abdominal wall with alloplastic meshes have reduced the recurrence rate to 1–10% depending on the type of hernia and the technique employed. A number of surgical repair techniques and mesh types are available. However, precise criteria for incorporating patient body type, risk factors for recurrence, hernia morphology, and the available biomaterials into planning of the surgical approach (open versus laparoscopic) have yet to be established. The elaboration of such criteria would require comparative evaluation of long-term results in a sufficiently large number of patients, e.g. in multicentre trials or meta-analyses of standardised data from different centres. Current classifications have the drawback that they fail to take account of prognostically relevant risk factors for recurrence and are not self-explanatory. The authors present a classification of incisional hernias that is self-explanatory and practicable in routine clinical practice. Based on the cornerstones of morphology (M), hernia size in cm (S), and risk factors for recurrence (RF), the scheme enables easy description and documentation of the hernia, and provides evidence for the indications and limitations of the main surgical repair techniques. Since randomised studies can scarcely be conducted on incisional hernias due to the numerous morphological variables, the classification presented here may offer an alternative means for comparative data analysis.

Derzeit befinden sich viele neue Substanzen zur Therapie gastrointestinaler Karzinome in klinischer und präklinischer Anwendung. Die Apoptose von malignen Zellen als natürliche Form der Zellzerstörung stellt ein ideales Ziel in der Krebstherapie dar. Die tatsächliche Effektivität und das Nebenwirkungsspektrum bisheriger Antikörper sind gegenwärtig von einer überzeugenden klinischen Anwendung zu weit entfernt. Verschiedene Substanzklassen von Antikörpern geben aber Hoffnung, dass in naher Zukunft die Verträglichkeit durch veränderte Herstellung (Humanisierung, Chimärisation oder komplett humane Antikörper) und die Wirkung durch höhere Selektivität substanziell verbessert werden.

BACKGROUND:Mesenchymal progenitor cells (MPCs or mesenchymal stem cells, MSC) have the capability for differentiation into various lineages of mesenchymal tissue. MPCs are widely distributed in a variety of tissues in the adult human body and also present in the fetal environment. However, MPCs are a rare population in these tissues. In this study we evaluated the possibility that MPCs or cells with MPC-like potency are present in the umbilical cord (UC).METHODS:Term UCs were collected and stored in sterile saline solution. The UCs (10 cm) were cut into 1 cm length, the vessels were striped manually and the tissue immersed in an enzyme cocktail for 3 h at 37 degrees C. The isolated umbilical cord mesenchymal progenitor cells (UCMPCs) were pelleted by low speed centrifugation, suspended and cultured.RESULTS:(1) Umbilical cord mesenchymal progenitor cells (UMPCs) could be isolated in sufficient quantities and (2) could be cultured easily. (3) These cells demonstrated a fibroblast-like phenotype. (4) They could be expanded in culture and induced to form several different types of cells. (5) In immunochemistry these cells express mesenchymal markers (CD 13, CD 105) but not haematopoetic lineage markers (CD 14 and CD 34).CONCLUSION:Our observation suggested that MPCs are present in human umbilical cord. Instead, it should be considered a valuable resource for the isolation of potent cells for cell-based therapies, especially in general and pediatric surgery.