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Methods: The burn comb model creates 4 rectangular burn surfaces intercalated by 3 unburned zones prone to progression. 24 Wistar rats were randomized to the following treatment regimens 1) control (CON) or EPO (i.p. 500 UI/kg body weight) once a day for 5 days starting 1 hour (EPO 1) or 6 hours (EPO 6) after burn injury. Histologic analyses assessing burn depth (score from superficial to deep dermis 1-5) and signs of inflammation (leukocyte count) and planimetric evaluation of burn progression, as well as perfusion (Laser Doppler flowmetry) were performed after 1, 4, and 7 days. Final scarring time was assessed one a weeks until complete healing was obtained. Results: Burn progression was significantly decreased with EPO 1 but not with EPO 6: progression of burn depth stopped in the intermediated dermis (3.3±0.6 vs. 4.75±0.25 for EPO 6, respectively 5±0 for CON at day 7, p
Conclusion: Pharmacological inhibition of SIRT1 alters cell morphology, impairs cell viability and induces G2-arrest. Proliferation and migration of HCC cells are reduced. These data suggest that the class III HDAC SIRT1 is involved in the growth and migration of HCC cells and my represent a new therapeutic option for patients diagnosed with HCC. 54.8 Extracorporeal shockwave therapy stimulates myofibroblast differentiation and function M. Tobalem 1 , E. Vigato 1 , G. Pietramaggiori 1 , H. Majd 1,2 , A. Modarressi 1 , B. Hinz 3 , B. Pittet-Cuénod 1 ( 1 Geneva, 2 Lausanne, 3 Toronto/CDN) Objective: Mechanical forces play an important role in the control of cell behavior. Based on this concept, shockwaves (SW), already widely used in lithotripsy and in the treatment of various musculoskeletal disorders over the past decade, have been recently introduced for the treatment of non-healing wounds. However, the mechanisms by which SW interfere with the healing process remains unclear. In this study, we investigated in vitro and in vivo the effects of SW on myofibroblasts, the major cell type promoting extracellular matrix remodeling and wound closure. Methods: In vitro, human dermal fibroblasts were subjected to increasing doses (250, 500 and 1000 impulses) of SW at 0.15mJ/mm^2 on day 1, 4 and 7 of culture. The presence of the myofibroblast marker alpha smooth muscle actin was quantified by immunofluorescence and Western blotting. The contractile function of myofibroblasts was evaluated by measuring collagen gel contraction. In vivo, we treated full thickness dorsal excisional wounds (1 cm 2 ) of healing-impaired db/db mice with 500 SW impulses at 0.15mJ/mm^2 3-times per week. Untreated wounds served as control. Wound healing was evaluated microscopically and macroscopically over a period of 28 days. (n=9 per group). Results: SW increased proliferation of dermal fibroblasts and enhanced myofibroblast differentiation and contractile function in a dose-dependent manner. Similar results were observed in vivo, resulting in a faster wound closure when using an optimal dose of 500 SW impulses. Conclusion: This study demonstrates that controlled application of mechanical forces induced by SW stimulates myofibroblast proliferation, and differentiation, thereby improving the closure of poorly healing wounds. 54.9 Expression and prognostic significance of putative cancer stem cell markers in colorectal cancer M. G. Muraro 1 , V. Mele 1 , D. M. Frey 1 , D. Oertli 1 , M. Zuber 2 , M. Heberer 1 , G. Spagnoli 1 , A. Lugli 1 , I. Zlobec 1 , G. Iezzi 1 ( 1 Basel, 2 Olten) Objective: Phenotypes and prognostic value of cancer stem cells (CSCs) in colorectal cancer (CRC) are still debated. We investigated the expression of putative CSC markers on human primary CRC and established cell lines, and we evaluated their correlation with CSC functional features and their prognostic significance. Methods: Expression of CD133, CD166, CD44 standard (CD44s), EpCAM and aldehyde dehydrogenase-1 (ALDH-1) molecules was analyzed on clinical CRC specimens and CRC cell lines by flow cytometry. Unsorted tumour cells or subsets, sorted based on specific phenotypes, were evaluated for CSC properties, including spheroid formation ability, clonogenicity, stemness-related gene expression, ALDH activity, side population (SP) phenotype, chemo-resistance, and tumorigenicity upon injection in NOD/SCID mice. CSC marker expression and prognostic relevance were evaluated, upon immunohistochemistry, on a tissue micro-array (TMA) including 1420 primary CRC, with full clinico-pathological data. Results: On established cell lines none of the CSC markers analyzed significantly correlated with CSC properties. On CRC specimens CD133, but not CD44s nor CD166, was associated with tumour initiating capacity in vivo. TMA analysis showed increased expression of CD166, CD44s and CD133 and decreased expression of EpCAM and ALDH1, in tumours as compared to normal mucosa. Loss of membranous CD166 and CD44s expression was significantly associated with features of tumour progression, and, in particular, with infiltrating tumour border configuration and shortened survival time. Conclusion: Putative CSC markers fail to identify CSC in CRC cell lines. On primary tumours, CSC marker expression is not predictive of poor prognosis per se. Loss, rather than over-expression, of CD166 and CD44s is linked to worse clinical outcome. 54.10 Prevalence, phenotype and prognostic significance of IL-17-producing cells infiltrating human colorectal cancers F. Amicarella 1 , I. Zlobec 1 , M. G. Muraro 1 , J. Han 1 , X. Huber 1 , M. Zuber 2 , D. Oertli 1 , A. Luigi 1 , G. Spagnoli 1 , G. Iezzi 1 ( 1 Basel, 2 Olten) Objective: Recent evidence suggests that IL-17 and T helper (Th) 17 cells might have an impact on antitumour immune responses. We have investigated prevalence, phenotype and prognostic significance of IL-17-producing cells in human colorectal cancer (CRC). Methods: IL-17 expression was evaluated by immunohistochemistry on a tissue micro-array (TMA) including 1420 cases of primary CRC with full clinico-pathological data. Furthermore, gene expression levels were assessed on CRC tissues by quantitative PCR. Finally, in order to characterize the phenotype of IL-17-positive cells, expression of IL-17, in combination with that of specific surface molecules, was analyzed on freshly excised CRC specimens by flow cytometry. Results: Frequencies of IL-17-producing cells, as well as IL-17 gene expression levels were significantly increased in tumour tissues as compared to autologous normal mucosa. Most importantly, high infiltration by IL-17 producing cells significantly correlated with prolonged survival time in mismatch repair proficient CRC. IL-17-producing cells isolated from clinical specimens were exclusively comprised within the lymphocyte population and expressed CD4, but not CD8 molecule. Conclusion: Our data suggest that tumour-infiltrating Th17 may play a favourable role in CRC outcome. 54.11 PD-L1 in expression MMR-proficient colorectal cancer is involved in early carcinogenesis and associated with a better survival, but not an independent prognostic factor R. A. Droeser, C. Hirt, X. Huber, D. Oertli, M. Heberer, D. M. Frey, I. Zlobec, A. Lugli, T. Terracciano, G. Spagnoli, L. Tornillo (Basel) Objective: The immune response is strongly involved in the pathogenesis of colorectal cancer (CRC) and therefore an important host-related prognostic factor. PD-L1 ligand 1 belongs to the CD28/cytotoxic T lymphocyte antigen 4 family and has been shown to provide an inhibitory signal down-modulating T cell activation, thus resulting in peripheral tolerance. PD-L1 expression could be detected in glioblastoma, ovarian and renal cell carcinomas and squamous cell carcinoma in head and neck, esophagus and NSCLC. Ligand expression in tumour cells suppresses the cytolytic activity of CD8+ T cells and is associated with decreased survival in cancer patients. The Aim of this study was to analyze the potential role of PD-L1 and determine the possible prognostic impact of its immunohistochemical expression in mismatch repair (MMR)-proficient CRC. Methods: Two colorectal cell lines (HCT116 and Colo205) were incubated for 24 hours in 10% fetal calf serum with or without addition of IFN-gamma. After 24 hours the cells were collected and a FACS analysis of PD-L1 was performed. Additionally, PD-L1 staining intensity (negative, weak, moderate and strong expression) was analysed immunohistochemically in 1197 MMR-proficient CRC using the TMA technique and the ROC curve approach. Results: PD-L1 expression was induced in one of the two CRC cell line (Colo205) by treatment with IFNgamma. A strong PD-L1 expression was observed in 433 CRC cases, whereas in 723 and 41 cases PD-L1 was expressed weakly/moderately or was absent. In univariate analysis, strong PD-L1 expression was associated with early T stage (p = 0.002), absence of lymph node metastasis (p = 0.015), lower tumour grade (p = 0.002), absence of vascular invasion (p = 0.017) and better 5-year survival (p < 0.001). In multivariable analysis including T stage, N stage, tumour grade and vascular invasion, high PD-L1 was not an independent prognostic factor (p = 0.068). PD-L1 was also expressed in normal colon mucosa and PD-L1 expression in CRC did not correlate with the CD8+ T-lymphocyte count. Conclusion: PD-L1 can be induced in some colorectal cancer cell lines by treatment with IFN-gamma. In a large patient sample analysis strong PD-L1 expression in CRC is observed in early stages and it is associated with a better survival. However, PD-L1 was not an independent prognostic factor. 54.12 Characterization of cancer-initiating cells derived from prostate malignancies C. Le Magnen, C. Rentsch, A. Bachmann, M. Heberer, G. Spagnoli, S. Wyler, C. Mengus (Basel) Objective: Recent data suggest that only small subsets of cells within human tumors might be endowed with the ability to proliferate widely and initiate a tumor. These Cancer-Initiating Cells (CIC), also called Cancer Stem Cells, might represent novel targets of therapeutic relevance. However their relative rarity and the frequently small size of prostate cancer (PCA) clinical specimens prevent their use in studies addressing functional features and sensitivity to drugs. In this context, the use of established cancer cell lines could represent a convenient alternative. Here, we aim at investigating the presence and the characterization of CIC in PCA cell lines and clinical specimens. Methods: In vitro studies were performed on PC3, Du145 and LNCaP PCA cell lines. Surface marker expression was assessed by flow cytometry, and Aldehyde dehydrogenase (ALDH) activity by using Aldefluor ® technology. Expression of genes associated with stemness features, including ALDH1A1 and Klf4 were evaluated by quantitative rtPCR. In vivo experiments were performed by sub-cutaneous injection of tumor cells in NOD/SCID mice. Clinical specimens (Benign Prostate Hyperplasia and PCA), were used directly for gene expression studies or digested overnight in an enzyme cocktail, prior to functional analysis. Results: Expression of CIC markers and of stemness genes was found to be heterogeneous among the different cell lines and the clinical specimens investigated. ALDH1 bright DU145 cells expressed higher levels of stem-associated genes and displayed an increased tumorigenic capacity in vivo, as compared to the ALDH1 low sub-population. Interestingly, a sizeable ALDH1 bright population could also be detected in PCA clinical specimens. Moreover, Klf4 gene was found to be significantly more expressed in tissues from PCA patients as compared to tissues from patients with BPH (P=0.038). Conclusion: These results indicate the possible presence of CIC cells in established PCA cell lines. Expression of CIC markers appears to be associated with stem-properties and a higher expression of stemness genes of potential clinical significance. 54.13 Chemical composition of hepatic lipids mediates reperfusion injury of the steatotic mouse liver A. El-Badry, J. H. Jang, A. Elsherbiny, C. Contaldo, Y. Tian, D. A. Raptis, E. Laczko, W. Moritz, R. Graf, P.-A. Clavien (Zurich) Objective: The impact of the morphologic pattern of steatosis on ischemia/reperfusion (I/R) injury of the steatotic liver was recently challenged while the chemical composition of hepatic lipids represents an evolving key player. The vasoactive eicosanoid thromboxane A2 (TXA2) is a lipid mediator derived from arachidonic acid (AA) which belongs to omega-6 fatty acids (Ω6FAs). We hypothesized that the reduced tolerance of the macrosteatotic liver to I/R is related to increased TXA2 synthesis due to predominance of Ω6FAs rather than the morphology of steatosis . Methods: We compared TXA2 levels elicited by I/R in ob/ob mice versus wild type controls. Subsequently, ob/ob mice were supplemented with Ω3FAs to decelerate the hepatic synthesis of AA and TXA2 or treated with selective TXA2 receptor blocker. Results: I/R triggered significantly higher levels of TXA2 in the ob/ob than wild type mice. Dietary n-3 FAs remarkably reduced the hepatic content of AA. TXA2 levels were significantly increased 30 minutes after reperfusion and correlated with sever reduction of red blood cell velocity (VRBC) and volumetric blood flow (VBF) and dramatic rise in transaminase levels. Ω3FA supplementation consistently blunt- swiss knife 2010; 7: special edition 47
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Page 3 and 4: Der Jahreskongress der Chirurgische
Page 5 and 6: Abstracts Session Topic Page 02 Vis
Page 7 and 8: Visceral Surgery - Cholecystitis &
Page 9 and 10: performed were recorded. Descriptiv
Page 11 and 12: avec délai dans le diagnostic, ang
Page 13 and 14: group (conventional: n=13, RS=1.8 +
Page 15 and 16: time-efficient all-in-one 3D visual
Page 17 and 18: (CHI=54 [6.49%]; SWI=27[4.98%]) wer
Page 19 and 20: Conclusion: Both procedures markedl
Page 21 and 22: 22.7 Transplantation of kidneys fro
Page 23 and 24: of the remaining 40 patients with a
Page 25 and 26: and 6/2009 and were prospectively f
Page 27 and 28: Conclusion: In our patient cohort,
Page 29 and 30: plantation. With the introduction o
Page 31 and 32: Results: SLN negative patients were
Page 33 and 34: Conclusion: This is the first study
Page 35 and 36: were grouped into four age groups a
Page 37 and 38: gain up to the 20 th procedure (Fig
Page 39 and 40: ��
Page 41 and 42: normal angiogenesis induced by cell
Page 43 and 44: 52.4 Sham-feeding of patients with
Page 45: Methods: Erfasst wurden Aggressions
Page 49 and 50: 54.19 Gene chip analysis of A20 exp
Page 51 and 52: 55.10 Optimized intrapleural cispla
Page 53 and 54: 62.7 Posttraumatic symptomatic cyst
Page 55 and 56: Conclusion: Only patients older 75
Page 57 and 58: no sign of occlusion. No further th
Page 59 and 60: packing as part of damage control s
Page 61 and 62: sonalführung und werden auch in de
Page 63 and 64: Figure 3 Figure 2 Figure 4 71.2 Tec
Page 65 and 66: formed 5 months later, again with a
Page 67 and 68: 99.16 3-D endo-stomal ultrasound (
Page 69 and 70: tional recanalization. Conclusion:
Page 71 and 72: 99.37 Extended Clavien-Dindo classi
Page 73 and 74: ial colitis was excluded by stool c
Page 75 and 76: 99.55 Complexes de von Meyenburg(ha
Page 77 and 78: 99.64 Traumatic abdominal wall hern
Page 79 and 80: 99.75 Isolated dorso-medial disloca
Page 81 and 82: FRAGMIN ® DER ERFAHRENE WEGGEFÄHR
Page 83 and 84: Kalbermatten Daniel, PD Dr., CHUV C
Page 85 and 86: Meyer Antoine, Dr., Hôpital canton
Page 87 and 88: Covidien Switzerland Limited multip

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