Saint-Clément-de-la-Place, France
Saint-Clément-de-la-Place, France

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Bousserouel S.,University of Strasbourg | Kauntz H.,University of Strasbourg | Gosse F.,University of Strasbourg | Bouhadjar M.,IRCAD EITS | And 3 more authors.
International Journal of Oncology | Year: 2010

The rat azoxymethane (AOM)-induced colon carcinogenesis model provides useful information for understanding human colorectal neoplasia. Here, we used the AOM model to measure the gene expression profiles of biomarkers related to tumor progression. We assessed tumor progression stages by computed tomographic (CT) colonography. Messenger RNAs were isolated from tumors and mucosal samples, and gene expression levels were assessed by real-time quantitative polymerase chain reaction (PCR). We show that early stages of tumor progression are associated with an upregulation of matrix metalloproteinase-7 (MMP-7) and of genes involved in the inflammatory response, including interleukin (IL1β) and tumor necrosis factor-α (TNFα). The ratio of B-cell lymphoma/leukemia 2 (Bcl-2)-associated X proteins (Bax) to Bcl-2 transcript (proapototic/antiapoptotic signals) is elevated in early stages of tumor progression (Bax/Bcl-2 >1) and reversed in more advanced stages of tumor development (Bax/Bcl-2 <1). These changes are associated with the reduced expression of TNF-related apoptosis-inducing ligand (TRAIL)-death receptor 5 (DR5) and FAS (also known as CD95) apoptotic receptors. Advanced stages of tumor development are characterized by an increase in MMP-9 expression associated with the upregulation of components of the innate immune system: α-defensin 5 (DEF-5) and neutrophil gelatinase-associated lipocalin (NGAL). The identification of specific gene expression profiles that correlate with tumor progression stages, as reported in the present study, may represent an important step in evaluating potential chemopreventive and/or chemotherapeutic agents prior to initiating clinical trials.


Kauntz H.,University of Strasbourg | Bousserouel S.,University of Strasbourg | Gosse F.,University of Strasbourg | Marescaux J.,IRCAD EITS | Raul F.,University of Strasbourg
International Journal of Oncology | Year: 2012

The flavonolignan silibinin, the major biologically active compound of the milk thistle (Silybum marianum), has been shown to possess anticancer properties in a variety of epithelial cancers. The present study investigated the potential of silibinin as a chemopreventive agent in colon carcinogenesis. The rat azoxymethane (AOM)-induced colon carcinogenesis model was used because of its molecular and clinical similarities to sporadic human colorectal cancer. One week after AOM injection (post-initiation), Wistar rats received daily intragastric feeding of 300 mg silibinin/kg body weight per day until their sacrifice after 7 weeks of treatment. Silibinin-treated rats exhibited a 2-fold reduction in the number of AOM-induced hyperproliferative crypts and aberrant crypt foci in the colon compared to AOM-injected control rats receiving the vehicle. Silibinin-induced apoptosis in the colon mucosal cells was demonstrated by flow cytometry after propodium iodide staining and by colorimetric measurement of caspase-3 activity. Mechanisms involved in silibinin-induced apoptosis included the downregulation of the anti-apoptotic protein Bcl-2 and upregulation of the pro-apoptotic protein Bax, inverting the Bcl-2/Bax ratio to <1. This modulation already takes place at the mRNA expression level as shown by real-time RT-PCR. Furthermore, silibinin treatment significantly (P<0.01) decreased the genetic expression of biomarkers of the inflammatory response such as IL1β, TNFα and their downstream target MMP7, all of them shown to be upregulated during colon carcinogenesis. The downregulation of MMP7 protein was confirmed by western blot analysis. The present findings show the ability of silibinin to shift the disturbed balance between cell renewal and cell death in colon carcinogenesis in rats previously injected with the carcinogen AOM. Silibinin administered via intragastric feeding exhibited potent pro-apoptotic, anti-inflammatory and multi-targeted effects at the molecular level. The effective reduction of preneoplastic lesions by silibinin supports its use as a natural agent for colon cancer chemoprevention.


PubMed | IRCAD EITS and University of Strasbourg
Type: Journal Article | Journal: Translational vision science & technology | Year: 2015

This study aims to investigate the feasibility of pterygium surgery using the DaVinci Si HD robotic surgical system, and to describe a porcine model for pterygium surgery and evaluate its usefulness.The pterygium models were constructed using enucleated pig eyes and cold cuts. Robotically-assisted pterygium surgeries in nonliving biological pterygium models were performed using the DaVinci Si HD robotic surgical system. Twelve models were prepared, and 12 pterygium excision and conjunctival autografts were performed.The DaVinci system provided the necessary dexterity to perform delicate ocular surface surgery and robotic tools were safe for the tissues. The mean duration of the surgical procedures was 36 minutes. There were no intraoperative complications and no unexpected events.Robotic-assisted pterygium surgery is technically feasible for porcine eyes using the DaVinci Si HD robotic surgical system. The pterygium model that we describe could be of interest for surgical training.Little research has been done in robotic microsurgery. Animal experimentation will allow the advantages of robotic-assisted microsurgery to be identified, while underlining the improvements and innovations necessary for clinical use.


Diemunsch P.A.,Hopitaux Universitaires | Noll E.,Hopitaux Universitaires | Pottecher J.,Hopitaux Universitaires | Diana M.,IRCAD EITS | And 2 more authors.
European Journal of Anaesthesiology | Year: 2016

BACKGROUND Nitrous oxide (N 2 O) is still considered an important component of general anaesthesia. However, should gas embolisation occur as result of carbon dioxide (CO 2) pneumoperitoneum, N 2 O may compromise safety, as the consequences of a gas embolus consisting of a combination of CO 2 and N 2 O may be more severe than CO 2 alone. OBJECTIVE This experimental study was designed to compare the cardiopulmonary consequences of gas embolisation with a N 2 O/CO 2 mixture, or CO 2 alone. DESIGN Experimental study. SETTING Research Institute Against Digestive Cancer laboratory, Strasbourg, France. ANIMALS Seven Large-White pigs receiving standardised inhalation anaesthesia. INTERVENTIONS Each animal, acting as its own control, was studied in two successive experimental conditions - intravenous gas injections of 2-ml-kg -1 of 100% CO 2 and 2-ml-kg -1 of a gas mixture consisting of 10% N 2 O and 90% CO 2. MAIN OUTCOMES MEASURES Haemodynamic and ventilatory consequences of embolisation with the gases. RESULTS We found that the haemodynamic (heart rate, mean arterial blood pressure, central venous pressure, mean pulmonary artery pressure, pulmonary artery occlusion pressure and transoesophageal echocardiography parameters) and ventilatory (arterial oxygen saturation, end-tidal CO 2 concentration and mixed venous oxygen saturation) consequences of embolisation with either 100% CO 2 or 10% N 2 O with 90% CO 2 were similar. CONCLUSION The findings of this study may alleviate concerns that the use of N 2 O, as a part of a balanced general anaesthesia technique, may have greater adverse consequences should embolisation of pneumoperitoneal gas containing N 2 O occur. © 2016 European Society of Anaesthesiology.


Cahill R.A.,European Institute of Surgical Research of Innovation | Asakuma M.,IRCAD EITS | Trunzo J.,Case Western Medical Center | Schomisch S.,Case Western Medical Center | And 5 more authors.
Journal of Gastrointestinal Surgery | Year: 2010

Introduction: Fibered optical coherence tomography (OCT) in conjunction with natural orifice transluminal endoscopic surgery (NOTES) could provide a facility for rapid, in situ pathological diagnosis of intraperitoneal tissues in a truly minimally invasive fashion. Materials and Methods: A large porcine model was established to test this hypothesis. A standard double channel gastroscope (Olympus) was used to achieve a transgastric access to the peritoneum and initiate the pneumoperitoneum. Magnetic retraction was used to display the sigmoid colon along with its mesentery. A commercially available fibered OCT probe (NIRIS system, Imalux) was inserted via a working channel of the gastroscope and used to assess intraperitoneal tissues. Separately, OCT images of human tissue specimens ex vivo were contrasted with representative standard histopathological slides. Results: Intraperitoneal OCT provided clear real-time images of both the serosal and muscularis propria mural layers as well as the submuscosal-muscularis interface. Examination of mesenteric lymph nodes (including sentinel nodes) allowed visualization of their subcapsular sinus. Comparison of representative cross-sections however failed to evince sufficient resolution for confident diagnosis. Conclusion: This approach is technically feasible and, if the technology is advanced and proven accurate in human patients, could potentially be used to individualize operative extent prior to definitive resection. © 2009 The Society for Surgery of the Alimentary Tract.


Leroy J.,IRCAD EITS | Barry B.D.,IRCAD EITS | Melani A.,IRCAD EITS | Mutter D.,IRCAD EITS | Marescaux J.,IRCAD EITS
JAMA Surgery | Year: 2013

Hypothesis: Because of the concerns over the operative platform, accidental organ injury, and viscerotomy closure, natural orifice transluminal endoscopic surgery (NOTES) currently remains an experimental technique. Transanal NOTES for colorectal surgery overcomes all of these issues; however, all of the reports to date have used hybrid laparoscopic techniques. We demonstrate herein the first case, to our knowledge, of pure transanal NOTES colorectal surgery. Design: Case report. Setting: University hospital. Patient: The patient was a 56-year-old woman with a midrectal neoplasia. Intervention: Pure transanal NOTES total mesorectal excision with a coloanal anastomosis and without a diverting stoma. Using a transanal endoscopic operation device as a surgical platform, we created a viscerotomy distal to an endoluminal purse-string suture. We performed a total mesorectal excision using a "bottom-up" approach. The sigmoid colon was mobilized by a posterior, retroperitoneal approach and the colon was divided intraperitoneally. A hand-sewn, side-to-end, coloanal anastomosis was performed. Because the viscerotomy was incorporated into the anastomosis, the concerns of both accidental organ damage and viscerotomy closure were abrogated. Results: The procedure was completed entirely by a transanal fashion. We successfully mobilized the rectum, mesorectum, and sigmoid colon. The specimen length was more than 20 cm. The patient required minimal analgesia and her pain was nonabdominal. Conclusions: To our knowledge, the first pure transanal NOTES total mesorectal excision with retroperitoneal sigmoid mobilization and coloanal, side-to-end anastomosis was successfully performed using what we called a Peri-Rectal Oncologic Gateway for Retroperitoneal Endoscopic Single Site Surgery (PROGRESSS). This monumental case could pave the way for a new era in pure transanal NOTES for colorectal surgery. © 2013 American Medical Association. All rights reserved.


Mutter D.,IRCAD EITS | Callari C.,IRCAD EITS | Diana M.,IRCAD EITS | Dallemagne B.,IRCAD EITS | And 2 more authors.
Journal of Hepato-Biliary-Pancreatic Sciences | Year: 2011

Background: Single port cholecystectomy is increasingly performed. This procedure can be challenging, and we lack factors predicting the operative difficulty. Aims: To assess the role of surgeon experience and identify possible predictive factors of intraoperative difficulties. Patients and methods: Sixty-one selected patients were prospectively enrolled between January 2008 and August 2010. Six surgeons were involved (3 seniors, 3 juniors). Anthropometrics of the patients, types of ports, exposure methods and intraoperative data were recorded. Pain was assessed with the visual analogic scale at postoperative day 1 (POD 1 VAS). Results: Fifty-eight patients with symptomatic gallstones and three with acute cholecystitis underwent single port cholecystectomy. The mean BMI, weight and height were 25.7 kg/m 2 (SD 4.45), 71.8 kg (SD 14.83) and 166 cm SD 0.07, respectively. Mean operative time was 68.4 min (SD 26.98). Anthropometrics had no influence on operative time. Senior surgeons performed more rapidly, but the difference was not significant. The overall mean POD 1 VAS was 2.26, (SD 1.81). The mean hospital stay was 2.22 days, (SD 0.9). No complications occurred. An additional exposure method was necessary in 19 procedures. This cluster presented a significantly higher operating time (81.5 min, SD 31.69 vs. 62.7, SD 22.74; p = 0.01) and POD 1 VAS (1.92 vs. 3; p = 0.031). Conclusion: Single trocar cholecystectomy can be implemented safely in teaching hospitals. Anthropometrics are not predictive of operative difficulties. The need for additional exposure systems affects the operative time and pain negatively, reflecting greater technical difficulties. Research to optimize instruments may help to solve these problems. © 2010 Japanese Society of Hepato-Biliary-Pancreatic Surgery and Springer.


PubMed | IRCAD EITS
Type: Journal Article | Journal: Medicine and law | Year: 2010

The gold standard of Evidence Based Medicine remains the randomised controlled trial (RCT), which is the only tool that allows an approach to the therapeutic truth. To reach credible conclusions, these trials need to be perfect in methodological and ethical quality. The purpose of this study is to evaluate methodological quality (MQ), ethical quality (EQ) and compliance with ethical requirements in phase III randomized clinical trials of breast cancer treatment.MQ was evaluated by the Jadad-scale and EQ by the Berdeu-score for all the randomised controlled clinical trials (RCT) (n = 137), published between January 2001 and December 2005 in 11 international journals.Mean MQ was 9.88 +/- 1.43. MQ was insufficient (Jadad score pound 9) for 49 RCT (35,8%). Mean EQ was 0.45 +/- 0.12. Mean EQ for RCT with insufficient MQ (n = 49) was 0.43 +/- 0.12; Mean EQ for RCT with good MQ (Jadad score > 9)(n = 88) was 0.46 +/- 0.11. There was significant improvement in MQ depending on the year in which the study was started (p = 0.002). EQ was independent of the year of studys start (p = 0.134).There was no relationship between MQ or EQ and the number of patients included in the study (p = 0.53 and p = 0.1). There was a tendency towards correlation between MQ and EQ (p = 0.052), but the correlation between these two variables could not be considered as significant (r = 0.67). Informed consent from patients (ICP) was not obtained in 5.8% (n = 8) of the RCTs and the approval of a research ethics committee (REC) was not mentioned in 26.3% (n = 36) of the RCTs.Good MQ and reporting of ethical requirements (EQ) reflects the respect shown to the patients during the whole research process. There are still deficiencies in EQ and MQ. Quality improvement requires education and appropriation by the scientific community, in particular, medical staff, of methodological and ethical basic rules concerning trials involving human beings.


PubMed | IRCAD EITS
Type: Comparative Study | Journal: Journal of hepato-biliary-pancreatic sciences | Year: 2011

Single port cholecystectomy is increasingly performed. This procedure can be challenging, and we lack factors predicting the operative difficulty.To assess the role of surgeon experience and identify possible predictive factors of intraoperative difficulties.Sixty-one selected patients were prospectively enrolled between January 2008 and August 2010. Six surgeons were involved (3 seniors, 3 juniors). Anthropometrics of the patients, types of ports, exposure methods and intraoperative data were recorded. Pain was assessed with the visual analogic scale at postoperative day 1 (POD 1 VAS).Fifty-eight patients with symptomatic gallstones and three with acute cholecystitis underwent single port cholecystectomy. The mean BMI, weight and height were 25.7 kg/m(2) (SD 4.45), 71.8 kg (SD 14.83) and 166 cm SD 0.07, respectively. Mean operative time was 68.4 min (SD 26.98). Anthropometrics had no influence on operative time. Senior surgeons performed more rapidly, but the difference was not significant. The overall mean POD 1 VAS was 2.26, (SD 1.81). The mean hospital stay was 2.22 days, (SD 0.9). No complications occurred. An additional exposure method was necessary in 19 procedures. This cluster presented a significantly higher operating time (81.5 min, SD 31.69 vs. 62.7, SD 22.74; p = 0.01) and POD 1 VAS (1.92 vs. 3; p = 0.031).Single trocar cholecystectomy can be implemented safely in teaching hospitals. Anthropometrics are not predictive of operative difficulties. The need for additional exposure systems affects the operative time and pain negatively, reflecting greater technical difficulties. Research to optimize instruments may help to solve these problems.

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