Patrick Baqué

Gastric necrosis: a rare complication of gastric banding.

In the last decade, laparoscopic gastric banding has become an increasingly popular surgical option for morbidly obese patients, because of the minimally invasive and easy surgical technique, its reversibility, and the possibility to calibrate the stoma. Gastric necrosis, as a complication of laparoscopic gastric banding, has been only rarely reported. Herein described is the case of a 45-year-old obese patient with gastric necrosis occurring 2 years after the placement of the band. After initial conservative management, the patient underwent urgent surgery. A huge anterior gastric prolapse through the band was found to be responsible for necrosis of the herniated stomach. An upper polar gastrectomy was performed. The mechanisms responsible for this life-threatening complication are discussed.

Preventive Cancer Stem Cell‐Based Vaccination Reduces Liver Metastasis Development in a Rat Colon Carcinoma Syngeneic Model

Cancer stem cells (CSCs) represent a minor population of self‐renewing cancer cells that fuel tumor growth. As CSCs are generally spared by conventional treatments, this population is likely to be responsible for relapses that are observed in most cancers. In this work, we analyzed the preventive efficiency of a CSC‐based vaccine on the development of liver metastasis from colon cancer in a syngeneic rat model. We isolated a CSC‐enriched population from the rat PROb colon carcinoma cell line on the basis of the expression of the aldehyde dehydrogenase‐1 (ALDH1) marker. Comparative analysis of vaccines containing lysates of PROb or ALDHhigh cells by mass spectrometry identifies four proteins specifically expressed in the CSC subpopulation. The expression of two of them (heat shock protein 27‐kDa and aldose reductase) is already known to be associated with treatment resistance and poor prognosis in colon cancer. Preventive intraperitoneal administration of vaccines was then performed before the intrahepatic injection of PROb cancer cells. While no significant difference in tumor occurrence was observed between control and PROb‐vaccinated groups, 50% of the CSC‐based vaccinated animals became resistant to tumor development. In addition, CSC‐based vaccination induced a 99.5% reduction in tumor volume compared to the control group. To our knowledge, this study constitutes the first work analyzing the potential of a CSC‐based vaccination to prevent liver metastasis development. Our data demonstrate that a CSC‐based vaccine reduces efficiently both tumor volume and occurrence in a rat colon carcinoma syngeneic model. STEM CELLS2013;31:423–432

Comparative Proteomics Study Reveals That Bacterial CpG Motifs Induce Tumor Cell Autophagy in Vitro and in Vivo

Unmethylated CpG dinucleotides, present in bacterial DNA, are recognized in vertebrates via the Toll-like receptor 9 (TLR9) and are known to act as an anticancer agent by stimulating immune cells to induce a proinflammatory response. Although the effects of CpG-oligodeoxynucleotides (CpG-ODNs) in immune cells have been widely studied, little is known regarding their molecular effects in TLR9-positive tumor cells. To better understand the role of these bacterial motifs in cancer cells, we analyzed proteome modifications induced in TLR9-positive tumor cells in vitro and in vivo after CpG-ODN treatment in a rat colon carcinoma model. Proteomics analysis of tumor cells by two-dimensional gel electrophoresis followed by mass spectrometry identified several proteins modulated by bacterial CpG motifs. Among them, several are related to autophagy including potential autophagic substrates. In addition, we observed an increased glyceraldehyde-3-phosphate dehydrogenase expression, which has been shown to be sufficient to trigger an autophagic process. Autophagy is a self-digestion pathway whereby cytoplasmic material is sequestered by a structure termed the autophagosome for subsequent degradation and recycling. As bacteria are known to trigger autophagy, we assessed whether bacterial CpG motifs might induce autophagy in TLR9-positive tumor cells. We showed that CpG-ODN can induce autophagy in rodent and human tumor cell lines and was TLR9-dependent. In addition, an increase in the number of autophagosomes can also be observed in vivo after CpG motif intratumoral injection. Our findings bring new insights on the effect of bacterial CpG motifs in tumor cells and may be relevant for cancer treatment and more generally for gene therapy approaches in TLR9-positive tissues.

Stress distribution in the temporo-mandibular joint discs during jaw closing: a high-resolution three-dimensional finite-element model analysis.

PurposeThis study aims at analysing the stresses distribution in the temporomandibular joint (TMJ) using a complete high-resolution finite element model (FE Model). This model is used here to analyse the stresses distribution in the discs during a closing jaw cycle. In the end, this model enables the prediction of the stress evolution in the TMJ disc submitted to various loadings induced by mandibular trauma, surgery or parafunction.Materials and methodsThe geometric data for the model were obtained from MRI and CT scans images of a healthy male patient. Surface and volume meshes were successively obtained using a 3D image segmentation software (AMIRA®). Bone components of skull and mandible, both of joint discs, temporomandibular capsules and ligaments and dental arches were meshed as separate bodies. The volume meshes were transferred to the FE analysis software (FORGE®). Material properties were assigned for each region. Boundary conditions for closing jaw simulations were represented by different load directions of jaws muscles. The von Mises stresses distribution in both joint discs during closing conditions was analyzed.ResultsThe pattern of von Mises stresses in the TMJ discs is non-symmetric and changed continuously during jaw movement. Maximal stress is reached on the surface disc in areas in contact with others bodies.ConclusionsThe three-dimension finite element model of masticatory system will make it possible to simulate different conditions that appear to be important in the cascade of events leading to joint damage.

Modeling the pregnant woman in driving position

Despite motor vehicle crashes being the leading cause of traumatic fetal morbidity, only a few researches have tried to study the automobile crashes on pregnant women. The possible negative effect of the restraint systems and the injuries mechanisms involved in car crashes with pregnant women are therefore still poorly understood. In this context, the aim of this study is to develop a numerical model of the whole human body with a gravid uterus, in order to investigate car crash scenarios and to evaluate alternative security systems to improve protection of both the woman and the fetus. A 3D reconstruction based on a set of MRI images led us to a good spatial representation of the pregnant woman in driving position. The anatomical precision will make progress possible in the field of traumatology of the pregnant woman.

Division of the right posterior attachments of the head of the pancreas with a linear stapler during pancreaticoduodenectomy: vascular and oncological considerations based on an anatomical cadaver-based study

BackgroundSection of the right posterior attachment (RPA) of the pancreatic head from the adventicia of the superior mesenteric artery (SMA) is the last step of pancreaticoduodenectomy. This procedure might be technically demanding, time consuming and potentially dangerous. A method using a stapler has been proposed to simplify this step of the pancreaticoduodenectomy.MethodsTo evaluate the potential consequences of RPA section using this new method, we used an experimental model of pancreaticoduodenectomy in 20 cadavers. After RPA stapling, the residual areolar tissue located between the staple line and SMA was removed (by sub adventicial dissection) and weighed. This allowed an evaluation of: (1) the theoretical risk of SMA injury and (2) the potential carcinological consequences of using stapling division, in comparison with the lymphadenectomy obtained with the conventional sub-adventicial dissection.ResultsA right hepatic artery was accidentaly injured in 10% of cases because of the lack of arterial dissection and arterial anatomy recognition. Forty-three percent of the RPA containing nerves and lymphatics remains in place. Using the stapling technique for RPA division theoretically increases the risk of micro or macroscopically positive margin after surgical resection.ConclusionThe result of this human cadaver-based dissection suggests that the use of the mechanical stapling device for final division of the RPA might increase the risk of SMA injury. The risk of vascular injury has been reported in surgical literature and is confirmed by this study. Such results (10% of accidentaly injury) may not be representative in leaving human patients, thanks to the use of a detectable palpable pulse of the SMA. The latter is important in avoiding vascular injury during RPA division. This study also shows that this new technique may increase the risk of incomplete tumor resection.

Cellular and molecular events associated with the antitumor response induced by the cytosine deaminase/5-fluorocytosine suicide gene therapy system in a rat liver metastasis model.

The bacterial cytosine deaminase (CD) gene converts the non-toxic prodrug 5-fluorocytosine (5-FC) into 5-fluorouracil. We have previously shown, in a rat liver metastasis model from colon carcinoma, that intratumoral injection of a CD-expressing plasmid into the animals followed by 5-FC treatment results in the regression of the treated tumor as well as distant uninjected tumors. The aim of this study was to further analyze the mechanisms associated with tumor regression induced upon application of suicide CD/5-FC strategy. Tumor regression was associated with an increased apoptosis, the recruitment of natural killer cells, CD4- and CD8 T lymphocytes within the tumors and an increased expression of several cytokines/chemokines mRNAs. These data indicate that the CD/5-FC suicide strategy is associated with the triggering of cellular and molecular events leading to an efficient antitumor immune response involving both innate and acquired immunity.

Tumor microenvironment modifications induced by soluble VEGF receptor expression in a rat liver metastasis model

Vascular endothelial growth factor is a potent pro-angiogenic growth factor which is also known to alter tumor microenvironment by inhibiting dendritic cell differentiation and promoting accumulation of myeloid-derived suppressor cells. In the present study, we analyzed the modifications induced by intratumoral expression of sFLT-1, a soluble VEGF receptor, in a rat metastatic colon carcinoma model. We generated colon cancer cell lines stably expressing sFLT-1 or a mock construct. Human umbilical vein endothelial cells cultured with conditioned medium from sFLT-1-expressing tumor cells exhibit a significantly decreased survival, demonstrating the functionality of the secreted sFLT-1. Invivo, sFLT-1 expression induced a 30% decrease in microvessel density in 15-day old experimental liver metastasis from colon carcinoma. Tumor growth was inhibited by 63% and 52% in left and right liver lobes respectively within 25days. In these tumors, sFLT-1 expression was associated with a decreased myeloid cell infiltration and a modification in the expression of several cytokines/chemokines. Altogether, these results suggest that VEGF trapping by sFLT-1 intratumoral expression results in reduced vascularization, tumor growth inhibition and modification of immune tumor microenvironment.

Treatment of hepatic metastases of colorectal cancer by electrochemotherapy: An experimental study in the rat ☆

BACKGROUND Electrochemotherapy, which consist of local or systemic administration of a cytotoxic agent followed by application of electric pulses to a tumor, has proved effective for various types of tumors in animals and for cutaneous and head and neck cancers in human beings. This is the first study to investigate the efficacy of electrochemotherapy for treatment of hepatic metastases of colorectal cancer in the rat. METHODS After induction of a solitary hepatic metastasis in 36 male BDIX rats, the animals were randomized to one of four groups: B-E-(no treatment), B+E-(intratumoral bleomycin), B-E+ (application of electric pulses to the tumor), and B+E+ (electrochemotherapy: intratumoral bleomycin followed by application of electric pulses). RESULTS Groups B-E and B-E+ had no tumor response. Group B+E had one partial response. Group B+E+ had seven partial responses and two complete responses. The difference in terms of response between group B+E+ and the other three groups was statistically significant (P < .05). Comparison of the mean posttherapy tumor volumes (B-E-, 50.6 mm3; B+E-, 58.7 mm3; B-E+, 46 mm3; and B+E+, 5.65 mm3) revealed a significantly smaller residual tumor in group B+E+ than in the other three groups (P < .05). CONCLUSIONS Electrochemotherapy is an effective means to reduce the volume of hepatic metastases of colorectal cancer in the rat. Additional research is required to determine the optimum treatment duration, dose effects, volume of tumor that can be treated by electrochemotherapy, and impact on survival. Such experimental studies are indispensable prerequisites for clinical trials.

Transfer of Pectoral Nerves to Suprascapular and Axillary Nerves: An Anatomic Feasibility Study

PURPOSE We conducted an anatomic study to provide detailed information on the pectoral nerves and anatomic data on the transfer of the pectoral nerves to the axillary nerve. Moreover, we experimentally determined the feasibility of transferring the pectoral nerves to the suprascapular nerve in upper brachial plexus injury. METHODS We dissected 26 brachial plexus from 15 fresh cadavers. The origin, location, course, and branching of the pectoral nerves were recorded. The length and the diameter of the pectoral nerves were measured. The diameter of the suprascapular and axillary nerves was recorded. In all dissections, we assessed the feasibility of directly transferring the pectoral nerves to the suprascapular and axillary nerves. RESULTS We found 3 constant branches of pectoral nerves arising from 3 distinct origins in 20 cases, and 3 constant branches arising from 2 distinct origins in 6 cases. The C7 sent nerve fibers to all 3 branches. The average length and diameter of the superior, middle, and inferior branches of the pectoral nerves were 65 mm, 110 mm, and 105 mm, and 2.0 mm, 2.3 mm, ad 2.4 mm, respectively. The average diameter of the suprascapular and axillary were 2.8 mm and 3.6 mm, respectively. The superior branch reached the suprascapular and axillary nerves in 17 and 8 cases. The middle and inferior branches reached the suprascapular and axillary nerve in all dissections. CONCLUSIONS With an adequate length, diameter, and nerve composition, the middle and inferior branches of the pectoral nerves are suitable donor nerves to the axillary nerve and a potential source of reinnervation of the suprascapular nerve in upper brachial plexus injury.