A New Software Suite in Orthognathic Surgery : Patient Specific Modeling, Simulation and Navigation.

Orthognathic surgery belongs to the scope of maxillofacial surgery. It treats dentofacial deformities consisting in discrepancy between the facial bones (upper and lower jaws). Such impairment affects chewing, talking, and breathing and can ultimately result in the loss of teeth. Orthognathic surgery restores facial harmony and dental occlusion through bone cutting, repositioning, and fixation. However, in routine practice, we face the limitations of conventional tools and the lack of intraoperative assistance. These limitations occur at every step of the surgical workflow: preoperative planning, simulation, and intraoperative navigation. The aim of this research was to provide novel tools to improve simulation and navigation. We first developed a semiautomated segmentation pipeline allowing accurate and time-efficient patient-specific 3D modeling from computed tomography scans mandatory to achieve surgical planning. This step allowed an improvement of processing time by a factor of 6 compared with interactive segmentation, with a 1.5-mm distance error. Next, we developed a software to simulate the postoperative outcome on facial soft tissues. Volume meshes were processed from segmented DICOM images, and the Bullet open source mechanical engine was used together with a mass-spring model to reach a postoperative simulation accuracy <1 mm. Our toolset was completed by the development of a real-time navigation system using minimally invasive electromagnetic sensors. This navigation system featured a novel user-friendly interface based on augmented virtuality that improved surgical accuracy and operative time especially for trainee surgeons, therefore demonstrating its educational benefits. The resulting software suite could enhance operative accuracy and surgeon education for improved patient care.

Virtual Reality Exploration and Planning for Precision Colorectal Surgery.

BACKGROUND: Medical software can build a digital clone of the patient with 3-dimensional reconstruction of Digital Imaging and Communication in Medicine images. The virtual clone can be manipulated (rotations, zooms, etc), and the various organs can be selectively displayed or hidden to facilitate a virtual reality preoperative surgical exploration and planning. OBJECTIVE: We present preliminary cases showing the potential interest of virtual reality in colorectal surgery for both cases of diverticular disease and colonic neoplasms. DESIGN: This was a single-center feasibility study. SETTINGS: The study was conducted at a tertiary care institution. PATIENTS: Two patients underwent a laparoscopic left hemicolectomy for diverticular disease, and 1 patient underwent a laparoscopic right hemicolectomy for cancer. The 3-dimensional virtual models were obtained from preoperative CT scans. The virtual model was used to perform preoperative exploration and planning. Intraoperatively, one of the surgeons was manipulating the virtual reality model, using the touch screen of a tablet, which was interactively displayed to the surgical team. MAIN OUTCOME MEASURES: The main outcome was evaluation of the precision of virtual reality in colorectal surgery planning and exploration. RESULTS: In 1 patient undergoing laparoscopic left hemicolectomy, an abnormal origin of the left colic artery beginning as an extremely short common trunk from the inferior mesenteric artery was clearly seen in the virtual reality model. This finding was missed by the radiologist on CT scan. The precise identification of this vascular variant granted a safe and adequate surgery. In the remaining cases, the virtual reality model helped to precisely estimate the vascular anatomy, providing key landmarks for a safer dissection. LIMITATIONS: A larger sample size would be necessary to definitively assess the efficacy of virtual reality in colorectal surgery. CONCLUSIONS: Virtual reality can provide an enhanced understanding of crucial anatomical details, both preoperatively and intraoperatively, which could contribute to improve safety in colorectal surgery.

The anatomical configuration of the splenic artery influences suprapancreatic lymph node dissection in laparoscopic gastrectomy: analysis using a 3D volume rendering program.

BACKGROUND: The aim of this study is to categorize splenic artery and vein configurations, and examine their influence on suprapancreatic lymph node (LN) dissection in laparoscopic gastrectomy. METHODS: Digital Imaging and Communications in Medicine images from 169 advanced cancer patients who underwent laparoscopic gastrectomy with D2 dissection were used to reconstruct perigastric vessels in 3D using a volume rendering program (VP Planning®). Splenic artery and vein configuration were classified depending on the relative position of their lowest part in regard to the pancreas. Number of resected LNs and surgical outcomes were analyzed. RESULTS: The splenic artery was categorized as superficial (36.7%), middle (49.1%), and concealed (14.2%), and the splenic vein was categorized as superior (6.5%), middle (42.0%), and inferior to the pancreas (51.5%). The number of resected LNs around the proximal half of the splenic artery (#11p) and the proportion of the splenic vein located inferiorly to the pancreas were significantly higher in splenic arteries of concealed types. LN metastasis of station #7 was an independent risk factor of LN metastasis in station #11p (p = 0.010). Concealed types showed a tendency towards longer operating times, more blood loss, longer hospital stays, and a higher postoperative morbidity. CONCLUSION: Concealed types of splenic artery are associated with an increased difficulty in the dissection of LN station #11p around the splenic artery. A 3D volume rendering program is a useful tool to rapidly and intuitively identify individual anatomical variations, to plan a tailored surgical strategy, and to predict potential challenges.

Prospective Evaluation of Precision Multimodal Gallbladder Surgery Navigation: Virtual Reality, Near-infrared Fluorescence, and X-ray-based Intraoperative Cholangiography.

OBJECTIVE: We aimed to prospectively evaluate NIR-C, VR-AR, and x-ray intraoperative cholangiography (IOC) during robotic cholecystectomy. BACKGROUND: Near-infrared cholangiography (NIR-C) provides real-time, radiation-free biliary anatomy enhancement. Three-dimensional virtual reality (VR) biliary anatomy models can be obtained via software manipulation of magnetic resonance cholangiopancreatography, enabling preoperative VR exploration, and intraoperative augmented reality (AR) navigation. METHODS: Fifty-eight patients were scheduled for cholecystectomy for gallbladder lithiasis. VR surgical planning was performed on virtual models. At anesthesia induction, indocyanine green was injected intravenously. AR navigation was obtained by overlaying the virtual model onto real-time images. Before and after Calot triangle dissection, NIR-C was obtained by turning the camera to NIR mode. Finally, an IOC was performed. The 3 modality performances were evaluated and image quality was assessed with a Likert-scale questionnaire. RESULTS: The three-dimensional VR planning enabled the identification of 12 anatomical variants in 8 patients, of which only 7 were correctly reported by the radiologists (P = 0.037). A dangerous variant identified at VR induced a "fundus first" approach. The cystic-common bile duct junction was visualized before Calot triangle dissection at VR in 100% of cases, at NIR-C in 98.15%, and in 96.15% at IOC.Mean time to obtain relevant images was shorter with NIR-C versus AR (P = 0.008) and versus IOC (P = 0.00000003). Image quality scores were lower with NIR-C versus AR (P = 0.018) and versus IOC (P < 0.0001). CONCLUSIONS: This high-tech protocol illustrates the multimodal imaging of biliary anatomy towards precision cholecystectomy. Those visualization techniques could complement to reduce the likelihood of biliary injuries (NCT01881399).

Superselective intra-arterial hepatic injection of indocyanine green (ICG) for fluorescence image-guided segmental positive staining: experimental proof of the concept.

BACKGROUND: Intraoperative liver segmentation can be obtained by means of percutaneous intra-portal injection of a fluorophore and illumination with a near-infrared light source. However, the percutaneous approach is challenging in the minimally invasive setting. We aimed to evaluate the feasibility of fluorescence liver segmentation by superselective intra-hepatic arterial injection of indocyanine green (ICG). MATERIALS AND METHODS: Eight pigs (mean weight: 26.01 ± 5.21 kg) were involved. Procedures were performed in a hybrid experimental operative suite equipped with the Artis Zeego®, multiaxis robotic angiography system. A pneumoperitoneum was established and four laparoscopic ports were introduced. The celiac trunk was catheterized, and a microcatheter was advanced into different segmental hepatic artery branches. A near-infrared laparoscope (D-Light P, Karl Storz) was used to detect the fluorescent signal. To assess the correspondence between arterial-based fluorescence demarcation and liver volume, metallic markers were placed along the fluorescent border, followed by a 3D CT-scanning, after injecting intra-arterial radiological contrast (n = 3). To assess the correspondence between arterial and portal supplies, percutaneous intra-portal angiography and intra-arterial angiography were performed simultaneously (n = 1). RESULTS: Bright fluorescence signal enhancing the demarcation of target segments was obtained from 0.1 mg/mL, in matter of seconds. Correspondence between the volume of hepatic segments and arterial territories was confirmed by CT angiography. Higher background fluorescence noise was found after positive staining by intra-portal ICG injection, due to parenchymal accumulation and porto-systemic shunting. CONCLUSIONS: Intra-hepatic arterial ICG injection, rapidly highlights hepatic target segment borders, with a better signal-to-background ratio as compared to portal vein injection, in the experimental setting.

Augmented Reality Guidance for the Resection of Missing Colorectal Liver Metastases: An Initial Experience.

BACKGROUND: Modern chemotherapy achieves the shrinking of colorectal cancer liver metastases (CRLM) to such extent that they may disappear from radiological imaging. Disappearing CRLM rarely represents a complete pathological remission and have an important risk of recurrence. Augmented reality (AR) consists in the fusion of real-time patient images with a computer-generated 3D virtual patient model created from pre-operative medical imaging. The aim of this prospective pilot study is to investigate the potential of AR navigation as a tool to help locate and surgically resect missing CRLM. METHODS: A 3D virtual anatomical model was created from thoracoabdominal CT-scans using customary software (VR RENDER(®), IRCAD). The virtual model was superimposed to the operative field using an Exoscope (VITOM(®), Karl Storz, Tüttlingen, Germany). Virtual and real images were manually registered in real-time using a video mixer, based on external anatomical landmarks with an estimated accuracy of 5 mm. This modality was tested in three patients, with four missing CRLM that had sizes from 12 to 24 mm, undergoing laparotomy after receiving pre-operative oxaliplatin-based chemotherapy. RESULTS: AR display and fine registration was performed within 6 min. AR helped detect all four missing CRLM, and guided their resection. In all cases the planned security margin of 1 cm was clear and resections were confirmed to be R0 by pathology. There was no postoperative major morbidity or mortality. No local recurrence occurred in the follow-up period of 6-22 months. CONCLUSIONS: This initial experience suggests that AR may be a helpful navigation tool for the resection of missing CRLM.

Towards cybernetic surgery: robotic and augmented reality-assisted liver segmentectomy.

BACKGROUND: Augmented reality (AR) in surgery consists in the fusion of synthetic computer-generated images (3D virtual model) obtained from medical imaging preoperative workup and real-time patient images in order to visualize unapparent anatomical details. The 3D model could be used for a preoperative planning of the procedure. The potential of AR navigation as a tool to improve safety of the surgical dissection is outlined for robotic hepatectomy. MATERIALS AND METHODS: Three patients underwent a fully robotic and AR-assisted hepatic segmentectomy. The 3D virtual anatomical model was obtained using a thoracoabdominal CT scan with a customary software (VR-RENDER®, IRCAD). The model was then processed using a VR-RENDER® plug-in application, the Virtual Surgical Planning (VSP®, IRCAD), to delineate surgical resection planes including the elective ligature of vascular structures. Deformations associated with pneumoperitoneum were also simulated. The virtual model was superimposed to the operative field. A computer scientist manually registered virtual and real images using a video mixer (MX 70; Panasonic, Secaucus, NJ) in real time. RESULTS: Two totally robotic AR segmentectomy V and one segmentectomy VI were performed. AR allowed for the precise and safe recognition of all major vascular structures during the procedure. Total time required to obtain AR was 8 min (range 6-10 min). Each registration (alignment of the vascular anatomy) required a few seconds. Hepatic pedicle clamping was never performed. At the end of the procedure, the remnant liver was correctly vascularized. Resection margins were negative in all cases. The postoperative period was uneventful without perioperative transfusion. CONCLUSIONS: AR is a valuable navigation tool which may enhance the ability to achieve safe surgical resection during robotic hepatectomy.

Enhanced-reality video fluorescence: a real-time assessment of intestinal viability.

OBJECTIVE: Our aim was to evaluate a fluorescence-based enhanced-reality system to assess intestinal viability in a laparoscopic mesenteric ischemia model. MATERIALS AND METHODS: A small bowel loop was exposed, and 3 to 4 mesenteric vessels were clipped in 6 pigs. Indocyanine green (ICG) was administered intravenously 15 minutes later. The bowel was illuminated with an incoherent light source laparoscope (D-light-P, KarlStorz). The ICG fluorescence signal was analyzed with Ad Hoc imaging software (VR-RENDER), which provides a digital perfusion cartography that was superimposed to the intraoperative laparoscopic image [augmented reality (AR) synthesis]. Five regions of interest (ROIs) were marked under AR guidance (1, 2a-2b, 3a-3b corresponding to the ischemic, marginal, and vascularized zones, respectively). One hour later, capillary blood samples were obtained by puncturing the bowel serosa at the identified ROIs and lactates were measured using the EDGE analyzer. A surgical biopsy of each intestinal ROI was sent for mitochondrial respiratory rate assessment and for metabolites quantification. RESULTS: Mean capillary lactate levels were 3.98 (SD = 1.91) versus 1.05 (SD = 0.46) versus 0.74 (SD = 0.34) mmol/L at ROI 1 versus 2a-2b (P = 0.0001) versus 3a-3b (P = 0.0001), respectively. Mean maximal mitochondrial respiratory rate was 104.4 (±21.58) pmolO2/second/mg at the ROI 1 versus 191.1 ± 14.48 (2b, P = 0.03) versus 180.4 ± 16.71 (3a, P = 0.02) versus 199.2 ± 25.21 (3b, P = 0.02). Alanine, choline, ethanolamine, glucose, lactate, myoinositol, phosphocholine, sylloinositol, and valine showed statistically significant different concentrations between ischemic and nonischemic segments. CONCLUSIONS: Fluorescence-based AR may effectively detect the boundary between the ischemic and the vascularized zones in this experimental model.

Robotic duodenopancreatectomy assisted with augmented reality and real-time fluorescence guidance.

BACKGROUND: The minimally invasive surgeon cannot use 'sense of touch' to orientate surgical resection, identifying important structures (vessels, tumors, etc.) by manual palpation. Robotic research has provided technology to facilitate laparoscopic surgery; however, robotics has yet to solve the lack of tactile feedback inherent to keyhole surgery. Misinterpretation of the vascular supply and tumor location may increase the risk of intraoperative bleeding and worsen dissection with positive resection margins. METHODS: Augmented reality (AR) consists of the fusion of synthetic computer-generated images (three-dimensional virtual model) obtained from medical imaging preoperative work-up and real-time patient images with the aim of visualizing unapparent anatomical details. RESULTS: In this article, we review the most common modalities used to achieve surgical navigation through AR, along with a report of a case of robotic duodenopancreatectomy using AR guidance complemented with the use of fluorescence guidance. CONCLUSIONS: The presentation of this complex and high-technology case of robotic duodenopancreatectomy, and the overview of current technology that has made it possible to use AR in the operating room, highlights the needs for further evolution and the windows of opportunity to create a new paradigm in surgical practice.

Accuracy of preoperative automatic measurement of the liver volume by CT-scan combined to a 3D virtual surgical planning software (3DVSP).

BACKGROUND: Liver volumetry is a critical component of safe hepatic surgery, in order to minimize the risk of postoperative liver failure. Liver volumes can be calculated routinely using the time-consuming gold standard method of manual volumetry. The current work sought to evaluate an alternative automatic technique based on a novel 3D virtual planning software, and to compare it to the manual technique. METHODS: A prospective study of patients undergoing liver resection was conducted. Every patient had a pre and 2-day postoperative CT-scan. For each patient, total, remnant and resected volumes were calculated manually and automatically. Planes of resection were verified by a hepatobiliary surgeon and compared with postoperative volumes. Paired t-tests and correlation coefficients were calculated. RESULTS: A major hepatectomy was carried out in 36/43 patients. The automatic TLV (1,759 mL) and the manual TLV (1,832 mL) were significantly different (p < 0.001), but extremely highly correlated (r = 0.989). The percentages of preoperative RLV (manual 58.5%, automatic 58.9%) were similar, with an excellent correlation of 0.917. The preoperative RLV were matched with the 2-day postoperative RLV showing a significant difference (p = 0.0301). The resected volumes using both techniques (871 and 832 mL) were compared with the resected specimen volume (670 mL), showing a significant difference (p < 0.001) but a high degree of correlation (r = 0.874). CONCLUSION: The 3D virtual surgical planning software is accurate and reliable in determining the total liver and future remnant liver volumes. This technique demonstrates a good correlation with the manual technique. Future work will be required to confirm these findings and to evaluate the clinical value of the three-dimensional planning platform.

Real-time navigation by fluorescence-based enhanced reality for precise estimation of future anastomotic site in digestive surgery.

BACKGROUND: Fluorescence-based enhanced reality (FLER) is a technique to evaluate intestinal perfusion based on the elaboration of the Indocyanine Green fluorescence signal. The aim of the study was to assess FLER's performances in evaluating perfusion in an animal model of long-lasting intestinal ischemia. MATERIALS AND METHODS: An ischemic segment was created in 18 small bowel loops in 6 pigs. After 2 h (n = 6), 4 h (n = 6), and 6 h (n = 6), loops were evaluated clinically and by FLER to delineate five regions of interest (ROIs): ischemic zone (ROI 1), presumed viable margins (ROI 2a-2b), and vascularized areas (3a-3b). Capillary lactates were measured to compare clinical vs. FLER assessment. Basal (V 0 ) and maximal (V max) mitochondrial respiration rates were determined according to FLER. RESULTS: Lactates (mmol/L) at clinically identified resection lines were significantly higher when compared to those identified by FLER (2.43 ± 0.95 vs. 1.55 ± 0.33 p = 0.02) after 4 h of ischemia. Lactates at 2 h at ROI 1 were 5.45 ± 2.44 vs. 1.9 ± 0.6 (2a-2b; p < 0.0001) vs. 1.2 ± 0.3 (3a-3b; p < 0.0001). At 4 h, lactates were 4.36 ± 1.32 (ROI 1) vs. 1.83 ± 0.81 (2a-2b; p < 0.0001) vs. 1.35 ± 0.67 (3a-3b; p < 0.0001). At 6 h, lactates were 4.16 ± 2.55 vs. 1.8 ± 1.2 vs. 1.45 ± 0.83 at ROI 1 vs. 2a--2b (p = 0.013) vs. 3a-3b (p = 0.0035). Mean V 0 and V max (pmolO2/second/mg of tissue) were significantly impaired after 4 and 6 h at ROI 1 (V 0 (4h) = 34.83 ± 10.39; V max (4h) = 76.6 ± 29.09; V 0 (6h) = 44.1 ± 12.37 and V max (6h) = 116.1 ± 40.1) when compared to 2a--2b (V 0 (4h) = 67.1 ± 17.47 p = 0.00039; V max (4h) = 146.8 ± 55.47 p = 0.0054; V 0 (6h) = 63.9 ± 28.99 p = 0.03; V max (6h) = 167.2 ± 56.96 p = 0.01). V 0 and V max were significantly higher at 3a-3b. CONCLUSIONS: FLER may identify the future anastomotic site even after repetitive assessments and long-standing bowel ischemia.

Probe-based confocal laser endomicroscopy and fluorescence-based enhanced reality for real-time assessment of intestinal microcirculation in a porcine model of sigmoid ischemia.

BACKGROUND AND AIM: Surgeons currently rely on visual clues to estimate the presence of sufficient vascularity for safe anastomosis. We aimed to assess the accuracy of endoluminal confocal laser endomicroscopy (CLE) and laparoscopic fluorescence-based enhanced reality (FLER), using near-infrared imaging and fluorescence from injected Indocyanine Green, to identify the transition from ischemic to vascular areas in a porcine model of mesenteric ischemia. METHODS: Six pigs underwent 1-h sigmoid segmental ischemia. The ischemic area was evaluated by clinical assessment and FLER to determine presumed viable margins. For each sigmoid colon, 5 regions of interest (ROIs) were identified: ischemic (ROI 1), presumed viable margins ROI 2a (distal) and 2b (proximal), and vascular areas 3a (distal) and 3b (proximal). After injection of fluorescein, CLE scanning of the mucosa from the ischemic area toward viable margins was performed. Capillary blood samples were obtained by puncturing the serosa at the ROIs, and capillary lactates were measured with the EDGE(®) analyzer. RESULTS: Capillary lactates were significantly higher at ROI 1 (4.91 mmol/L) when compared to resection margins (2.8 mmol/L; mean difference: 2.11; p < 0.05) identified by FLER. There was no significant difference in lactates between ROI1 and resection margins identified by clinical evaluation. In 50 % of cases, ROI 2aCLINIC-2bCLINIC were considered to match (<1 cm distance) with ROI 2aFLER-2bFLER. Confocal analysis revealed specific clues to identify the transition from ischemic to viable areas corresponding to those assessed by FLER in 11/12 cases versus 7/12 for those identified by clinical evaluation. CONCLUSIONS: In this experimental model, FLER and CLE were more accurate than clinical evaluation to delineate bowel vascularization.

Three-dimensional metabolic and radiologic gathered evaluation using VR-RENDER fusion: a novel tool to enhance accuracy in the localization of parathyroid adenomas.

BACKGROUND: The aim of this study was to assess the accuracy of a novel imaging modality, three-dimensional (3D) metabolic and radiologic gathered evaluation (MeRGE), for localizing parathyroid adenomas (PAs). METHODS: Consecutive patients presenting with primary hyperparathyroidism who underwent both thin-slice cervical computed tomography (CT) and (99m)Tc-sestamibi (MIBI) scanning were included. 3D-CT reconstruction was obtained using VR-RENDER, which was used to perform 3D virtual neck exploration (3D-VNE). The MIBI scan was then fused with the 3D reconstruction to obtain 3D-MeRGE. Sensitivity, specificity, and accuracy were assessed. Parathyroid gland volume and preoperative parathormone (PTH) levels were analyzed as predictive factors of correct localization (i.e., correct quadrant). RESULTS: A total of 108 cervical quadrants (27 patients) were analyzed. Sensitivities were 79.31, 75.86, 65.51, and 58.61 % with 3D-MeRGE, 3D-VNE, MIBI, and CT, respectively. Specificity was highest with CT (94.93 %) followed by 3D-VNE (92.4 %). MIBI and 3D-MeRGE had the same specificity (88.6 %). 3D-MeRGE and 3D-VNE achieved higher accuracy than MIBI or CT alone. Mean PTH values were significantly higher in patients with lesions that were correctly identified (true positive, TP) than in those whose lesions were missed (false negative, FN) with 3D-VNE (219.60 ± 212.77 vs. 98.75 ± 12.76 pg/ml; p = 0.01) and 3D-MeRGE (217.69 ± 213.76 vs. 09.75 ± 20.48 pg/ml; p = 0.02). The mean parathyroid gland volume difference between TP and FN was statistically significant with all modalities except CT. CONCLUSIONS: 3D-MeRGE and 3D-VNE showed high accuracy for localization of PAs. 3D-MeRGE performed better than MIBI or CT alone for detecting small adenomas and those with a low PTH level.

Feasibility and clinical value of virtual reality for deep infiltrating pelvic endometriosis: A case report.

Deep infiltrating pelvic endometriosis and its surgical management is associated with a risk of major postoperative complications. Magnetic Resonance Imaging (MRI) is recommended preoperatively in order to obtain the most precise mapping of the extent of endometriotic lesions. The aim of this work was to assess the feasibility and clinical interest of 3D modeling by surface rendering as a preoperative planning tool in a patient with deep infiltrating pelvic endometriosis. We report on a 42 years old patient with history of endometriosis and persistent pain underwent pre operative imaging with MRI that was consistent with deep infiltrating endometriosis. A 3D model of the deep infiltrating endometriosis was generated from the MRI and retrospectively compared to the intra-operative findings. The nodule's location and relationship to the uterus and the rectum was clearly defined by the 3D model and correlated with surgical findings. Virtual reality based on 3D models could be an interesting tool to assist in the preoperative planning of complex surgeries.

3D spatial priors for semi-supervised organ segmentation with deep convolutional neural networks.

PURPOSE: Fully Convolutional neural Networks (FCNs) are the most popular models for medical image segmentation. However, they do not explicitly integrate spatial organ positions, which can be crucial for proper labeling in challenging contexts. METHODS: In this work, we propose a method that combines a model representing prior probabilities of an organ position in 3D with visual FCN predictions by means of a generalized prior-driven prediction function. The prior is also used in a self-labeling process to handle low-data regimes, in order to improve the quality of the pseudo-label selection. RESULTS: Experiments carried out on CT scans from the public TCIA pancreas segmentation dataset reveal that the resulting STIPPLE model can significantly increase performances compared to the FCN baseline, especially with few training images. We also show that STIPPLE outperforms state-of-the-art semi-supervised segmentation methods by leveraging the spatial prior information. CONCLUSIONS: STIPPLE provides a segmentation method effective with few labeled examples, which is crucial in the medical domain. It offers an intuitive way to incorporate absolute position information by mimicking expert annotators.

Myo-InositolTrisPyroPhosphate treatment leads to HIF-1α suppression and eradication of early hepatoma tumors in rats.

Myo-inositol trispyrophosphate (ITPP), a synthetic allosteric effector of hemoglobin, increases the regulated oxygen-releasing capacity of red blood cells (RBCs), leading to suppression of hypoxia-inducible factor 1α (HIF-1α) and to down-regulation of hypoxia-inducible genes such as vascular endothelial growth factor (VEGF). As a consequence, tumor growth is markedly affected. The effect of weekly intravenous injection of ITPP on an orthotopic, syngenic rat hepatocellular carcinoma (HCC) model was compared to that for untreated animals and animals subjected to conventional Doxorubicin chemotherapy. The longitudinal examination of HCC was performed by microCT imaging, and the cellular and molecular changes were evaluated by histology and Western blotting analysis of HIF-1α, VEGF, and caspase-3 gene expression in the tumor and in the surrounding liver. Hematologic impact was evaluated by blood cell-count measurement and determination of P50 (oxygen partial pressure for a 50 % oxygen saturation of hemoglobin). The HCC evaluation by microCT revealed a high potency of ITPP for tumor growth inhibition, thus allowing long-term survival and even cure of almost all the treated animals. The P50 value of hemoglobin in RBCs underwent a shift of 30 % following ITPP injection. Under these conditions, HIF-1α activity was strongly decreased, VEGF expression was down-regulated, and apoptosis was induced in HCC and surrounding liver cells, as indicated by Caspase-3 expression. ITPP did not affect hematologic parameters during treatment. The observations of in vivo tumor eradication suggest a significant clinical potential for ITPP in cancer therapy.

Neurological defects in trichothiodystrophy reveal a coactivator function of TFIIH.

Mutations in the XPD subunit of the DNA repair/transcription factor TFIIH yield the rare genetic disorder trichothiodystrophy (TTD). Although this syndrome was initially associated with a DNA repair defect, individuals with TTD develop neurological features, such as microcephaly and hypomyelination that could be connected to transcriptional defects. Here we show that an XPD mutation in TTD mice results in a spatial and selective deregulation of thyroid hormone target genes in the brain. Molecular analyses performed on the mice brain tissue demonstrate that TFIIH is required for the stabilization of thyroid hormone receptors (TR) to their DNA-responsive elements. The limiting amounts of TFIIH found in individuals with TTD thus contribute to the deregulation of TR-responsive genes. The discovery of an unexpected stabilizing function for TFIIH deepens our understanding of the pathogenesis and neurological manifestations observed in TTD individuals.

Totally endoscopic magnetic enteral bypass by external guided rendez-vous technique.

OBJECTIVE: This study aimed to assess the feasibility of a totally endoscopic enteral bypass using a self-orienting, dual ring, magnetic anastomosis system (MAGNAMOSIS) guided by a magnetic tracking system (3D METRIS). MATERIALS AND METHODS: In an anesthetized pig, 2 endoscopes were advanced, one each into the stomach and the colon. Both endoscopes were equipped with a MAGNAMOSIS ring secured with an endoscopic snare and a 3D METRIS within one working channel. The whole procedure was followed laparoscopically. The tracking system guided tips of endoscopes to a "rendez-vous" location between the colon and stomach. RESULTS: MAGNAMOSIS magnets automatically joined in the correct configuration when guided to within 2 cm of each other. At necropsy, magnetic rings were secure without entrapment of excess bowel or mesentery. CONCLUSION: An endoscopic enteral bypass with magnetic anastomosis and magnetic tracking device was feasible. More accurate tracking and advanced techniques could enable endoscopic bypasses at multiple sites in the gastrointestinal tract.

[Simulation in pediatric surgery]. / Simulation en chirurgie pédiatrique.

Simulation in paediatric surgery is essential for educational, ethical, medicolegal and economic reasons, and is particularly important for rare procedures. There are three different levels of simulation:--simulation of basic techniques in order to learn or improve surgical skills (dissection, intracorporeal knots, etc.);--preparation for surgery using virtual reality, to perfect and test various procedures on a virtual patient, and to determine the best approaches for individual cases;--behavioral simulation underlines the importance of the preoperative check-list and facilitates crisis management (complications, conversion, etc.).