Robust Tumor Detection from Coarse Annotations via Multi-Magnification Ensembles

Cancer detection and classification from gigapixel whole slide images of stained tissue specimens has recently experienced enormous progress in computational histopathology. The limitation of available pixel-wise annotated scans shifted the focus from tumor localization to global slide-level classification on the basis of (weakly-supervised) multiple-instance learning despite the clinical importance of local cancer detection. However, the worse performance of these techniques in comparison to fully supervised methods has limited their usage until now for diagnostic interventions in domains of life-threatening diseases such as cancer. In this work, we put the focus back on tumor localization in form of a patch-level classification task and take up the setting of so-called coarse annotations, which provide greater training supervision while remaining feasible from a clinical standpoint. To this end, we present a novel ensemble method that not only significantly improves the detection accuracy of metastasis on the open CAMELYON16 data set of sentinel lymph nodes of breast cancer patients, but also considerably increases its robustness against noise while training on coarse annotations. Our experiments show that better results can be achieved with our technique making it clinically feasible to use for cancer diagnosis and opening a new avenue for translational and clinical research

Infected pancreatic necrosis increases the severity of experimental necrotizing pancreatitis in mice

OBJECTIVE Infection of pancreatic necrosis in necrotizing pancreatitis increases the lethality of patients with acute pancreatitis. To examine mechanisms underlying this clinical observation, we developed and tested a model, in which primary infection of necrosis is achieved in taurocholate-induced pancreatitis in mice. METHODS Sterile necrosis of acute necrotizing pancreatitis was induced by retrograde injection of 4% taurocholate into the common bile duct of Balb/c mice. Primary infection of pancreatic necrosis was induced by coinjecting 10 colony-forming units of Escherichia coli. Animals were killed after 6, 12, 24, 48, and 120 hours, and pancreatic damage and pancreatitis-associated systemic inflammatory response were assessed. RESULTS Mice with pancreatic acinar cell necrosis had an increased bacterial concentration in all tissues and showed sustained bacteremia. Acute pancreatitis was induced only by coinjection of taurocholate and not by bacterial infection alone. Infection of pancreatic necrosis increased pancreatic damage and the pulmonary vascular leak. Serum glucose concentrations serving as a parameter of hepatic function were reduced in mice with infected pancreatic necrosis. CONCLUSIONS Primary infection of pancreatic necrosis with E. coli increases both pancreatic damage and pulmonary and hepatic complications in acute necrotizing pancreatitis in mice

The statistical shape model as a quality assurance measure in the treatment of complex midface fractures: a case control study

Background!#!Complex bilateral midface fractures necessitate a surgically challenging procedure to preserve or restore the occlusion and the sensitive eye area. In this case control study, we aim to show the potential of a statistical shape model (SSM) for measuring the quality of the midface reconstruction, compared to the estimated preoperative situation.!##!Methods!#!An individualized SSM was postoperatively registered on 19 reconstructed complex bilateral midface fractures. Using this SSM, the distances from the simulated preoperative situation to the postoperative positions of the fracture segments were calculated. The fracture lines for Le Fort II, Le Fort III, and NOE fractures were chosen as reference points for the distance measurements.!##!Results!#!The SSM could be registered on all 19 complex bilateral midface fractures. All analyzed fractures showed a dorsal impaction (negative values) of the midface. Le Fort II fractures showed deviation values of -0.98 ± 4.6 mm, Le Fort III fractures showed values of -3.68 ± 3.6 mm, NOE type 2 fractures showed values of -0.25 ± 4.6 mm, and NOE type 1 fractures showed values of -0.25 ± 4.6 mm.!##!Conclusions!#!The SSM can be used to measure the quality of the achieved reduction of complex bilateral midface fractures based on the estimated preoperative situation.!##!Trial registration!#!DRKS00009719

Evaluation of computed tomography settings in the context of visualization and discrimination of low dose injections of a novel liquid soft tissue fiducial marker in head and neck imaging

Background!#!Intraoperative incorporation of radiopaque fiducial markers at the tumor resection surface can provide useful assistance in identifying the tumor bed in postoperative imaging for RT planning and radiological follow-up. Besides titanium clips, iodine containing injectable liquid fiducial markers represent an option that has emerged more recently for this purpose. In this study, marking oral soft tissue resection surfaces, applying low dose injections of a novel Conformité Européenne (CE)-marked liquid fiducial marker based on sucrose acetoisobutyrate (SAIB) and iodinated SAIB (x-SAIB) was investigated.!##!Methods!#!Visibility and discriminability of low dose injections of SAIB/x-SAIB (10 µl, 20 µl, 30 µl) were systematically studied at different kV settings used in clinical routine in an ex-vivo porcine mandible model. Transferability of the preclinical results into the clinical setting and applicability of DE-CT were investigated in initial patients.!##!Results!#!Markers created by injection volumes as low as 10 µl were visible in CT imaging at all kV settings applied in clinical routine (70-120 kV). An injection volume of 30 µl allowed differentiation from an injection volume of 10 µl. In a total of 118 injections performed in two head and neck cancer patients, markers were clearly visible in 83% and 86% of injections. DE-CT allowed for differentiation between SAIB/x-SAIB markers and other hyperdense structures.!##!Conclusions!#!Injection of low doses of SAIB/x-SAIB was found to be a feasible approach to mark oral soft tissue resection surfaces, with injection volumes as low as 10 µl found to be visible at all kV settings applied in clinical routine. With the application of SAIB/x-SAIB reported for tumors of different organs already, mostly applying relatively large volumes for IGRT, this study adds information on the applicability of low dose injections to facilitate identification of the tumor bed in postoperative CT and on performance of the marker at different kV settings used in clinical routine

Computed Tomography-Based Investigation on the Effects of Intravenous Bisphosphonate Administration on Tooth Growth in a Minipig Animal Model

Background and Objectives: The objective of this study was to evaluate the effects of bisphosphonate (BP) administration on tooth growth, using CT-data of a minipig animal model investigation. Materials and Methods: Tooth growth was evaluated in minipigs, with eight animals receiving weekly zoledronate (ZOL) and three animals serving as the control group. Tooth growth was evaluated at the right 2nd molar (M2) in the maxilla. A computed tomography-based measuring method was applied to evaluate tooth growth in the coronal-apical, buccal-oral and mesial-distal axis. Results: ZOL-administration was found to impact tooth growth in all evaluated measuring axes, with the highest effect observed in the coronal-apical axis. Conclusions: Detrimental effects of BP administration on growing teeth have been reported by a number of investigators. The results of this investigation demonstrate that intravenous ZOL affects the growth of the whole tooth within a short period of administration. With BPs being administered to a growing number of pediatric patients, further studies should be conducted to qualify and quantify the effects of BPs on developing teeth

Concentration of Penicillin G in Jawbone Affected by Antiresorptive Agent-Related Osteonecrosis Following a Single Preoperative Dose

The aim of this study was to evaluate the concentration of penicillin G in bone affected by antiresorptive agent-related osteonecrosis of the jaw (ARONJ) following a single preoperative dose of 10 million international units (6000 mg). ARONJ is a major concern in patients administered antiresorptive agents for conditions associated with pathologically increased bone resorption. Antibiotic therapy is a key component of most treatment approaches for ARONJ and penicillin based regimens, providing a cost effective therapy option with a favorable side effect profile, are administered most frequently. In this study, high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) was applied to evaluate penicillin G concentration in serum and bone samples of 19 patients suffering from ARONJ and undergoing surgical treatment under perioperative intravenous (IV) antibiotic therapy. Penicillin G bone concentrations were above the limit of detection (0.1 μg/g bone tissue) in 16 out of 19 samples, with a median concentration of 2.7 μg/g (range 0.1–8.8 μg/g). Penicillin G concentrations in intraoperative serum samples were above the limit of detection in all serum samples, with a median concentration of 116 μg/mL (range 1–232 μg/mL). Thus, considering bacteria frequently found in ARONJ lesions, penicillin G at levels providing adequate antimicrobial activity was detected in the serum and 16 out of 19 osteonecrotic lesions of patients suffering from ARONJ

Analyzing the Fitting of Novel Preformed Osteosynthesis Plates for the Reduction and Fixation of Mandibular Fractures

Purpose: The known preformed osteosynthesis plates for the midface are helpful tools for a precise and fast fixation of repositioned fractures. The purpose of the current study is to analyze the precision of newly developed prototypes of preformed osteosynthesis plates for the mandible. Methods: Four newly designed preformed osteosynthesis plates, generated by a statistical shape model based on 115 CT scans, were virtually analyzed. The used plates were designed for symphyseal, parasymphyseal, angle, and condyle fractures. Each type of plate has three different sizes. For analysis, the shortest distance between the plate and the bone surface was measured, and the sum of the plate-to-bone distances over the whole surface was calculated. Results: A distance between plate and bone of less than 1.5 mm was defined as sufficient fitting. The plate for symphyseal fractures showed good fitting in 90% of the cases for size M, and in 84% for size L. For parasymphyseal fractures, size S fits in 80%, size M in 68%, and size L in 65% of the cases. Angle fractures with their specific plate show good fitting for size S in 53%, size M in 60%, and size L in 47%. The preformed plate for the condyle part fits for size S in 75%, for size M in 85%, and for size L in 74% of the cases. Conclusion: The newly developed mandible plates show sufficient clinical fitting to ensure adequate fracture reduction and fixation