Virtual tumor mapping and margin control with 3-D planning and navigation.

Computer technology-based treatment approaches like intraoperative navigation and intensity-modulated radiation therapy have become important components of state of the art head and neck cancer treatment. Multidirectional exchange of virtual three-dimensional patient data via an interdisciplinary platform allows all medical specialists involved in the patients treatment to take full advantage of these technologies. This review article gives an overview of current technologies and future directions regarding treatment approaches that are based on a virtual, three-dimensional patient specific dataset: storage and exchange of spatial information acquired via intraoperative navigation allow for a highly precise frozen section procedure. In the postoperative setting, virtual reconstruction of the tumor resection surface provides the basis for improved radiation therapy planning and virtual reconstruction of the tumor with integration of molecular findings creates a valuable tool for postoperative treatment and follow-up. These refinements of established treatment components and novel approaches have the potential to make a major contribution to improving the outcome in head and neck cancer patients.

AI-Based Detection of Oral Squamous Cell Carcinoma with Raman Histology.

Stimulated Raman Histology (SRH) employs the stimulated Raman scattering (SRS) of photons at biomolecules in tissue samples to generate histological images. Subsequent pathological analysis allows for an intraoperative evaluation without the need for sectioning and staining. The objective of this study was to investigate a deep learning-based classification of oral squamous cell carcinoma (OSCC) and the sub-classification of non-malignant tissue types, as well as to compare the performances of the classifier between SRS and SRH images. Raman shifts were measured at wavenumbers k1 = 2845 cm-1 and k2 = 2930 cm-1. SRS images were transformed into SRH images resembling traditional H&E-stained frozen sections. The annotation of 6 tissue types was performed on images obtained from 80 tissue samples from eight OSCC patients. A VGG19-based convolutional neural network was then trained on 64 SRS images (and corresponding SRH images) and tested on 16. A balanced accuracy of 0.90 (0.87 for SRH images) and F1-scores of 0.91 (0.91 for SRH) for stroma, 0.98 (0.96 for SRH) for adipose tissue, 0.90 (0.87 for SRH) for squamous epithelium, 0.92 (0.76 for SRH) for muscle, 0.87 (0.90 for SRH) for glandular tissue, and 0.88 (0.87 for SRH) for tumor were achieved. The results of this study demonstrate the suitability of deep learning for the intraoperative identification of tissue types directly on SRS and SRH images.

X-Linked Hypophosphatemia: Does Targeted Therapy Modify Dental Impairment?

X-linked hypophosphatemia is a rare, hereditary disorder that significant influences teeth and alveolar bone. The first clinical sign leading to the diagnosis of X-linked hypophosphatemia is often dental impairment with dental abscesses and dentin mineralization defects. Genetic analysis helped find the responsible gene and therefore opened up new ways of therapeutically managing X-linked hypophosphatemia. The human monoclonal antibody Burosumab represents a milestone in the targeted therapy of this hereditary disease by directly addressing its pathophysiology. Targeted therapy has been shown to improve skeletal impairment, pain, and phosphate metabolism. However, the influence of this new therapy on dental impairment has only been addressed in a few recent studies with varying results. Therefore, in this review, we aim to summarize the dental phenotype and analyze the different treatment modalities with a focus on dental impairment.

New insights into redox-related risk factors and therapeutic targets in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common cancer in the oral cavity accounting for 90 % of oral cancer with a global incidence of 350.000 new cases per year. Curative resection along with adjuvant radiation therapy or a combination of radiotherapy with chemotherapy remain as gold standard in treating OSCC. Still, local recurrence, lymph nodal recurrence, and complications of radiation remain the main cause of tumor-related mortality. Reactive oxygen species are not only correlated to the etiology of OSCC due to oxidative DNA damage, lipid peroxidation or effecting signal transduction cascades that effect cell proliferation and tumorigenesis, but are also of great interest in the therapy of OSCC patients. As induced oxidative stress can be used therapeutically for the induction of tumor cell death, redox targets might be a therapeutic addition to the conventional treatment options. In this review, we discuss markers of impaired redox homeostasis as well as potential redox-related treatment targets in OSCC.

Metastases of OSCC Based on Oral Lichen Ruber Planus.

Oral lichen ruber planus (OLP) is a poorly understood chronically inflammatory disease of the oral mucosa. Malignant transformation into oral squamous cell carcinoma (OSCC) is reported in between 1-2% of cases in the literature. After malignant transformation, surgical treatment-meaning tumor resection combined with neck dissection-is recommended. The recommended extent of treatment is controversial in the literature because this kind of OSCC is often a highly differentiated tumor with a lower risk for lymph nodal spreading. This study aims to overview 103 patients treated in our department due to OLP. The primary outcome parameter was the development of metastases in OLP patients compared to a group of OSCC patients without OLP and the comparison of survival in between both groups. Statistical analysis showed a significantly lower risk for patients with OSCC and with OLP for lymph nodal spreading (p = 0.013). Patients with OSCC and without OLP had a 4.76-higher risk for lymph nodal spreading. On the other hand, second metachronous tumor occurred more often in patients with OSCC and OLP. Overall, OSCC based on OLP occurs more often in female patients, is more highly differentiated and comes with a lower risk for metastases but has a higher risk for second metachronous tumors. Therefore, special attention should be paid to patients with OSCC based on OLP when planning adjuvant therapy and clinical follow-up. The indication for postoperative radiation should be made cautiously in this case, and clinical controls should be performed more closely due to the risk of recurrent disease or tumors at different locations.

Stimulated Raman histology for histological evaluation of oral squamous cell carcinoma.

OBJECTIVES: To investigate whether in patients undergoing surgery for oral squamous cell carcinoma, stimulated Raman histology (SRH), in comparison with H&E-stained frozen sections, can provide accurate diagnoses regarding neoplastic tissue and sub-classification of non-neoplastic tissues. MATERIALS AND METHODS: SRH, a technology based on Raman scattering, was applied to generate digital histopathologic images of 80 tissue samples obtained from 8 oral squamous cell carcinoma (OSCC) patients. Conventional H&E-stained frozen sections were then obtained from all 80 samples. All images/sections (SRH and H&E) were analyzed for squamous cell carcinoma, normal mucosa, connective tissue, muscle tissue, adipose tissue, salivary gland tissue, lymphatic tissue, and inflammatory cells. Agreement between SRH and H&E was evaluated by calculating Cohen's kappa. Accuracy of SRH compared to H&E was quantified by calculating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) as well as area under the receiver operating characteristic curve (AUC). RESULTS: Thirty-six of 80 samples were classified as OSCC by H&E-based diagnosis. Regarding the differentiation between neoplastic and non-neoplastic tissue, high agreement between H&E and SRH (kappa: 0.880) and high accuracy of SRH (sensitivity: 100%; specificity: 90.91%; PPV: 90.00%, NPV: 100%; AUC: 0.954) were demonstrated. For sub-classification of non-neoplastic tissues, SRH performance was dependent on the type of tissue, with high agreement and accuracy for normal mucosa, muscle tissue, and salivary glands. CONCLUSION: SRH provides high accuracy in discriminating neoplastic and non-neoplastic tissues. Regarding sub-classification of non-neoplastic tissues in OSCC patients, accuracy varies depending on the type of tissue examined. CLINICAL RELEVANCE: This study demonstrates the potential of SRH for intraoperative imaging of fresh, unprocessed tissue specimens from OSCC patients without the need for sectioning or staining.

Donor site morbidity after computer assisted surgical reconstruction of the mandible using deep circumflex iliac artery grafts: a cross sectional study.

BACKGROUND: Computer Assisted Design and Computer Assisted Manufacturing (CAD/CAM) have revolutionized oncologic surgery of the head and neck. A multitude of benefits of this technique has been described, but there are only few reports of donor site comorbidity following CAD/CAM surgery. METHODS: This study investigated comorbidity of the hip following deep circumflex iliac artery (DCIA) graft raising using CAD/CAM techniques. A cross-sectional examination was performed to determine range of motion, muscle strength and nerve disturbances. Furthermore, correlations between graft volume and skin incision length with postoperative donor site morbidity were assessed using Spearman's rank correlation, linear regression and analysis of variance (ANOVA). RESULTS: Fifteen patients with a mean graft volume of 21.2 ± 5.7 cm3 and a mean incision length of 228.0 ± 30.0 mm were included. Patients reported of noticeable physical limitations in daily life activities (12.3 ± 11.9 weeks) and athletic activities (38.4 ± 40.0 weeks in mean) following surgery. Graft volume significantly correlated with the duration of the use of walking aids (R = 0.57; p = 0.033) and impairment in daily life activities (R = 0.65; p = 0.012). The length of the scar of the donor-site showed a statistically significant association with postoperative iliohypogastric nerve deficits (F = 4.4, p = 0.037). Patients with anaesthaesia of a peripheral cutaneous nerve had a larger mean scar length (280 ± 30.0 mm) than subjects with hypaesthesia (245 ± 10.1 mm) or no complaints (216 ± 27.7 mm). CONCLUSIONS: Despite sophisticated planning options in modern CAD/CAM surgery, comorbidity of the donor site following  iliac graft harvesting is still a problem. This study is the first to investigate comorbidity after DCIA graft raising in a patient group treated exclusively with CAD/CAM techniques. The results indicate that a minimal invasive approach in terms of small graft volumes and small skin incisions could help to reduce postoperative symptomatology. Trial registration Retrospectively registered at the German Clinical Trials Register (DRKS-ID: DRKS00029066); registration date: 23/05/2022.

[Midface traumatology: one focus-more than two specialist disciplines?] / Traumatologie des Mittelgesichts: ein Fokus ­ mehr als zwei Fachdisziplinen?

Midface fractures are a common occurrence and may be associated with other injuries. It is important to perform diagnosis and treatment planning on an interdisciplinary basis. CT is the gold standard diagnostic modality. Classification according to the pattern of fracture is via the LeFort and other systems. Treatment objectives are anatomic repositioning to preserve the function of the eyes, the infraorbital nerve, and facial symmetry, as well as to preserve masticatory function. The number of surgical access routes should be minimized and incisions of the facial skin avoided wherever possible.

Analysis of the accuracy of computer-assisted DCIA flap mandibular reconstruction applying a novel approach based on geometric morphometrics.

BACKGROUND: This study evaluated the accuracy of computer-assisted surgery (CAS)-driven DCIA (deep circumflex iliac artery) flap mandibular reconstruction by traditional morphometric methods and geometric morphometric methods (GMM). METHODS: Reconstruction accuracy was evaluated by measuring distances and angles between bilateral anatomical landmarks. Additionally, the average length of displacements vectors between landmarks was computed to evaluate factors assumed to influence reconstruction accuracy. Principal component analysis (PCA) was applied to unveil main modes of dislocation. RESULTS: High reconstruction accuracy could be demonstrated for a sample consisting of 26 patients. The effect of the number of segments and length of defect on reconstruction accuracy were close to the commonly used significance threshold (p = 0.062/0.060). PCA demonstrated displacement to result mainly from sagittal and transversal shifts. CONCLUSIONS: CAS is a viable approach to achieve high accuracy in mandibular reconstruction and GMM can facilitate the evaluation of factors influencing reconstruction accuracy and unveil main modes of dislocation in this context.

Automated segmentation of head CT scans for computer-assisted craniomaxillofacial surgery applying a hierarchical patch-based stack of convolutional neural networks.

PURPOSE: Computer-assisted techniques play an important role in craniomaxillofacial surgery. As segmentation of three-dimensional medical imaging represents a cornerstone for these procedures, the present study was aiming at investigating a deep learning approach for automated segmentation of head CT scans. METHODS: The deep learning approach of this study was based on the patchwork toolbox, using a multiscale stack of 3D convolutional neural networks. The images were split into nested patches using a fixed 3D matrix size with decreasing physical size in a pyramid format of four scale depths. Manual segmentation of 18 craniomaxillofacial structures was performed in 20 CT scans, of which 15 were used for the training of the deep learning network and five were used for validation of the results of automated segmentation. Segmentation accuracy was evaluated by Dice similarity coefficient (DSC), surface DSC, 95% Hausdorff distance (95HD) and average symmetric surface distance (ASSD). RESULTS: Mean for DSC was 0.81 ± 0.13 (range: 0.61 [mental foramen] - 0.98 [mandible]). Mean Surface DSC was 0.94 ± 0.06 (range: 0.87 [mental foramen] - 0.99 [mandible]), with values > 0.9 for all structures but the mental foramen. Mean 95HD was 1.93 ± 2.05 mm (range: 1.00 [mandible] - 4.12 mm [maxillary sinus]) and for ASSD, a mean of 0.42 ± 0.44 mm (range: 0.09 [mandible] - 1.19 mm [mental foramen]) was found, with values < 1 mm for all structures but the mental foramen. CONCLUSION: In this study, high accuracy of automated segmentation of a variety of craniomaxillofacial structures could be demonstrated, suggesting this approach to be suitable for the incorporation into a computer-assisted craniomaxillofacial surgery workflow. The small amount of training data required and the flexibility of an open source-based network architecture enable a broad variety of clinical and research applications.

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.

Aspirin, heparin and ischemia time in microvascular free flap surgery - their influence and an optimal anticoagulation protocol.

BACKGROUND: Microvascular surgery has become a standardized technique for reconstruction of large tissue defects in Head and Neck Reconstructive Surgery. However, the main dreaded complications are thrombosis of blood vessels or major bleeding after surgery. Several different anticoagulation protocols have been established in the last decades to overcome these problems with varying degrees of success. METHODS: Over a period of six years, a standardized anticoagulation protocol including acetylsalicylic acid (ASA) and unfractionated heparin (UFH) for direct intraoperative and postoperative administration was established, optimized and compared to a previously used non-standardized protocol. A total of 178 flap surgeries were included in the development and optimization process of the protocol. RESULTS: ASA significantly increased the risk of complications when used for longer than 72 h (OR = 2.52; p = 0.002; 95% CI 1.39-4.59). Administration of UFH reduced flap loss (bolus: OR 0.68; p = 0.47; 95% CI 0.24-1.93; continuous UFH administration: OR = 0.61; p = 0.33; 95% CI 0.22-1.66), however doses greater than 500 IU/ h of UFH as continuous infusion increased the risk of complications. Reduction in ischemia time had no effect on the occurrence of complications. CONCLUSION: Anticoagulation regimes in microvascular surgery can influence the postoperative complication rate. The optimal protocol should consist of a combination of ASA and UFH for the intraoperative and direct postoperative phase. Prolonged administration of ASA as well as doses >500 IU/ h of UFH are to be avoided due to the increased complication rate.

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.

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.

Transitioning the Molecular Tumor Board from Proof of Concept to Clinical Routine: A German Single-Center Analysis.

Molecular precision oncology faces two major challenges: first, to identify relevant and actionable molecular variants in a rapidly changing field and second, to provide access to a broad patient population. Here, we report a four-year experience of the Molecular Tumor Board (MTB) of the Comprehensive Cancer Center Freiburg (Germany) including workflows and process optimizations. This retrospective single-center study includes data on 488 patients enrolled in the MTB from February 2015 through December 2018. Recommendations include individual molecular diagnostics, molecular stratified therapies, assessment of treatment adherence and patient outcomes including overall survival. The majority of MTB patients presented with stage IV oncologic malignancies (90.6%) and underwent an average of 2.1 previous lines of therapy. Individual diagnostic recommendations were given to 487 patients (99.8%). A treatment recommendation was given in 264 of all cases (54.1%) which included a molecularly matched treatment in 212 patients (43.4%). The 264 treatment recommendations were implemented in 76 patients (28.8%). Stable disease was observed in 19 patients (25.0%), 17 had partial response (22.4%) and five showed a complete remission (6.6%). An objective response was achieved in 28.9% of cases with implemented recommendations and for 4.5% of the total population (22 of 488 patients). By optimizing the MTB workflow, case-discussions per session increased significantly while treatment adherence and outcome remained stable over time. Our data demonstrate the feasibility and effectiveness of molecular-guided personalized therapy for cancer patients in a clinical routine setting showing a low but robust and durable disease control rate over time.

Intraoperative marking of the tumour resection surface for improved radiation therapy planning in head and neck cancer: preclinical evaluation of a novel liquid fiducial marker.

OBJECTIVE: To evaluate a novel liquid fiducial marker for intraoperative marking of the tumour resection surface in oral cancer patients to facilitate precise postoperative delineation of the interface between the tumour resection border and reconstructed tissue for intensity-modulated radiation therapy. METHODS: A total of 200 markers were created by injecting the volumes of 10 µl, 20 µl, 30 µl, 40 µl and 50 µl of a liquid marker composed of sucrose acetoisobutyrate (SAIB) and iodinated sucrose acetoisobutyrate (x-SAIB) into the soft tissue of porcine mandible segments. Visibility of the resulting markers was quantified by threshold-based segmentation of the marker volume in CT- and CBCT imaging and by a comparison of signal intensities in MRI. RESULTS: Even the lowest volume of SAIB-/x-SAIB investigated (10 µl) resulted in a higher visibility (CTSoft tissue: 88.18 ± 13.23 µl; CTBone: 49.55 ± 7.62 µl; CBCT: 54.65 ± 12.58 µl) than observed with the incorporation of titanium ligature clips (CTSoft tissue: 50.15 ± 7.50 mm3; CTBone: 23.90 ± 3.39 mm3; CBCT: 33.80 ± 9.20 mm3). Markers created by the injection of 10 µl and 20 µl could reliably be delineated from markers created by the injection of higher volumes. CONCLUSION: SAIB/x-SAIB, which has recently become available as a Conformité Européenne (CE)-marked fiducial marker, provides an option for fast and reliable production of markers with excellent visibility in imaging modalities used in oral cancer radiation therapy (RT) planning routine.

Effects of Red Blood Cell Transfusions on Distant Metastases of Oral Squamous Cell Carcinomas.

There is no consensus on the effect of red blood cell (RBC) transfusions on patients with oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the association between RBC administration and the occurrence of distant metastases (M+) after surgical treatment of OSCC. All medical records of patients who underwent primary surgery for OSCC in our department (2003-2019) were analyzed retrospectively (n = 609). Chi and Cox regression models were used to analyze the influence of transfusion on the development of M+, and survival rates. Kaplan-Meier curves were used for graphical presentation. A multitude of patient-specific factors showed a statistical impact in univariate analysis (transfusion, age, gender, diabetes, pT, pN, L, V, Pn, G, UICC, adjuvant therapy, free microvascular transplant, preoperative hemoglobin level). Transfusion status and pN stage were the only variables that showed a significant correlation to M+ in the multivariate Cox model. The hazard ratios for the occurrence of M+ were 2.42 for RBC transfusions and 2.99 for pN+. Administration of RBC transfusions was identified as a significant prognostic parameter for the occurrence of distant metastases after surgical treatment of OSCC. Hence, the administration of RBC transfusions should be considered carefully in the perioperative management.

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.