Neoadjuvant Radiochemotherapy Alters the Immune and Metabolic Microenvironment in Oral Cancer-Analyses of CD68, CD163, TGF-β1, GLUT-1 and HIF-1α Expressions.

Background: The first-line treatment of oral squamous cell carcinoma (OSCC) involves surgical tumor resection, followed by adjuvant radio(chemo)therapy (R(C)T) in advanced cases. Neoadjuvant radio- and/or chemotherapy has failed to show improved survival in OSCC. Recently, neoadjuvant immunotherapy has shown promising therapeutic efficacy in phase 2 trials.

Does surgery affect systemic immune response? a perioperative analysis of TGF-β, IL-8 and CD45RO.

Background: The options of (neo-)adjuvant immunotherapy in addition to surgery in the treatment of oral squamous cell carcinoma (OSCC) are steadily increasing, but patients do not always respond to therapy as intended. The objectives of this study were to investigate the systemic perioperative course of the biomarkers CD45RO, TGF-β, and IL-8 in non-tumor-related minor and tumor-related major maxillofacial surgery and to perform association analyses with demographic and histomorphologic parameters. A deeper understanding of surgery-related changes in various of different immune biomarkers could help to better understand the immunologic consequences of surgery which could influence immunotherapeutic protocols.

Postoperative Changes in Systemic Immune Tolerance Following Major Oncologic versus Minor Maxillofacial Surgery.

Background: There is increasing evidence of the benefits of adjuvant and neoadjuvant immunotherapy in the treatment of solid malignancies like oral squamous cell carcinoma (OSCC). To optimize (neo-)adjuvant treatment, the systemic immunomodulatory effects of tumor surgery itself need to be considered. Currently, there is little evidence on the immunological effects of major surgery, such as free microvascular flap reconstruction.

Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions - an experiment.

Purpose: Medication-related osteonecrosis occurs exclusively in the jaw bones. However, the exact pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) and the unique predisposition of the jaw bones have not been elucidated, making its treatment a challenge. Recent evidence indicates that macrophages might play a pivotal role in MRONJ pathogenesis.

Recipient bed perfusion as a predictor for postoperative complications in irradiated patients with microvascular free tissue transfer of the head and neck area: a clinical analysis of 191 microvascular free flaps.

Purpose: Despite microvascular free tissue transfer being the mainstay of care in the reconstruction of larger maxillofacial defects, a significant number of patients experience postoperative complications due to impaired blood supply of the flap. In this context, the early influence of recipient bed perfusion remains unclear, but there is evidence that it is associated with free flap viability immediately after surgery.

Methods: We analyzed flap and recipient bed perfusion within the first 2 weeks after surgery by using the oxygen-to-see device.

Importance of the PD-1/PD-L1 Axis for Malignant Transformation and Risk Assessment of Oral Leukoplakia.

Background: The programmed cell death ligand 1/programmed cell death receptor 1 (PD-L1/PD-1) Immune Checkpoint is an important modulator of the immune response. Overexpression of the receptor and its ligands is involved in immunosuppression and the failure of an immune response against tumor cells. PD-1/PD-L1 overexpression in oral squamous cell carcinoma (OSCC) compared to healthy oral mucosa (NOM) has already been demonstrated.

Lineage-associated connexin 43 expression in bisphosphonate-exposed rat bones.

Expression of signaling proteins in bone cells depends on their embryological mesoderm-derived (e.g. tibia) or cranial neural crest (CNC)-derived (e.

Endothelial inflammatory and thrombogenic expression changes in microvascular anastomoses - An immunohistochemical analysis.

The aim of this study was to investigate intraluminal vessel diameters and endothelial expression levels of pro-inflammatory and -thrombotic mediators in patent and non-patent microvascular anastomoses. Endothelial expression of CD31, VCAM-1, E- and P-Selectin, eNOS, iNOS and PAI-1 was evaluated by immunohistochemistry and compared to non-anastomosed arteries as controls. Intraluminal diameters were determined via H.

Zoledronate Causes a Systemic Shift of Macrophage Polarization towards M1 In Vivo.

Background: Immunomodulatory properties of bisphosphonates (BP) are suggested to contribute to the development of medication-associated osteonecrosis of the jaw (MRONJ). Furthermore, bisphosphonate-derived immune modulation might contribute to the anti-metastatic effect observed in breast cancer patients. Macrophages are potential candidates for the mediation of immunomodulatory effects of bisphosphonates.

The Special Developmental Biology of Craniofacial Tissues Enables the Understanding of Oral and Maxillofacial Physiology and Diseases.

Maxillofacial hard tissues have several differences compared to bones of other localizations of the human body. These could be due to the different embryological development of the jaw bones compared to the extracranial skeleton. In particular, the immigration of neuroectodermally differentiated cells of the cranial neural crest (CNC) plays an important role.

Free Gingival Graft and Collagen Matrix Revascularization in an Enoral Open Wound Situation.

Purpose: Vestibuloplasty with free gingival grafting is a frequently performed surgical procedure to generate sufficient keratinized mucosa (KM) around dental implants. Avascular porcine collagen matrices (CM) have been proclaimed to be sufficient substitutes as alternatives to free gingival grafts (FGGs). However, the process of graft integration and vascularization is still incompletely understood.

Osteocyte necrosis triggers osteoclast-mediated bone loss through macrophage-inducible C-type lectin.

Although the control of bone-resorbing osteoclasts through osteocyte-derived RANKL is well defined, little is known about the regulation of osteoclasts by osteocyte death. Indeed, several skeletal diseases, such as bone fracture, osteonecrosis, and inflammation are characterized by excessive osteocyte death. Herein we show that osteoclasts sense damage-associated molecular patterns (DAMPs) released by necrotic osteocytes via macrophage-inducible C-type lectin (Mincle), which induced their differentiation and triggered bone loss.

Craniofacial Osteosarcoma-Pilot Study on the Expression of Osteobiologic Characteristics and Hypothesis on Metastasis.

Craniofacial osteosarcomas (COS) and extracranial osteosarcomas (EOS) show distinct clinical differences. COS show a remarkably lower incidence of metastases and a better survival. However, in contrast to EOS, they show a poor response to neoadjuvant chemotherapy.

Saliva diagnostics in patients suffering from bisphosphonate-associated osteonecrosis of the jaw: Results of an observational study.

Objective: One of the severe side effects of bisphosphonate (BP) therapy is bisphosphonate-associated osteonecrosis of the jaw (BONJ). However, there is no information available about its pathogenesis. Hence, the aim of this observational study was to contribute to discerning this pathogenesis by comparing salivary quantity and quality in patients with BONJ and undergoing BP treatment.

Correction to: Long-term endothelial dysfunction in irradiated vessels: an immunohistochemical analysis.

Correction to: Strahlenther Onkol 2018 https://doi.org/10.1007/s00066-018-1382-3 The original version of this article unfortunately contained a mistake.

Differences in Inflammation and Bone Resorption between Apical Granulomas, Radicular Cysts, and Dentigerous Cysts.

Introduction: Dental cysts can be of inflammatory (radicular cysts) or noninflammatory (dentigerous cysts) origin. Apical periodontitis is a necrosis of the pulp and infection of the root canal causing the development of apical granulomas or radicular cysts. The immunology of granuloma and cyst formation is important because modern root filling materials are immunologically active and can contribute to the resolution of apical granulomas.

Fluorescence-guided bone resection: A histological analysis in medication-related osteonecrosis of the jaw.

Purpose: Surgical treatment of medication-related osteonecrosis of the jaw (MRONJ) consists of necrotic bone removal followed by dense mucosal closure. Fluorescence-guided surgery has become a promising tool to intraoperatively distinguish between healthy and necrotic bone. Until now, there has been a lack of histopathological studies correlating the intraoperative fluorescence situation to histopathological analyses of the respective bone areas in order to further validate this method.

Collagen Matrix Vascularization in a Peri-Implant Vestibuloplasty Situation Proceeds Within the First Postoperative Week.

Purpose: Vestibuloplasty is a frequently performed surgical procedure to create or increase soft tissue mucosal sealing around dental restorations. Collagen matrices have exhibited comparable clinical results as free gingival grafts in the context of intraoral tissue augmentation. However, the process of matrix vascularization, the basic requirement for local healing, is incompletely understood.

MAGE-A expression in oral and laryngeal leukoplakia predicts malignant transformation.

Leukoplakia is a potential precursor of oral as well as laryngeal squamous cell carcinoma. Risk assessment of malignant transformation based on the grade of dysplasia of leukoplakia often does not lead to reliable results. However, oral squamous cell carcinoma, laryngeal squamous cell carcinoma, and leukoplakia express single or multiple members of the melanoma-associated antigens A (MAGE-A) family, while MAGE-A are absent in healthy mucosal tissue.

Osteoclastic expression of higher-level regulators NFATc1 and BCL6 in medication-related osteonecrosis of the jaw secondary to bisphosphonate therapy: a comparison with osteoradionecrosis and osteomyelitis.

Background: With an increasing indication spectrum of antiresorptive drugs, the medication-related osteonecrosis of the jaw secondary to bisphosphonate therapy [MRONJ (BP)] is continuously gaining clinical relevance. Impaired osteoclast function, accompanied by altered cell morphology and expression of osteoclastic effector proteins, contributes to the pathogenesis of MRONJ (BP). However, the underlying regulatory mechanisms at a transcriptional level are unaddressed so far.

Prognostic significance of PD-L2 expression in patients with oral squamous cell carcinoma-A comparison to the PD-L1 expression profile.

Background: Despite the observed association of increased PD-L1 expression in peripheral blood of oral squamous cell carcinoma (OSCC) patients with histomorphologic parameters, the role of the PD1 ligands-PD-L1 and PD-L2-is insufficiently understood. Aim of the study was to investigate whether the alterations of PD-L1 and PD-L2 expression in blood are associated with survival and could serve as immune monitoring parameter. Moreover, it should be analyzed if PD-L2 is differentially expressed in tissue and blood samples of OSCC patients compared to healthy controls and if there is an association of PD-L2 expression with histomorphologic and prognostic tumor parameters.

The altered expression levels of miR-186, miR-494 and miR-3651 in OSCC tissue vary from those of the whole blood of OSCC patients.

Background: Altered expressions of miR-186, miR-494 and miR-3651 in whole blood of OSCC patients have already been demonstrated. However, nothing is known about their expression in tumor tissues. This study aimed at evaluating differences in miRNA expression in OSCC tissues compared to healthy oral mucosa and at checking if the altered expression is reflected in corresponding blood.

Long-term endothelial dysfunction in irradiated vessels: an immunohistochemical analysis.

Background: Microvascular free flap reconstruction has become a standard technique in head and neck reconstructive surgery. Pre-operative radiotherapy is associated with a higher incidence of free flap malperfusion and the need for operative revision. Irradiated vessels present characteristic histomorphological and structural changes.