Osseointegration of titanium implants after surface treatment with ultraviolet light or cold atmospheric plasma in vivo.

PURPOSE: To determine the histological effects of ultraviolet light and cold atmospheric plasma treatment on the osseointegration of titanium implants in vivo. MATERIALS AND METHODS: Six juvenile pigs were divided into three groups of two animals each. A total of 54 titanium implants were placed randomly in the pigs' calvarial bone (nine implants per pig). Of these, 18 implants served as untreated controls. The remaining 36 implants served as the experimental group and were treated with either ultraviolet light or argon plasma for 12 minutes each prior to insertion. Two pigs in each group were kept until 2, 4 and 8 weeks and then sacrificed. Resonance frequency analysis was conducted after implant placement and at the time of sacrifice. Osseointegration was evaluated using microcomputed tomography scans and histomorphometrical analysis. RESULTS: After initial loss, all implants showed a constant increase in implant stability quotient values over time without significant differences between the groups. The bone-implant contact values increased steadily for all implants over 8 weeks of healing. Surface-treated implants showed significantly higher bone-implant contact values compared to untreated implants at each time point. Bone area fraction occupancy values were almost always higher following both treatment methods; however, differences were only significant after 4 and 8 weeks for the cold atmospheric plasma group and after 4 weeks for the ultraviolet light group. CONCLUSIONS: Ultraviolet light and cold atmospheric plasma may improve histomorphometrical osseointegration of titanium implants significantly.

Degradation, Bone Regeneration and Tissue Response of an Innovative Volume Stable Magnesium-Supported GBR/GTR Barrier Membrane.

INTRODUCTION: Bioresorbable collagenous barrier membranes are used to prevent premature soft tissue ingrowth and to allow bone regeneration. For volume stable indications, only non-absorbable synthetic materials are available. This study investigates a new bioresorbable hydrofluoric acid (HF)-treated magnesium (Mg) mesh in a native collagen membrane for volume stable situations. MATERIALS AND METHODS: HF-treated and untreated Mg were compared in direct and indirect cytocompatibility assays. In vivo, 18 New Zealand White Rabbits received each four 8 mm calvarial defects and were divided into four groups: (a) HF-treated Mg mesh/collagen membrane, (b) untreated Mg mesh/collagen membrane (c) collagen membrane and (d) sham operation. After 6, 12 and 18 weeks, Mg degradation and bone regeneration was measured using radiological and histological methods. RESULTS: In vitro, HF-treated Mg showed higher cytocompatibility. Histopathologically, HF-Mg prevented gas cavities and was degraded by mononuclear cells via phagocytosis up to 12 weeks. Untreated Mg showed partially significant more gas cavities and a fibrous tissue reaction. Bone regeneration was not significantly different between all groups. DISCUSSION AND CONCLUSIONS: HF-Mg meshes embedded in native collagen membranes represent a volume stable and biocompatible alternative to the non-absorbable synthetic materials. HF-Mg shows less corrosion and is degraded by phagocytosis. However, the application of membranes did not result in higher bone regeneration.

Perioperative Management in Patients With Undergoing Direct Oral Anticoagulant Therapy in Oral Surgery - A Multicentric Questionnaire Survey.

AIM: The purpose of this study was to survey the current opinions of hospitals and medical practices concerning the perioperative management of patients undergoing direct oral anticoagulant therapy (DOAC) and discuss recommendations for the clinical practice. MATERIALS AND METHODS: A questionnaire with 13 topics and multiple ordinal-polytomous subitems was designed and sent to 120 Departments of Oral and Maxillofacial Surgery in Austria, Switzerland and Germany, as well as to 85 oral and maxillofacial/oral surgeons in medical offices in Hamburg, Germany. The data were statistically evaluated by Chi-square, Fisher's exact and Jonckheere-Terpstra tests. RESULTS: The rate of response was 42%. Thirty-seven percent of respondents reported treating over 50 patients per year with undergoing DOAC therapy and only 18% assess a high bleeding risk [33% for vitamin K antagonists (VKA)]. In contrast to that, 62% of respondents would interrupt the DOAC therapy for extraction of one tooth, while 94% would continue VKA therapy. Significantly more clinicians apply suture than those in a medical office. The use of additional hemostatic measures varied between clinic and medical practice. There was a clear request for more detailed guidelines. CONCLUSION: The study shows the current opinion for perioperative management of patients undergoing DOAC therapy. Multi-centric studies under controlled conditions are needed for a safer treatment of anticoagulated patients as therapy strategies differ greatly between institutions and therefore a complication analysis is hardly possible.

Pin-up Glottoplasty: Feasibility Study of a Novel Approach Medializing or Lateralizing Immobile Vocal Folds.

Principles in medializing and lateralizing vocal folds have not changed a lot within the last decades (Isshiki et al, 1974; Bruenings, 1911). We present a feasibility study for a completely new approach to perform medialization and lateralization of immobile vocal folds. The method was tested on 20 human larynges by inserting a 21G needle into the vocal fold, medializing (or, in other cases, lateralizing) the vocal cord and fixing the needle at the cricoid cartilage posteriorly. The anterior and posterior fixation points of the needle allow for a stable positioning of the needle, which we consider necessary in both cases of medialization or lateralization. The needle position was examined visually as well as three-dimensionally via cone beam computed tomography.

Influence of UV Irradiation and Cold Atmospheric Pressure Plasma on Zirconia Surfaces: An In Vitro Study

PURPOSE: To compare the influence of ultraviolet (UV) irradiation and cold atmospheric pressure plasma (CAP) treatment on surface structure, surface chemistry, cytocompatibility, and cell behavior on zirconia in vitro. MATERIALS AND METHODS: Zirconia samples (TZ-3YSBE) were treated by UV irradiation, oxygen plasma, or argon plasma for 12 minutes each and compared with the nontreated samples. Surface analysis was conducted using scanning electron microscopy, roughness analysis, and x-ray photoelectron spectroscopy. Cell proliferation, viability, and cell attachment as well as cytotoxicity were evaluated using MC3T3-E1 murine osteoblasts cultivated directly on the zirconia samples. RESULTS: Surface structure and roughness were not affected by the surface treatments. CAP and UV irradiation significantly reduced organic material and increased the surface oxidation on the zirconia samples. Furthermore, CAP and UV treatment significantly decreased the contact angle on the zirconia samples, indicating superhydrophilicity. Cell attachment was significantly increased on oxygen plasma-treated zirconia samples compared with the nontreated samples at all times (P < .001). After 24 and 48 hours, cell proliferation and viability (P < .001) were significantly increased on oxygen plasma-treated samples in comparison with the nontreated, UV-treated, and argon plasma-treated samples. Neither UV nor CAP treatment led to cytotoxicity. CONCLUSION: In vitro, surface treatment by UV irradiation or CAP causes a significant reduction of organic material, increases the hydrophilicity of zirconia, and improves the conditions for osteoblasts. Results stipulate that treatment of zirconia surfaces with oxygen plasma may favor cell proliferation.

Sensitivity and specificity of sentinel lymph node biopsy in patients with oral squamous cell carcinomas using indocyanine green fluorescence imaging.

PURPOSE: The purpose of this clinical study was to evaluate the sensitivity and specificity of cervical sentinel lymph node biopsy after mapping with indocyanine green fluorescence (ICG) for imaging early-stage oral cancer. PATIENTS AND METHODS: A sentinel lymph node biopsy (SLNB) was performed during a selective neck dissection (SND) in 20 patients with oral squamous cell carcinoma (OSCC, cT1 or cT2, N0 status). The sentinel lymph nodes (SLN) were identified using an infrared video camera after ICG injection. Lymph nodes were examined histologically. The endpoint of this study was to investigate the rate of false-negative results in SLNB. RESULTS: Sentinel lymph nodes could be detected after 8.1 min (range 1-22 min). In eight out of 20 cases, lymph node metastases were found during histopathological evaluation of the neck dissection specimen. In four cases a metastasis could be found in the detected SLN (sensitivity 50%). In the other four cases metastases were found in different lymph nodes. Specificity was 100%, positive predictive value 100%, and negative predictive value 75%. CONCLUSION: In this study, reliability of sentinel lymph node biopsy after ICG imaging could not be verified, as there were false-negative results in 50% of the cases. Therefore, SND can still be recommended as for patients with cT1 or cT2 OSCC, and a N0 neck status.

Plasma Electrolytic Oxidation of Titanium Implant Surfaces: Microgroove-Structures Improve Cellular Adhesion and Viability.

BACKGROUND/AIM: Plasma electrolytic oxidation (PEO) is an established electrochemical treatment technique that can be used for surface modifications of metal implants. In this study we to treated titanium implants with PEO, to examine the resulting microstructure and to characterize adhesion and viability of cells on the treated surfaces. Our aim was to identify an optimal surface-modification for titanium implants in order to improve soft-tissue integration. MATERIALS AND METHODS: Three surface-variants were generated on titanium alloy Ti6Al4V by PEO-treatment. The elemental composition and the microstructures of the surfaces were characterized using energy dispersive X-ray spectroscopy, scanning electron microscopy and profilometry. In vitro cytocompatibility of the surfaces was assessed by seeding L929 fibroblasts onto them and measuring the adhesion, viability and cytotoxicity of cells by means of live/dead staining, XTT assay and LDH assay. RESULTS: Electron microscopy and profilometry revealed that the PEO-surface variants differed largely in microstructure/topography, porosity and roughness from the untreated control material as well as from one another. Roughness was generally increased after PEO-treatment. In vitro, PEO-treatment led to improved cellular adhesion and viability of cells accompanied by decreased cytotoxicity. CONCLUSION: PEO-treatment provides a promising strategy to improve the integration of titanium implants with surrounding tissues.

Changes in surface characteristics of titanium and zirconia after surface treatment with ultraviolet light or non-thermal plasma.

Positive effects of irradiation with ultraviolet (UV) light or treatment with non-thermal plasma on titanium and zirconia surfaces have been described in various studies. The aim of this study was to assess and compare the changes in the physicochemical surface conditions of titanium and zirconia surfaces after a short treatment with UV light or with non-thermal plasmas of argon or oxygen. Titanium and zirconia samples with moderately rough surfaces were treated for 12 min either in a UV-light oven or in a non-thermal plasma reactor that generates non-thermal plasmas of oxygen or argon. Changes in surface conditions were assessed by confocal microscopy, dynamic contact angle measurement, and X-ray photoelectron spectroscopy (XPS). No changes in roughness occurred. Ultraviolet irradiation and non-thermal plasma significantly increased the wettability of the titanium and zirconia surfaces. X-ray photoelectron spectroscopy showed an increase of oxygen and a significant decrease of carbon after treatment with either method. Thus, ultraviolet light and non-thermal plasma were found to be able to improve the chemical surface conditions of titanium and zirconia following a short exposure time. However, further in vitro and in vivo studies are needed to determine the relevance of the results.

Photofunctionalization and non-thermal plasma activation of titanium surfaces.

OBJECTIVE: The aim of this study was to compare UV light and non-thermal plasma (NTP) treatment regarding the improvement of physical material characteristics and cell reaction on titanium surfaces in vitro after short-term functionalization. MATERIALS AND METHODS: Moderately rough (Ra 1.8-2.0 µm) sandblasted and acid-etched titanium disks were treated by UV light (0.05 mW/cm2 at λ = 360 nm and 2 mW/cm2 at λ = 250 nm) or by NTP (24 W, -0.5 mbar) of argon or oxygen for 12 min each. Surface structure was investigated by scanning electron microscopy, confocal microscopy and X-ray photoelectron spectroscopy (XPS). Hydrophilicity was assessed by dynamic contact angle measurement. Cell attachment, viability, cell proliferation and cytotoxicity were assessed in vitro using murine osteoblast-like cells. RESULTS: UV irradiation or NTP treatment of titanium surfaces did not alter the surface structure. XPS analysis revealed a significantly increased oxidation of the surface and a decrease of carbon after the use of either method. NTP and UV light led to a significant better cell attachment of murine osteoblasts; significantly more osteoblasts grew on the treated surfaces at each time point (p < 0.001). CONCLUSIONS: UV light as well as NTP modified the surface of titanium and significantly improved the conditions for murine osteoblast cells in vitro. However, results indicate a slight advantage for NTP of argon and oxygen in a short time interval of surface functionalization compared to UV. CLINICAL RELEVANCE: UV light and NTP are able to improve surface conditions of dental implants made of titanium.

Biocompatibility and Osseointegration of Titanium Implants with a Silver-Doped Polysiloxane Coating: An In Vivo Pig Model.

PURPOSE: To test the antimicrobial properties, surface topography, reaction of surrounding tissue (biocompatibility), and osseointegration of ultrathin implant surfaces containing polysiloxane and nanoscaled silver particles. MATERIALS AND METHODS: Implants with polysiloxane coating and nanoscaled silver particles (Ag/SiOxCy; HyProtect, Bio-Gate) were compared with implants with polysiloxane coating alone and with noncoated (grit-blasted and acid-etched) implants. A total of 72 implants were inserted into the calvaria of eight domestic pigs (nine implants each, three of each type). After 3 months, histologic sections were evaluated for inflammatory cell infiltration and bone implant contact. RESULTS: Roughness parameters did not differ between all three implant types. The Ag/SiOxCy coating exhibited a good antimicrobial effect in vitro and no sign of inflammatory cell infiltration in vivo. The noncoated implants demonstrated 10.85% and 14.48% more bone contact than the polysiloxane-coated implants (P = .003) and the Ag/SiOxCy­coated implants (P ≤ .001), respectively. Osseointegration was not significantly different between the Ag/SiOxCy­coated and polysiloxane-coated implants (P = .72). CONCLUSION: The osseointegration capability of the Ag/SiOxCy-coated implants was equal to that of the polysiloxane-coated implants but less than that of the grit-blasted and acid-etched implants. Because of the biocompatibility of the polysiloxane coating, further studies should be conducted in load-bearing models and in the oral cavity to investigate the antimicrobial effect of the embedded silver clusters.

Cytocompatibility of Direct Laser Interference-patterned Titanium Surfaces for Implants.

In an effort to generate titanium surfaces for implants with improved osseointegration, we used direct laser interference patterning (DLIP) to modify the surface of pure titanium grade 4 of four different structures. We assessed in vitro cytoxicity and cell attachment, as well as the viability and proliferation of cells cultured directly on the surfaces. Attachment of the cells to the modified surfaces was comparably good compared to that of cells on grit-blasted and acid-etched reference titanium surfaces. In concordance with this, viability and proliferation of the cells directly cultured on the specimens were similar on all the titanium surfaces, regardless of the laser modification, indicating good cytocompatibility.

Accuracy of Bone Measurements in the Vicinity of Titanium Implants in CBCT Data Sets: A Comparison of Radiological and Histological Findings in Minipigs.

PURPOSE: The aim of this animal study was the determination of accuracy of bone measurements in CBCT (cone-beam computed tomography) in close proximity to titanium implants. MATERIAL AND METHODS: Titanium implants were inserted in eight Göttingen minipigs. 60 implants were evaluated histologically in ground section specimen and radiologically in CBCT in regard to thickness of the buccal bone. With random intercept models, the difference of histologic measurements and CBCT measurements of bone thickness was calculated. RESULTS: The mean histological thickness of the buccal bone was 5.09 mm (CI 4.11-6.08 mm). The four raters measured slightly less bone in CBCT than it was found in histology. The random effect was not significant (p value 1.000). Therefore, the Intraclass Correlation Coefficient (ICC) was 98.65% (CI 100.00-96.99%). CONCLUSION: CBCT is an accurate technique to measure even thin bone structures in the vicinity of titanium implants.

Lack of evidence for prognostic value of epidermal growth factor receptor intron-1 CA repeats for oral carcinomas.

Epidermal growth factor receptor (EGFR) expression is altered in several malignancies, including oral squamous cell carcinoma. A CA-repeat polymorphism in intron-1 (CA-SSR-1) of the EGFR gene is reported to influence EGFR expression and is associated with features of various solid tumors and outcomes of cancer patients. In the present study we evaluated the influence of length and zygosity of CA-SSR-1 on the survival of patients with oral squamous cell carcinoma. The length and zygosity of CA-SSR-1 was obtained through microsatellite analysis in 91 patients with oral cancer, who were treated in the Department of Oral and Maxillofacial Surgery of the University Medical Centre Hamburg Eppendorf, Germany, during the years 1998-2008. Follow up was conducted until 2016. Outcome measures were age, gender, tumor stage, occurrence of metastases, and date of recurrence or death. Statistical analysis was conducted using the chi-square test and the log-rank test. Neither length nor zygosity of the CA-SSR-1 in patients with oral squamous cell carcinoma was significantly correlated with sex, age, tumor size, tumor localization, lymph node involvement, metastasis status, disease-free survival, or overall survival. Length and zygosity of the CA-SSR-1 polymorphism in EGFR is not able to serve as a prognostic biomarker in White European patients with oral squamous cell carcinoma.

Implants inserted with graftless osteotome sinus floor elevation - A 5-year post-loading retrospective study.

PURPOSE: To report the outcome of graftless osteotome sinus floor elevation (OSFE) in order to evaluate whether apical bone gain depends on the initial residual bone height and whether the initial residual bone height has an influence on the amount of marginal bone loss. Furthermore the study aimed to assess if perforations of the Schneiderian membrane or residual bone height are potential predictors of implant survival. MATERIALS AND METHODS: In this retrospective study all patients were included who were treated between 2001 and 2010 and received dental implants in combination with OSFE in a private practice. Patients having 1 to 11 mm of residual bone height were subjected to crestal sinus lift elevation. One hundred and thirteen patients with 233 implants were included in this study. The follow-up period was 5-years post-loading for all patients. The average initial bone level height was 5.9 ±â€…1.7 mm. No bone graft or substitute material was used. All implants healed transgingivally and were loaded 3 months after insertion. Outcome measures were prosthetic success, implant success, complications, radiographic crestal bone level changes and apical (sinus floor) bone height. RESULTS: Sixty-three patients dropped out during the 5-year post-loading follow-up. Seven implants in 7 patients failed. Implant survival rate 5 years after loading was 93.8% at patient level. Implants succeeded in 92.7% of all cases. In six patients (5.3%), prostheses failed and had to be remade. Minor complications like small ceramic fractures and loosening of prosthetics were observed in seven patients (6.2%). Average marginal bone loss at 5 years of follow-up was 0.5 ±â€…0.8 mm per patient. No correlation was found between marginal bone loss and initial residual bone height. Average gained bone height was 4.5 ±â€…1.4 mm after 5 years of loading. We found a significantly negative linear correlation for apical bone gain depending on the baseline bone level (P < 0.001). The apical bone gain was higher in cases with less residual bone. CONCLUSIONS: Implants after graftless osteotome sinus floor elevation showed excellent survival and success rates after 5 years of loading. Apical gain of newly formed bone was positively correlated with the initial bone height showing a statistical significance. However, initial residual bone height is also a predictor for implant survival, i.e. survival increases by 1.6 times with every additional millimetre of initial residual bone height. Conflict-of-interest statement: All authors declare that they have neither financial nor non-financial competing interests.

Impact of Dental Implant Surface Modifications on Osseointegration.

Objective. The aim of this paper is to review different surface modifications of dental implants and their effect on osseointegration. Common marketed as well as experimental surface modifications are discussed. Discussion. The major challenge for contemporary dental implantologists is to provide oral rehabilitation to patients with healthy bone conditions asking for rapid loading protocols or to patients with quantitatively or qualitatively compromised bone. These charging conditions require advances in implant surface design. The elucidation of bone healing physiology has driven investigators to engineer implant surfaces that closely mimic natural bone characteristics. This paper provides a comprehensive overview of surface modifications that beneficially alter the topography, hydrophilicity, and outer coating of dental implants in order to enhance osseointegration in healthy as well as in compromised bone. In the first part, this paper discusses dental implants that have been successfully used for a number of years focusing on sandblasting, acid-etching, and hydrophilic surface textures. Hereafter, new techniques like Discrete Crystalline Deposition, laser ablation, and surface coatings with proteins, drugs, or growth factors are presented. Conclusion. Major advancements have been made in developing novel surfaces of dental implants. These innovations set the stage for rehabilitating patients with high success and predictable survival rates even in challenging conditions.

The benefit of abdominal sonography and chest X-ray for staging oral squamous cell carcinomas in stages UICC I and II.

PURPOSE: The purpose of this study was to evaluate how often distant metastases occur in localized oral squamous cell carcinomas (OSCC). The investigators hypothesize that abdominal sonography and chest X-ray may not be necessary for initial staging of early oral squamous cell carcinoma in UICC stage I/II. MATERIAL AND METHODS: The investigators implemented a retrospective study. The study collective was composed of 124 patients with OSCC, who were treated in the department of oral and maxillofacial surgery during the years 2011-2015 at the University Medical Center Hamburg Eppendorf, Germany. We focused on age, gender, date of diagnosis, tumour stage (clinical and pathological), HPV status, occurrence of metastases, recurrences, date and frequency of staging and restaging (abdominal sonography, chest X-ray, CT Abdomen/Thorax, PET CT), follow up time and date of death. Descriptive and bivariate statistics were computed (chi-square test) and the P value was set at .05. RESULTS: 19 distant metastases were found in 13 out of 124 patients (10.48%). Of those 20 metastases 5 were found in the liver (26.32%), 11 in the lung (57.89%) and 4 in the bone (15.79%). Hepatic metastases co-occurred in every case with pulmonary metastases. In one case bone metastases occurred without the presence of pulmonary metastases. There was no significant correlation of metastasis rate to T stage. But distant metastases were solely found in node positive patients. This was significant for pulmonary metastases, not for liver metastases. Only one out of 11 pulmonary metastases was diagnosed by chest X-ray. CONCLUSION: Abdominal sonography and chest X-ray can be omitted as a standard procedure in staging of localized node negative oral squamous cell carcinoma. A thoracic CT including the liver should be performed in patients with suspected lymph nodes metastases in the neck on CT. A skeletal scintigraphy or alternatively a PET/PET-CT should be added if there are signs and symptoms suspicious for bone metastases.

PEO-generated Surfaces Support Attachment and Growth of Cells In Vitro with No Additional Benefit for Micro-roughness in Sa (0.2-4 µm).

BACKGROUND/AIM: Plasma electrolytic oxidation (PEO), also known as micro-arc oxidation, is a promising electrochemical surface treatment technique for metals which has been used for the generation of various material surfaces and has been the focus of recent biomaterial research. It has been hypothesized that rough PEO surfaces should generally have properties that support cellular attachment and proliferation. However, this has not yet been demonstrated in systematically conducted studies. The present study investigated fibroblast cell proliferation and attachment to ground, electric discharge machining (EDM) and PEO-treated titanium surfaces differing in roughness and porosity. MATERIALS AND METHODS: Three surface variants with 'smoother', 'medium-coarse' and 'rough' surface topographies were generated by PEO and EDM on specimens of titanium alloy (with 6 wt% aluminum and 4 wt% vanadium) for comparison with more smoothly ground specimens. The in vitro effects on cellular attachment and proliferation were determined in 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT), 5-bromo-2'-deoxyuridine (BrdU) and live/dead staining assays with L929 fibroblasts cultivated directly on the metal specimens. Cytocompatibility was determined in accordance with DIN 10993-5/-12 regulations by extract assays. RESULTS: Besides cytocompatibility, all PEO specimens exhibited similar biocompatibility and attachment properties, with vital, spindle-shaped adherent cells growing on the surface, regardless of their surface topology. There were no significant differences in cellular proliferation between the different surfaces and negative controls (cells growing in cell-culture plates). DISCUSSION/CONCLUSION: With no differences in cellular proliferation and attachment between PEO surfaces with different roughness, we find no evidence to support the notion that rougher PEO surfaces are more favorable for cellular growth of fibroblasts in vitro.

Lack of evidence for increased postoperative bleeding risk for dental osteotomy with continued aspirin therapy.

OBJECTIVE: Dental osteotomy, the removal of an impacted, ankylosed, or severely destroyed tooth requiring an osteotomy, is more invasive than other minor dental procedures and therefore also has a higher bleeding risk. A considerable number of patients under antiplatelet therapy interrupt their therapy perioperatively, which, however, increases the risk of thromboembolism. STUDY DESIGN: This retrospective study assessed postoperative bleeding incidence for a total of 297 dental osteotomies with continued aspirin therapy, compared with that of 179 similar procedures on patients who were not on any anticoagulation or anti-platelet therapy. All procedures were carried out on an outpatient basis. RESULTS: Postoperative bleeding event was rare in both groups, 5 (1.7%) and 2 (1.1%), respectively, and the difference was not significant (P = .7). CONCLUSIONS: Continued aspirin therapy in patients undergoing dental osteotomies has no effect on the incidence of postoperative bleeding and should not be interrupted.

ABO blood group IgM isoagglutinins interact with tumor-associated O-glycan structures in pancreatic cancer.

PURPOSE: The ABO gene locus is associated with the risk of developing pancreatic ductal adenocarcinoma (PDAC) resulting in an increased incidence in individuals with non-O blood groups. Up to 90% of PDAC specimens display alterations in mucin type O-GalNAc glycosylation. Because aberrant O-GalNAc glycans (Tn and T antigen) are structurally related to blood group A and B glycans, we investigated the role of IgM isoagglutinins in PDAC. EXPERIMENTAL DESIGN: Binding studies of IgM isoagglutinins toward blood group A, B, Tn antigen, and T antigen glycoconjugates from patients with PDAC and healthy individuals were conducted. Isoagglutinin titers and total IgM were compared between patients with PDAC and control group. An anti-A antibody was used for immunoprecipitation of aberrant O-glycosylated tumor proteins and subsequent mass spectromic analysis. RESULTS: We found that IgM isoagglutinins bind blood group antigens, Tn and T glycoconjugates as well as tumor-derived glycoproteins. Blood group A isoagglutinins exhibited a strong binding toward blood group B antigen and T antigen, whereas blood group B showed binding to blood group A antigen and Tn antigen. Furthermore, we confirmed a decreased frequency in individuals with blood group O and observed a significant decrease of IgM isoagglutinin titers in PDAC sera compared with control sera, whereas total IgM levels were unaltered. We identified new PDAC-derived O-GalNAc glycoproteins by mass spectrometry using a blood group A-specific antibody. CONCLUSION: Our data elucidated a novel interaction of blood group IgM isoagglutinins and PDAC O-GalNAc glycoproteins that may contribute to the pathogenesis and progression of pancreatic cancer.

First description of a hybrid tumor of the sublingual gland.

BACKGROUND: Hybrid tumours of the salivary glands are rare neoplasms. They are composed of at least two different tumour entities located in the same topographic area and account for only 0.1% of all salivary gland tumours. The most common component is an adenoid cystic carcinoma. There are several possible forms of hybrid tumours, which are most commonly located in the parotid gland. CASE REPORT: We report on a 59-year-old female, who presented with a lesion of the caruncula of the left sublingual gland. The biopsy showed an adenoid cystic carcinoma in combination with a salivary duct carcinoma. Treatment consisted of tumour resection, bilateral selective neck dissection and adjuvant radiotherapy. Histopathologically, at least 30% of the tumour mass was composed of a salivary duct carcinoma and 70% of an adenoid cystic carcinoma. At 58 months after treatment, the patient is alive without evidence of recurrent disease. CONCLUSION: To our knowledge, the presented case is the first description of a hybrid tumour of the sublingual gland. Furthermore, the post-therapeutic course is encouraging, as hybrid tumours of the salivary glands usually have a poor prognosis.