RESUMO
OBJECTIVES: Pre-vascularization of the collagen membranes with autologous platelet concentrates is a standard procedure in oral and maxillofacial surgery. This study analyzed the possible interaction of an acellular collagen membrane of porcine origin (NM) with platelet-rich fibrin (PRF) regarding its rehydration protocol with differences in pH values and effect on angiogenesis. MATERIALS AND METHODS: NM was analyzed alone and combined with solid PRF by plotting or co-culturing with injectable PRF. Different media (venous blood, buffer solution with a fixed pH value of 7, saline solution, and injectable PRF) were used to analyze the influence on pH value during rehydration. Chorion allantois membrane assay (CAM) was applied to check pro-angiogenic effects after 24, 48, and 72 h, followed by immunohistochemical analysis. RESULTS: Rehydration in injectable PRF showed acidity over time (p < 0.05). A definite pro-angiogenic effect of NM alone was found regarding neo-vessel formation supported by the respective light microscopically analysis without significant differences to PRF alone (p > 0.005). This pro-angiogenic effect could not be exaggerated when NM was combined with liquid/solid PRF (each p > 0.005). CONCLUSIONS: Rehydration with liquid PRF of the collagen membrane results in acidity compared to a saline solution or patient's blood. The significant pro-angiogenic potential of the membrane alone resulted in enhanced neo-vessel formation that could not be optimized with the addition of PRF. CLINICAL RELEVANCE STATEMENT: Using injectable PRF for rehydration protocol of the collagen membrane leads to acidosis that can ultimately optimize wound healing. Differences in the physio-mechanical interplay of collagen matrices and autologous platelet concentrates must result in clinical algorithms if pre-vascularization can maximize outcomes.
Assuntos
Fibrina Rica em Plaquetas , Suínos , Humanos , Animais , Solução Salina , Colágeno , Matriz Extracelular , Neovascularização Patológica , HidrataçãoRESUMO
We report on a compact, ultrahigh-vacuum compatible optical assembly to create large-scale, two-dimensional optical lattices for use in experiments with ultracold atoms. The assembly consists of an octagon-shaped spacer made from ultra-low-expansion glass, to which we optically contact four fused silica cavity mirrors, making it highly mechanically and thermally stable. The mirror surfaces are nearly plane-parallel, which allows us to create two perpendicular cavity modes with diameters â¼1m m. Such large mode diameters are desirable to increase the optical lattice homogeneity, but lead to strong angular sensitivities of the coplanarity between the two cavity modes. We demonstrate a procedure to precisely position each mirror substrate that achieves a deviation from coplanarity of d=1(5)µm. Creating large optical lattices at arbitrary visible and near-infrared wavelengths requires significant power enhancements to overcome limitations in the available laser power. The cavity mirrors have a customized low-loss mirror coating that enhances the power at a set of relevant visible and near-infrared wavelengths by up to 3 orders of magnitude..
RESUMO
OBJECTIVES: Monocarboxylate transporters (MCT) 1, 2 and 4 play an important role in tumor metabolism. The amount of lactate transported by MCT's highly correlates with overall survival. Furthermore, glycolysis and hypoxia are possible causes for radiation resistance. MATERIALS AND METHODS: An oral squamous cell carcinoma cell line (CAL27, ATCC) was analyzed in an in vitro cell assay. After incubation with two different inhibitors for MCT1 (AR-C122982/SR-13800 and AR-C155858/SR-13801, Tocris) or for MCT4 (simvastatin, Sigma-Aldrich and 2-cyano-3-(4-hydroxyphenyl)-2-propenoic acid (CHC), Tocris), cells were irradiated with six gray with a Gammacell 2000 (Nuklear Data). For analysis, cell counting assay, wound healing assay, MTT assay and clonogenic assay were applied. RESULTS: Cell counting assay showed significant lower results for simvastatin, CHC and for the highest concentrations of AR-C122982 and AR-C155858 (p < 0.03). Additionally, cell counts decreased significantly with irradiation after 72 hours (p < 0.05) only for AR-C122982, CHC and simvastatin. The clonogenic assay confirmed these results with substantially reduced growth when incubated with CHC, simvastatin and AR-C155858 (p < 0.002). Furthermore, MCT1 and 4 inhibition led to highly reduced migration (p < 0.05). There again, comparing the wound healing assay of irradiated to non-irradiated tests showed contrary results (controls: p < 0.001; AR-C155858: p > 0.05; AR-C122982: p > 0.32; CHC: p > 0.1; simvastatin p > 0.1). The MTT assay presented significant effects with MCT1 and 4 inhibition (simvastatin/AR-C122982/CHC: p < 0.007). Irradiated cells showed significantly lower expression after only 48 h compared to non-irradiated cells (simvastatin/AR-C122982/CHC: p < 0.02). CONCLUSIONS: Inhibition of MCT, especially MCT4 may represent a possible tool to overcome radiation resistance in tumor cell lines. CLINICAL RELEVANCE: MCT Inhibitors may be used as a possible therapeutic approach to sensitize OSCC to radiation.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Radiação , Simportadores , Carcinoma de Células Escamosas/radioterapia , Contagem de Células , Linhagem Celular Tumoral , Humanos , Transportadores de Ácidos MonocarboxílicosRESUMO
OBJECTIVES: There is an increasing number of oral squamous cell carcinoma (OSCC) associated with HPV-16. However, p16 expression by immunohistochemistry as the current gold standard for a surrogate marker for virus infection reveals unsatisfying diagnostic accuracy. The aim of this study was to investigate a new rapid test for L1 antibody detection (Prevocheck®) and to validate its diagnostic performance. MATERIALS AND METHODS: In a prospective study, the HPV 16 association of all consecutive patients with an OSCC treated between 2015 and 2019 were analyzed by L1 seropositivity (via PrevoCheck®), p16 immunostaining, and partly multiplex PCR for subtype analysis. RESULTS: Overall (n = 107), p16 expression was positive in 17 cases (15.9%), and L1 antibody seropositivity in 7 cases (6.5%). In PCR analysis, two cases of HPV35 and 50 were found. Total HPV prevalence was 8.4% overall and 6.5% for HPV-16. An inferior diagnostic accuracy for HPV-16-associated OSCC in comparison to PrevoCheck® was revealed. CONCLUSION: The rapid test for L1 antibodies showed an optimal sensitivity and specificity, positive and negative predictive value, and an overall diagnostic accuracy of 100%. However, HPV prevalence seems low in OSCC. CLINICAL RELEVANCE: L1 rapid test may represent an additional diagnostic staging method to detect HPV-16 association rather than p16 immunohistochemistry.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Infecções por Papillomavirus , Carcinoma de Células Escamosas/diagnóstico , Inibidor p16 de Quinase Dependente de Ciclina , Humanos , Papillomaviridae , Infecções por Papillomavirus/diagnóstico , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Resultado do TratamentoRESUMO
OBJECTIVES: Porcine-derived collagen matrices (CM) can be used for oral tissue regeneration, but sufficient revascularization is crucial. The aim of this study was to analyze the influence of platelet-rich fibrin (PRF) on angiogenesis of different CM in vitro and in vivo. MATERIALS AND METHODS: Three different CM (mucoderm®, jason®, collprotect®) were combined with PRF in a plotting process. Growth factor release (VEGF, TGF-ß) was measured in vitro via ELISA quantification after 1,4 and 7 days in comparison to PRF alone. In ovo yolk sac (YSM) and chorion allantois membrane (CAM) model, angiogenic potential were analyzed in vivo with light- and intravital fluorescence microscopy after 24 h, then verified with immunohistochemical staining for CD105 and αSMA. RESULTS: Highest growth factor release was seen after 24 h for all three activated membranes in comparison to the native CM (VEGF 24 h: each p < 0.05; TGF-ß: each p < 0.001) and the PRF (no significant difference). All activated membranes revealed a significantly increased angiogenic potential in vivo after 24 h (vessels per mm2: each p < 0.05; branching points per mm2: each p < 0.01; vessel density: each p < 0.05) and with immunohistochemical staining for CD105 (each p < 0.01) and αSMA (each p < 0.05). CONCLUSIONS: PRF improved the angiogenesis of CM in vitro and in vivo. CLINICAL RELEVANCE: Bio-functionalization of CM with PRF could easily implemented in the clinical pathway and may lead to advanced soft tissue healing.
Assuntos
Colágeno/química , Animais , Peptídeos e Proteínas de Sinalização Intercelular , Fibrina Rica em Plaquetas , Suínos , CicatrizaçãoRESUMO
PURPOSE: Especially in oral and maxillofacial surgery, where procedures involving the aero-digestive tract considered clean contaminated, surgical site infections (SSI) represent a severe health care burden. To improve implementation and methodological standard, an upgrade of the existing S1 guideline to a consensus-guided S3 guideline was initiated by the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V., AWMF, register number 067/009) and 25 collaborating medical societies. METHODS: A systematic literature search based on the Scottish Intercollegiate GL Network (SIGN)-search string for the guideline "Antibiotic prophylaxis in surgery" from 2014 was performed and equivalent exclusion/inclusion criteria were applied. An additional hand search provided latest evidence. RESULTS: In total, 80 clinical trials, retrospective studies, reviews, and meta-analysis were analyzed. For orthognathic surgery, prolonged antibiotic regimen may reduce risk for SSI but there is lack of evidence for the effects of short- vs. long-term therapy. For maxillofacial traumatology, antibiotic prophylaxis might reduce SSI but prolonged postoperative dosing shows no benefit. For clean-contaminated oncological interventions, anti-infectious therapy for 24 h only can reduce SSI; patients may not benefit from prolonged regimen. In contrast, for dentoalveolar procedures such as implantology or third molar removal, literature reveals ambivalent results. CONCLUSION: In summary, consensus process of the planned S3 guideline is much in need to transfer the indecisive results for antibiotic prophylaxis in dentoalveolar surgery in clinical praxis and encourage adherence to guidelines.
Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Procedimentos Cirúrgicos Bucais/métodos , Antibioticoprofilaxia/estatística & dados numéricos , Humanos , Procedimentos Cirúrgicos Bucais/estatística & dados numéricosRESUMO
OBJECTIVES: The aim of this murine in vivo study was to investigate whether buffy coat-derived putative endothelial progenitor cells (BCEPC) alter tumor growth and neovascularization in oral squamous cell carcinomas (OSCC). MATERIALS AND METHODS: A murine xenograft model using the PCI-13 oral cancer cell line was deployed of which n = 24 animals received 2 × 106 BCEPC by transfusion whereas the control group (n = 24) received NaCl (0.9%) instead. Tumor size, volume, and capillary density were determined by sonography and measurement with a caliper. Immunohistochemical analysis was carried out with antibodies specific for Cytokeratins, Flt-4, Podoplanin, and Vimentin. RESULTS: In the experimental group, systemic application of BCEPC significantly increased tumor volume to 362.49% (p = 0.0012) and weight to 352.38% (p = 0.0018) as well as vascular densities to 162.15% (p = 0.0021) compared with control tumors. In addition, BCEPC-treated xenografts exhibited higher Cytokeratin expression levels by a factor of 1.47 (p = 0.0417), Podoplanin by a factor of 3.3 (p = 0.0020) and Vimentin by a factor of 2.5 (p = 0.0001), respectively. CONCLUSIONS: Immunohistochemical investigations support the notion that BCEPC transfusion influences neovascularization and lymphatic vessel density, thereby possibly promoting tumor progression. Future studies, which will include gene expression analysis, should help to define the possible role of BCEPC during OSCC progression in more detail. CLINICAL RELEVANCE: Endothelial progenitor cells (EPCs) could serve as a target structure for the treatment of OSCC and possibly other solid tumors.
Assuntos
Carcinoma de Células Escamosas/patologia , Células Progenitoras Endoteliais/citologia , Neoplasias Bucais/patologia , Neovascularização Patológica , Animais , Buffy Coat , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Transplante HeterólogoRESUMO
BACKGROUND: Inflammation and cell-mediated immunity have a key role in different stages of carcinogenesis. The aim of this prospective study was to assess serum levels of proinflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), soluble interleukin-2 receptor (sIL-2R), tumor necrosis factor alpha (TNF-α), and MHC class I polypeptide-related sequence B (MICB) in patients with oral premalignant lesion (OPL), oral squamous cell carcinoma (OSCC), and healthy controls in a multi-biomarker approach as a potential diagnostic and prognostic tool for OSCC. MATERIAL AND METHODS: A total of 205 patients (81 with OSCC, 75 with OPL, and 49 healthy controls) were included in this prospective study. Cytokine concentrations were measured by commercial enzyme linked immunoassay and chemiluminescence immunoassay. RESULTS: IL-6, IL-8, and sIL-2R were significantly elevated in OSCC patients compared to healthy controls and to OPL patients. Higher T-Grade (>T2) and positive lymph node involvement resulted in significantly higher IL-6 values (P < .001 and P = .037). IL-6 serum values ≥5 pg/mL (n = 45) and sIL-2R serum values ≥623 U/mL (n = 19) indicated a significant lower survival rate compared to OSCC patients with low IL-6 (n = 36) and sIL-2R values (n = 62, P = .023 and P = .026). ROC and classification tree analyses identified the combination of IL-6 and IL-8 as diagnostic markers with good diagnostic accuracy. CONCLUSION: In conclusion, IL-6, IL-8, and sIL-2R are strongly associated with OSCC oncogenesis and IL-6 and sIL-2R seem to be promising and potent biomarkers for evaluating patients' prognosis.
Assuntos
Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/mortalidade , Citocinas/sangue , Neoplasias Bucais/sangue , Neoplasias Bucais/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Prognóstico , Estudos Prospectivos , Adulto JovemRESUMO
OBJECTIVES: Chronic accumulation of lactate in malignant tumor tissue is associated with increased malignancy and radioresistance. For this study, biopsies of primary head and neck squamous cell carcinoma (HNSCC) and of the normal gingiva of the same patient were compared via metabolic profiling to the healthy gingiva from cancer-free patients. MATERIALS AND METHODS: Cryobiopsies of 140 HNSCC patients were used to determine ATP, lactate, and glucose concentrations of the tumor and normal gingiva via induced metabolic bioluminescence imaging (imBI). Additionally, these metabolites were quantified in a collective of 79 healthy (non-tumor-bearing) patients. Furthermore, tumor samples were analyzed via immunofluorescence imaging and quantitative real-time PCR for the expression of lactate and glucose transporters. RESULTS: There were significant differences in ATP concentrations detectable between the tumor, normal gingiva of tumor patients, and gingiva from healthy patients. Lactate concentrations were significantly increased in tumor tissue compared to the normal gingiva of tumor patients as well as the gingiva from healthy patients. Concerning glucose, there was a significant decrease in glucose concentrations detectable in the tumor biopsies compared to the normal gingiva of tumor patients. On the other hand, tumor samples from patients revealed significantly elevated relative expression levels of monocarboxylate transporters (MCT-1 and MCT-4), as well as glucose transporters (GLUT-1 and GLUT-3) compared to the corresponding normal gingiva of each patient. CONCLUSIONS: We could demonstrate that the lactate concentration in HNSCC correlates with primary tumor (T) stage. CLINICAL RELEVANCE: The aim of this study was to identify metabolic parameters to improve early cancer diagnosis, allow predictions on the degree of malignancy, and contribute to a personalized tumor therapy.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Gengiva/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Trifosfato de Adenosina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma de Células Escamosas/patologia , Transportador 2 de Aminoácido Excitatório/metabolismo , Feminino , Glucose/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Lactatos/metabolismo , Masculino , Pessoa de Meia-Idade , Transportadores de Ácidos Monocarboxílicos/metabolismo , Proteínas Musculares/metabolismo , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase em Tempo Real , Carcinoma de Células Escamosas de Cabeça e Pescoço , Simportadores/metabolismoRESUMO
OBJECTIVES: Because of the low proportion of squamous cell carcinomas (SCCs) of the buccal mucosa within the carcinomas of the oral cavity in the Western population, data concerning metastatic pattern are sparse. Therefore, this retrospective study is focusing on the occurrence of cervical metastases (CM) and the overall outcome of this tumor entity. MATERIALS AND METHODS: From January 1988 to October 2013, 113 patients were treated in the Department of Oral and Maxillofacial Surgery, Mainz, for an oral SCC of the cheek. Metastatic pattern and clinical parameters that are possibly associated with an increased risk for CM as well as overall outcome were analyzed. RESULTS: The average follow-up was 48 months (range: 1-248 months). A total of 55 (49%) patients were female and 58 (51%) male, with an average age of 65 ± 13 years (â68 ± 14 years; â63 ± 11 years). In total, 55% of the patients either smoked and/or consumed alcohol. In total, 34% of the patients had a stage III or IV tumor, with overall 23% having CM at the time of diagnosis. During the follow-up, 50% (n = 56) of the patients developed a relapse after 12 months (median). Tumor size (P = 0.002*) and grading (P < 0.001*) are significantly associated with the occurrence of CM. Metastases (P = 0.008*) and advanced tumor size (P = 0.018) had an influence on the survival, whereas the relapse had no significant influence (P = 0.928). Five-year survival rate was 80%. CONCLUSIONS: SCC of the buccal mucosa shows aggressive behavior with a considerably high proportion of relapse. Since overall outcome is significantly decreased by the cervical metastatic pattern, a selective, ipsilateral neck dissection for this patient group is recommended as the primary management.
Assuntos
Carcinoma de Células Escamosas/secundário , Neoplasias de Cabeça e Pescoço/secundário , Mucosa Bucal/patologia , Neoplasias Bucais/patologia , Pescoço/patologia , Idoso , Carcinoma de Células Escamosas/cirurgia , Bochecha , Feminino , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Neoplasias Bucais/cirurgia , Esvaziamento Cervical , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
OBJECTIVES: The clinical management of the neck of patients with early-stage oral squamous cell cancer (OSCC) is still controversially discussed in the current literature. This study analyzes histo-clinical factors influencing the occurrence of cervical lymph node metastases (CM). MATERIALS AND METHODS: In a retrospective mono-center study, patients with a primary T1-2 OSCC between 2000 and 2014 were analyzed regarding histo-clinical parameters possibly influencing the CM rate and the outcome. RESULTS: Two hundred eighty-five patients (66 %) were male and 146 female (44 %), with a mean age of 60 ± 12 years at the time of diagnosis. Seventy-seven percent showed a positive risk profile (nicotine/alcohol) and 69 % underlying diseases. Forty-four percent of the patients were staged as T2 (30 % with CM). Advanced tumor size (T1 vs. T2) and grading (G1-2 vs. G3) were statistically significantly (p < 0.001) associated with the occurrence of CM. The localization within the oral cavity, age, gender, risk profile, or underlying diseases had no influence on CM occurrence. During the follow-up, tumor size (p = 0.001), CM (p < 0.001), and tumor relapse (p < 0.001) were significantly associated with a worse outcome. CONCLUSIONS: Early-stage OSCC showed aggressive lymphatic metastatic behavior that depends on the size and the grading of the tumor. CLINICAL RELEVANCE: A watch-and-wait policy as the primary management for cN0 may likely be inferior to a selective neck dissection for this patient group and should only be considered for very small tumors with a good differentiation.
Assuntos
Carcinoma de Células Escamosas/patologia , Metástase Linfática/patologia , Neoplasias Bucais/patologia , Feminino , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Esvaziamento Cervical , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND/AIM: There are no data available to show whether there is a relationship between mandibular fractures and isolated fractures of the posterior and/or lateral walls of the maxillary sinus. The aim of this study was to determine whether there is a coincidence between these fracture patterns. METHODS: Four hundred large volume cone beam computed tomography scans (CBCT) of patients with a fracture of the mandible between 2008 and 2013 were analyzed retrospectively. Patients with multiple midfacial fractures were excluded. The radiographic findings were correlated with epidemiological and clinical data of the patients such as gender, age, treatment methods, or complications. RESULTS: The most frequent fracture sites of the mandible were the jaw angle, the parasymphysis region, and the condyle. Nineteen of the 400 patients (4.75%) had an isolated fracture of the lateral and/or posterior maxillary sinus. Odds-ratio analysis revealed a high tendency for significant correlation of condylar process fractures with isolated maxillary sinus fractures. Chi-square test demonstrated a P-value near statistical significance (P=.054). No other fracture site of the mandible could be associated with an isolated fracture of the maxillary sinus. CONCLUSION: A condylar process fracture of the mandible after trauma without any further injury of the midface may be associated with an isolated fracture of the lateral and/or posterior maxillary sinus.
Assuntos
Fraturas Mandibulares/complicações , Fraturas Maxilares/complicações , Seio Maxilar/lesões , Adulto , Tomografia Computadorizada de Feixe Cônico , Feminino , Alemanha , Humanos , Masculino , Fraturas Mandibulares/diagnóstico por imagem , Fraturas Maxilares/diagnóstico por imagem , Seio Maxilar/diagnóstico por imagem , Estudos RetrospectivosRESUMO
OBJECTIVES: Angiogenesis and neovascularisation plays a crucial role for tumorigenesis and tumor progression in head and neck squamous cell carcinoma (HNSCC). The aim of our study was to investigate the neovascularization capacity by endothelial progenitor cells (EPC) in tumor patient as a possible predictor for tumor progression and tumor stage. MATERIALS AND METHODS: Therefore, we investigated the cell number and biologic activity by cell migration and colony-forming ability of EPC. Cells were isolated from the peripheral venous blood of 79 patients who suffer HNSCC in different stages of disease. Thirty-three healthy individuals served as the control group. RESULTS: Significantly increased biological activities were reflected by expression of the migration rate (1027 ± 1510) in comparison to the control group (632 ± 269) and the clonal potency measured by colony-forming unit (CFU) (tumor patients (19.7 ± 12.3) vs. control group (10.84 ± 4.8)). To determine whether or not EPC number can be used as a valid prognostic marker for clinical outcome of tumor patients, we furthermore compared a "high EPC-number-subgroup" (HI) with a "low EPC-number-subgroup" (LO) in a Kaplan-Meier survival curve. The HI-subgroup shows herein clearly a worse outcome. CONCLUSIONS: Our findings indicate a possible pathway for EPC to play a critical role in the vasculogenesis and consequently in the progression of HNSCC. CLINICAL RELEVANCE: Our findings could serve as possible predictors for the neovascularisation potential in HNSCC tumor patients.
Assuntos
Carcinogênese/patologia , Carcinoma de Células Escamosas/patologia , Células Progenitoras Endoteliais/patologia , Neoplasias de Cabeça e Pescoço/patologia , Neovascularização Patológica/patologia , Idoso , Biomarcadores Tumorais , Estudos de Casos e Controles , Movimento Celular , Transformação Celular Neoplásica/patologia , Progressão da Doença , Feminino , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Células-TroncoRESUMO
OBJECTIVES: Lactate as a key regulator of the glycolytic phenotype has been recently described in fueling tumor growth and metastatic spread in head and neck squamous cell carcinoma (HNSCC). However, in context of tumor recurrence following adjuvant radiation, the underlying mechanisms remain uncertain. We therefore investigate the role of lactate towards radioresistance in HNSCC in this prospective study for the first time in vivo. MATERIALS AND METHODS: Herein, we analyzed biopsies of primary squamous cell carcinoma after surgery and adjuvant irradiation in 17 patients. Tumor tissue levels of ATP, glucose, and lactate were detected using induced metabolic bioluminescence imaging (imBI) and correlated with clinical data within an observation period of up to 15 years. RESULTS: High amounts of lactate levels in tumors of HNSCC are significantly negatively correlated with overall patient survival. Moreover, high expression of lactate in a primary tumor site is significantly correlated with tumor recurrence post radiation, whereas ATP and/or glucose showed no such correlation. CONCLUSION: Lactate can be seen not only as a waste product of altered glycolytic metabolism but also as a key master of malignancy as well as resistance mechanism towards irradiation. CLINICAL RELEVANCE: High expression of lactate levels in tumor tissue, obtained by metabolic bioluminescence imaging, may therefore serve as a predictor for overall and recurrence-free survival and could represent a future biomarker in the validation of adjuvant irradiation.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Ácido Láctico/metabolismo , Recidiva Local de Neoplasia , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Medições Luminescentes , Masculino , Pessoa de Meia-Idade , Imagem Molecular/métodos , Estudos Prospectivos , Tolerância a Radiação , Taxa de SobrevidaRESUMO
We demonstrate site-resolved imaging of individual fermionic ^{6}Li atoms in a single layer of a 3D optical lattice. To preserve the density distribution during fluorescence imaging, we simultaneously cool the atoms with 3D Raman sideband cooling. This laser cooling technique, demonstrated here for the first time for ^{6}Li atoms, also provides a pathway to rapid low-entropy filling of an optical lattice. We are able to determine the occupation of individual lattice sites with a fidelity >95%, enabling direct, local measurement of particle correlations in Fermi lattice systems. This ability will be instrumental for creating and investigating low-temperature phases of the Fermi-Hubbard model, including antiferromagnets and d-wave superfluidity.
RESUMO
PURPOSE: Particulate bovine bone substitutes (BS) are commonly used in oral regeneration. However, more literature is needed focusing on comparative analyses among various particulate bovine BS. This study evaluates pre-clinical and clinical data of different particulate bovine BS in oral regeneration. METHODS: A narrative review was conducted by screening the PubMed database Included in the review were pre-clinical and clinical studies until 2024 comparing a minimum of two distinct particulate bovine BS. In addition to examining general data concerning manufacturing and treatment processes, biological safety, physical and chemical characteristics, and graft resorption, particular emphasis was placed on assessing pre-clinical and clinical data related to ridge preservation, sinus floor elevation, peri-implant defects, and various forms of alveolar ridge augmentation utilizing particulate bovine BS. RESULTS: Various treatment temperatures ranging from 300 to 1,250 °C and the employment of chemical cleaning steps were identified for the manufacturing process of particulate bovine BS deemed to possess biosecurity. A notable heterogeneity was observed in the physical and chemical characteristics of particulate bovine BS, with minimal or negligible graft resorption. Variations were evident in particle and pore sizes and the porosity of particulate bovine BS. Pre-clinical assessments noted a marginal inclination towards favorable outcomes for particulate bovine BS subjected to higher treatment temperatures. However, clinical data are insufficient. No distinctions were observed regarding ridge preservation, while slight advantages were noted for high-temperature treated particulate bovine BS in sinus floor elevation. CONCLUSIONS: Subtle variances in both pre-clinical and clinical outcomes were observed in across various particulate bovine BS. Due to inadequate data, numerous considerations related to diverse particulate bovine BS, including peri-implant defects, must be more conclusive. Additional clinical studies are imperative to address these knowledge gaps effectively.
Assuntos
Substitutos Ósseos , Bovinos , Animais , Substitutos Ósseos/uso terapêutico , Humanos , Aumento do Rebordo Alveolar/métodos , Regeneração Óssea/fisiologiaRESUMO
In this retrospective study, the clinical and economic implications of microvascular reconstruction of the mandible were assessed, comparing immediate versus delayed surgical approaches. Utilizing data from two German university departments for oral and maxillofacial surgery, the study included patients who underwent mandibular reconstruction following continuity resection. The data assessed included demographic information, reconstruction details, medical history, dental rehabilitation status, and flap survival rates. In total, 177 cases (131 male and 46 females; mean age: 59 years) of bony free flap reconstruction (72 immediate and 105 delayed) were included. Most patients received adjuvant treatment (81% with radiotherapy and 51% combined radiochemotherapy), primarily for tumor resection. Flap survival was not significantly influenced by the timing of reconstruction, radiotherapy status, or the mean interval (14.5 months) between resection and reconstruction. However, immediate reconstruction had consumed significantly fewer resources. The rate of implant-supported masticatory rehabilitation was only 18% overall. This study suggests that immediate jaw reconstruction is economically advantageous without impacting flap survival rates. It emphasizes patient welfare as paramount over financial aspects in clinical decisions. Furthermore, this study highlights the need for improved pathways for masticatory rehabilitation, as evidenced by only 18% of patients with implant-supported dentures, to enhance quality of life and social integration.
RESUMO
Free flap failure represents a substantial clinical burden. The role of intraoperative volume management remains controversial, with valid studies lacking. Here, using a large animal model, we investigated the influence of volume management on free flap perfusion and metabolism. Autotransfer of a musculocutaneous gracilis flap was performed on 31 German domestic pigs, with arterial anastomosis and catheterization of the pedicle vein for sequential blood sampling. Flap reperfusion was followed by induction of a hemorrhagic shock with maintenance for 30 min and subsequent circulation stabilization with crystalloid solution, crystalloid solution and catecholamine, autotransfusion or colloidal solution. Flap perfusion and oxygenation were periodically assessed using hyperspectral imaging. Flap metabolism was assessed via periodic blood gas analyses. Hyperspectral imaging revealed no difference in either superficial or deep tissue oxygen saturation, tissue hemoglobin or tissue water content between the test groups at any time point. Blood gas analyses showed that lactate levels were significantly increased in the group that received crystalloid solution and catecholamine, after circulatory stabilization and up to 2 h after. We conclude that, in hemorrhagic shock, volume management impacts acid-base balance in free flaps. Crystalloid solutions with norepinephrine increase lactate levels, yet short-term effects on flap perfusion seem minimal, suggesting that vasopressors are not detrimental.
Assuntos
Retalhos de Tecido Biológico , Choque Hemorrágico , Animais , Retalhos de Tecido Biológico/irrigação sanguínea , Choque Hemorrágico/metabolismo , Suínos , Soluções Cristaloides/farmacologia , Soluções Cristaloides/administração & dosagem , Gasometria , Soluções Isotônicas/farmacologia , Perfusão/métodosRESUMO
Introduction: Autologous platelet concentrate (APC) are pro-angiogenic and can promote wound healing and tissue repair, also in combination with other biomaterials. However, challenging defect situations remain demanding. 3D bioprinting of an APC based bioink encapsulated in a hydrogel could overcome this limitation with enhanced physio-mechanical interface, growth factor retention/secretion and defect-personalized shape to ultimately enhance regeneration. Methods: This study used extrusion-based bioprinting to create a novel bioink of alginate/cellulose hydrogel loaded with thrombocyte concentrate. Chemico-physical testing exhibited an amorphous structure characterized by high shape fidelity. Cytotoxicity assay and incubation of human osteogenic sarcoma cells (SaOs2) exposed excellent biocompatibility. enzyme-linked immunosorbent assay analysis confirmed pro-angiogenic growth factor release of the printed constructs, and co-incubation with HUVECS displayed proper cell viability and proliferation. Chorioallantoic membrane (CAM) assay explored the pro-angiogenic potential of the prints in vivo. Detailed proteome and secretome analysis revealed a substantial amount and homologous presence of pro-angiogenic proteins in the 3D construct. Results: This study demonstrated a 3D bioprinting approach to fabricate a novel bioink of alginate/cellulose hydrogel loaded with thrombocyte concentrate with high shape fidelity, biocompatibility, and substantial pro-angiogenic properties. Conclusion: This approach may be suitable for challenging physiological and anatomical defect situations when translated into clinical use.
RESUMO
PURPOSE: This study aimed to investigate the effect of three different osteosynthesis plate systems on failure rates and complications after continuity-interrupting mandibular resections with alloplastic reconstructions. MATERIALS AND METHODS: Records of respective patients from 2010 to 2020 were analyzed retrospectively. The analyses included the osteosynthesis plate type (2.4 MANDIBULAR (RP1: MANDIBULAR [Medicon®, Tuttlingen, Germany]; RP2: Modus® Reco 2.5 [Medartis®, Basel, Switzerland]; and RP3: Modus 2 Mandible [Medartis®, Basel, Switzerland]), extent & location of the defect, age, sex, radiotherapy, and nicotine abuse. In case of failure, timepoint, and the problem, namely oral/extraoral dehiscence, screw loosening, and plate fractures that led to removal, were analyzed. Complications were classified according to Clavien-Dindo system. RESULTS: A total of 136 patients were included. The mean follow-up time was 18 ± 26 months. Survival rates after 1, 2, and 5 years were 69.9%, 66.9%, and 64.7%, respectively. Although survival was not significantly associated with the reconstruction system, the most frequent complications were seen in cases of RP1 & RP2 when compared to RP3 (p = 0.033). In brief, dehiscences were seen significantly less often in cases of RP3 (12.5%) when compared to RP1 (44.7%) and RP2 (26.9%; p = 0.024). Fractures of the osteosynthesis systems occurred in 3 of 4 cases (75%) with RP1, in 1 of 4 cases (25%) using RP2, and in no single case using the RP3 system (p = 0.03). Most of the observed complications occurred up to 12 months postoperatively. A total plate survival rate of 64.7% and a total plate complication rate of 47.8% were seen. CONCLUSION: In conclusion, it seems that RP3 should be preferred over RP1 and RP2 regarding failure rates and complications.